Systemic antibiotics adjuvants to scaling and root planing in type 2 diabetic and periodontitis individuals: Systematic review with network meta-analysis.

Targeting inflammatory pathways is considered a common strategy to control type 2 diabetes (T2D) and periodontitis. This overview was to validate systemic antibiotics as an adjuvant to scaling and root planing (SRP) for the treatments of periodontal patients with T2D. Literature searches were conducted using Web of Science, PubMed, Cochrane, and EMBASE. Randomized trials comparing SRP and systemic antibiotics on glycated hemoglobin (HbA1c) and probing pocket depth (PPD) in adults with T2D and periodontitis were analyzed using network meta-analysis and meta-regression. At 3-month postintervention, meta-analyses of 16 studies revealed that SRP and SRP plus systemic antibiotics (SRPa) had similar significant effects in reducing HbA1c levels of - 0.72% and - 0.96% respectively. While SRP and SRPa also, respectively, reduced PPD of - 0.67 and - 0.89 mm, SRPa showed a better reduction than SRP. At 6-month postintervention, meta-analyses of 7 trials revealed that only SRP was effective in reducing HbA1c levels (-0.29%) but not SRPa. Although both SRP and SRPa still significantly reduced PPD by - 0.56 and - 0.81 mm, respectively, there was no difference between them. The current overview suggested that routine SRP alone is highly recommended for patients with T2D and periodontitis, since systemic antibiotics as an adjuvant provide a rather short-term effect.

Machine learning of cell population data, complete blood count, and differential count parameters for early prediction of bacteremia among adult patients with suspected bacterial infections and blood culture sampling in emergency departments.

BACKGROUND: Bacteremia is a life-threatening complication of infectious diseases. Bacteremia can be predicted using machine learning (ML) models, but these models have not utilized cell population data (CPD). METHODS: The derivation cohort from emergency department (ED) of China Medical University Hospital (CMUH) was used to develop the model and was prospectively validated in the same hospital. External validation was performed using cohorts from ED of Wei-Gong Memorial Hospital (WMH) and Tainan Municipal An-Nan Hospital (ANH). Adult patients who underwent complete blood count (CBC), differential count (DC), and blood culture tests were enrolled in the present study. The ML model was developed using CBC, DC, and CPD to predict bacteremia from positive blood cultures obtained within 4 h before or after the acquisition of CBC/DC blood samples. RESULTS: This study included 20,636 patients from CMUH, 664 from WMH, and 1622 patients from ANH. Another 3143 patients were included in the prospective validation cohort of CMUH. The CatBoost model achieved an area under the receiver operating characteristic curve of 0.844 in the derivation cross-validation, 0.812 in the prospective validation, 0.844 in the WMH external validation, and 0.847 in the ANH external validation. The most valuable predictors of bacteremia in the CatBoost model were the mean conductivity of lymphocytes, nucleated red blood cell count, mean conductivity of monocytes, and neutrophil-to-lymphocyte ratio. CONCLUSIONS: ML model that incorporated CBC, DC, and CPD showed excellent performance in predicting bacteremia among adult patients with suspected bacterial infections and blood culture sampling in emergency departments.

Value of monocyte distribution width for predicting severe cholecystitis: a retrospective cohort study.

OBJECTIVES: Acute cholecystitis is a gallbladder inflammation, and the Tokyo Guidelines 2018 (TG18) can be used to predict its presence and severity with high sensitivity and specificity. However, TG18 grading require the collection of excessive parameters. Monocyte distribution width (MDW) is a parameter used to detect sepsis early. Therefore, we investigated the correlation between MDW and cholecystitis severity. METHODS: We conducted a retrospective study of patients with cholecystitis admitted to our hospital from November 1, 2020, to August 31, 2021. The primary outcome was severe cholecystitis analyzed as a composite of intensive care unit (ICU) admission and mortality. The secondary outcomes were length of hospital stay, ICU stay, and TG18 grade. RESULTS: A total of 331 patients with cholecystitis were enrolled in this study. The average MDWs for TG18 grades 1, 2, and 3 were 20.21 ± 3.99, 20.34 ± 3.68, and 25.77 ± 6.61, respectively. For patients with severe cholecystitis, the average MDW was 25.42 ± 6.83. Using the Youden J statistic, we set a cutoff MDW of 21.6. Multivariate logistic regression revealed that patients with an MDW≥21.6 had a higher risk of severe cholecystitis (odds ratio=4.94; 95 % CI, 1.71-14.21; p=0.003). The Cox model revealed that patients with an MDW≥21.6 were more likely to have a prolonged hospital stay. CONCLUSIONS: MDW is a reliable indicator of severe cholecystitis and prolonged length of stay. Additional MDW testing and a complete blood count may provide simple information for predicting severe cholecystitis early.

