Conventional Clinical Therapy Research Articles

Developments in Alloplastic Bone Grafts and Barrier Membrane Biomaterials for Periodontal Guided Tissue and Bone Regeneration Therapy.

Periodontitis is a serious form of oral gum inflammation with recession of gingival soft tissue, destruction of the periodontal ligament, and absorption of alveolar bone. Management of periodontal tissue and bone destruction, along with the restoration of functionality and structural integrity, is not possible with conventional clinical therapy alone. Guided bone and tissue regeneration therapy employs an occlusive biodegradable barrier membrane and graft biomaterials to guide the formation of alveolar bone and tissues for periodontal restoration and regeneration. Amongst several grafting approaches, alloplastic grafts/biomaterials, either derived from natural sources, synthesization, or a combination of both, offer a wide variety of resources tailored to multiple needs. Examining several pertinent scientific databases (Web of Science, Scopus, PubMed, MEDLINE, and Cochrane Library) provided the foundation to cover the literature on synthetic graft materials and membranes, devoted to achieving periodontal tissue and bone regeneration. This discussion proceeds by highlighting potential grafting and barrier biomaterials, their characteristics, efficiency, regenerative ability, therapy outcomes, and advancements in periodontal guided regeneration therapy. Marketed and standardized quality products made of grafts and membrane biomaterials have been documented in this work. Conclusively, this paper illustrates the challenges, risk factors, and combination of biomaterials and drug delivery systems with which to reconstruct the hierarchical periodontium.

Chemically Programmed Hydrogels for Spatiotemporal Modulation of the Cardiac Pathological Microenvironment.

After myocardial infarction (MI), sustained ischemic events induce pathological microenvironments characterized by ischemia-hypoxia, oxidative stress, inflammatory responses, matrix remodeling, and fibrous scarring. Conventional clinical therapies lack spatially targeted and temporally responsive modulation of the infarct microenvironment, leading to limited myocardial repair. Engineered hydrogels have a chemically programmed toolbox for minimally invasive localization of the pathological microenvironment and personalized responsive modulation over different pathological periods. Chemically programmed strategies for crosslinking interactions, interfacial binding, and topological microstructures in hydrogels enable minimally invasive implantation and in situ integration tailored to the myocardium. This enhances substance exchange and signal interactions within the infarcted microenvironment. Programmed responsive polymer networks, intelligent micro/nanoplatforms, and biological therapeutic cues contribute to the formation of microenvironment-modulated hydrogels with precise targeting, spatiotemporal control, and on-demand feedback. Therefore, this review summarizes the features of the MI microenvironment and chemically programmed schemes for hydrogels to conform, integrate, and modulate the cardiac pathological microenvironment. Chemically programmed strategies for oxygen-generating, antioxidant, anti-inflammatory, provascular, and electrointegrated hydrogels to stimulate iterative and translational cardiac tissue engineering are discussed.

Recent advances in periodontal regeneration – A review

Periodontal Disease (PD) is one of the most common inflammatory oral diseases, affecting approximately 47% of adults aged 30 years or older in the United States. If not treated properly, PD leads to degradation of periodontal tissues, causing tooth movement, and eventually tooth loss. Conventional clinical therapy for PD aims at eliminating infectious sources and reducing inflammation to arrest disease progression, which cannot achieve the regeneration of lost periodontal tissues. Over the past two decades, various regenerative periodontal therapies, such as Guided Tissue Regeneration (GTR), enamel matrix derivative, bone grafts, growth factor delivery, and the combination of cells and growth factors with matrix-based scaffolds, have been developed to target the restoration of lost tooth-supporting tissues, including the periodontal ligament, alveolar bone, and cementum. This review discusses recent progress in periodontal regeneration using tissue-engineering and regenerative medicine approaches. Specifically, the focus is on the advances in biomaterials and controlled drug delivery for periodontal regeneration in recent years. Special attention is given to the development of advanced bio-inspired scaffolding biomaterials and temporospatial control of multi-drug delivery for the regeneration of the cementum-periodontal ligament-alveolar bone complex. Challenges and future perspectives are presented to provide inspiration for the design and development of innovative biomaterials and delivery systems for new regenerative periodontal therapy.

