An Improved Theory for Designing and Numerically Calibrating Circular Touch Mode Capacitive Pressure Sensors.

The design, especially the numerical calibration, of a circular touch mode capacitive pressure sensor is highly dependent on the accuracy of the analytical solution of the contact problem between the circular conductive membrane and the rigid plate of the sensor. In this paper, the plate/membrane contact problem is reformulated using a more accurate in-plane equilibrium equation, and a new and more accurate analytical solution is presented. On this basis, the design and numerical calibration theory for circular touch mode capacitive pressure sensors has been greatly improved and perfected. The analytical relationships of pressure and capacitance are numerically calculated using the new and previous analytical solutions, and the gradually increasing difference between the two numerical calculation results with the gradual increase in the applied pressure is graphically shown. How to use analytical solutions and analytical relationships to design and numerically calibrate a circular touch mode capacitive pressure sensor with a specified pressure detecting range is illustrated in detail. The effect of changing design parameters on capacitance-pressure analytical relationships is comprehensively investigated; thus, the direction of changing design parameters to meet the required or desired range of pressure or capacitance is clarified.

Prediction model of stress ulcer after laparoscopic surgery for colorectal cancer established by machine learning algorithm.

BACKGROUND: Patients with colorectal cancer (CRC) are prone to stress ulcer after laparoscopic surgery. The analysis of risk factors for stress ulcer (SU) in patients with CRC is important to reduce mortality and improve patient prognosis. AIM: To identify risk factors for SU after laparoscopic surgery for CRC, and develop a nomogram model to predict the risk of SU in these patients.METHODSThe clinical data of 135 patients with CRC who underwent laparoscopic surgery between November 2021 and June 2022 were reviewed retrospectively. They were divided into two categories depending on the presence of SUs: The SU group (n = 23) and the non-SU group (n = 112). Univariate analysis and multivariate logistic regression analysis were used to screen for factors associated with postoperative SU in patients undergoing laparoscopic surgery, and a risk factor-based nomogram model was built based on these risk factors. By plotting the model's receiver operating characteristic (ROC) curve and calibration curve, a Hosmer-Lemeshow goodness of fit test was performed. RESULTS: Among the 135 patients with CRC, 23 patients had postoperative SU, with an incidence of 17.04%. The SU group had higher levels of heat shock protein (HSP) 70, HSP90, and gastrin (GAS) than the non-SU group. Age, lymph node metastasis, HSP70, HSP90, and GAS levels were statistically different between the two groups, but other indicators were not statistically different. Logistic regression analysis showed that age ≥ 65 years, lymph node metastasis, and increased levels of HSP70, HSP90 and GAS were all risk factors for postoperative SU in patients with CRC (P < 0.05). According to these five risk factors, the area under the ROC curve for the nomogram model was 0.988 (95%CI: 0.971-1.0); the calibration curve demonstrated excellent agreement between predicted and actual probabilities, and the Hosmer-Lemeshow goodness of fit test revealed that the difference was not statistically significant (χ2 = 0.753, P = 0.999), suggesting that the nomogram model had good discrimination, calibration, and stability. CONCLUSION: Patients with CRC aged ≥ 65 years, with lymph node metastasis and elevated HSP70, HSP90, GAS levels, are prone to post-laparoscopic surgery SU. Our nomogram model shows good predictive value.

The Thermal Stress Problem of Bimodular Curved Beams under the Action of End-Side Concentrated Shear Force.

A bimodular material is a kind of material that presents two elastic moduli in tension and compression. In classical thermoelasticity, however, the bimodular material is rarely considered due to its complexity in analysis. In fact, almost all materials will present, more or less, bimodular characteristics, and in some cases, the mechanical properties of materials cannot be fully utilized simply by ignoring the bimodular characteristics. In this study, the thermal stress problem of bimodular curved beams under the action of end-side concentrated shear force is analytically and numerically investigated, in which the temperature rise modes in a thermal environment are considered arbitrary. Using the stress function method based on compatibility conditions, a two-dimensional solution of thermoelasticity of the bimodular curved beam subjected to end-side concentrated shear force was obtained. The results show that the solution for a bimodular curved beam with a thermal effect can be reduced to that of a bimodular curved beam without a thermal effect. At the same time, the numerical simulation for the problem verifies the correctness of the theoretical solution. The results may serve as a theoretical reference for the refined analysis and optimization of curved beams in a thermal environment.

