An amendment to this paper has been published and can be accessed via the original article.
Objective: GDF11 is a member of the TGF-β superfamily that was recently implicated as potential "rejuvenating" factor, which can ameliorate metabolic disorders. The main objective of the presented study was to closely characterize the role of GDF11 signaling in the glucose homeostasis and in the differentiation of white adipose tissue. Methods: We performed microscopy imaging, biochemical and transcriptomic analyses of adipose tissues of 9 weeks old ob/ob mice and murine and human pre-adipocyte cell lines. Results: Our in vivo experiments employing GDF11 treatment in ob/ob mice showed improved glucose/insulin homeostasis, decreased weight gain and white adipocyte size. Furthermore, GDF11 treatment inhibited adipogenesis in pre-adipocytes by ALK5-SMAD2/3 activation in cooperation with the WNT/β-catenin pathway, whose inhibition resulted in adipogenic differentiation. Lastly, we observed significantly elevated levels of the adipokine hormone adiponectin and increased glucose uptake by mature adipocytes upon GDF11 exposure. Conclusion: We show evidence that link GDF11 to adipogenic differentiation, glucose, and insulin homeostasis, which are pointing towards potential beneficial effects of GDF11-based "anti-obesity" therapy.
Purpose The aim of this study was to assess the biomechanical performance of different screw configurations for fixation of Sanders type II B joint-depression calcaneal fractures. Methods Fifteen human cadaveric lower limbs were amputated and Sanders II B fractures were simulated. The specimens were randomized to three groups for fixation with different screw configurations. The calcanei in Group 1 were treated with two parallel longitudinal screws, entering superiorly the Achilles tendon insertion, and two screws fixing the intraarticular posterior facet fracture line. In Group 2 two screws entered the tuberosity inferiorly to the Achilles tendon insertion and two transverse screws fixed the posterior facet. In Group 3 two screws were inserted along the bone axis, one transverse screw fixed the posterior facet and one oblique screw was inserted from the posteroplantar part of the tuberosity supporting the posterolateral part of the posterior facet. All specimens were biomechanically tested to failure under progressively increasing cyclic loading. Results Initial stiffness did not differ significantly between the groups, P = 0.152. Cycles to 2 mm plantar movement were significantly higher in both Group 1 (15,847 ± 5250) and Group 3 (13,323 ± 4363) compared with Group 2 (4875 ± 3480), P ≤ 0.048. No intraarticular displacement was observed in any group during testing. Conclusions From a biomechanical perspective, posterior facet support by means of buttress or superiorly inserted longitudinal screws results in less plantar movement between the calcaneal tuberosity and the anterior fragments. Inferiorly inserted longitudinal screws are associated with bigger interfragmentary movements.
Mucormycosis is a relatively rare infection but with a high mortality rate due to the difficult and time-consuming diagnostic and therapeutic process. The authors present the first case of rhino-orbital-cerebral mucormycosis, histologically and microbiologically proven, in a patient after COVID-19 infection in Bulgaria.
Depression in chronic pain often manifests with symptoms of anxiety. Purpose: The aim of the study is to investigate the influence of depression, state and trait anxiety on pain intensity in patients with chronic pain and depression. Materials and Methods: Sixty-one patients with chronic pain and depression were studied. The study was phased. Тhe second stage was carried out three months after the first. All participants received antidepressant treatment. The severity of depression was assessed with HAM-D-17, the level of state and trait anxiety – with Spielberger's STAI and pain intensity – with VAS. The trait anxiety was studied during the first stage. Regression analysis was used to perform the purpose of the study. Results: The mean age of the sample was 55.6066±10.90608. Women comprised 91.8% of the sample, and men – 8.2%. A reduction in the mean values of the indicators in the second stage was reported. A regression analysis during the first stage showed that 60% of the variations in pain intensity were explained by the influence of the three variables (R=,616; R2=,379). Depression had the greatest impact and degree of influence on pain (t=3,372; p=,001), compared to state anxiety (t=,513; p=,015). The influence of trait anxiety was negligible (t=-,484; p=,630). The results of the analysis of the second stage were similar (R=,644, R2=,415). The influence of depression was significant (p=,011; t=2,626), compared to that of state anxiety (t=2,012; p=,049). Conclusions: Depression is the main variable influencing pain intensity. The search for symptoms of depression and their treatment is crucial for the management of chronic pain.