Software Design for Users with Autism Using Human-Centered Design and Design Thinking Techniques

This paper details a method, which has been called FRIDA, applied by the authors within this study based on the collaborative and interdisciplinary development of accessible software that is usable by people with autism spectrum disorder (ASD). To this end, the context of this study is based on the adaptation of the Design Thinking model as a strategy for interdisciplinary collaborative work between clinical therapists and software developers. This is complemented by a human-centered design (DCH) approach to obtain accessible software aimed at people with ASD level 1. Each of the stages of Design Thinking is detailed in order to obtain the personalized design of accessible software, as well as the activities carried out in case studies in Colombia, Spain, and Portugal with eight children diagnosed with ASD. As a result, we present the design of FRIDA’s components for interdisciplinary collaborative work and the design of personalized software that was developed for some children with ASD who participated in this study. For these children, it is demonstrated that the use of personalized and collaboratively designed software facilitates the development of specific social skills more quickly than with conventional clinical therapies.

The machine learning methods to analyze the using strategy of antiplatelet drugs in ischaemic stroke patients with gastrointestinal haemorrhage

BackgroundFor ischaemic stroke patients with gastrointestinal haemorrhage, stopping antiplatelet drugs or reducing the dose of antiplatelet drugs was a conventional clinical therapy method. But not a study to prove which way was better. And the machinery learning methods could help to obtain which way more suit for some patients.MethodsData from consecutive ischaemic stroke patients with gastrointestinal haemorrhage were prospectively collected. The outcome was a recurrent stroke rate, haemorrhage events, mortality and favourable functional outcome (FFO). We analysed the data using conventional logistic regression methods and a supervised machine learning model. We used unsupervised machine learning to group and analyse data characters. ResultsThe patients of stopping antiplatelet drugs had a lower rate of bleeding events (p = 0.125), mortality (p = 0.008), rate of recurrence of stroke (p = 0.161) and distribution of severe patients (mRS 3–6) (p = 0.056). For Logistic regression, stopping antiplatelet drugs (OR = 2.826, p = 0.030) was related to lower mortality. The stopping antiplatelet drugs in the supervised machine learning model related to mortality (AUC = 0.95) and FFO (AUC = 0.82). For group by unsupervised machine learning, the patients of better prognosis had more male (p < 0.001), younger (p < 0.001), had lower NIHSS score (p < 0.001); and had a higher value of serum lipid level (p < 0.001).ConclusionsFor ischemic stroke patients with gastrointestinal haemorrhage, stopping antiplatelet drugs had a better prognosis. Patients who were younger, male, with lesser NIHSS scores at admission, with the fewest history of a medical, higher value of diastolic blood pressure, platelet, blood lipid and lower INR could have a better prognosis.

Bioinspired gradient scaffolds for osteochondral tissue engineering.

Repairing articular osteochondral defects present considerable challenges in self-repair due to the complex tissue structure and low proliferation of chondrocytes. Conventional clinical therapies have not shown significant efficacy, including microfracture, autologous/allograft osteochondral transplantation, and cell-based techniques. Therefore, tissue engineering has been widely explored in repairing osteochondral defects by leveraging the natural regenerative potential of biomaterials to control cell functions. However, osteochondral tissue is a gradient structure with a smooth transition from the cartilage to subchondral bone, involving changes in chondrocyte morphologies and phenotypes, extracellular matrix components, collagen type and orientation, and cytokines. Bioinspired scaffolds have been developed by simulating gradient characteristics in heterogeneous tissues, such as the pores, components, and osteochondrogenesis-inducing factors, to satisfy the anisotropic features of osteochondral matrices. Bioinspired gradient scaffolds repair osteochondral defects by altering the microenvironments of cell growth to induce osteochondrogenesis and promote the formation of osteochondral interfaces compared with homogeneous scaffolds. This review outlines the meaningful strategies for repairing osteochondral defects by tissue engineering based on gradient scaffolds and predicts the pros and cons of prospective translation into clinical practice.