Translation and validation of modified dental anxiety scale based on adult Taiwan population.

BACKGROUND: Dental anxiety is associated with negative experiences of dental treatment and dental-visiting behavior. The Modified Dental Anxiety Scale (MDAS) is widely used for assessing dental anxiety. The study aims to establish the psychometric properties of a Chinese version of the MDAS based on the Taiwan sample (i.e., T-MDAS). METHODS: The T-MDAS and dental-visiting behavior and experience were assessed for 402 adult subjects recruited from community and clinical sites. The following psychometric properties were assessed: (a) internal consistency, (b) temporal stability, (c) criterion-related validity (i.e., the association with the score of Index of Dental Anxiety and Fear, IDAF-4C), (d) discrimination validity (i.e., the difference in scores between the subjects with and without a habit of a regular dental visit, and (e) the construct validity from a confirmatory factor analysis (CFA). RESULTS: The T-MDAS showed good internal consistency (Cronbach's α = 0.88) and temporal stability (ρ = 0.69, p < 0.001). The score was significantly correlated with the score of the IDAF-4C (ρ = 0.76, p < 0.001) and differed between subjects who regularly visited a dentist or not, supporting good criterion-related validity and discrimination validity. Results from CFA supports good construct validity. Furthermore, higher dental anxiety was related to the lack of a regular dental visit, feeling pain during treatment, and feeling insufficient skills and empathy of dentists. A higher proportion of high-dental anxiety subjects in female subjects (8.5%), compared to male subjects (5.0%), was noted. CONCLUSIONS: The T-MDAS is a valid tool for assessing adult dental anxiety. The score is highly associated with dental-visiting behavior and experience of dental patients.

Periodontal conditions in patients with Sjögren's syndrome: A meta-analysis.

Sjögren's syndrome (SS) is a chronic autoimmune rheumatic disease characterized by a progressive lymphocytic infiltration of salivary glands, resulting in xerostomia and other oral diseases. The pathogenesis and mechanisms of SS on periodontal tissues are not well understood. Furthermore, results of two systemic reviews and meta-analyses in which compared periodontal parameters of patients with SS to healthy subjects were different. To determine whether periodontal conditions in SS were different from healthy controls, we re-examined the issue with a random-effect model, avoiding recruiting active controls and inadequate data conversion. Outcome measures included probing pocket depth (PPD), clinical attachment loss (CAL), plaque index (PI), and gingival index (GI). Recruited individuals comprised 198 patients with SS and 180 subjects for healthy controls. Quantitative analysis revealed higher PI (WMD = 0.76, 95% CI: 0.30, 1.23) and GI (WMD of total = 0.50, 95% CI: 0.01, 0.98) in SS patients who were not categorized into primary or secondary types of SS. PPD and CAL in SS patients was comparable with control subjects. However, heterogeneity was observed among included studies. Thus, results from this and previous analyses should be interpretated carefully, and a well-designed observational study regarding this issue should be conducted.

Derivation and Validation of the SWAP Score for Very Early Prediction of Neurologic Outcome in Patients With Out-of-Hospital Cardiac Arrest.

STUDY OBJECTIVE: For patients with out-of-hospital cardiac arrest who receive cardiopulmonary resuscitation in an emergency department (ED), the early evaluation of their neurologic prognosis is essential for emergency physicians. The aim of this study is to establish a simple and useful assessment tool for rapidly estimating the prognosis of patients with out-of-hospital cardiac arrest after their arrival at an ED. METHODS: A total of 852 patients admitted from January 1, 2015, to June 30, 2017, were prospectively registered and enrolled in the derivation cohort. Multivariate logistic regression on this cohort identified 4 independent factors associated with unfavorable outcomes: initial nonshockable rhythm (odds ratio [OR] 3.40; 95% confidence interval [CI] 1.58 to 7.32), no witness of collapse (OR 3.19; 95% CI 1.51 to 6.75), older than 60 years (OR 3.65; 95% CI 1.64 to 8.09), and pH less than or equal to 7.00 (OR 3.27; 95% CI 1.42 to 7.54). The shockable rhythm-witness-age-pH (SWAP) score was developed and 1 point was assigned to each predictor. RESULTS: For a SWAP score of 4, the specificity was 97.14% (95% CI 91.62% to 100%) for unfavorable outcomes in the derivation cohort. For validation, we retrospectively collected data for 859 patients with out-of-hospital cardiac arrest from January 1, 2012, to December 31, 2014. A SWAP score of 4 was 100% specific (95% CI 99.9% to 100%) for unfavorable outcomes in the validation cohort. CONCLUSION: The SWAP score is a simple and useful predictive model that may provide information for the very early estimation of prognosis for patients with out-of-hospital cardiac arrest. Further research is required to integrate ultrasonographic findings and validate the SWAP score's application in other populations.