Insights into Advanced Neurological Dysfunction Mechanisms Following DBS Surgery in Parkinson's Patients: Neuroinflammation and Pyroptosis.

Parkinson's disease is a severe neurodegenerative disorder. Currently, deep brain electrical stimulation (DBS) is the first line of surgical treatment. However, serious neurological impairments such as speech disorders, disturbances of consciousness, and depression after surgery limit the efficacy of treatment. In this review, we summarize the recent experimental and clinical studies that have explored the possible causes of neurological deficits after DBS. Furthermore, we tried to identify clues from oxidative stress and pathological changes in patients that could lead to the activation of microglia and astrocytes in DBS surgical injury. Notably, reliable evidence supports the idea that neuroinflammation is caused by microglia and astrocytes, which may contribute to caspase-1 pathway-mediated neuronal pyroptosis. Finally, existing drugs and treatments may partially ameliorate the loss of neurological function in patients following DBS surgery by exerting neuroprotective effects.

Application of the Variational Method to the Large Deformation Problem of Thin Cylindrical Shells with Different Moduli in Tension and Compression.

In this study, the variational method concerning displacement components is applied to solve the large deformation problem of a thin cylindrical shell with its four sides fully fixed and under uniformly distributed loads, in which the material that constitutes the shell has a bimodular effect, in comparison to traditional materials, that is, the material will present different moduli of elasticity when it is in tension and compression. For the purpose of the use of the displacement variational method, the physical equations on the bimodular material model and the geometrical equation under large deformation are derived first. Thereafter, the total strain potential energy is expressed in terms of the displacement component, thus bringing the possibilities for the classical Ritz method. Finally, the relationship between load and central deflection is obtained, which is validated with the numerical simulation, and the jumping phenomenon of thin cylindrical shell with a bimodular effect is analyzed. The results indicate that the bimodular effect will change the stiffness of the shell, thus resulting in the corresponding change in the deformation magnitude. When the shell is relatively thin, the bimodular effect will influence the occurrence of the jumping phenomenon of the cylindrical shell.

Polymer Conductive Membrane-Based Circular Capacitive Pressure Sensors from Non-Touch Mode of Operation to Touch Mode of Operation: An Analytical Solution-Based Method for Design and Numerical Calibration.

Polymer-based conductive membranes play an important role in the development of elastic deflection-based pressure sensors. In this paper, an analytical solution-based method is presented for the design and numerical calibration of polymer conductive membrane-based circular capacitive pressure sensors from non-touch mode of operation to touch mode of operation. The contact problem of a circular membrane in frictionless contact with a rigid flat plate under pressure is analytically solved, and its analytical solution is used for the design of touch mode circular capacitive pressure sensors for the first time. The analytical relationship with input pressure as independent variable and output capacitance as dependent variable is precisely derived and is used for the numerical calibrations of the analytical relationships with input capacitance as the independent variable and output pressure as the dependent variable in order to meet the capacitive pressure sensor mechanism of detecting pressure by measuring capacitance. For the first time, an example showing the design and numerical calibration of a given (given design parameters) polymer conductive membrane-based circular capacitive pressure sensor from non-touch mode of operation to touch mode of operation is provided. Then, the influence of changing several important design parameters on input capacitance-output pressure relationships is comprehensively investigated in order to clarify the desired input-output relationships when changing design parameters.

Polymer Conductive Membrane-Based Non-Touch Mode Circular Capacitive Pressure Sensors: An Analytical Solution-Based Method for Design and Numerical Calibration.

In this paper, an analytical solution-based method for the design and numerical calibration of polymer conductive membrane-based non-touch mode circular capacitive pressure sensors is presented. The accurate analytical relationship between the capacitance and applied pressure of the sensors is derived by using the analytical solution for the elastic behavior of the circular polymer conductive membranes under pressure. Based on numerical calculations using the accurate analytical relationship and the analytical solution, the analytical relationship between the pressure as output and the capacitance as input, which is necessary to achieve the capacitive pressure sensor mechanism of detecting pressure by measuring capacitance, is accurately established by least-squares data fitting. An example of how to arrive at the design and numerical calibration of a non-touch mode circular capacitive pressure sensor is first given. Then, the influence of changing design parameters such as membrane thickness and Young's modulus of elasticity on input-output relationships is investigated, thus clarifying the direction of approaching the desired input-output relationships by changing design parameters.