Anomalous kinetic study of atenolol release from ATN@DNA a core-shell like structure

The need for more efficient drug delivery strategies with ultraprecision and control over the release of drugs has led to the growth of more sophisticated drug-releasing systems as a promising alternative to conventional clinical therapies. This new seed of strategies has explored an encouraging property to overcome the inherent problems of traditional therapies. One of the major challenges for any drug delivery system is the introduction of a complete view of the delivery system. In this article, we intend to elucidate the theoretical proof of concept of the electrosynthesis ATN@DNA core-shell like structure as a model system. Therefore, we present a fractal kinetic model (non-exponential model) taking into consideration the concept of time-dependent diffusion coefficient, which was developed using a numerical method with the help of COMSOL Multiphysics. In addition to that, we present here a general fractional kinetic model in sense of the tempered fractional operator, which leads to better characterized memory properties of the release process. Also, the fractional model is compared with the fractal kinetic model and both offer a good description of drug release processes that present anomalous kinetics. The solutions of the fractal and fractional kinetic models are also fitted successfully with our real-release results.

Lung Cancer Targeted Chemoradiotherapy via Dual-Stimuli Responsive Biodegradable Core-Shell Nanoparticles.

Lung cancer is one of the major causes of cancer-related deaths worldwide, primarily because of the limitations of conventional clinical therapies such as chemotherapy and radiation therapy. Side effects associated with these treatments have made it essential for new modalities, such as tumor targeting nanoparticles that can provide cancer specific therapies. In this research, we have developed novel dual-stimuli nanoparticles (E-DSNPs), comprised of two parts; (1) Core: responsive to glutathione as stimuli and encapsulating Cisplatin (a chemo-drug), and (2) Shell: responsive to irradiation as stimuli and containing NU7441 (a radiation sensitizer). The targeting moieties on these nanoparticles are Ephrin transmembrane receptors A2 (EphA2) that are highly expressed on the surfaces of lung cancer cells. These nanoparticles were then evaluated for their enhanced targeting and therapeutic efficiency against lung cancer cell lines. E-DSNPs displayed very high uptake by lung cancer cells compared to healthy lung epithelial cells. These nanoparticles also demonstrated a triggered release of both drugs against respective stimuli and a subsequent reduction in in vitro cancer cell survival fraction compared to free drugs of equivalent concentration (survival fraction of about 0.019 and 0.19, respectively). Thus, these nanoparticles could potentially pave the path to targeted cancer therapy, while overcoming the side effects of conventional clinical therapies.

IRGD Tumor-Penetrating Peptide-Modified Nano-Delivery System Based on a Marine Sulfated Polysaccharide for Enhanced Anti-Tumor Efficiency Against Breast Cancer.

BackgroundBreast cancer is a common malignancy in women. Conventional clinical therapies for breast cancer all display moderate clinical efficacies and limitations. It is urgent to explore the novel and combined therapeutic strategies for breast cancer to meet clinical demand.MethodsAn iRGD tumor-penetrating peptide-modified nano-delivery system (denoted as iRGD-PSS@PBAE@JQ1/ORI nanoparticles) based on a marine sulfated polysaccharide was developed by codelivery of JQ1 (BET inhibitor) and oridonin (ORI, bioactive diterpenoid derived from traditional Chinese medicine herb). The iRGD-PSS@PBAE@JQ1/ORI NPs, surface modified with iRGD peptide conjugated propylene glycol alginate sodium sulfate (iRGD-PSS). The antitumor efficacy was evaluated both in vitro and in vivo.ResultsThe prepared iRGD-PSS@PBAE@JQ1/ORI NPs effectively enhanced the tumor targeting and cellular internalization of JQ1 and ORI. Thus, JQ1 exerted the reversal effect on immune tolerance by decreasing the expression of PD-L1, while ORI displayed multiple antitumor effects, such as antiproliferation, inhibition of intracellular ROS production and inhibition of lactic acid secretion.ConclusionOur data revealed that iRGD peptide could significantly improve the cellular internalization and tumor penetration of the nano-delivery system. The combination of JQ1 and ORI could exert synergistic antitumor activities. Taken together, this study provides a multifunctional nanotherapeutic system to enhance the anti-tumor efficiency against breast cancer.

