Contemporary Aspects of Orthognathic Surgery

U proteklih pet godina ortognatska kirurgija je postala standardni postupak u kirurgiji glave, čeljusti i lica. Temeljen na radovima Obwegesera koji je uveo sagitalnu osteotomiju ramusa ranih 50-tih godina, danas je taj postupak postao zlatni standard u ortognatskoj kirurgiji donje čeljusti diljem svijeta. Uvođenjem naprava za osiguranje centrične pozicije kondila tijekom cijeloga kirurškog postupka Luhr je ranih 80-tih godina dao drugi doprinos modernom razumijevanju cijele funkcionalne rehabilitacije disgnatija. Premda je LeFort-ova osteotomija uvedena od Wassmunda 20-tih godina, trebalo je sljedećih 50 godina da ta metoda bude prihvaćena u kirurgiji, uglavnom zbog straha od mogućega krvarenja. Uvođenjem naprave za pozicioniranje kondila za vrijeme osteotomije gornje i donje čeljusti ili kombinirane bimaksilarne osteotomije, kao i upotrebom distrakcijskih naprava, danas smo u mogućnosti rije- πiti i najteže disgnacijske probleme. U Zavodu za kirurgiju glave, čeljusti i lica Sveučilišta u Würzburgu u zadnja dva desetljeća s više od 2000 ortognatskih kirurških zahvata želimo prikazati razvoj suvremenih kirurških tehnika i kliničke rezultate. Napredak ne bi bio moguć bez primarne i stalne pripreme od strane ortodonta i interdisciplinarno određenih indikacija za kirurško liječenje, ortognatsku obradu pacijenta kao i za postoperativni postupak. Posebna se pozornost daje ortognatskom liječenju i tehničkim preduvjetima za kirurški postupak.Orthognathic surgery within the past half decade has become a standard procedure in cranio-maxillo- facial surgery. Based upon the elementary works by Obwegeser introducing the sagittal split ramus osteotomy in the early 50is, today this procedure has become the gold standard in mandibular orthognathic procedures worldwide. The introduction of devices to ensure the centric condyle position throughout the entire surgery by Luhr in the early 80ies gives another impact to modern understanding on complete functional rehabilitation after dysgnathia. Even though the LeFort-I-Osteotomy was already introduced by Wassmund in the 20is it took almost another 50 years before this procedure became accepted in surgery, mainly based on the fear of severe bleeding that may occur during surgery. By introducing a compund condyle positioning device to ensure the exact condyle position throughout both procedures of maxillary and mandibular osteotomy respectively, during combined bimaxillary osteotomies, as well as the targeted use of distraction devices, today we are able to solve even the severest dysgnathia problems. At the Department of Cranio-Maxillo-Facial Surgery of the University of Würzburg, during the past two decades and far more than 2000 orthognathic surgery cases, we are trying to present a broad overview of the development of the latest surgical techniques and clinical results. This progress is not possible without the primary and consistent treatment by a specifically skilled orthodontist during primary treatment including the interdisciplinary indication for surgery, the orthognathic preparation of the patient as well as the postoperative treatment. Therefore special emphasis will be put on the orthognathic treatment, as well as on technical prerequisites for the surgical procedure

Assessment of a mouse xenograft model of primary colorectal cancer with special reference to perfluorooctane sulfonate

