Patient-Specific Implants for Correction of Midfacial Aging.

The nasolabial folds (NLFs) may be shallowed with the use of nostril base augmentation. This study aimed to design and customize patient-specific implants (PSIs) with computer-aided design/computer-aided manufacturing (CAD/CAM) to correct NLF deepening caused by midfacial aging. The patient's head computed tomography data obtained and were used for reconstruction. The PSIs were customized by CAD/CAM techniques, which were implanted into a nasal base for shallow NLFs caused by midfacial aging. Preoperative and postoperative photos and a wrinkle severity rating scale were used to evaluate the changes in NLFs. Also, the global esthetic improvement scale was used to investigate the surgical satisfaction of patients. Eleven patients (22 NLFs) received PSIs in the nasal base (22 implants). The customized PSI matched well with premaxilla, reducing the difficulty of operation. After 3 to 12 months of follow-up, PSI was stable without foreign body reaction or inflammatory reaction. Postoperative wrinkle severity rating scale scores showed that NLF severity was reduced in all patients, with a significant esthetic improvement compared with preoperatively ( P < 0.01). The global esthetic improvement scale showed an extremely satisfied improved NLF in 27.27% of patients, much improved in 63.63%, and improved in 9.90% (2/22), and none reported change or poor NLF. Patient satisfaction with their midface appearance differed significantly before and after surgery ( P < 0.01). Individualized PSI designed with high precision and matching degree by CAD and prepared using CAM could be applied to overcome the limitations of noncustomized implants.

Decoquinate liposomes: highly effective clearance of Plasmodium parasites causing severe malaria.

BACKGROUND: Severe malaria caused by Plasmodium falciparum leads to most malaria-related deaths globally. Decoquinate (DQ) displays strong activity against multistage infection by Plasmodium parasites. However, the development of DQ as an oral dosage form for the treatment of malaria at the blood stage has not been successful. In this study, liposome formulations of DQ were created for intravenous (IV) injection to suppress Plasmodium berghei, a parasite that causes severe malaria in mice. METHODS: DQ liposomes were prepared by conventional ethanol injection method with slight modifications and encapsulation efficiency evaluated by the well-established centrifugation method. Potency of the DQ liposomes against P. falciparum was assessed in vitro using freshly isolated human red blood cells. The efficacy of the DQ liposomes was examined in the mouse model of severe malaria. RESULTS: The DQ liposomes were around 150 nm in size and had the encapsulation efficiency rates > 95%. The freshly prepared and lyophilized liposomes were stable after storage at - 20 °C for 6 months. The liposomes were shown to have excellent activity against P. falciparum in vitro with DQ IC50 0.91 ± 0.05 nM for 3D7 (chloroquine sensitive strain) and DQ IC50 1.33 ± 0.14 nM for Dd2 (multidrug resistant strain), which were 18- and 14-fold more potent than artemisinin, respectively. Mice did not have any signs of toxicity after receiving high dose of the liposomes (DQ 500 mg/kg per mouse) by IV injection. In the mouse model of severe malaria, the liposomes had impressive efficacy against P. berghei with DQ ED50 of 0.720 mg/kg. CONCLUSION: The DQ liposomes prepared in this study were stable for long term storage and safe for IV injection in mammalian animals. The newly created liposome formulations had excellent activity against Plasmodium infection at the blood-stage, which encourages their application in the treatment of severe malaria.

Genetic variation in FCER1A predicts peginterferon alfa-2a-induced hepatitis B surface antigen clearance in East Asian patients with chronic hepatitis B.