Systemic metastasis-targeted nanotherapeutic reinforces tumor surgical resection and chemotherapy

Failure of conventional clinical therapies such as tumor resection and chemotherapy are mainly due to the ineffective control of tumor metastasis. Metastasis consists of three steps: (i) tumor cells extravasate from the primary sites into the circulation system via epithelial-mesenchymal transition (EMT), (ii) the circulating tumor cells (CTCs) form “micro-thrombi” with platelets to evade the immune surveillance in circulation, and (iii) the CTCs colonize in the pre-metastatic niche. Here, we design a systemic metastasis-targeted nanotherapeutic (H@CaPP) composed of an anti-inflammatory agent, piceatannol, and an anti-thrombotic agent, low molecular weight heparin, to hinder the multiple steps of tumor metastasis. H@CaPP is found efficiently impeded EMT, inhibited the formation of “micro-thrombi”, and prevented the development of pre-metastatic niche. When combined with surgical resection or chemotherapy, H@CaPP efficiently inhibits tumor metastasis and prolonged overall survival of tumor-bearing mice. Collectively, we provide a simple and effective systemic metastasis-targeted nanotherapeutic for combating tumor metastasis.

Ivacaftor Inhibits Glioblastoma Stem Cell Maintenance and Tumor Progression.

Glioblastoma (GBM) is the most common and malignant primary brain tumor. Glioblastoma stem cells (GSCs) not only initiate and sustain uncontrolled cell proliferation but also resistant to conventional clinical therapies including temozolomide (TMZ) dependent chemotherapy and radiotherapy, implying that there is an urgent need to identify new therapeutic strategies especially specific targeting GSCs. Here, we provide evidence showing that ivacaftor commonly applied in cystic fibrosis therapy acts as a potent inhibitor for GSCs maintenance. We found that ivacaftor promotes cellular apoptosis in vitro and represses patient-derived xenograft (PDX) tumor growth in vivo. In addition, we demonstrate that ivacaftor decreases stemness marker gene expressions of GSCs, including CD133, CD44, and Sox2. In summary, our findings reveal that ivacaftor inhibits glioblastoma progression via specifically eliminating GSCs, which opens a new avenue for GBM clinical therapy in the future.

Effect of tai chi on glycaemic control, lipid metabolism and body composition in adults with type 2 diabetes: A meta-analysis and systematic review.

ObjectiveThe aim of this systematic review was to evaluate the effects of tai chi on metabolic control and body composition indicators in patients with type 2 diabetes mellitus.DesignSystematic review and meta-analysis of existing literature.MethodsElectronic resource databases were searched to collect eligible studies. Two reviewers selected studies and independently evaluated methodological quality.ResultsTwenty-three studies were included in this meta-analysis. The pooled results showed that tai chi had significant effects in improving metabolic indices, such as fasting blood glucose (mean difference (MD) = –1.04; 95% confidence interval (95% CI) –1.42 to 0.66; p < 0.01) and total cholesterol (MD = –0.50; 95% CI –0.86 to –0.13; p < 0.01) compared with conventional clinical therapy. Most indices did not support the use of tai chi over aerobic exercise, except for glycated haemoglobin (HbA1c) (MD = –0.24; 95% CI –0.49 to 0.00; p < 0.01) and high-density lipoprotein (MD = 0.07; 95% CI 0.01 to 0.12; p < 0.01).ConclusionTai chi had better effects on metabolic control and body composition indicators than clinical conventional therapy, but only on HbA1c and HDL were superior than that of aerobic exercise. The best time-window for tai chi intervention may differ with different metabolic indices.LAY ABSTRACTExercise therapy is a possible alternative and effective strategy for blood glucose control in patients with type 2 diabetes, since drug therapy is associated with side-effects, long-term loss of efficacy, and poor adherence to lifelong treatment. A review of evidence was performed regarding the effects of tai chi on glycaemic control and other indicators in patients with type 2 diabetes mellitus. The results indicate that tai chi not only improves metabolic control, e.g. fasting blood glucose and total cholesterol, but also improves body composition indicators, e.g. body mass index. However, benefits of tai chi over aerobic exercise were seen in only a few outcome measures. The type and methodology of studies varied widely, with discrepancies in intensity, frequency, and duration of tai chi; therefore, further high-quality research is needed in order to draw specific and accurate conclusions.

