Adipocytokines may delay pubertal maturation of human Sertoli cells.

Reproduction is an important target of obesity complications, including adverse effects on spermatogenesis and steroidogenesis. Adipocytokines are key mediators in various complications of obesity. Our aim was to study the potential of adipocytokines to affect Sertoli cell function, which is crucial for spermatogenesis, and possibly link these findings to the observed attenuation of spermatogenesis in obese males. Testicular biopsies were obtained from healthy donors. Highly purified adult human Sertoli cells (HSCs) were isolated by fluorescence-activated cell sorting. Cells were cultured and exposed to different concentrations of adipocytokines (10-1000ngmL-1 ) for 2-7 days. Expression of selected Sertoli cell genes was quantified by quantitative polymerase chain reaction. Long-term treatment (7 days) of HSCs with higher concentrations of chemerin, irisin, nicotinamide phosphoribosyltransferase (Nampt), resistin and progranulin significantly suppressed FSH receptor expression (by 79%, 83%, 64%, 71% and 26% respectively; P P invitro , may negatively affect Sertoli cell maturation and retain these cells in a more prepubertal stage. This could negatively affect testis function and add to fertility problems in obese adults.

Insulin-Like Peptide 5 Interacts with Sex Hormones and Metabolic Parameters in a Gender and Adiposity Dependent Manner in Humans.

Insulin-like peptide 5 (INSL5) is a gut hormone produced by L-cells in the colorectal epithelium and may play a role in the regulation of metabolic processes. The biological role of INSL5 is poorly investigated and nothing is known about the role of this hormone in obese and lean humans. Two cohorts were analyzed in the study. In the first cohort (n=76) the relationship between serum levels of INSL5 and different metabolic and hormonal parameters in obese and lean men and women were investigated. In the second cohort 14 male subjects underwent bariatric surgery. Circulating levels of INSL5 were then measured before and after interventions.We report for the first time that circulating INSL5 interacts with multiple metabolic and hormonal variables in lean and obese men and women and is affected by bariatric surgery. Serum levels of INSL5 negatively correlated with testosterone and blood lipids but positively with cortisol in obese men. In contrast to males, obese women had a strong negative correlation of plasma levels of INSL5 with C-reactive protein (CRP). We observed that adipose tissue loss after bariatric surgery significantly reduced serum levels of INSL5 in obese men with and without Type 2 Diabetes Mellitus (T2DM) that was associated with the restoration of circulating levels of testosterone. All together, our data demonstrated that INSL5 may interact with some metabolic parameters in obese humans and this process is dependent of gender and obesity state.

An electronic oral health record to document, plan and educate.

The University of British Columbia (UBC) in collaboration with a software developer (Planmeca Oy, Finland) created an electronic oral health record based on the principles of cognitive ergonomics rooted in the European research and development project 'ORQUEST' to guide students through medical, dental, social histories, examinations, treatment planning and progress notes. Clinicians in each dental specialty of the Faculty of Dentistry and software engineers cooperated to define the clinical content and workflow of clinical procedures in three phases: (i) development of a radiographic module, (ii) development of medical, dental, social and family histories, intra- and extra-oral examinations, progress notes and treatment planning and (iii) development of the orthodontic section accompanied by an optimisation phase to correct technical problems and clinical content issues. From a practical perspective, this EOHR enhances the clinical performance of students and the quality assurance capacity of the institution. It facilitates audits of clinical productivity and research, and it can be modified with relative ease to suit similar educational and clinical environments in either public or private healthcare settings.

Diurnal rythm of Nampt is gender and weight dependent.

RESEARCH AIM: Nicotinamide phosphoribosyltransferase (Nampt) is an adipocytokine that is elevated in obesity, type 2 diabetes and increased levels are associated with inflammatory processes. Nampt serum concentrations have been suggested to follow a diurnal rhythm peaking in the afternoon in lean males. However, no data exists regarding the effects of gender and body weight. MATERIAL AND METHODS: We measured Nampt serum levels over 24 h in a cohort of healthy individuals living with either normal weight or obesity. Furthermore, effects of meals, oral glucose tolerance test and physical exercise on Nampt concentrations were evaluated. Correlation analyses to other hormonal- and lab parameters and anthropometric measurements were performed. RESULTS: Nampt showed a diurnal rhythm with increased levels at daytime and a peak in the early afternoon. This diurnal rhythm was significant for all groups but obese males. The Nampt amplitude, measured both relatively and absolutely, was significantly higher in females than in males. Meals did not influence Nampt serum levels, whereas physical exercise and an OGTT did significantly influence Nampt serum levels. CONCLUSION: In conclusion, we found gender specific differences in Nampt amplitude and coefficient variation with both being higher in females. The circadian rhythm of Nampt was independent of gender in healthy lean individuals, whereas it was disturbed in men with obesity.