Introduction: Psoriasis is a complex, chronically recurrent, multifactorial disease that affects the somatic health (musculoskeletal, nervous, endocrine, cardiovascular, digestive systems) as well as the psyche and social adaptation. The organism’s individual characteristics and tolerance to the applied therapy impose the need for complex treatment in order to achieve long-term clinical remission and change in the quality of life. Aim: to monitor the effectiveness of the patient-centered approach in the complex treatment of patients with psoriasis vulgaris. Case report: A 40-year-old woman with a 20-year-old history of psoriasis vulgaris visited the University Center for Eastern Medicine (UCEM-MU-Varna) with complaints of extensive, itchy erythemo-squamous plaques covering the body, face, scalp and limbs. The patient’s disease progresses in a chronically recurrent course without long-term remission. We applied combined physical therapy, including laser acupuncture, magnetic therapy and aromatherapy. Results: After a 10-day treatment, we reported a reduction in the number and size of the plaques, subjective complaints and an improved psycho-emotional tone. When monitoring the condition during the 3rd, 6th and 9th month of the treatment, the patient reported no activation of the plaques and no other subjective complaints. The complex treatment, including conventional and unconventional physical factors, ensured a long-term remission of the disease. Conclusion: The patient-centered approach in the treatment of psoriasis vulgaris increases the effectiveness of the applied complex treatment. The selection and combination of conventional and unconventional physical factors selected according to the patient’s tolerance help to slow the progression and ensure long-term remission of the disease.
Three dimensional (3D) printing technology has been widely evaluated for the fabrication of various anthropomorphic phantoms during the last couple of decades. The demand for such high quality phantoms is constantly rising and gaining an ever-increasing interest. Although, in a short time 3D printing technology provided phantoms with more realistic features when compared to the previous conventional methods, there are still several aspects to be explored. One of these aspects is the further development of the current 3D printing methods and software devoted for radiological applications. The current 3D printing software and methods usually employ 3D models, while the direct association of medical images with the 3D printing process is needed in order to provide results of higher accuracy and closer to the actual tissues’ texture. Another aspect of high importance is the development of suitable printing materials. Ideally, those materials should be able to emulate the entire range of soft and bone tissues, while still matching the human’s anatomy. Five types of 3D printing methods have been mainly investigated so far: a) solidification of photo-curing materials; b) deposition of melted plastic materials; c) printing paper-based phantoms with radiopaque ink; d) melting or binding plastic powder; and e) bio-printing. From the first and second category, polymer jetting technology and Fused Filament Fabrication (FFF), also known as Fused Deposition Modelling (FDM), are the most promising technologies for the fulfilment of the requirements of realistic and radiologically equivalent anthropomorphic phantoms. Another interesting approach is the fabrication of radiopaque paper-based phantoms using inkjet printers. Although, this may provide phantoms of high accuracy, the utilized materials during the fabrication process are restricted to inks doped with various contrast materials. A similar condition applies to the polymer jetting technology, which despite being quite fast and very accurate, the utilized materials are restricted to those capable of polymerization. The situation is better for FFF/FDM 3D printers, since various compositions of plastic filaments with external substances can be produced conveniently. Although, the speed and accuracy of this 3D printing method is lower compared to the others, the relatively low-cost, constantly improving resolution, sufficient printing volume and plethora of materials are quite promising for the creation of human size heterogeneous phantoms and their adaptation to the treatment procedures of patients in the current health systems.