A Further Theoretical Study of Capacitive Pressure Sensors Based on Thin Film Elastic Deflection and Parallel Plate Capacitor: Refined Closed-Form Solution and Numerical Calibration.

The capacitive pressure sensor based on thin film elastic deflection and a parallel plate capacitor uses a non-conductive elastic annular thin film centrally connected to a conductive, rigid, flat, concentric-circular thin plate as a pressure sensing unit. On application of pressure, the non-conductive thin film deflects elastically, which in turn moves the conductive thin plate (as a movable upper electrode plate of the parallel plate capacitor) towards the lower electrode plate, resulting in a change in the capacitance of the capacitor. Therefore, the applied pressure can be determined by measuring the capacitance change, based on the closed-form solution for the elastic behavior of the annular thin film under pressure. Such capacitive pressure sensors are more suitable for large-sized sensors such as those used for building-facade wind pressure measurements, etc. In this paper, a further theoretical study of such capacitive pressure sensors is presented. The newly presented, more refined closed-form solution can greatly reduce the output pressure error under the same input capacitance, in comparison with the previously presented closed-form solution. A numerical example of how to use the resulting closed-form solution to numerically calibrate input-output characteristics is given for the first time. The variation trend of pressure operation ranges and input-output characteristics with important parametric variations, which can be used for guiding the design of such capacitive pressure sensors, is investigated.

Impact of the COVID-19 pandemic on career intention amongst undergraduate medical students: a single-centre cross-sectional study conducted in Hubei Province.

BACKGROUND: Undergraduate medical (UM) students faced the difficulties inherent in medical careers due to the coronavirus (COVID-19) outbreak. Thus, imperative containment measures might affect UM students' career intentions. Information on the factors that may be associated with these students' career change intentions is limited. METHODS: We conducted a cross-sectional survey in August 2020 to investigate the impact of the COVID-19 pandemic on career intention and the associated factors in UM students. Univariate analyses and logistic regression analysis were performed to identify said factors. RESULTS: A total of 2040 medical students from the Hubei University of Medicine were surveyed. Univariate analyses showed that grade, attitude towards healthcare, and the degree of the COVID-19 pandemic's impact on the students' lives were associated with changes in career choice (P<0.05). Logistic regression analysis showed that Grade 2, Grade 5, attitude towards a medical career, and having relatives with a medical background were associated with changes in career choice. The degree of the COVID-19 pandemic's impact was a common and significant factor associated with career preference, career perspective, and ideal workplace. CONCLUSIONS: Changes in career intentions were particularly influenced by grade, attitude towards being a health worker, and the degree of COVID-19's impact on the participants' lives. Treating large-scale public health emergencies rationally, setting up correct views of occupation choice, and building reasonable career planning may reduce the loss of medical talent.

Large Deflection Analysis of Peripherally Fixed Circular Membranes Subjected to Liquid Weight Loading: A Refined Design Theory of Membrane Deflection-Based Rain Gauges.

The anticipated use of elastic membranes for deflection-based rain gauges has provided an impetus for this paper to revisit the large deflection problem of a peripherally fixed circular membrane subjected to liquid weight loading, a statics problem when the fluid-structure interaction of membrane and liquid reaches static equilibrium. The closed-form solution of this statics problem of fluid-structure interaction is necessary for the design of such membrane deflection-based rain gauges, while the existing closed-form solution, due to the use of the small rotation angle assumption of the membrane, cannot meet the design requirements for computational accuracy. In this paper, the problem under consideration is reformulated by giving up the small rotation angle assumption, which gives rise to a new and somewhat intractable nonlinear integro-differential equation of the governing out-of-plane equilibrium. The power series method has played an irreplaceable role in analytically solving membrane equations involving both integral and differential operations, and a new and more refined closed-form solution without the small rotation angle assumption is finally presented. Numerical examples conducted show that the new and more refined closed-form solution presented has satisfactory convergence, and the effect of giving up the small rotation angle assumption is also investigated numerically. The application of the closed-form solution presented in designing such membrane deflection-based rain gauges is illustrated, and the reliability of the new and more refined closed-form solution presented was confirmed by conducting a confirmatory experiment.