[Does childhood obesity affect sexual development?]. / Beeinflusst die kindliche Adipositas die Pubertätsentwicklung?

The process of pubertal development is only partly understood and is influenced by many different factors. During the twentieth century there was a general trend toward earlier pubertal development. Fat mass is thought to be a major inducer of puberty. Owing to the rising epidemic of childhood obesity, the relationship between body composition in children and the rate and timing of puberty needs to be investigated. Some studies suggest that central obesity is associated with an earlier onset of pubertal development. Rapid weight gain in early life is linked to advanced puberty in both sexes. A clear correlation exists between increasing body mass index (BMI) and earlier pubertal development in girls. In boys the data are controversial: The majority of studies propose that there is an earlier puberty and voice break in obese boys, but some studies show the opposite. There are several factors and mechanisms that seem to link obesity and puberty, for example, leptin, adipocytokines, and gut peptides. Important players include genetic variation and environmental factors (e.g., endocrine-disrupting chemicals). This article presents the latest studies and evidence on this topic, underlining the inconsistencies in the data and, therefore, the need for further research in this area.

A critical evaluation of the EU-virtual consultation platform (CPMS) within the European Reference Network on Rare Endocrine Conditions.

In 2017, the European Commission installed 24 European Reference Networks (ERNs) for different categories of rare and complex conditions to facilitate cross-border health care via virtual case consultations in a secure Clinical Patient Management System (CPMS). The ERN for rare endocrine conditions (Endo-ERN) previously reviewed the CPMS, in which they detailed the difficulties physicians encountered with the system and proposed solutions to these that should enable the system to be used to a greater extent. This paper will further the endeavor of the first by performing a critical evaluation of the CPMS, assessing how these suggested improvements have been implemented, and if these have affected the usage of the system. The evaluation involves an assessment of CPMS usage statistics since its conception that takes into consideration the technical updates and the external factors that may have affected these, including data from a review survey following a training workshop for our new healthcare providers (HCPs) added in January 2022. It appears that the improvements made to the system since the first review, in particular the implementation of the Operational Helpdesk, have had a positive effect in increasing CPMS membership; however, the regular usage of the system continues to fluctuate. Several suggestions are made on how to further facilitate the use of CPMS by our members both individually and network-wide, by integrating CPMS activities with other network initiatives and further integrating these into national health care systems as well as looking for ways to measure patient satisfaction from the CPMS discussions outcomes.

Quality assurance and quality enhancement by use of digital clinical documentation.

Clinical documentation, including medical/dental history, oral status findings, treatment planning, and progress notes, are prerequisites for the use of retrospective evaluation procedures as well as for quality assessment and enhancement. A substantial condition for making full profit of these advantages of digital clinical records is that their design is based on established physiologic- and cognitive-ergonomic concepts.

An object-relational model for structured representation of medical knowledge.

Domain specific knowledge is often not static but continuously evolving. This is especially true for the medical domain. Furthermore, the lack of standardized structures for presenting knowledge makes it difficult or often impossible to assess new knowledge in the context of existing knowledge. Possibilities to compare knowledge easily and directly are often not given. It is therefore of utmost importance to create a model that allows for comparability, consistency and quality assurance of medical knowledge in specific work situations. For this purpose, we have designed on object-relational model based on structured knowledge elements that are dynamically reusable by different multi-media-based tools for case-based documentation, disease course simulation, and decision support. With this model, high-level components, such as patient case reports or simulations of the course of a disease, and low-level components (e.g., diagnoses, symptoms or treatments) as well as the relationships between these components are modeled. The resulting schema has been implemented in AMOS II, on object-relational multi-database system supporting different views with regard to search and analysis depending on different work situations.

Prepubertal onset of obesity negatively impacts on testicular steroidogenesis in rats.

Obesity is a global health problem and impacts negatively on levels of testosterone and quality of sperm production. At present little is known about mechanisms that attenuate testicular function in obese males. Our study characterized testicular steroidogenesis and explored levels of relevant paracrine and hormonal factors in rats with short- and long-term obesity. We have found that obesity state increased serum levels of estradiol and leptin in both groups of obese rats and inhibited the expression of StAR and Cyp11a1 associated with low levels of intratesticular testosterone in rats with long-term obesity. Further, long-term obesity reduced the number of Leydig cells, increased the testicular levels of the proinflammatory adipocytokine TNFα and the number of testicular macrophages. All together, our data indicate that long-term obesity may cause chronic inflammation in the testis and negatively impacts on Leydig cell steroidogenesis.

IT-based evaluation and automatic improvement of the quality of intraoral radiographs.