Brain activations associated with fearful experience show common and distinct patterns between younger and older adults in the hippocampus and the amygdala.

Revisiting threat-related scenes elicits fear and activates a brain network related to cognitive-affective processing. Prior experience may contribute to the present fearful experience. We aimed to investigate (a) patterns of brain activation associated with individual differences in past fearful experiences (pFear) and the present fear elicited by watching videos (eFear) and (b) age-related differences in the activation patterns. Forty healthy adults, including 20 younger adults (YA) and 20 older adults (OA), underwent functional magnetic resonance imaging while watching videos containing high- and low-threat scenes of medical treatment. Both age subgroups showed positive correlations between pFear and bilateral hippocampal activation. Only YA showed threat-related activation in the bilateral anterior insula and activation positively correlated with pFear in the bilateral S1 and the amygdala. The evidence suggests that the hippocampus, amygdala and S1 may play key roles in bridging past fearful experiences and the present fear elicited by revisiting visual scenes and that the interaction between memory and emotional processing may be age dependent.

Association between monocyte chemoattractant protein-1 -2518 A/G gene polymorphism and the outcome of the nonsurgical periodontal treatment.

BACKGROUND/PURPOSE: Elevated monocyte chemoattractant protein-1 (MCP-1) is related to severe periodontal destruction. Furthermore, MCP-1 -2518 A/G gene polymorphism affects MCP-1 after inflammatory stimuli. This study analyzed the association between MCP-1 -2518 gene polymorphism and the outcome of nonsurgical periodontal treatment. METHODS: Forty periodontal patients were recruited and MCP-1 -2518 A/G gene polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism assay. The clinical periodontal parameters, including probing depth (PD), clinical attachment level (CAL), gingival index (GI), bleeding index (BI) and plaque index (PI), were recorded before and six weeks after nonsurgical periodontal therapy. Patients were divided into chronic periodontitis (CP) or aggressive periodontitis (AP). Multiple linear regression analysis was performed to investigate certain predictors of the therapy outcome. RESULTS: The frequency of MCP-1 -2518 genotype-positive (carrying allele G) was 42.5%. Poor treatment outcome in PD, GI and BI improvement could be predicted with MCP-1 -2518 A/G genotype and aggressive periodontitis status as the predictor variables. In contrast, MCP-1 -2518 A/A genotype and aggressive periodontitis status could predict better treatment response in PD and BI improvement. However, MCP-1 -2518 genotype did not affect the treatment outcome in patients with chronic periodontitis. CONCLUSION: MCP-1 -2518 A/G genotype might be useful in predicting less favorable nonsurgical treatment outcome in patients with aggressive periodontitis. However, MCP-1 -2518 gene polymorphism may not play a role in patients with chronic periodontitis. This study suggests that MCP-1 -2518 genotype may influence the outcome of nonsurgical periodontal treatment in aggressive periodontitis patients.

Age- and sex-related differences in masseter size and its role in oral functions.