Application of Variational Method to Stability Analysis of Cantilever Vertical Plates with Bimodular Effect.

In the design of cantilevered balconies of buildings, many stability problems exist concerning vertical plates, in which reaching a critical load plays an important role during the stability analysis of the plate. At the same time, the concrete forming vertical plate, as a typical brittle material, has larger compressive strength but lower tensile strength, which means the tensile and compression properties of concrete are different. However, due to the complexities of such analyses, this difference has not been considered. In this study, the variational method is used to analyze stability problems of cantilever vertical plates with bimodular effect, in which different loading conditions and plate shapes are also taken into account. For the effective implementation of a variational method, the bending strain energy based on bimodular theory is established first, and critical loads of four stability problems are obtained. The results indicate that the bimodular effect, as well as different loading types and plate shapes, have influences on the final critical loads, resulting in varying degrees of buckling. In particular, if the average value of the tensile modulus and compressive modulus remain unchanged, the introduction of the bimodular effect will weaken, to some extent, the bending stiffness of the plate. Among the four stability problems, a rectangular plate with its top and bottom loaded is most likely to buckle; next is a rectangular plate with its top loaded, followed by a triangular plate with its bottom loaded. A rectangular plate with its bottom loaded is least likely to buckle. This work may serve as a theoretical reference for the refined analysis of vertical plates. Plates are made of concrete or similar material whose bimodular effect is relatively obvious and cannot be ignored arbitrarily; otherwise the greater inaccuracies will be encountered in building designs.

Extracellular matrix protein laminin ß1 regulates pain sensitivity and anxiodepression-like behaviors in mice.

Patients with neuropathic pain often experience comorbid psychiatric disorders. Cellular plasticity in the anterior cingulate cortex (ACC) is assumed to be a critical interface for pain perception and emotion. However, substantial efforts have thus far been focused on the intracellular mechanisms of plasticity rather than the extracellular alterations that might trigger and facilitate intracellular changes. Laminin, a key element of the extracellular matrix (ECM), consists of one α-, one ß-, and one γ-chain and is implicated in several pathophysiological processes. Here, we showed in mice that laminin ß1 (LAMB1) in the ACC was significantly downregulated upon peripheral neuropathy. Knockdown of LAMB1 in the ACC exacerbated pain sensitivity and induced anxiety and depression. Mechanistic analysis revealed that loss of LAMB1 caused actin dysregulation via interaction with integrin ß1 and the subsequent Src-dependent RhoA/LIMK/cofilin pathway, leading to increased presynaptic transmitter release probability and abnormal postsynaptic spine remodeling, which in turn orchestrated the structural and functional plasticity of pyramidal neurons and eventually resulted in pain hypersensitivity and anxiodepression. This study sheds new light on the functional capability of ECM LAMB1 in modulating pain plasticity and identifies a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified cingulate LAMB1/integrin ß1 signaling as a promising therapeutic target for the treatment of neuropathic pain and associated anxiodepression.

A Theoretical Study on an Elastic Polymer Thin Film-Based Capacitive Wind-Pressure Sensor.

This study is devoted to the design of an elastic polymer thin film-based capacitive wind-pressure sensor to meet the anticipated use for real-time monitoring of structural wind pressure in civil engineering. This sensor is composed of four basic units: lateral elastic deflection unit of a wind-driven circular polymer thin film, parallel plate capacitor with a movable circular electrode plate, spring-driven return unit of the movable electrode plate, and dielectric materials between electrode plates. The capacitance of the capacitor varies with the parallel move of the movable electrode plate which is first driven by the lateral elastic deflection of the wind-driven film and then is, after the wind pressure is reduced or eliminated, returned quickly by the drive springs. The closed-form solution for the contact problem between the wind-driven thin film and the spring-driven movable electrode plate is presented, and its reliability is proved by the experiment conducted. The numerical examples conducted show that it is workable that by using the numerical calibration based on the presented closed-form solution the proposed sensor is designed into a nonlinear sensor with larger pressure-monitoring range and faster response speed than the linear sensor usually based on experimental calibration.

A Refined Theory for Characterizing Adhesion of Elastic Coatings on Rigid Substrates Based on Pressurized Blister Test Methods: Closed-Form Solution and Energy Release Rate.

