Regulation of osteoblast differentiation by Pasteurella multocida toxin (PMT): a role for Rho GTPase in bone formation.

The role of the Rho-Rho kinase signaling pathway on osteoblast differentiation was investigated using primary mouse calvarial cells. The bacterial toxin PMT inhibited, whereas Rho-ROK inhibitors stimulated, osteoblast differentiation and bone nodule formation. These effects correlated with altered BMP-2 and -4 expression. These data show the importance of Rho-ROK signaling in osteoblast differentiation and bone formation. INTRODUCTION: The signal transduction pathways controlling osteoblast differentiation are not well understood. In this study, we used Pasteurella multocida toxin (PMT), a unique bacterial toxin that activates the small GTPase Rho, and specific Rho inhibitors to investigate the role of Rho in osteoblast differentiation and bone formation in vitro. MATERIALS AND METHODS: Primary mouse calvarial osteoblast cultures were used to investigate the effects of recombinant PMT and Rho-Rho kinase (ROK) inhibitors on osteoblast differentiation and bone nodule formation. Osteoblast gene expression was analyzed using Northern blot and RT-PCR, and actin rearrangements were visualized after phalloidin staining and confocal microscopy. RESULTS: PMT stimulated the proliferation of primary mouse calvarial cells and markedly inhibited the differentiation of osteoblast precursors to bone nodules with a concomitant inhibition of osteoblastic marker gene expression. There was no apparent causal relationship between the stimulation of proliferation and inhibition of differentiation. PMT caused cytoskeletal rearrangements because of activation of Rho, and the inhibition of bone nodules was completely reversed by the Rho inhibitor C3 transferase and partly reversed by inhibitors of the Rho effector, ROK. Interestingly, Rho and ROK inhibitors alone potently stimulated osteoblast differentiation, gene expression, and bone nodule formation. Finally, PMT inhibited, whereas ROK inhibitors stimulated, bone morphogenetic protein (BMP)-2 and -4 mRNA expression, providing a possible mechanism for their effects on bone nodule formation. CONCLUSIONS: These results show that PMT inhibits osteoblast differentiation through a mechanism involving the Rho-ROK pathway and that this pathway is an important negative regulator of osteoblast differentiation. Conversely, ROK inhibitors stimulate osteoblast differentiation and may be potentially useful as anabolic agents for bone.     

Provision of healthcare in the context of financial crisis: approaches to the Greek health system and international implications

Both healthcare professionals and the healthcare system must defend each patient's health individually while simultaneously seeking to protect the population's health in general. Nowadays, there is an important increase in the cost of healthcare supply, mainly due to the developments of medical science, the public's expectations and the demographic ageing. Since healthcare resources are not unlimited, it is obvious that immoderate consumption of them by certain patients limits the use of the same funds by others. Therefore, we have to seek an optimal distribution of the existing resources in order to manage a constriction of expenses, especially under the circumstances of the modern economic crisis. The criteria of effectiveness and efficiency should be used. Health policies focus on both the public's behaviour and the rules of medical practice. Under the modern challenges the physician's role is particularly important for the protection of the patient's health and the promotion of public health.     

Oral Fine Motor Control of Teeth Treated with Endodontic Microsurgery: A Single-Blinded Case-control Study

IntroductionPeriodontal mechanoreceptors (PMRs) are refined neural receptors present in abundance at the root apex and have a pivotal role in oral fine motor control. This case-control study aimed to evaluate the oral fine motor control of teeth treated with endodontic microsurgery (EMS) in comparison with the control teeth using a standardized behavioral biting task.MethodsFourteen eligible participants performed 5 trials of an oral fine motor control task that involved holding and splitting half of a peanut positioned on a force transducer with their EMS treated tooth and its contralateral control incisor tooth (28 teeth in total). The outcome variables were the mean food holding force, intra- and intertrial variability of the holding force, food splitting force, splitting duration, and the frequency of the stepwise splitting phase. The data were analyzed with parametric and nonparametric tests.ResultsThe results showed no statistically significant differences in the holding force, inter- and intratrial variability of the holding force, splitting force, or splitting duration between the teeth treated with EMS and the control (P > .05). However, there was a significantly higher frequency of stepwise ramp increase during the splitting phase with EMS treated teeth compared with the control (48% and 37%, respectively; P < .05).ConclusionsEMS treated teeth showed similar force regulation and oral fine motor control as the contralateral control. The findings of this study suggest that EMS treatment does not perturb the sensory information of PMRs and maintains the force regulation and oral fine motor control of the teeth.     

Nasogastric aspiration/lavage in patients with gastrointestinal bleeding: a review of the evidence

Introduction: The usefulness of nasogastric aspiration and nasogastric lavage in patients with gastrointestinal bleeding is controversial, as evidenced by conflicting recommendations, both among and within society guidelines.