In a multicentre, genome-wide association study to identify host genetic factors associated with treatment response in adult chronic hepatitis B patients, genotype data were obtained by microarray analysis from 1669 patients who received peginterferon alfa-2a for ≥ 24 weeks with/without a nucleos(t)ide analog. Treatment response was assessed at least 24 weeks post-treatment, using serological and/or virological endpoints. Thirty-six single-marker analyses and a gene-by-gene analysis were conducted. No single nucleotide polymorphisms (SNPs) achieved genome-wide significance (P < 5 × 10-8 ) in single-marker analyses, but suggestive associations (P < 1 × 10-5 ) were identified for 116 SNPs. In gene-by-gene analyses, one gene, FCER1A (rs7549785), reached genome-wide significance (P = 2.65 × 10-8 ) in East Asian patients for hepatitis B surface antigen (HBsAg) clearance, with a moderate effect size (odds ratio = 4.74). Eleven of 44 carriers (25%) of the A allele at rs7549785 achieved HBsAg clearance compared with 69/1051 (7%) noncarriers. FCER1A encodes the alpha subunit of the immunoglobulin E receptor. In a post hoc analysis of a homogenous patient subset, the strongest intragenic association was for rs7712322 (POLR3G, P = 7.21 × 10-7 ). POLR3G encodes the G subunit of the polymerase (RNA) III enzyme, involved in sensing and limiting infection by intracellular bacteria and DNA viruses, and as a DNA sensor in innate immune responses. FCER1A (rs7549785) and possibly POLR3G (rs7712322) are shown to be associated with peginterferon alfa-2a response in adult patients with chronic hepatitis B. Independent confirmation of these findings is warranted (clinicaltrials.gov number NCT01855997).

Biomolecular interaction analysis for carbon nanotubes and for biocompatibility prediction.

The interactions between carbon nanotubes (CNTs) and biologics have been commonly studied by various microscopy and spectroscopy methods. We tried biomolecular interaction analysis to measure the kinetic interactions between proteins and CNTs. The analysis demonstrated that wheat germ agglutinin (WGA) and other proteins have high affinity toward carboxylated CNT (f-MWCNT) but essentially no binding to normal CNT (p-MWCNT). The binding of f-MWCNT-protein showed dose dependence, and the observed kinetic constants were in the range of 10(-9) to 10(-11) M with very small off-rates (10(-3) to 10(-7) s(-1)), indicating a relatively tight and stable f-MWCNT-protein complex formation. Interestingly in hemolysis assay, p-MWCNT showed good biocompatibility, f-MWCNT caused 30% hemolysis, but WGA-coated f-MWCNT did not show hemolysis. Furthermore, the f-MWCNT-WGA complex demonstrated enhanced cytotoxicity toward cancer cells, perhaps through the glycoproteins expressed on the cells' surface. Taken together, biomolecular interaction analysis is a precise method that might be useful in evaluating the binding affinity of biologics to CNTs and in predicting biological actions.

Endoscopic-Assisted Intraoral Three-Dimensional Reduction Mandibuloplasty.

BACKGROUND: Oriental people have a square face with a prominent mandibular angle, which means masculine and coarse and is considered to be an unappealing feature. Reduction mandibuloplasty has become popular in the orient in the past 2 decades, and the operation was frequently performed through the intraoral approach. But an invisible mandibular angle forces the surgeon to perform blind ostectomy which leads to difficulty in performing an accurate ostectomy as planned, leaving unnatural mandibular contours and severe complications. METHODS: From January 2010 to January 2013, a total of 112 patients with prominent mandibular angles underwent one-stage long-curved ostectomy combined with splitting corticectomy through an intraoral approach with endoscopic assistance for reduction of the lower face. A retractor with an adjustable endoscope provides a clear operative field; the ostectomy line was marked. The one-stage long-curved ostectomy and corticectomy were performed following the marked ostectomy line using an oscillating saw with angles of various degrees and length under direct vision. RESULTS: Mandibular contouring was 3-dimensionally refined; the width of the lower face was reduced in the frontal view and the mandibular angle appeared natural and inconspicuous in the lateral view. The majority of patients were satisfied with both their frontal and lateral appearances. The gonial angle and the mandibular plane angle were increased effectively. No major complications such as fracture or facial nerve injury occurred. CONCLUSIONS: Intraoral approach of long-curved ostectomy combined with splitting corticectomy with endoscopic assistance allows surgeons to perform accurate, safe, and reproducible ostectomies and to recontour mandible 3-dimensionally, which can make the face look thinner from the frontal view and, in the lateral view, keeps it more natural looking with smooth ostectomized borders.