Effect of variable periodontal ligament thickness and its non-linear material properties on the location of a tooth’s centre of resistance

In orthodontics, the 3D translational and rotational movement of a tooth is determined by the force–moment system applied and the location of the tooth’s centre of resistance (CR). Because of the practical constraints of in-vivo experiments, the finite element (FE) method is commonly used to determine the CR. The objective of this study was to investigate the geometric model details required for accurate CR determination, and the effect of material non-linearity of the periodontal ligament (PDL). A FE model of a human lower canine derived from a high-resolution µCT scan (voxel size: 50 µm) was investigated by applying four different modelling approaches to the PDL. These comprised linear and non-linear material models, each with uniform and realistic PDL thickness. The CR locations determined for the four model configurations were in the range 37.2–45.3% (alveolar margin: 0%; root apex: 100%). We observed that a non-linear material model introduces load-dependent results that are dominated by the PDL regions under tension. Load variation within the range used in clinical orthodontic practice resulted in CR variations below 0.3%. Furthermore, the individualized realistic PDL geometry shifted the CR towards the alveolar margin by 2.3% and 2.8% on average for the linear and non-linear material models, respectively. We concluded that for conventional clinical therapy and the generation of representative reference data, the least sophisticated modelling approach with linear material behaviour and uniform PDL thickness appears sufficiently accurate. Research applications that require more precise treatment monitoring and planning may, however, benefit from the more accurate results obtained from the non-linear constitutive law and individualized realistic PDL geometry.

Autologous Hematopoietic Stem Cell Transplantation in Refractory Crohn's Disease. Experience of Tertiary Medical Center in Brazil

Background Crohn's disease (CD) is a chronic inflammatory and relapsing disease that can affect any segment of the gastrointestinal tract. A significant percentage of these patients suffer an aggressive disease course, refractory to conventional clinical therapy . Surgery may be required, however the disease tends to recur after the resection. Aim Describe the potential clinical benefit of autologous hematopoietic stem cell with T-lymphocyte-depletion as a treatment for aggressive and refractory CD patients. Evaluate its efficacy, safety, toxicity and adverse events and primary and secondary clinical outcomes of follow up after 1year and 3 years. Methods We evaluated 6 patients submitted to an autologous HSCT. All patients were mobilized with cyclophosphamide (Cy) and G-CSF at the dose of 10mcg/kg/dia, The collection of HSC was initiated when the CD34+ count in the peripheral blood was greater than 15cels/mm3. The harvested product was enriched with CD34 + cells through a CliniMacs (Miltenyi Biotec) with a target CD34 + cells above 2.0 × 10E6/kg and less than 1 × 10E4Tcells/kg. The conditioning regimen consisted of cyclophosphamide 50mg/kg for 4 consecutive days, thymoglobulin 1.5mg/kg and methylprednisolone 1g/day from d-5 to d-2. Results Five patients refractory CD, between 43y and 19y (median age 38y), were included and follow the autologous HSCT. Corporal index mass 20 Kg/m2, median course of illness 14y, all negative for X-linked inhibitor apoptosis protein (XIAP). Four patients had penetrating disease and two patients had nonstricturing nonpenetrating phenotipe. Five patients had 2 to 3 previous intestinal surgeries. All patients used aminosalicylates steroids, thiopurines, metotrexate and more than one immunobiological therapies (IFX, ADA, VDZ). All six patients completed the mobilization, conditioning and transplantation phases, during a median time of hospitalization of 35 days. The median of CD34+ cels infused was 7.7 × 10e6/kg. All patients achieved engraftment, with a sustained median neutrophil count of 0.5 × 109/L at a median of 11 days and platelet grafting was 10 days. All patients had life-threatening complications as infectious (KPC, Staphylococcus aureus and septic by E. coli), febrile neutropenia and non-infectious complications as anemia mucositis and red cell transfusion was required. After 1y HSCT, all patients achieved the 1ary and 2nd outcomes: clinical and endoscopic remission (fig) and were steroid and immunosuppressive free remission (CDAI Conclusion HSCT is a complex treatment strategy for severe CD associated with mortality and serious adverse events. Due to its high complexity, risk of infections and death the balance between risks and benefits becomes significantly important in this therapy.