The quality of intraoral radiographs made in dental practices is too often not adequate for diagnostic purposes. This necessitates standardized measures for the quality of intraoral radiographs and controlled techniques for automatic image improvement. For the evaluation of the quality of digitized intraoral radiographs the authors have defined two parameters which enable the measurement of radiographic image quality with regard to contrast and gray value distribution. A two-dimensional feature space based on these parameters is used for separation of images with 'good diagnostic quality' from images with 'insufficient diagnostic quality'. Specific image improvement techniques based on piecewise linear gray scale transformation allow the automatic improvement of over- and under-exposed radiographs as well as the automatic improvement of suspected pathological regions of interest.

Three-dimensional visualization of the mandible: a new method for presenting the periodontal status and diseases.

A three-dimensional representation of an ideal human jaw was reconstructed from a series of 178 digitized photographic cross-sections. The two-dimensional images were taken from the slices of an artificial skull and have been digitized by means of a high resolution scanner with a spatial resolution of 860 dots per inch. On the basis of that sequence of cross-sections, a semi-automatic segmentation algorithm was developed to reduce the information to a quadriliteral surface-representation of the teeth and the bone. An algorithm was developed which simulates the individual pathology of a patient both on the basis of the findings stored in this patient's dental record and by using the representation of the reference jaw. The results of the modeling module were automatically prepared for rendering with visualization tools compatible to the RenderMan standard. This new method of presenting periodontal situations in especially helpful for the diagnostic support of periodontologists and for dental educational purposes.

Oral implant treatment planning in a virtual reality environment.

A system for three-dimensional oral implant treatment planning is presented. Virtual reality technologies are used in order to improve the human image interpretation and planning performance. The methods described are based on computer tomography (CT) data of the mandible and of the maxilla. A novel approach to volume rendering and voxel based modelling of implants is introduced which allows interactive three-dimensional manipulation of the anatomic model and real-time manipulation of virtual implants. A spline-based reconstruction method is described to assess the implant site in a clinically oriented view with regard to bone structures and angulation. Two parameters are deduced which represent the bone properties at the surface of implants. While an implant is navigated with six degrees of freedom, these parameters are acoustically rendered which is a novel approach to exploration of spatial bone properties in a CT data set.

Controlled diagnosis-oriented enhancement of automatically segmented radiographs in dentistry.

A method for controlled diagnosis-oriented enhancement of selected regions of interest in intraoral radiographs is presented. Image enhancement is accomplished by adaptive non-linear grey scale transformation depending on the result of objective quality measurement. In order to assure reliable image quality measurement as well as controlled image enhancement, automatic image segmentation is applied to avoid the influence of disturbing factors (e.g. metallic restorations) on quality measurement and image enhancement. Based on existing a-priori knowledge about object structure and composition of the selected regions of interest in intraoral radiographs, different image segmentation algorithms and image enhancement procedures were developed for different types of diagnosis.

Computer based decision support in dentistry.

Work analyses in dental practices have revealed a need for improvements especially in regard to patient dental record, decision support for diagnosis and therapy and patient recall. An adequate decision support for diagnosis, therapy and prevention requires the use of the most advanced methods of informatics and computer bases interactive multimedia technology as well as of advanced human-computer interface techniques.

Effective and quality-controlled use of digital radiography in dental practice.

During the last years, the number of commercially available digital radiographic systems has increased rapidly. Nevertheless, they are hardly used in practice because several drawbacks still hinder dental practitioners from using digital radiography effectively in their routine work. In order to allow effective use of such systems in the dental practice, they must be integrated into the daily routine in an ergonomically optimal way and be driven by software following the rules of cognitive ergonomy and perception. The most important prerequisite for meaningful use of digital radiography in the dental practice is that it supports instead of disturbs daily clinical work. The underlying software should be easily comprehensible and intuitively applicable. This paper discusses advantages and disadvantages of digital compared to conventional radiography and how the introduction of digital radiography in dental practice affects clinical work. A concept is introduced that enables effective and quality-controlled use of digital radiographic systems in the dental practice by taking cognitive ergonomic aspects of the clinical work situation into account. This concept comprises the design of image databases for efficient storage and retrieval, the quality-controlled use of image manipulation methods adapted to the clinical requirements during diagnostic interpretation, and the usage of decision support systems for diagnosis and therapy of radiographic lesions.

Design of a 3D workbench interface for training in dental implantology.

The recent technological advances in the area of image processing and interactive computer graphics have lead to many sophisticated systems which support clinical experts in diagnosis and treatment planning tasks. In dentistry, the treatment with implants becomes more and more important. Although in the near future there will be increased demand for dentists who are trained in dental implantology, little effort has been made to introduce technologically new teaching methods into the curriculum of dentists. This paper describes the design of a virtual implant treatment planning system which is based on the concept of a three-dimensional horizontal display. The system is utilizing different VR and multimedia techniques to achieve a highly interactive virtual workbench environment which is suited for class-room experimental education in dental implantology.