Extended peginterferon alfa-2a (Pegasys) therapy in Chinese patients with HBeAg-negative chronic hepatitis B.

The present study compared the efficacy of standard and extended durations of PEG-IFNα-2a monotherapy for treatment of HBeAg-negative Chinese patients with chronic hepatitis B. Patients were randomized to receive standard therapy (n = 38; 48 weeks treatment) or extended therapy (n = 42; 72 weeks treatment). Extended therapy resulted in a significantly higher HBV DNA inhibition at 24 and 48 weeks after the end of treatment, a significantly higher sustained HBV DNA inhibition at the end of treatment, and a significantly lower HBsAg level at 24 and 48 weeks after the end of treatment (P < 0.05 for all comparisons). The HBsAg clearance rate was significantly greater in the extended therapy group than in the standard therapy group at 24 and 48 weeks post-treatment (33.3% vs. 10.5% and 35.7% vs. 10.5%, respectively; P < 0.05 for both). In addition, patients with an increase of more than 1 log10 IU/ml in HBsAg level from baseline to week 24 had a significantly lower level of HBsAg at end of treatment (0.54 ± 1.76 vs. 2.89 ± 1.27, P < 0.001), but a higher level of HBsAg clearance (64.3% vs. 7.6%, P < 0.001). Assessment of HBsAg level at week 24 appears to be a suitable checkpoint. These results indicate that 72 weeks of PEG-IFNα-2a monotherapy benefits HBeAg-negative Chinese patients with chronic hepatitis B who are infected with HBV genotype B or C.

[HBeAg seroconversion achieved by sequential peginterferon alfa-2a therapy in chronic hepatitis B patients with unsatisfactory end point following entecavir treatment].

OBJECTIVE: To investigate the efficacy and safety of peginterferon alfa-2a (Peg-IFNa-2a) therapy for treating chronic hepatitis B (CHB) in patients who failed to achieve a satisfactory end point with entecavir (ETV) treatment. METHODS: Fifty-seven CHB patients with positivity for hepatitis B e antigen (HBeAg) who had completed a standard ETV monotherapy course, of at least 96 weeks, and who had achieved a virological response (defined as HBV DNA less than 500 copies/ml) but without HBeAg seroconversion (defined as 0.227 PEI U/ml less than HBeAg less than or equal to 50 PEI U/ml) were enrolled in the study. The patients were randomly assigned to receive a 48-week treatment with Peg -IFNa-2a (experimental group, n = 27) or continued ETV therapy (control group, n = 30). Serum samples were collected from all patients for assessment of biochemical, virological and serological responses to treatment. Inter-group differences were statistically evaluated by t-test or Chi-squared test. RESULTS: The baseline levels of alanine aminotransferase, hepatitis B surface antigen (HBsAg), and HBeAg were similar between the patients comprising the experimental and controls groups. At treatment week 48, the experimental group showed significantly higher rates of HBeAg clearance (Peg-IFNa-2a: 40.7% vs. ETV: 16.7%, x2 = 4.079, P less than 0.05) and seroconversion (37.0% vs. 13.3%, x2 = 5.110, P less than 0.05). The experimental group also showed higher rates of HBsAg clearance (7.4% vs. 0%) and HBV DNA relapse (11.1% vs. 0%), but the differences did not reach statistical significance (x2 = 2.307 and 3.519, both P more than 0.05). However, the level of HBsAg was significantly lower in the experimental group (2866.0+2580.4 vs. 4335.8+2650.0 IU/ml, t = 5.11, P less than 0.05). CONCLUSION: HBeAg-positive CHB patients with unsatisfactory response to initial ETV monotherapy achieved HBeAg seroconversion and clearance following sequential Peg-IFN a-2a treatment.

Modified technique of chin augmentation with MEDPOR for Asian patients.