Areas covered: Considering these controversies, we reviewed the evidence regarding the following questions: 1) Can nasogastric lavage stop or slow down the bleeding and improve subsequent endoscopic visualization? 2) Is nasogastric aspiration helpful for the localization of bleeding? 3) Can nasogastric aspiration identify high risk patients that might benefit from earlier endoscopy? 4) Is there evidence for benefit in terms of outcomes from using nasogastric aspiration? 5) Is nasogastric intubation safe in patients with possible esophageal varices? Our review was conducted according to PRISMA guidelines.

Expert commentary: Based on the available literature, nasogastric lavage or aspiration cannot be routinely recommended unless a large properly designed randomized trial (which is currently lacking) proves otherwise. It is a painful and time-consuming procedure with no demonstrated benefit for the patient in terms of outcomes. Other clinical and laboratory parameters, and risk scores, are less invasive and are effective for guiding the stratification and management of patients, while pre-endoscopic erythromycin infusion is a good if not better alternative for improving visualization of the stomach.     

Bite or brain: Implication of sensorimotor regulation and neuroplasticity in oral rehabilitation procedures

Tooth loss, decreased mass and strength of the masticatory muscles leading to difficulty in chewing have been suggested as important determinants of eating and nutrition in the elderly. To compensate for the loss of teeth, in particular, a majority of the elderly rely on dental prosthesis for chewing. Chewing function is indeed an important aspect of oral health, and therefore, oral rehabilitation procedures should aim to restore or maintain adequate function. However, even if the possibilities to anatomically restore lost teeth and occlusion have never been better; conventional rehabilitation procedures may still fail to optimally restore oral functions. Perhaps this is due to the lack of focus on the importance of the brain in the rehabilitation procedures. Therefore, the aim of this narrative review was to discuss the importance of maintaining or restoring optimum chewing function in the superageing population and to summarise the emerging studies on oral motor task performance and measures of cortical neuroplasticity induced by systematic training paradigms in healthy participants. Further, brain imaging studies in patients undergoing or undergone oral rehabilitation procedures will be discussed. Overall, this information is believed to enhance the understanding and develop better rehabilitative strategies to exploit training‐induced cortical neuroplasticity in individuals affected by impaired oral motor coordination and function. Training or relearning of oral motor tasks could be important to optimise masticatory performance in dental prosthesis users and may represent a much‐needed paradigm shift in the approach to oral rehabilitation procedures.     

Administration of low-molecular-weight heparin in patients with two or more unsuccessful IVF/ICSI cycles: a multicenter cohort study

To compare the effects of the administration of low-molecular-weight heparin (LMWH) in subfertile patients with two or more unsuccessful IVF/ICSI cycles. In this six-center two-arm retrospective cohort study, the study population (230 women) underwent a GnRH-antagonist protocol and was classified into two groups, according to the couse of LMWH or not. Groups were compared regarding the clinical and IVF/ICSI cycle characteristics and reproductive outcomes, whereas clinical pregnancy and miscarriage constituted the primary endpoints. Logistic regression analysis was performed to determine the potential predictors of clinical pregnancy, miscarriage and live birth rates using the Enter method. Baseline characteristics were comparable in the two groups. There was no statistically significant difference between the two study groups with regard neither to clinical pregnancy and miscarriage rates (33/133 vs. 20/97, p?=?.456 and 15/133 vs. 9/97, p?=?.624, respectively), nor to the secondary outcomes preset for this study (all p values?>.05). Logistic regression revealed that age of the woman and ICSI and dose of gonadotrophins used were predictors of clinical pregnancy and live birth, respectively. In conclusion, there is no evidence to support the standard addition of LMWH in patients with two or more unsuccessful IVF/ICSI cycles.     

Eleven Patients With Testicular Leydig Cell Tumors

We present the sonographic and magnetic resonance imaging findings of Leydig cell tumors in a series of patients, along with a brief review of the literature. We evaluated the sonographic features of 11 cases of Leydig cell tumors, including echogenicity, size, margins, and patterns of vascularity. The magnetic resonance imaging characteristics of 9 patients were also assessed, with special attention to the appearance of the tumors on T2-weighted imaging and postcontrast T1-weighted imaging. Seven tumors were hypoechoic, and 4 were almost isoechoic. Ten patients showed various patterns of hypervascularity in the tumors, combined in some cases with feeding vessels. One case presented with a single feeding vessel. The tumors showed homogeneous or heterogeneous low signal intensity on T2-weighted imaging and marked enhancement on postcontrast T1-weighted imaging. The small size of these tumors, the various patterns of vascularity on color and power Doppler sonography, and the marked enhancement on postcontrast T1-weighted imaging are considered valuable but generally nonspecific for identification of these tumors.