Colorectal cancer ranks third among the most commonly diagnosed cancers in the United States. Current therapies have a range of side effects, and the development of a reliable animal model to speed the discovery of safe effective preventative therapies would be of great value. A cross-sectional study in a large Appalachian population recently showed an association between low circulating levels of perfluorooctane sulfonate (PFOS) and a reduced prevalence of colorectal cancer. A study using APCmin (C57BL/6J-ApcMin/J) mice prone to familial adenomatous polyposis found PFOS was protective when exposure occurred during tumor development. To test the possible benefit of PFOS on spontaneous colorectal cancer, we developed a mouse model utilizing primary patient colorectal cancer implants into NSG (NOD.Cg-PrkdcscidIl2rgtm1Wjl/Sz) mice. Study goals included: (1) to assess potential factors supporting the successful use of colorectal cancer from heterogeneous tumors for PDX studies; and, (2) evaluate PFOS as a therapy in tumor matched pairs of mice randomized to receive PFOS or vehicle. The time in days for mice to grow primary tumors to 5 mm took almost 2 months (mean = 53.3, se = 5.7, range = 17–136). Age of mice at implantation, patient age, gender and race appeared to have no discernable effect on engraftment rates. Engraftment rates for low and high-grade patient tumors were similar. PFOS appeared to reduce tumor size dramatically in one group of tumors, those from the right ascending colon. That is, by 5 weeks of treatment in two mice, PFOS had eliminated their 52.4 mm3 and 124.6 mm3 masses completely, an effect that was sustained for 10 weeks of treatment; in contrast, their corresponding matched vehicle control mice had tumors that grew to 472.7 mm3 and 340.1 mm3 in size respectively during the same period. In a third xenograft mouse, the tumor growth was dramatically blunted although not eliminated, and compared favorably to their matched vehicle controls over the same period. These preliminary findings suggested that this mouse model may be advantageous for testing compounds of potential value in the treatment of colorectal cancer, and PFOS may have utility in selected cases

FTO Obesity Variant Circuitry and Adipocyte Browning in Humans

Background Genomewide association studies can be used to identify disease-relevant genomic regions, but interpretation of the data is challenging. The FTO region harbors the strongest genetic association with obesity, yet the mechanistic basis of this association remains elusive. Methods We examined epigenomic data, allelic activity, motif conservation, regulator expression, and gene coexpression patterns, with the aim of dissecting the regulatory circuitry and mechanistic basis of the association between the FTO region and obesity. We validated our predictions with the use of directed perturbations in samples from patients and from mice and with endogenous CRISPR–Cas9 genome editing in samples from patients. Results Our data indicate that the FTO allele associated with obesity represses mitochondrial thermogenesis in adipocyte precursor cells in a tissue-autonomous manner. The rs1421085 T-to-C single-nucleotide variant disrupts a conserved motif for the ARID5B repressor, which leads to derepression of a potent preadipocyte enhancer and a doubling of IRX3 and IRX5 expression during early adipocyte differentiation. This results in a cell-autonomous developmental shift from energy-dissipating beige (brite) adipocytes to energy-storing white adipocytes, with a reduction in mitochondrial thermogenesis by a factor of 5, as well as an increase in lipid storage. Inhibition of Irx3 in adipose tissue in mice reduced body weight and increased energy dissipation without a change in physical activity or appetite. Knockdown of IRX3 or IRX5 in primary adipocytes from participants with the risk allele restored thermogenesis, increasing it by a factor of 7, and overexpression of these genes had the opposite effect in adipocytes from nonrisk-allele carriers. Repair of the ARID5B motif by CRISPR–Cas9 editing of rs1421085 in primary adipocytes from a patient with the risk allele restored IRX3 and IRX5 repression, activated browning expression programs, and restored thermogenesis, increasing it by a factor of 7. Conclusions Our results point to a pathway for adipocyte thermogenesis regulation involving ARID5B, rs1421085, IRX3, and IRX5, which, when manipulated, had pronounced pro-obesity and anti-obesity effects. (Funded by the German Research Center for Environmental Health and others.)National Institutes of Health (U.S.) (R01HG004037)National Institutes of Health (U.S.) (R01GM113708)National Institutes of Health (U.S.) (R01HG008155)National Institutes of Health (U.S.) (RC1HG005334

The global subject of precarity

Peer reviewedPostprin

The descriptive epidemiology of DSM-IV Adult ADHD in the World Health Organization World Mental Health Surveys