BACKGROUND: Commonly used chin implants are made of silicone, expanded polytetrafluoroethylene (e-PTFE), or high-density porous polyethylene (MEDPOR). Although MEDPOR is an effective implant for chin augmentation, modification of the external aspect of the implant is recommended, particularly for Asian patients, to create an appropriate shape for the new chin. It is often difficult to contour the inner aspect of the implant to conform to the patient's mandible. Without modification, a gap may exist between the implant and mandible. To address this problem, a modified augmentation technique was developed. OBJECTIVES: The authors describe their modified technique for MEDPOR chin augmentation, which includes removal of the genial tubercles and, if necessary, the mental protuberance. METHODS: Ninety-five patients underwent the modified MEDPOR technique of chin augmentation. Before placement of the contoured implant, a drill was used to remove the patient's genial tubercles. If the mental protuberance was deemed too prominent, it was removed as well. The implant was inserted and fixed to the mandible with 2 titanium screws. RESULTS: Results were satisfactory in 90 cases. Chin shape was too "strong" in 4 patients, and another patient had poor transition between the implant and mandible. Complications were minimal. The most common complication in this modified technique was lower lip numbness, which was transient in all cases. CONCLUSIONS: The MEDPOR chin implant can be effectively contoured to the mandible by removing the genial tubercle and/or mental protuberance. This technique is less invasive than chin osteotomy. Successful results can be achieved with minimal risks.

Transition of tumor-associated macrophages from MHC class II(hi) to MHC class II(low) mediates tumor progression in mice.

BACKGROUND: Tumor-associated macrophages (TAMs) are the most abundant immune cells within the tumor stroma and play a crucial role in tumor development. Although clinical investigations indicate that high levels of macrophage (MΦ) infiltration into tumors are associated with a poor prognosis, the exact role played by TAMs during tumor development remains unclear. The present study aimed to investigate dynamic changes in TAM major histocompatibility complex (MHC) class II expression levels and to assess the effects of these changes on tumor progression. RESULTS: Significant inhibition of tumor growth in the murine hepatocellular carcinoma Hepa1-6 model was closely associated with partial TAM depletion. Strikingly, two distinct TAM subsets were found to coexist within the tumor microenvironment during Hepa1-6 tumor development. An MHC class II(hi) TAM population appeared during the early phase of tumor development and was associated with tumor suppression; however, an MHC class II(low) TAM population became increasingly predominant as the tumor progressed. CONCLUSIONS: Tumor progression was positively correlated with increasing infiltration of the tumor tissues by MHC class II(low) TAMs. Thus, targeting the transition of MΦ may be a novel strategy for drug development and immunotherapy.

PEI fluorination reduces toxicity and promotes liver-targeted siRNA delivery.

Polyethyleneimine (PEI) has been extensively investigated as an efficient carrier for nucleic acid delivery. Yet, it suffers from a high toxicity profile that hinders clinical translation. Fluorination has proven to be a valid approach to reduce the cytotoxicity of PEI and improve the in vitro siRNA delivery potency. Hydrophobicity and lipophobicity can be controllably introduced into the side chains of PEI. However, the effect of fluorination on siRNA delivery in vivo, particularly the biodistribution of siRNA polyplex nanoparticles with fluorinated PEIs, has not been extensively explored. Here, we introduce two series of fluorinated PEIs via amidation with ethyl trifluoroacetate and perfluorobutyryl chloride. Fluorination substantially improved the performance of PEI for siRNA delivery by reducing the cytotoxicity to MDA-MB-231 cells. Importantly, fluorinated PEI enabled the major accumulation of siRNA polyplex nanoparticles in the liver while non-fluorinated PEI delivered siRNA nanoparticles mainly to the lungs after intravenous administration to mice. It is envisioned that fluorination may be an important general strategy for lowering toxicity of cationic polymers, and that the fluorination-induced alteration of biodistribution may be applicable for improved delivery to different organs. Graphical abstract.

Temporal augmentation using a polytetrafluoroethylene implant with the assistance of an endoscope.