Optogenetic Modulation of Urinary Bladder Contraction for Lower Urinary Tract Dysfunction

As current clinical approaches for lower urinary tract (LUT) dysfunction such as pharmacological and electrical stimulation treatments lack target specificity, thus resulting in suboptimal outcomes with various side effects, a better treatment modality with spatial and temporal target-specificity is necessary. In this study, we delivered optogenetic membrane proteins, such as channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR), to bladder smooth muscle cells (SMCs) of mice using either the Cre-loxp transgenic system or a viral transfection method. The results showed that depolarizing ChR2-SMCs with blue light induced bladder contraction, whereas hyperpolarizing NpHR-SMCs with yellow light suppressed PGE2-induced overactive contraction. We also confirmed that optogenetic contraction of bladder smooth muscles in this study is not neurogenic, but solely myogenic, and that optogenetic light stimulation can modulate the urination in vivo. This study thus demonstrated the utility of optogenetic modulation of smooth muscle as a means to actively control the urinary bladder contraction with spatial and temporal accuracy. These features would increase the efficacy of bladder control in LUT dysfunctions without the side effects of conventional clinical therapies.

Milkvetch root improves immune function in patients with acute exacerbation of COPD.

Milkvetch root as a medicine has been used for more over 2000 years in China, can strengthen immune function, protect liver, promote urination, resist aging and stress, reduce blood pressure and extensively resist bacterium. This study explored the effects of milkvetch root on the immune function of patients with a definitive diagnosis of acute exacerbation of chronic obstructive pulmonary disease (COPD). The patients were randomly assigned to either the experimental or control group. All patients received conventional clinical therapy; those in the experimental group were also administered milkvetch root. The serum levels of cytokines including tumor necrosis factor alpha (TNF-α), interleukin-8 (IL-8), IL-1β, and IL-32 and immunocytes including T helper (Th), cytotoxic T (Tc), natural killer (NK), regulatory T (Treg) and B cells were measured 1 day before treatment and 7 and 14 days post-treatment. After bronchodilator inhalation, pulmonary function was evaluated at these same time points. The serum TNF-α, IL-8, IL-1β, and IL-32 levels were significantly lower in the experimental group than in the control group 14 days post-treatment. The Th/Tc ratio and NK cell ratio was significantly higher but the Treg cell ratio was significantly lower in the experimental group than in the control group. The forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC) were significantly higher in the experimental group than in the control group 14 days post-treatment. These results indicate that milkvetch root can improve the immune function of patients with acute exacerbation of COPD.

Balloon Sinuplasty: Novel Technique for Treatment of Sinusitis

Sinusitis or rhinosinusitis is inflammation of the paranasal sinuses. It can be due to infection, allergy, or autoimmune issues. Balloon catheter dilation of paranasal sinusostia aims to help open up blocked sinus passages by gently inflating a small balloon, introduced through the nose via a flexible tube. The aim is to restore normal sinus drainage and improve symptoms of sinusitis. Sinuplasty is a medical procedure with dilation by means of a balloon of the Paranasal Sinusitis ostia region. This procedure is currently used in the maxillary, frontal and sphenoidal sinuses. These tools functioning basic concept are that the dilation of the desired region, which may lead to Sixteen atmospheres pressure in the balloon, produces local micro fractures that end up remodeling the anatomy, dilates the Ostia and allows a PNS normal aeration without, however, the removal of the tissues and damage to the nasal mucosa. Balloon sinuplasty is safe and appears to be effective in the improvement of the quality of life of patients not responsive to conventional clinical therapy. Balloon Sinuplasty is a procedure followed by ENT surgeons use for the treatment of blocked sinuses. Unlike traditional sinus surgery, Balloon Sinuplasty requires no cutting and no removal of bone and tissue