BACKGROUND: The masseter muscle plays a key structural and functional role in the stomatognathic system. Researchers' cumulative evidence has suggested that the variation in the size of a person's masseter muscle may be a critical factor related to individual differences in oral functions. However, researchers have not yet investigated systematically the effect of a person's age and sex on masseter muscle size and the association of masseter muscle size with other clinical metrics, including masticatory performance (MP) and salivary flow rate (SFR). Using T1-weighted magnetic resonance imaging (MRI) data provides a noninvasive method for assessing masseter muscle volume (MMV). METHODS: Using T1-weighted MRI data, the authors developed a voxel-based method to assess MMV and investigated the associations among MMV, MP, and SFR. RESULTS: The authors acquired T1-weighted MRI data from scans of the heads of 62 healthy adults and assessed MMV by means of using a voxel-based approach. The authors' assessment results had acceptable rates of inter-rater and intrarater reliability. MMV was significantly lower in the older subgroup and in the female subgroup. In addition, the correlation for MMV was significantly positive with MP and stimulated SFR. CONCLUSIONS: The study results revealed evidence that the authors' voxel-based approach, which they designed on the basis of T1-weighted MRI data, would be a reliable method for quantifying MMV. PRACTICAL IMPLICATIONS: The findings suggest that the variation in masseter muscle size may be a critical factor to assess individual differences in oral functions.

Age-Related Difference in Functional Brain Connectivity of Mastication.

The age-related decline in motor function is associated with changes in intrinsic brain signatures. Here, we investigated the functional connectivity (FC) associated with masticatory performance, a clinical index evaluating general masticatory function. Twenty-six older adults (OA) and 26 younger (YA) healthy adults were recruited and assessed using the masticatory performance index (MPI) and resting-state functional magnetic resonance imaging (rs-fMRI). We analyzed the rs-fMRI FC network related to mastication, which was constructed based on 12 bilateral mastication-related brain regions according to the literature. For the OA and the YA group, we identified the mastication-related hubs, i.e., the nodes for which the degree centrality (DC) was positively correlated with the MPI. For each pair of nodes, we identified the inter-nodal link for which the FC was positively correlated with the MPI. The network analysis revealed that, in the YA group, the FC between the sensorimotor cortex, the thalamus (THA) and the cerebellum was positively correlated with the MPI. Consistently, the cerebellum nodes were defined as the mastication-related hubs. In contrast, in the OA group, we found a sparser connection within the sensorimotor regions and cerebellum and a denser connection across distributed regions, including the FC between the superior parietal lobe (SPL), the anterior insula (aINS) and the dorsal anterior cingulate cortex (dACC). Compared to the YA group, the network of the OA group also comprised more mastication-related hubs, which were spatially distributed outside the sensorimotor regions, including the right SPL, the right aINS, and the bilateral dACC. In general, the findings supported the hypothesis that in OA, higher masticatory performance is associated with a widespread pattern of mastication-related hubs. Such a widespread engagement of multiple brain regions associated with the MPI may reflect an increased demand in sensorimotor integration, attentional control and monitoring for OA to maintain good mastication.

Functional and Structural Signatures of the Anterior Insula are associated with Risk-taking Tendency of Analgesic Decision-making.

In a medical context, decision-making is associated with complicated assessment of gains, losses and uncertainty of outcomes. We here provide novel evidence about the brain mechanisms underlying decision-making of analgesic treatment. Thirty-six healthy participants were recruited and completed the Analgesic Decision-making Task (ADT), which quantified individual tendency of risk-taking (RPI), as the frequency of choosing a riskier option to relieve pain. All the participants received resting-state (rs) functional magnetic resonance imaging (MRI) and structural MRI. On rs-functional connectome, degree centrality (DC) of the bilateral anterior insula (aINS) was positively correlated with the RPI. The functional connectivity between the aINS, the nucleus accumbens and multiple brain regions, predominantly the medial frontal cortex, was positively correlated with the RPI. On structural signatures, the RPI was positively correlated with grey matter volume at the right aINS, and such an association was mediated by DC of the left aINS. Regression analyses revealed that both DC of the left aINS and participants' imagined pain relief, as the utility of pain reduction, could predict the individual RPI. The findings suggest that the functional and structural brain signature of the aINS is associated with the individual differences of risk-taking tendency in the context of analgesic decision-making.

Systematic Review and Meta-Analysis on Incidence of Altered Sensation of Mandibular Implant Surgery.