Aim: to investigate the slime production in isolates of Staphylococcus spp., associated with bacteremia in patients after hematopoietic stem-cell transplantation (HSCT) and to determine the relationship between the slime production and ica genes carriage, as well as the correlation of ica and methicillin resistance. Materials and methods: Between 2019 and 2020, twenty-one clinically significant Staphylococcus spp. isolates were obtained from blood cultures of 17 patients after HSCT. The species identification and the susceptibility to cefoxitin were determined by BD Phoenix M50. Two phenotypic tests (Congo red agar, CRA; Christensen’s method, TT) and PCR for icaA and icaD were used to detect slime production. A PCR method was also used to detect the mecA, mecC genes. Results: In the studied group of 21 isolates (S. epidermidis, n = 12; S. haemolyticus, n = 4; S. hominis, n = 2; S. aureus, n = 3), the phenotypic tests were positive in 13 isolates. Ten isolates (47.6%) were identified as carriers of ica genes (S. epidermidis, n = 9, and S. haemolyticus, n = 1). Five isolates (23.8%) were detected as slime producers by all three methods. The mecA gene was identified in 18 isolates (85.7%). All ica positive isolates were also mecA carriers. Conclusion: A relatively high proportion of the blood isolates of Staphylococcus spp. were slime producers, associ-ated with ica genes. A combination of both phenotypic and genetic methods should be used to detect alternative routes of slime production. The co-expression of ica and mecA is associ-ated with the occurrence of difficult-to-eradicate isolates.
Introduction Nutrition education attempts to maintain and enhance good eating habits to achieve optimal metabolic control in people with type 1 diabetes (T1D). Recommendations for patients with T1D are comparable to those of the general population. This Study Aimed To investigate dietary habits and adherence to nutritional recommendations of patients with T1D as compared with age, gender, and BMI matched people in Bulgaria. Methods A case-control study included 124 patients with T1D with long disease duration (mean duration 25.3 ± 8.2 years) followed up at a diabetes clinic in Varna, Bulgaria for 2 years (2017–2019) and 59 controls matched for gender, age and BMI. A 24-h dietary recall method was used to assess the nutrition of both groups. A standardized questionnaire was applied to assess the frequency of food consumption (Feel4Diabtes). Height and weight were standardly measured, and BMI was calculated. Findings were compared with Bulgarian recommendations and reference values for energy and nutrient intake for healthy adults. The data were analyzed with the statistical package SPSSv21.0 and Jamovi v.22.5. Results The nutritional characteristics of T1D men and women differ. Men with T1D had a higher intake of total carbohydrates (CHO) ( p = 0.009), a lower intake of total fats ( p = 0.007), and monounsaturated fatty acids ( p = 0.029) as a percentage of total daily energy compared with the controls. Women with T1D had a different distribution of energy intake per meal compared to controls: they consumed more energy ( p = 0.001) and a corresponding share of CHO for lunch, less for dinner ( p = 0.015) and had a higher overall healthy diet score when compared to controls ( p = 0.02). Adherence to dietary recommendations (e.g., CHO, total fats, saturated fat, fibers) was low in both genders, but lower in the general population compared to people with T1D. Conclusion Our data demonstrate that people with T1D consume a healthier diet than the general population, which could be attributed to healthier diet awareness, still far from the recommendations. Introduction of annual consultations with a dietitian may improve long-term outcomes.
Background Artificial intelligence (AI) has the potential to reshape medical practice and the delivery of healthcare. Online discussions surrounding AI's utility in these domains are increasingly emerging, likely due to considerable interest from healthcare practitioners, medical technology developers, and other relevant stakeholders. However, many practitioners and medical students report limited understanding and familiarity with AI.Objective To promote research, events, and resources at the intersection of AI and medicine for the online medical community, we created a Twitter-based campaign using the hashtag #MedTwitterAI.Methods In the present study, we analyze the use of #MedTwitterAI by tracking tweets containing this hashtag posted from 26th March, 2019 to 26th March, 2021, using the Symplur Signals hashtag analytics tool. The full text of all #MedTwitterAI tweets was also extracted and subjected to a natural language processing analysis.ResultsOver this time period, we identified 7,441 tweets containing #MedTwitterAI, posted by 1,519 unique Twitter users which generated 59,455,569 impressions. The most common identifiable locations for users including this hashtag in tweets were the United States (378/1,519), the United Kingdom (80/1,519), Canada (65/1,519), India (46/1,519), Spain (29/1,519), France (24/1,519), Italy (16/1,519), Australia (16/1,519), Germany (16/1,519), and Brazil (15/1,519). Tweets were frequently enhanced with links (80.2%), mentions of other accounts (93.9%), and photos (56.6%). The five most abundant single words were AI (artificial intelligence), patients, medicine, data, and learning. Sentiment analysis revealed an overall majority of positive single word sentiments (e.g., intelligence, improve) with 230 positive and 172 negative sentiments with a total of 658 and 342 mentions of all positive and negative sentiments, respectively. Most frequently mentioned negative sentiments were cancer, risk, and bias. Most common bigrams identified by Markov chain depiction were related to analytical methods (e.g., label-free detection) and medical conditions/biological processes (e.g., rare circulating tumor cells).Conclusion These results demonstrate the generated considerable interest of using #MedTwitterAI for promoting relevant content and engaging a broad and geographically diverse audience. The use of hashtags in Twitter-based campaigns can be an effective tool to raise awareness of interdisciplinary fields and enable knowledge-sharing on a global scale.