New concept of an integrated IT&T-based dental workstation for quality assurance in oral health care.

During the last five years, quality development has become a most important issue in oral health care. In every day practice, quality development meets, however, a considerable number of objective obstacles, mainly due to the lack of direct access to the information necessary in a specific clinical work situation and due to the absence of knowledge on own performance in relation to quality goals. The EU-TAP project ORQUEST has identified different clinical work situations and built up an integrated IT&T-platform composed of different software modules and hardware components for each clinical work situation in order to allow for adequate IT&T-support in specific clinical situations.

Clinical evidence-based cutoff limits for GH stimulation tests in children with a backup of results with reference to mass spectrometry.

CONTEXT: Cutoff limits of GH stimulation tests to diagnose GH deficiency (GHD) in children and adolescents are not sufficiently validated by clinical studies due to discrepancies in the performance of GH immunoassays and lack of available study populations. OBJECTIVE: We aimed to establish new cutoff limits for GH stimulation tests based on clinical evidence and compared these immunoassay-based values with an antibody-independent mass spectrometric method. DESIGN AND SETTING: In a retrospective study, GH cutoff limits for eight different immunoassays and isotope dilution mass spectrometry (ID-MS) were calculated from hGH peak concentrations of short-statured children with and without GHD. PATIENTS: We compared the serum GH peak concentrations at GH stimulation test of 52 short-statured children and adolescents, who have normal GH secretion at initial workup and normal growth in the follow-up, with the serum GH peak concentrations of 44 GHD patients in the same age range, in order to optimize the cutoff limit calculation. RESULTS: Discriminant analysis of re-measured GH led to a new cutoff limit of 7.09 µg/l using the iSYS assay (IDS) and the limits for the other seven hGH assays varied between 4.32 and 7.77 µg/l. For ID-MS, cutoffs of 5.48 µg/l (22k GH) and 7.43 µg/l (total GH) were ascertained. CONCLUSION: The establishment of method-specific clinical evidence-based GH cutoff limits is of importance to ensure adequate clinical diagnosis and treatment of children and adolescents with GHD. ID-MS may become an important tool for providing both reliable and sustainable SI traceability of GH measurements in the future.

Cannabinoid type 1 receptor mediates depot-specific effects on differentiation, inflammation and oxidative metabolism in inguinal and epididymal white adipocytes.

OBJECTIVE: The endocannabinoid system is a major component in the control of energy metabolism. Cannabinoid 1 (CB1)-receptor blockade induces weight loss and reduces the risk to develop the metabolic syndrome with its associated cardiovascular complications. These effects are mediated by central and peripheral pathways. Interestingly, weight loss is mainly achieved by a reduction of visceral fat mass. We analyzed fat depot-specific differences on adipocyte differentiation, inflammation and oxidative metabolism in CB1-receptor knockout cells. MATERIALS AND METHODS: We used newly generated epididymal/inguinal adipose cell lines from CB1-receptor knockout mice. Differences in differentiation were measured by fat-specific Oil Red O staining and quantitative analysis of key differentiation markers. Induction of apoptosis was evaluated by cell death detection and investigation of p53 phosphorylation. Inflammation markers were quantified by real-time PCR. For analyzing the process of transdifferentiation we measured oxygen consumption and mitochondrial biogenesis. RESULTS: Differentiation was reduced in visceral adipocytes from CB1-receptor knockout mice as compared with wild-type controls. Moreover, we found an induction of apoptosis in these cells. In contrast, subcutaneous adipocytes from CB1-receptor knockout mice showed an accelerated differentiation and a reduced rate of apoptosis. Inflammation was increased in visceral fat cells, as analyzed by the expression pattern of interleukin-6, monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor-α, whereas in subcutaneous adipocytes these markers were decreased. Furthermore, subcutaneous CB1-receptor knockout cells were more sensitive toward a conversion into a brown fat phenotype. Uncoupling protein-1 as well as PGC-1α expression was significantly elevated. This was accompanied by an increase in mitochondrial biogenesis and oxygen consumption. CONCLUSION: In conclusion, we found depot-specific effects on differentiation, apoptosis, inflammation and oxidative metabolism in CB1-receptor knockout cells. Thus, CB1-receptor-mediated pathways differentially target adipose tissue depots to a dual effect that minimizes cardiometabolic risk, on the one hand, by diminishing visceral fat, and that enhances thermogenesis in subcutaneous adipocytes, on the other.