Altered sensation (including paresthesia, dysesthesia and hypoesthesia) after mandibular implant surgery may indicate transient or permanent injury of the inferior alveolar nerve and the mental branch, and considerably lower patients' satisfaction about the therapy. Previous studies have shown a great degree of variability on the incidence of altered sensation. We here reported the incidence of altered sensation after mandibular implant surgery based on a meta-analysis of 26 articles published between 1990.1.1 and 2016.1.1. Study quality and risk of bias was assessed and the studies with a lower score were excluded in the meta-analysis. Data synthesis was performed using the logistic-normal random-effect model. The meta-analyses revealed that the short-term (10 days after implant placement) and long-term (1 year after implant placement) incidence was 13% (95% CI, 6%-25%) and 3% (95% CI, 1%-7%), respectively. (2) For the patients who initially reported altered sensation, 80% (95% CI, 52%-94%) of them would return to normal sensation within 6 months after surgery, and 91% (95% CI, 78%-96%) of them would return to normal sensation one year after surgery. We concluded that dentist-patient communication about the risk of altered sensation is critical to treatment planning, since the short-term incidence of altered sensation is substantial (13%). When a patient reports altered sensation, regular assessment for 6 months would help tracing the changes of symptoms. In terms of long-term follow-up (1 year after surgery), the incidence is much lower (3%) and most patients (91%) would return to normal sensation.

The anterior insula and anterior cingulate cortex are associated with avoidance of dental treatment based on prior experience of treatment in healthy adults.

BACKGROUND: Fear concerning stressful medical or dental procedures is one of the major factors that distance patients from health care. Fear and avoidance of dental treatments can be shaped by a patient's prior experience with receiving dental procedures or by imagining the procedures. METHODS: We performed two functional magnetic resonance imaging (fMRI) experiments to investigate the role of the anterior insula (aINS) and dorsal anterior cingulate cortex (dACC), which are both critical to threat perception, in dental avoidance. Dental avoidance based on both prior treatment experience and imagination was assessed using a customized questionnaire. In an fMRI task-based study, we investigated brain activation in 17 healthy participants when they viewed images depicting dental procedures that evoked a moderate degree of fear. Region-of-interest analysis was performed to assess the association between dental avoidance and aINS as well as dACC activation. In a resting state fMRI study, we investigated 18 healthy participants for the association between the intrinsic functional connectivity of the aINS and dACC and dental avoidance. RESULTS: We found that (1) the participants showed a higher activation of the right aINS and bilateral dACC when they viewed images of dental procedures compared with the brain activation observed when they viewed scrambled images (p < 0.05 corrected for small volume and family-wise error). (2) The avoidance ratings based on prior experience of dental treatment were significantly positively correlated with the activation in the right aINS (r = 0.67, p = 0.003), right dACC (r = 0.65, p = 0.005) and left dACC (r = 0.63, p = 0.007). (3) The intrinsic functional connectivity between the aINS and the orbitofrontal cortex was positively correlated with the avoidance ratings based on experience (uncorrected p < 0.001). CONCLUSIONS: The findings highlight prior experience of dental treatment as a predominant factor in shaping patients' avoidance behavior. Individual differences in threat perception may play a key role in the development of dental avoidance.

Preferences for Analgesic Treatments Are Influenced by Probability of the Occurrence of Adverse Effects and the Time to Reach Maximal Therapeutic Effects.

Research on shared medical decision-making suggested that both the potency of a treatment and the probability of it being successful influence individual treatment preferences. Patients also need to consider the negative attributes of treatments, such as the occurrence of adverse effects or a slow start to the therapeutic effects. It remains unclear how these attributes influence individual treatment preferences. We investigated how the analgesic effect, the adverse effect, and the time-course effect influenced the preference of analgesic treatments. Forty-five healthy volunteers participated in three hypothetical analgesic decision-making tasks. They were instructed to imagine that they were experiencing pain and choose between two hypothetical analgesic treatments: the more potent radical treatment and the less potent conservative treatment. The potency of a treatment was countered by the following attributes: the probability of working successfully, the probability of inducing an adverse effect, and the time required for the treatment to reach its maximal effect. We found that (a) when the overall probability that a treatment would induce an adverse effect decreased, the participants changed their preference from a conservative treatment to a radical treatment; (b) when the time-course for a treatment to reach its maximal effect was shortened, the participants changed their preference from a conservative treatment to a radical treatment, and (c) individual differences in prior clinical pain and the degree of imagined pain relief were associated with preferences. The findings showed that the adverse effects and the time course of treatments guide the analgesic treatment preferences, highlighting the importance of sharing information about negative attributes of treatments in pain management. The findings imply that patients may over-emphasize the occurrence of adverse effect or a slow time-course of treatment effect. In terms of shared medical decision-making, clinicians should clarify these negative attributes related to treatment to patients.