Adhesion between coatings and substrates is an important parameter determining the integrity and reliability of film/substrate systems. In this paper, a new and more refined theory for characterizing adhesion between elastic coatings and rigid substrates is developed based on a previously proposed pressurized blister method. A compressed air driven by liquid potential energy is applied to the suspended circular coating film through a circular hole in the substrate, forcing the suspended film to bulge, and then to debond slowly from the edge of the hole as the air pressure intensifies, and finally to form a blister with a certain circular delamination area. The problem from the initially flat coating to the stable blistering film under a prescribed pressure is simplified as a problem of axisymmetric deformation of peripherally fixed and transversely uniformly loaded circular membranes. The adhesion strength depends on the delamination area and is quantified in terms of the energy released on per unit delamination area, the so-called energy release rate. In the present work, the problem of axisymmetric deformation is reformulated with out-of-plane and in-plane equilibrium equations and geometric equations, simultaneously improved, and a new closed-form solution is presented, resulting in the new and more refined adhesion characterization theory.

A Multi-Parameter Perturbation Solution and Experimental Verification for Bending Problem of Piezoelectric Cantilever Beams.

The existing studies indicate that the application of piezoelectric polymers is becoming more and more extensive, especially in the analysis and design of sensors or actuators, but the problems of piezoelectric structure are usually difficult to solve analytically due to the force-electric coupling characteristics. In this study, the bending problem of a piezoelectric cantilever beam was investigated via theoretical and experimental methods. First, the governing equations of the problem were established and non-dimensionalized. Three piezoelectric parameters were selected as perturbation parameters and the perturbation solution of the equations was finally obtained using a multi-parameter perturbation method. In addition, the relevant experiments of the piezoelectric cantilever beam were carried out, and the experimental results were in good agreement with the theoretical solutions. Based on the experimental results, the effect of piezoelectric properties on the bending deformation of piezoelectric cantilever beams was analyzed and discussed. The results indicated that the multi-parameter perturbation solution obtained in this study is effective and it may serve as a theoretical reference for the design of sensors or actuators made of piezoelectric polymers.

Adipose-derived mesenchymal stem cells ameliorate the inflammatory reaction in CLP-induced septic acute lung injury rats via sTNFR1.

We hypothesized that the adipose-derived mesenchymal stem cells (ADMSCs), which secrete high amounts of soluble molecules, such as soluble tumor necrosis factor receptor 1 (sTNFR1), may ameliorate sepsis-induced acute lung injury (ALI). A total of 120 male adult Sprague-Dawley rats were separated into four groups: the sham control (SC), sepsis induced by cecal ligation and puncture (CLP), CLP-ADMSCs, and CLP-sTNFR1 small interfering RNA (siRNA) groups; CLP groups underwent CLP and then received 1 × 106 ADMSCs with or without knockdown of sTNFR1 intravenously at 1 hr after surgery. Rats were killed at 3, 6, 24, and 48 hr after the SC or CLP procedures. 5-Ethynyl-2'-deoxyuridine-labeled ADMSCs extensively colonized the lungs at 6, 24, and 72 hr after injection. The lung wet/dry (W/D) weight ratios in the CLP group were higher than those in SC group; however, ADMSCs ameliorated the W/D weight ratios following CLP, and this effect was abolished by sTNFR1 siRNA treatment. The levels of serum sTNFR1 and interleukin-10 (IL-10) were higher in the CLP-ADMSCs group and lower in the SC group than in other groups; interestingly, these levels were higher in CLP and CLP-sTNFR1 siRNA groups than in SC group. Tumor necrosis factor-α and IL-6 levels increased significantly after CLP, and ADMSCs could alleviate these changes, but the effect was weakened by sTNFR1 siRNA treatment. The lung cell apoptosis and edema levels were consistent with IL-6 levels among all groups. Therapeutically administered ADMSCs secrete sTNFR1, which most likely protects against ALI in septic rats by ameliorating inflammation and lung edema.

An Electroelastic Solution for Functionally Graded Piezoelectric Circular Plates under the Action of Combined Mechanical Loads.