BACKGROUND: Expanded polytetrafluoroethylene (e-PTFE), invented by W. L. Gore in the late 1960s, has become a popular material in facial plastic and reconstructive surgery. The use of e-PTFE sheets in the temporal region is reported by some authors and achieving good results. Endoscopic techniques, characterized by small incisions, slight injury, and fewer complications, can be applied in many fields. With the assistance of an endoscope, temporal augmentation with e-PTFE is performed under direct sight, and complications can be reduced. This study aimed to investigate endoscopically assisted temporal augmentation using e-PTFE. METHODS: In this study, 16 patients with concave temporal regions underwent temporal augmentation using e-PTFE with the assistance of an endoscope. The implants were inserted in the plane overlying the deep temporal fascia. RESULTS: Most of the patients were satisfied with the result. One patient had mild temporal area asymmetry, which did not need revision. Another patient had paralysis of the temporal branch of the facial nerve and recovered 3 months after surgery. No infection, foreign body reaction, implant rejection or extrusion, hematoma, seroma, or curling of the edge of the implant occurred. CONCLUSION: Endoscopic procedures are characterized by small incisions, slight tissue injury, direct vision, and fewer complications. Such procedures are helpful in the reconstruction of concave temporal regions using e-PTFE.

[Individualized respond guidance treatment of chronic hepatitis C with combination of peginterferon α-2a and ribavirin].

OBJECTIVE: To study individualized treatment of chronic hepatitis C (CHC) genotype 1 patients using respond guided therapy (RGT) of peginterferon α-2a in combination with ribavirin. METHODS: 140 patients with CHC genotype 1 received peginterferon α-2a 180 microg injection once a week in combination with ribavirin 800-1200 mg/d. Patients achieved RVR after 4 weeks treatment (group A) were randomized into 2 subgroups and proceeded with 24 and 48 weeks treatments (subgroups A1 and A2) respectively. Patients who had not received RVR but achieved cEVR at week 12 (group B) were further divided into 2 subgroups randomly and treated for 48 and 72 weeks (subgroups B1 and B2), respectively. Patients with PVR at week 24 were treated for 72 weeks (group C1), while patients without PVR at week 24 discontinued treatment (group C2). All Patients were followed-up for 24 weeks after the end of treatment. RESULTS: For patients treated for 24 weeks, the ETR rate was 100%, the SVR rate was 65.9%, and the relapse rate was 34.1%. For those treated for 48 weeks, the ETR, SVR and relapse rate were 95.3% , 82.8% and 12.5% respectively. For those treated for 72 weeks, the above rates were 82.1%, 67.9% and 14.3% respectively. SVR rates of subgroup A1 and A2 were 65.9% and 84.4% respectively and the difference was statistically significant (P<0.00). The HCV RNA loads were less than 1x10(6) copy/ml in group A and the SVR were 72.7% and 100% respectively with 24 and 48 weeks treatment, and the difference was insignificant statistically (P>0.05). SVR in subgroup B1 and B2 were 78.9% and 73.7% respectively and the difference was statistically insignificant (P>0.05). The SVR in group C1 was raised to 55. 6%. CONCLUSIONS: RVR and cEVR were respond guided prediction factors for CHC treatment. SVR among patients with RVR was higher in 48-week treatment than those with 24 weeks treatment. For patients with baseline virus load less than 1x10(6) copy/ml and achieved RVR, treatment duration can be shortened to 24 weeks. Treatment extension to 72 weeks can not result in SVR increase among patients without RVR but with cEVR. However, treatment extension to 72 weeks can increase SVR among those patients with PVR.

Combined toxicity of microplastics and cadmium on the zebrafish embryos (Danio rerio).

The effects of microplastics (MPs) on organisms have drawn a worldwide attention in the recent years. In this study, zebrafish embryos were employed to assess the combined effects of MPs and cadmium (Cd) on the aquatic organisms. Lethal and sublethal effects were recorded at 8, 24, 32, 48 and 96 hpe (hour post exposure, hpe). The exposure under a series concentration of MPs and/or an environmental level Cd has the negative impacts on survival and heart rate (HR). And there was a positive correlation between MPs concentration and lethal and sublethal toxicity under combined exposure. The physiological parameters showed that the mixture of two stressors had the antagonistic toxicity under low concentration of MPs (0.05, 0.1 mg/L) while the synergistic sublethal toxicity under high levels of MPs (1, 5, 10 mg/L) on zebrafish embryos. Both the scanning electron micrographs (SEM) and fluorescence microscope photos suggested an electrostatic interaction and weak physical forces generated between MPs and chorion membrane. It is inferred that the 10 µm MPs could induce the protective effect of chorion membrane and cause complex toxicities with Cd. But when it involved with other pollutants, the toxic effects and mechanism are still waiting to be figured out.