Gray Matter Volume and Resting-State Functional Connectivity of the Motor Cortex-Cerebellum Network Reflect the Individual Variation in Masticatory Performance in Healthy Elderly People.

Neuroimaging studies have consistently identified brain activation in the motor area and the cerebellum during chewing. In this study, we further investigated the structural and functional brain signature associated with masticatory performance, which is a widely used index for evaluating overall masticatory function in the elderly. Twenty-five healthy elderly participants underwent oral examinations, masticatory performance tests, and behavioral assessments, including the Cognitive Abilities Screening Instrument and the short-form Geriatric Depression Scale. Masticatory performance was assessed with the validated colorimetric method, using color-changeable chewing gum. T1-weighted structural magnetic resonance imaging (MRI) and resting-state function MRI were performed. We analyzed alterations in gray matter volume (GMV) using voxel-based morphometry and resting-state functional connectivity (rsFC) between brain regions using the seed-based method. The structural and functional MRI analyses revealed the following findings: (1) the GMV change in the premotor cortex was positively correlated with masticatory performance. (2) The rsFC between the cerebellum and the premotor cortex was positively correlated with masticatory performance. (3) The GMV changes in the dorsolateral prefrontal cortex (DLPFC), as well as the rsFC between the cerebellum and the DLPFC, were positively correlated with masticatory performance. The findings showed that in the premotor cortex, a reduction of GMV and rsFC would reflect declined masticatory performance. The positive correlation between DLPFC connectivity and masticatory performance implies that masticatory ability is associated with cognitive function in the elderly. Our findings highlighted the role of the central nervous system in masticatory performance and increased our understanding of the structural and functional brain signature underlying individual variations in masticatory performance in the elderly.

Red cell distribution width is an independent predictor of mortality in necrotizing fasciitis.

INTRODUCTION: Necrotizing fasciitis (NF) is a rapidly progressing and potentially lethal infectious disease of the soft tissue. An elevated red blood cell distribution width (RDW) is associated with increased risk of death in patients with heart disease and infectious disease. We retrospectively assessed the association of elevated RDW with in-hospital mortality due to NF. METHODS: All patients had diagnoses of NF and were admitted to the emergency department of a single institution in Taiwan over a 4-year period. Demographics, comorbidities, clinical presentations, and laboratory parameters were retrospectively reviewed. Red blood cell distribution width was categorized as elevated (>14.5%) or not elevated. Multivariate regression analysis was used to identify risk factors associated with mortality. RESULTS: A total of 98 patients were enrolled, and the mortality rate was 23%. Univariate analysis indicated that advanced age, initial hypotension, low hemoglobin level, and elevated RDW (69.6% vs 20%, OR = 9.14, P < .001) were significantly associated with mortality. Multivariate analysis indicated that RDW was a significant and independent predictor of mortality in enrolled patients. CONCLUSIONS: Elevated RDW is a significant and independent predictor of in-hospital mortality for patients with NF.

Aortoiliac occlusive disease presenting as sudden onset paraplegia.

Thromboembolism and atherosclerotic stenosis both can cause arterial occlusion. Aortoiliac occlusive disease involving bifurcation of the aortoiliac artery induces symptoms of ischemia such as claudication and pain of buttocks and thighs, decreased bilateral femoral pulses, and impotence. Here, we describe a 58-year-old woman with a past history of atrial fibrillation and lacuna stroke with minimal right side weakness. She presented to our emergency department with sudden onset bilateral pain in the legs and paraplegia. A comprehensive examination revealed paresthesia and decreasing bilateral distal pulses. Computed tomographic imaging showed filling defects over the low abdominal aorta just above the bifurcation of the common iliac artery and bilateral femoral arteries. Acute aortic embolic occlusion was suspected. Her symptoms were resolved after emergent thrombectomy for acute limb ischemia. Physicians need to be aware of aortoiliac embolic occlusive disease which may present as acute paraplegia.

The Bro1-domain-containing protein Myopic/HDPTP coordinates with Rab4 to regulate cell adhesion and migration.