Objective: Congenital Adrenal Hyperplasia (CAH) requires exogenous steroid replacement. Treatment is commonly monitored by measuring 17-OH progesterone (17OHP) and androstenedione (D4). Design: Retrospective cohort study using real world data to evaluate 17OHP and D4 in relation to hydrocortisone (HC) dose in CAH patients treated in 14 countries. Patients: Pseudonymized data from children with 21-hydroxylase deficiency (21OHD) recorded in the International CAH Registry. Measurements: Assessments between January 2000 and October 2020 in patients prescribed HC were reviewed to summarise biomarkers 17OHP and D4 and HC dose. Longitudinal assessment of measures was carried out using linear mixed effects models (LMEM). Results: Cohort of 345 patients, 52.2% female, median age 4.3 years (Interquartile Range 3.1-9.2) were taking a median 11.3 mg/m2 /day (8.6-14.4) of HC. Median 17OHP was 35.7 nmol/l (3.0-104.0). Median D4 under 12 years was 0 nmol/L (0-2.0) and above 12 years was 10.5 nmol/L (3.9-21.0). There were significant differences in biomarker values between centres (p<0.05). Correlation between D4 and 17OHP was good in multiple regression with age (p<0.001, R2 =0.29). In longitudinal assessment, 17OHP levels did not change with age, whereas D4 levels increased with age (p<0.001, R2 =0.08). Neither biomarker varied directly with dose or weight (p>0.05). Multivariate LMEM showed HC dose decreasing by 1.0 mg/m2 /day for every 1 point increase in weight standard deviation score. Discussion: Registry data show large variability in 17OHP and D4 between centres. 17OHP correlates with D4 well when accounting for age. Prescribed HC dose per body surface area (BSA) decreased with weight gain. This article is protected by copyright. All rights reserved.
Background: Melanotic schwannoma is a melanin producing nerve sheath tumors. Rarely, it can be associated with psammoma bodies, called psammomatous melanotic schwannoma. Psammomatous melanotic schwannomas are associated in up to 10% of the cases with Carney's syndrome. The rarity of the lesion, which may present at different localizations create difficulty in placing a correct initial diagnosis. Definitive diagnosis is made after complete tumor excision and pathomorphological evaluation. The prognosis depends on the anatomical localization, local invasion and presence of a high mitotic index. The main pathomorphological differential diagnosis includes schwannomas and other melanin producing tumors as melanoma. Case presentation: We present a case of an 11-year-old female with cystic lesion adjacent to right adrenal gland, mimicking adrenal cyst. Ultrasound guided biopsy was undertaken due to the cystic appearance of the formation and the lack of certain diagnosis from the non-invasive diagnostic tests. No signs of cellular and nuclear atypism were observed. The diagnosis of benign endothelial cyst with spontaneous hemorrhage was suggested. The patient underwent transabdominal laparoscopic adrenalectomy en-bloc with the cyst to prevent spillage of the cyst content due to the intimate adhesion of the lesion to the adrenal gland and vena cava inferior. Pathomorphological examination revealed malignant psammomatous melanotic schwannoma. The adrenal gland was intact with no tumor infiltration. The patient was followed up on the 1st and 2nd month afterwards the surgery by MRI with no signs of local recurrence and postoperative complications. Conclusion: Psammomatous melanotic schwannoma near adrenal gland are rare and present difficulty with exact preoperative diagnosis. Complete resection should always be provided. Laparoscopic surgery is feasible if radical excision is not compromised. Long-term follow-up and Carney's syndrome surveillance after complete excision are recommended especially in young patients.