Poly(styrene-alt-maleic anhydride) derivatives as potent anti-HIV microbicide candidates.

Topical microbicides offer women the opportunity to protect themselves from sexual HIV transmission under their own control. A series of poly[styrene-alt-(maleic anhydride)] derivatives were prepared by amidation or hydrolysis of the anhydride moiety. The derivatives were shown to be of low cell toxicity and effectively inhibited HIV-1 infections in an in vitro cellular model. Poly[styrene-alt-(maleic acid, sodium salt)] was the most potent inhibitor, being 100-fold more potent than dextran sulfate suggesting its potential application as a new class of polyanionic microbicides.

Formulation, Characterization And Evaluation Of Curcumin- Loaded PLGA- TPGS Nanoparticles For Liver Cancer Treatment.

BACKGROUND: Liver cancer is a major health problem facing mankind. Currently, the focus of research is to improve the treatment of liver cancer using a variety of treatment options such as providing chemotherapy drugs through nanocarriers. PURPOSE: The aim of this study was to prepare a curcumin-loaded (PLGA/TPGS) NPs delivery system by the emulsification-solvent evaporation method in order to achieve synergistic antitumor activity against liver cancer. METHODS: Curcumin-loaded (PLGA/TPGS) NPs were prepared by the emulsification and solvent evaporation method. The physical and chemical characteristics of NPs such as size, morphology, and release profiles were discussed. In vitro and in vivo studies were carried out to evaluate its anti-tumor activity in target cells. RESULTS: Curcumin-loaded (PLGA/TPGS) NPs could be successfully internalized by HepG2 cells and play a synergistic role in inhibiting the growth of hepatocellular carcinoma cells. They exhibited high target organ accumulation, superior antitumor efficiency, and lower toxicity in vivo. CONCLUSION: The present study indicates that the curcumin-loaded (PLGA/TPGS) NPs provide a promising platform for the treatment of liver cancer.

Big data analysis of associations between patient reported outcomes, observer reported toxicities, and overall quality of life in head and neck cancer patients treated with radiation therapy.

PURPOSE: To assess associations between a variety of patient-reported outcomes (PROs), observer reported toxicities (ORTs), and patient-reported overall quality of life (QOL) for head and neck cancer patients treated with radiotherapy, in order to identify important items for inclusion in prospective patient reporting in the clinic. METHODS: 612 patients completed 27 PRO items from three questionnaires at 1273 follow-up visits, and clinicians provided ORTs according to CTCAE criteria. Using a big data approach, we measured associations among all PROs, between all PROs and ORTs, and between PROs/ORTs and QOL with Pearson (ρ) and Kendall (τ) correlation coefficients, and a novel analysis method based on receiver operating characteristic (ROC) curves used to detect thresholds in response levels demonstrating strong interactions. RESULTS: PROs most strongly associated with QOL were recreation/entertainment, activity, and fatigue, with ρ = 0.51-0.60. Several PROs assessing a common functional outcome (eg. xerostomia) were highly associated with each other (PRO-PRO), with maximum ρ = 0.84. Maximum ORT-PRO correlations were ρ = 0.61 (dysgeusia versus taste), and ρ = 0.5 for ORT-QOL (dry mouth - day). The ROC method identified response thresholds with high area under the curve (AUC) scores for many ORT-PRO associations with maximum AUCavg = 0.78. CONCLUSIONS: PRO associations identified activity, lifestyle and fatigue as items for strong consideration for inclusion in questionnaires in the clinic, and suggest that outcome information can be captured in fewer items than the 27 in this study. The ability of clinicians to assess patient toxicities is highest with more severe toxicities, underscoring the need for PRO collection in patient visits to understand and address patient symptoms.