Protein tyrosine phosphatases (PTPs) are a group of tightly regulated enzymes that coordinate with protein tyrosine kinases to control protein phosphorylation during various cellular processes. Using genetic analysis in Drosophila non-transmembrane PTPs, we identified one role that Myopic (Mop), the Drosophila homolog of the human His domain phosphotyrosine phosphatase (HDPTP), plays in cell adhesion. Depletion of Mop results in aberrant integrin distribution and border cell dissociation during Drosophila oogenesis. Interestingly, Mop phosphatase activity is not required for its role in maintaining border cell cluster integrity. We further identified Rab4 GTPase as a Mop interactor in a yeast two-hybrid screen. Expression of the Rab4 dominant-negative mutant leads to border cell dissociation and suppression of Mop-induced wing-blade adhesion defects, suggesting a critical role of Rab4 in Mop-mediated signaling. In mammals, it has been shown that Rab4-dependent recycling of integrins is necessary for cell adhesion and migration. We found that human HDPTP regulates the spatial distribution of Rab4 and integrin trafficking. Depletion of HDPTP resulted in actin reorganization and increased cell motility. Together, our findings suggest an evolutionarily conserved function of HDPTP-Rab4 in the regulation of endocytic trafficking, cell adhesion and migration.

The roles and mechanisms of PAR4 and P2Y12/phosphatidylinositol 3-kinase pathway in maintaining thrombin-induced platelet aggregation.

BACKGROUND AND PURPOSE: Activation of human platelets by thrombin is mediated predominately through two proteinase-activated receptors (PARs), PAR1 and PAR4. Phosphatidylinositol 3-kinase (PI3K) inhibition leads to reversible PAR1-mediated platelet aggregation, but has no effect on the stability of platelet aggregation induced by thrombin. In the present study, the molecular mechanisms underlying this difference were investigated. EXPERIMENTAL APPROACH: The functions of PI3K and PAR4 were assessed using specific inhibitors and aggregometry. The duration of platelet glycoprotein (GP) IIb/IIIa exposure was determined by flow cytometry with the antibody PAC-1. Western blotting and fluo-3 was used to evaluate the activation of Akt and protein kinase C (PKC) and intracellular Ca(2+) mobilization respectively. KEY RESULTS: When PAR4 function was inhibited either by the PAR4 antagonist YD-3 [1-benzyl-3-(ethoxycarbonylphenyl)-indazole] or by receptor desensitization, the PI3K inhibitor wortmannin turned thrombin-elicited platelet aggregation from an irreversible event to a reversible event. Moreover, wortmannin plus YD-3 markedly accelerated the inactivation of GPIIb/IIIa in thrombin-stimulated platelets. The aggregation-reversing activity mainly resulted from inhibition of both PI3K-dependent PKC activation and PAR4-mediated sustained intracellular Ca(2+) rises. Blockade of ADP P2Y(12) receptor with 2-methylthioadenosine 5'-monophosphate triethylammonium salt mimicked the inhibitory effect of wortmannin on PI3K-dependent PKC activation and its ability to reverse PAR1-activating peptide-induced platelet aggregation. Co-administration of 2-methylthioadenosine 5'-monophosphate triethylammonium salt with YD-3 also decreased the stability of thrombin-induced platelet aggregation. CONCLUSIONS AND IMPLICATIONS: These results suggest that PAR4 acts in parallel with the P2Y(12)/PI3K pathway to stabilize platelet aggregates, and provide new insights into the mechanisms of thrombus stabilization and potential applications for antithrombotic therapy.

Comparison of clinical outcomes following guided tissue regeneration treatment with a polylactic acid barrier or a collagen membrane.

This prospective, randomized, controlled clinical trial compared the clinical outcomes for a polylactic acid barrier versus a collagen membrane in conjunction with guided tissue regeneration (GTR). Thirty patients with chronic periodontitis and at least one intrabony defect of a minimum 4 mm were enrolled. Following full-mouth scaling, GTR using a collagen membrane or a polylactic acid barrier was performed at one site in each patient. At 1 week before and 6 months after surgery, probing pocket depth (PPD), clinical attachment level (CAL), marginal tissue recession, and bone fill were assessed. A significant reduction in PPD (2.50 +/- 1.35 mm for the polylactic acid barrier and 2.60 +/- 1.08 mm for the collagen membrane) was obtained, in addition to gains in CAL (2.40 +/- 1.17 mm for the polylactic acid barrier and 2.60 +/- 1.26 mm for the collagen membrane) and bone fill (0.33 +/- 1.89 mm for polylactic acid barrier and 2.57 +/- 1.64 mm for collagen membrane), for each group compared to baseline. Significantly, the results from 6 months after surgery showed that there was greater bone fill when the collagen membrane was used compared to the polylactic acid barrier.