The current review aims to summarize published research on nutrition transition patterns (depicting changes in dietary consumption) in European populations over the last three decades (1990–2020), with a focus on East-West regional comparisons. Pubmed and Google-Scholar databases were searched for articles providing information on repeated dietary intakes in populations living in countries across Europe, published between January 1990 and July 2021. From the identified 18,031 articles, 62 were found eligible for review (17 from Eastern and 45 from Western European populations). Overall, both in Eastern and Western Europe, there have been pronounced changes in dietary consumption patterns over the last three decades characterized by reductions in average reported intakes of sugar, carbohydrates and saturated fats and increases in reported fruit and vegetable consumption. There has also been a tendency toward a reduction in traditional foods, such as fish, observed in some Mediterranean countries. Overall, these data suggests that European countries have undergone a nutrition transition toward adopting healthier dietary behaviors. These processes occurred already in the period 1990–2000 in many Western European, and in the last decades have been also spreading throughout Eastern European countries. Firm conclusions are hampered by the lack of standardized methodologies depicting changes in dietary intakes over time and the limited coverage of the full variety of European populations. Future studies based on standardized dietary assessment methods and representative for the whole range of populations across Europe are warranted to allow monitoring trends in nutrition transition within and among European countries.
Objective The current study aims to investigate the association of diet quality with fasting glycemia, insulinemia and insulin resistance in a cross-sectional sample of adults from high-risk families for Type 2 diabetes mellitus (T2DM) from 6 European countries, taking into account their socioeconomic status (SES). Methods Baseline data from non-diabetic adults from the Feel4Diabetes study were used and diet was assessed by the Healthy Diet Score (HDS). Insulin resistance was determined by Homeostasis Model Assessment (HOMA-IR). Socio-demographic and lifestyle characteristics were assessed through standardized questionnaires. Multiple linear regressions were adjusted for many confounders, in the total sample and by SES category. Results In 1980 adults, the third tertile of diet quality was inversely associated with insulin levels (-1.48 95% CI -2.34 to - 0.62), and HOMA-IR (-0.33 95% CI -0.57 to - 0.09), yet with no statistically significant results for glucose levels. In the SES subgroup analysis, in the high SES group, both second and third diet score tertiles were inversely associated with insulin levels (-1.81 95% CI -2.66 to - 0.95) and HOMA-IR values (-0.45 95% CI -0.69 to - 0.21), independent of age, sex, smoking and body mass index. No such associations were observed for glucose levels in high SES group and for all indices in the low SES group. Conclusion In adults from high-risk families for T2DM higher diet quality was negatively associated with fasting insulin levels and insulin resistance, only in the high SES group and not in the low SES group. Future larger studies may be able to explore further this association, as well as the potential factors that mitigate its strength in the low SES groups.
Light chain deposition disease (LCDD) is a rare condition associated with the overproduction and deposition of monoclonal light chain immunoglobulins. The kidneys are universally affected in LCDD, with the development of renal failure with nephrotic syndrome, microscopic hematuria, and proteinuria. Most cases are associated with a plasma cell neoplasm (multiple myeloma or plasmacytoma) or other lymphoproliferative disorders, with a reasonable number of cases also being idiopathic. Other organs can be affected in rare cases, without producing significant symptoms, predominantly the liver and heart. In this report, we discuss a case of a 72-year-old female presenting with the aforementioned symptoms. Percutaneous ultrasound-guided kidney biopsy revealed nodular sclerosis with periodic acid-Schiff stain (PAS)-positive, Congo red-negative, silver impregnation weakly-positive, and Masson's trichrome-positive (red reaction) deposits with ribbon-like changes together with light chain deposits in the tubular basement membranes. As LCDD was diagnosed, the patient was subjected to further tests, with multiple myeloma of the thoracic vertebrae also being diagnosed. The patient was started on myeloma treatment; however, she subsequently developed a severe lower limb infection that required amputation, after which she developed sepsis and expired.