In this study, we obtained an electroelastic solution for functionally graded piezoelectric circular plates under the action of combined mechanical loads which include the uniformly distributed loads on the upper surface of the plate and the radial force and bending moment at the periphery of the plate. All electroelastic materials parameters are assumed to vary according to the same gradient function along the thickness direction. The influence of different functionally graded parameters on the elastic displacement and elastic stress, as well as the electric displacement and electric potential, was discussed by a numerical example. The solution presented in this study is not only applicable to the case of combined loads, but also to the case of a single mechanical load. In addition, this solution reflects the influence of the function gradient on the pure piezoelectric plate, which is helpful to the refined analysis and optimization design of similar structures.

One-Dimensional and Two-Dimensional Analytical Solutions for Functionally Graded Beams with Different Moduli in Tension and Compression.

The material considered in this study not only has a functionally graded characteristic but also exhibits different tensile and compressive moduli of elasticity. One-dimensional and two-dimensional mechanical models for a functionally graded beam with a bimodular effect were established first. By taking the grade function as an exponential expression, the analytical solutions of a bimodular functionally graded beam under pure bending and lateral-force bending were obtained. The regression from a two-dimensional solution to a one-dimensional solution is verified. The physical quantities in a bimodular functionally graded beam are compared with their counterparts in a classical problem and a functionally graded beam without a bimodular effect. The validity of the plane section assumption under pure bending and lateral-force bending is analyzed. Three typical cases that the tensile modulus is greater than, equal to, or less than the compressive modulus are discussed. The result indicates that due to the introduction of the bimodular functionally graded effect of the materials, the maximum tensile and compressive bending stresses may not take place at the bottom and top of the beam. The real location at which the maximum bending stress takes place is determined via the extreme condition for the analytical solution.

Theoretical Study on Synchronous Characterization of Surface and Interfacial Mechanical Properties of Thin-Film/Substrate Systems with Residual Stress Based on Pressure Blister Test Technique.

In this study, based on the pressure blister test technique, a theoretical study on the synchronous characterization of surface and interfacial mechanical properties of thin-film/substrate systems with residual stress was presented, where the problem of axisymmetric deformation of a blistering film with initial stress was analytically solved and its closed-form solution was presented. The expressions to determine Poisson's ratios, Young's modulus, and residual stress of surface thin films were derived; the work done by the applied external load and the elastic energy stored in the blistering thin film were analyzed in detail and their expressions were derived; and the interfacial adhesion energy released per unit delamination area of thin-film/substrate (i.e., energy release rate) was finally presented. The synchronous characterization technique presented here has theoretically made a big step forward, due to the consideration for the residual stress in surface thin films.

Baicalin inhibits toll-like receptor 2/4 expression and downstream signaling in rat experimental periodontitis.

Periodontitis is a severe inflammatory response, leading to characteristic periodontal soft tissue destruction and alveolar bone resorption. Baicalin possesses potent anti-inflammatory activity; however, it is still unclear whether baicalin regulates toll-like receptor (TLR) 2/4 expression and downstream signaling during the process of periodontitis. In this study, the cervical area of the maxillary second molars of rats was ligated and inoculated with Porphyromonas gingivalis (P. gingivalis) for 4weeks to induce periodontitis. Some rats with periodontitis were treated intragastrically with baicalin (50, 100 or 200mg/kg/day) or vehicle for 4weeks. Compared with the sham group, the levels of TLR2, TLR4 and MyD88 expression and the p38 MAPK and NF-κB activation were up-regulated in the experimental periodontitis group (EPG), accompanied by marked alveolar bone loss and severe inflammation. Treatment with 100 or 200mg/kg/day baicalin dramatically reduced the alveolar bone loss, the levels of HMGB1, TNF-α, IL-1ß, and MPO expression, and the numbers of inflammatory infiltrates in the gingival tissues. Importantly, treatment with 100 or 200mg/kg/day baicalin mitigated the periodontitis-up-regulated TLR2, TLR4 and MyD88 expression, and the p38 MAPK and NF-κB activation. Hence, the blockage of the TLR2 and TLR4/MyD88/p38 MAPK/NF-κB signaling by baicalin may contribute to its anti-inflammatory effects in rat model of periodontitis. In conclusion, these novel findings indicate that baicalin inhibits the TLR2 and TLR4 expression and the downstream signaling and mitigates inflammatory responses and the alveolar bone loss in rat experimental periodontitis. Therefore, baicalin may be a potential therapeutic agent for treatment of periodontitis.