We previously reported on the cross-national epidemiology of ADHD from the first 10 countries in the WHO World Mental Health (WMH) Surveys. The current report expands those previous findings to the 20 nationally or regionally representative WMH surveys that have now collected data on adult ADHD. The Composite International Diagnostic Interview (CIDI) was administered to 26,744 respondents in these surveys in high-, upper-middle-, and low-/lower-middle-income countries (68.5% mean response rate). Current DSM-IV/CIDI adult ADHD prevalence averaged 2.8% across surveys and was higher in high (3.6%)- and upper-middle (3.0%)- than low-/lower-middle (1.4%)-income countries. Conditional prevalence of current ADHD averaged 57.0% among childhood cases and 41.1% among childhood subthreshold cases. Adult ADHD was significantly related to being male, previously married, and low education. Adult ADHD was highly comorbid with DSM-IV/CIDI anxiety, mood, behavior, and substance disorders and significantly associated with role impairments (days out of role, impaired cognition, and social interactions) when controlling for comorbidities. Treatment seeking was low in all countries and targeted largely to comorbid conditions rather than to ADHD. These results show that adult ADHD is prevalent, seriously impairing, and highly comorbid but vastly under-recognized and undertreated across countries and cultures

The knee meniscus : investigating the regenerative potential of meniscal cartilage exposed to recombinant growth factors in vitro

Meniscal tears are common debilitating injuries that can have dramatic consequences especially for young athletes.  Healing of meniscal tears following surgical repair is essentially only feasible for tears within the peripheral vascular zone.  By comparison, tears that occur within the inner avascular zone do not heal and most commonly are treated by excision.  This in turn greatly increases the potential for secondary osteoarthrosis.  Clearly, there is a clinical need to augment surgical techniques, extending meniscal repair to the avascular zone. In this study, monolayer cell cultures were prepared from the inner, middle, and outer zones of the lateral menisci of sheep and from humans obtained following total knee arthroplasty and partial meniscectomy.  Various concentrations of Platelet Derived Growth Factor (PDGF-AB), Insulin-like Growth Factor type I (IGF-I), and basic Fibroblast Growth Factor (bFGF) were used individually to assess their effects upon cell proliferation and extracellular matrix formation. This study found that the growth factors under investigation stimulated the fibrochondrocytes, both human and sheep, in a similar dose dependent fashion, although the specifics and extent of stimulation differed for each of the growth factors, and for each species.  Interestingly, fibrochondrocytes cultured from the avascular zone were stimulated in a similar fashion to those cultured from the vascular zone.  The action of the growth factors was not dependent upon serum being present. Therefore, the results of this study are an encouraging first step towards enhancing the regeneration and potentially the repair of injured meniscal tissue.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Enhanced Trajectory Tracking of 3D Overhead Crane Using Adaptive Sliding-Mode Control and Particle Swarm Optimization

Cranes hold a prominent position as one of the most extensively employed systems across global industries. Given their critical role in various sectors, a comprehensive examination was necessary to enhance their operational efficiency, performance, and facilitate the control of transporting loads. Furthermore, due to the complexities involved in disassembling and reinstalling cranes, as well as the challenges associated with precisely determining system parameters, it became essential to implement adaptive control methods capable of efficiently managing the system with minimal resource requirements. This work proposes a trajectory tracking control using adaptive sliding-mode control (SMC) with particle swarm optimization (PSO) to control the position and rope length of a 3D overhead crane system with unknown parameters. The PSO is mainly used to identify the model and estimate the uncertain parameters. Then, sliding-mode control is adapted using the PSO algorithm to minimize the tracking error and ensure robustness against model uncertainties. A model of the systems is derived assuming changing rope length. The model is nonlinear of second order with five states, three actuated states: position x and y, and rope length l, and two unactuated states, which are the rope angles θx and θy. The system has uncertain parameters, which are the system’s masses Mx, My and Mz, and viscous damping coefficients Dx, Dy and Dy. A simulation study is established to illustrate the influence and robustness of the developed controller and it can enhance the tracking trajectory under different scenarios to test the scheme