Polyethylene glycol loxenatide injections added to metformin effectively improve glycemic control and exhibit favorable safety in type 2 diabetic patients.

BACKGROUND: The aim of the present study was to evaluate the efficacy and safety of polyethylene glycol loxenatide (PEX168) injections in Chinese type 2 diabetic (T2D) patients. METHODS: The present multicenter randomized double-blind parallel placebo-controlled clinical trial enrolled patients who had been treated with a stable dose of metformin (≥1500 mg/day) for ≥12 weeks and had an HbA1c level between 7% and 11%. Subjects were randomly divided into three groups (1: 1: 1) and were treated with once weekly subcutaneous injections of either placebo or 100 or 200 µg PEX168 for 12 weeks. All subjects continued to receive metformin daily. RESULTS: After 12 weeks treatment, the adjusted least-squares mean of HbA1c reductions from baseline values in the 100 and 200 µg PEX168 groups were significantly higher than in the placebo group (-1.02% [95% confidence interval {CI} -1.33, -0.71), -1.36% [95% CI -1.68, -1.04], and 0.13% [95% CI -0.20, 0.45], respectively; P < 0.05). After treatment, 50% and 60.5% of subjects in the 100 and 200 µg PEX168 groups, respectively, achieved HbA1c levels <7% (P < 0.01 for both vs placebo [HbA1c 11.1%]). The most frequent adverse reactions in the PEX168 groups were mild to moderate dose-dependent gastrointestinal reactions. There were no reports of hypoglycemia or pancreatitis in any of the groups. CONCLUSIONS: Continuous 12 week treatment with PEX168 showed excellent safety and efficacy in T2D patients whose glucose was not well controlled with metformin alone.

Dental noise exposed mice display depressive-like phenotypes.

BACKGROUND: Studies have indicated that depressive disorders are observed frequently in dentists. It's suggested that dentists encounter numerous sources of stress in their professional career. We noticed that the noises in dental environments are very unpleasant. The animal modeling studies suggested that stressful noise could produce depressive-like phenotypes in rodent animals. We hypothesize that the dental noise may be one of the primary stressors causing depressive disorders in dentists. RESULTS: We treated C57BL/6 mice with programmatically played wide-spectrum dental noise for 8 h/day at 75 ± 10 dB SPL level for 30 days, and then tested the behaviors. After exposure to dental noise, animals displayed the depressive-like phenotypes, accompanied by inhibition of neurogenesis in hippocampus. These deficits were ameliorated by orally administered with antidepressant fluoxetine. CONCLUSIONS: Our results suggested that dental noise could be one of the primary stressors for the pathogenesis of depressive disorders and the dental noise mouse model could be used in further depression studies.

Polydopamine Integrated Nanomaterials and Their Biomedical Applications.

In the past few decades, the applications of nanomaterials in biologic systems have become one of the most studied areas. Many novel syntheses and processing methods have been developed to generate nanomaterials to enhance biomedical applications. Among those methods, polydopamine (PDA) integrated nanomaterials have attracted considerable interest for various types of biomedical applications. This concise review outlines the basic chemistry and material science regarding PDA and discusses its successful applications in drug delivery, biosensing, antifouling and antimicrobial activities, as well as its interaction with cells.

Application of organic polymeric flocculants in centrifugal dewatering of oil refinery sludge.

In order to evaluate the applicability of the organic polymeric flocculants (OPF) in the treatment of oil refinery sludge, experiments were conducted to show that OPF have better performance of flocculation than inorganic flocculants. Both the anionic and cationic OPF have satisfactory flocculation efficiency in oil sludge treatment, but the latter are more cost-efficient. Among the over 20 types of flocculants tested, 2 OPF (CPAM-2 and HPAM-2) were selected as the treatment agents, based on their good treatment performances, oil-resistance and economic feasibility. It was demonstrated in the industrial-scale centrifugal dewatering experiments that the application of either CPAM-2 or HPAM-2 could achieve high treatment efficiency of the oil sludge dewatering and reduce the COD of centrifugal liquid to less than 1000 mg/L.