Ischemic heart disease (IHD) affects > 110 million individuals worldwide and represents an important contributor to the rise in the prevalence of heart failure and the associated mortality and morbidity. Despite modern therapies, up to one-third of patients with acute myocardial infarction would develop heart failure. IHD is a pathologic condition of the myocardium resulting from the imbalance in a given moment between its oxygen demands and the actual perfusion. Acute and chronic forms of the disease may potentially lead to extensive and permanent damage of the cardiac muscle. From a clinical point of view, determination of the still viable extent of myocardium is crucial for the therapeutic protocol – since ischemia is the underlying cause, then revascularization should provide for a better prognosis. Different methods for evaluation of myocardial viability have been described – each one presenting some advantages over the others, being, in the same time, inferior in some respects. The review offers a relatively comprehensive overview of methods available for determining myocardial viability. Key words: myocardial viability, factor, treatment, IHD
Diffuse astrocytic gliomas and their most common and aggressive representation, glioblastoma (GBM), which as per the 2021 World Health Organization (WHO) guidelines is an isocitrate dehydrogenase (IDH) wildtype without alteration in histone 3 and has glomeruloid vascular proliferation, tumor necrosis, telomerase reverse transcriptase (TERT) promoter mutation, epidermal growth factor receptor (EGFR) gene amplification, or +7/−10 chromosome copy-number changes, are fast-growing tumors with a dismal patient prognosis. Herein, we present cases of a 63-year-old male who, despite no evidence of tumor growth, developed a 6-cm tumor, histologically verified as GBM, WHO CNS grade 4, within eight months, and a 74-year-old female in whom a 1.5-cm tumor grew to 43 mm within 28 days, once again histologically confirmed as GBM, WHO CNS grade 4. Other studies using previous WHO guidelines and including up to 106 cases have shown that these tumors have a daily growth rate of 1.4% and can double their size in a period varying from two weeks to 49.6 days. These growth rates further underline the need for extensive surgical resection as disease progression is rapid, with studies reporting that resection of more than 85% of the tumor volume determined on neuroradiology improves survival compared to biopsy or limited resection and resection of more than 98% of the tumor volume statistically improves patient survival.
Next-generation sequencing (NGS) is now widely used in diagnosing rare diseases. However, it has some limitations, such as variants of uncertain significance (VUS). This can present difficulties even for nurse practitioners involved in clinical genetics. We present three cases from our clinical practice: two targeted panel testing and one exome sequencing. Whole blood samples were collected and sent for NGS analysis. In case 1, a VUS was found in the LITAF gene, which is associated with autosomal dominant Charcot–Marie–Tooth disease type 1C. In case 2, a VUS was reported in the MEFV gene, which is associated with autosomal recessive and autosomal dominant familial Mediterranean fever. In these cases, the reported VUS corresponded to the clinical diagnosis. Incase 3,two variants in the heterozygous state were found in the ATP7B gene,which is associated with Wilson disease,and the disorder was later clinically recognized. According to the published guidelines,VUSs should not be discussed as a cause for an observed genetic condition. Nevertheless, if the reported variant is in a gene associated with the clinically diagnosed disorder, and there is a strong genotype-phenotype correlation, it could be suggestive of the etiological role of this variant.
Aronia melanocarpa L. (black chokeberry), belonging to the Rosaceae family, contains high amounts of polyphenolics and therefore exhibits one of the highest antioxidant and anti-inflammatory activities among berry fruits. Chokeberries are used in the food industry for juice, nectar, and wine production and as colorants. We aimed to compare the phytochemical composition of three chokeberry juices commercially available in the local market as sources of beneficial phytochemicals. Using GC-MS and LC-MS/MS, we performed the identification and quantitation of polar compounds and polyphenolics. The concentrations of 13 amino acids, including 6 essential amino acids, 10 organic acids, 20 sugar alcohols and derivatives, 14 saccharides, 12 fatty acids and esters, and 38 polyphenols, were estimated. One of the analyzed juices had the highest polyphenolic content (5273.87 ± 63.16 µg/mL), possibly due to 2.9 times higher anthocyanin concentration compared to anthocyanins in other tested juices. This study provides new data concerning phytochemical composition in terms of amino acids, organic acids, sugar acids, fatty acids and their esters, and polyphenols as phytocomponents of commercially available chokeberry juices. Results show that after all processing techniques and possibly different plant growth conditions, chokeberry juices are a valuable source of health-promoting phytochemicals such as phenolic acids, pro-anthocyanins, and anthocyanins, thus considering them as functional foods. We demonstrated a diversity of the active substances in bioactive foods marketed as "same"; therefore, the standardized therapeutic effect could be expected only by the utilization of food supplements with guaranteed constant content.
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