RNA Interference-Mediated Silencing of Atp6i Prevents Both Periapical Bone Erosion and Inflammation in the Mouse Model of Endodontic Disease

Dental caries is one of the most prevalent infectious diseases in the United States, affecting approximately 80% of children and the majority of adults. Dental caries may lead to endodontic disease, where the bacterial infection progresses to the root canal system of the tooth, leading to periapical inflammation, bone erosion, severe pain, and tooth loss. Periapical inflammation may also exacerbate inflammation in other parts of the body. Although conventional clinical therapies for this disease are successful in approximately 80% of cases, there is still an urgent need for increased efficacy of treatment. In this study, we applied a novel gene-therapeutic approach using recombinant adeno-associated virus (AAV)-mediated Atp6i RNA interference (RNAi) knockdown of Atp6i/TIRC7 gene expression to simultaneously target periapical bone resorption and periapical inflammation. We found that Atp6i inhibition impaired osteoclast function in vitro and in vivo and decreased the number of T cells in the periapical lesion. Notably, AAV-mediated Atp6i/TIRC7 knockdown gene therapy reduced bacterial infection-stimulated bone resorption by 80% in the mouse model of endodontic disease. Importantly, Atp6i(+/-) mice with haploinsufficiency of Atp6i exhibited protection similar to that in mice with bacterial infection-stimulated bone erosion and periapical inflammation, which confirms the potential therapeutic effect of AAV-small hairpin RNA (shRNA)-Atp6i/TIRC7. Our results demonstrate that AAV-mediated Atp6i/TIRC7 knockdown in periapical tissues can inhibit endodontic disease development, bone resorption, and inflammation, indicating for the first time that this potential gene therapy may significantly improve the health of those who suffer from endodontic disease.

Outcomes of Critical Pathway in Laparoscopic and Open Surgical Treatments for Gastric Cancer Patients: Patients Selection for Fast-Track Program through Retrospective Analysis

PurposeThe aim of this study is to investigate the clinical factors affecting on the cure rate by invasive and open surgery for gastric cancer and to establish a subgroup of patients who can be applied by the early recovery after surgery program through this retrospective analysis.Materials and MethodsIn this retrospective study, we analyzed 425 patients who underwent gastric cancer surgery between January 2011 and December 2011 and were managed with conventional clinical therapies. This clinical algorithm was made when the patient was in minimally invasive surgery group and discharged from hospital one day faster than them in open surgery group.ResultsThe completion rate of the clinical pathway was 62.4%. Despite the different applications of clinical pathway, completion rate in minimally invasive surgery group was significantly higher than that of open group (P<0.001). In multivariate analysis, the surgical procedure of minimally invasive surgery (odds ratio=4.281) was the most predictable factor to complete clinical pathway. Additionally, younger patients (odds ratio=1.933) who underwent distal gastrectomy (odds ratio=1.999) without combined resection (odds ratio=3.069) were predicted to accomplish the clinical pathway without any modifications.ConclusionsWe concluded that high efficacy of the clinical pathway for gastric cancer surgery was expected to selected patients through retrospective analysis (expected completion rate=85.4%). In addition, these patients would become enrolled criteria for early recovery program in gastric cancer surgery.

Development of a cell-based medicinal product: regulatory structures in the European Union

New therapies with genes, tissues and cells have taken the emerging field for the treatment of many diseases. Advances on stem cell therapy research have led to international regulatory agencies to harmonize and regulate the development of new medicines with stem cells. European Medicines Agency on September 15, 2012. Cell therapy medicinal products should be subjected to the same regulatory principles than any other medicine. Their technical requirements for quality, safety and efficacy must be more specific and stringent than other biologic products and medicines. Cell therapy medicinal products are at the cutting edge of innovation and offer a major hope for various diseases for which there are limited or no therapeutic options. The development of cell therapy medicinal products constitutes an alternative therapeutic strategy to conventional clinical therapy, for which no effective cure was previously available.