Association between Single Nucleotide Polymorphisms in Monoamine Oxidase and the Severity of Addiction to Betel Quid.

Betel quid (BQ) is the fourth most popular psychoactive substance in the world, and BQ use disorder (BUD) is prevalent in Asian countries. Although the mechanisms underlying BUD remain unclear, studies have reported influences from monoamine oxidase inhibitor. We enrolled 50 patients with BUD and assessed their BQ consumption habits, emotional conditions, and the clinical severity of addiction-assessed using the Diagnostic and Statistical Manual of Mental Disorders [Fifth Edition] (DSM-5) criteria, Substance Use Severity Rating Scale, and Yale-Brown Obsessive Compulsive Disorder Rating Scale for BQ. Patients were categorized into the severe group when showing six or more symptoms defined by DSM-5. A genome-wide association study was conducted for single nucleotide polymorphisms in BRCA1, COL9A1, NOTCH1, HSPA13, FAT1, and MAOA by using patients' blood samples. More severe BUD symptoms were associated with younger age of using BQ and poor oral hygiene and with severe craving for and more anxiety toward BQ use. The MAOA rs5953210 polymorphism was significantly associated with severe BUD (odds ratio, 6.43; 95% confidence interval, 5.12-7.74; p < 0.01) and might contribute to BQ-associated cancer risk. Further studies are required to investigate the addictive properties of BQ and the development of novel diagnostic tools and pharmacotherapeutic alternatives to BUD treatment.

Suppression of Ventilation-Induced Diaphragm Fibrosis through the Phosphoinositide 3-Kinase-γ in a Murine Bleomycin-Induced Acute Lung Injury Model.

Mechanical ventilation (MV), used in patients with acute lung injury (ALI), induces diaphragmatic myofiber atrophy and contractile inactivity, termed ventilator-induced diaphragm dysfunction. Phosphoinositide 3-kinase-γ (PI3K-γ) is crucial in modulating fibrogenesis during the reparative phase of ALI; however, the mechanisms regulating the interactions among MV, myofiber fibrosis, and PI3K-γ remain unclear. We hypothesized that MV with or without bleomycin treatment would increase diaphragm muscle fibrosis through the PI3K-γ pathway. Five days after receiving a single bolus of 0.075 units of bleomycin intratracheally, C57BL/6 mice were exposed to 6 or 10 mL/kg of MV for 8 h after receiving 5 mg/kg of AS605240 intraperitoneally. In wild-type mice, bleomycin exposure followed by MV 10 mL/kg prompted significant increases in disruptions of diaphragmatic myofibrillar organization, transforming growth factor-ß1, oxidative loads, Masson's trichrome staining, extracellular collagen levels, positive staining of α-smooth muscle actin, PI3K-γ expression, and myonuclear apoptosis (p < 0.05). Decreased diaphragm contractility and peroxisome proliferator-activated receptor-γ coactivator-1α levels were also observed (p < 0.05). MV-augmented bleomycin-induced diaphragm fibrosis and myonuclear apoptosis were attenuated in PI3K-γ-deficient mice and through AS605240-induced inhibition of PI3K-γ activity (p < 0.05). MV-augmented diaphragm fibrosis after bleomycin-induced ALI is partially mediated by PI3K-γ. Therapy targeting PI3K-γ may ameliorate MV-associated diaphragm fibrosis.

Trends in suicide attempts and suicide deaths before and during the COVID-19 pandemic in New Taipei City, Taiwan: an interrupted time-series analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is an unprecedented global health crisis that may cause mental health problems and heighten suicide risk. We investigated the impact of the COVID-19 pandemic on trends in suicide attempts and suicide deaths in New Taipei City, Taiwan. METHODS: The current study used the official daily data on suicide attempts and deaths in New Taipei City, Taiwan (4 million inhabitants) between 2015 and 2020 from the Taiwan National Suicide Prevention Reporting System. Interrupted time-series (ITS) analyses with parameters corrected by the estimated autocorrelations were applied on weekly aggregated data to examine whether the suicide trends during the early COVID-19 pandemic (late January to July 2020) deviated from previous trends (January 2015 to late January 2020). The impact due to the suicide prevention policy change was also examined (since August 2020). RESULTS: ITS analyses revealed no significant increases in both mean and trend on weekly suicide deaths during the COVID-19 pandemic and after the policy change. In contrast, there was a significant increasing trend in weekly suicide attempts since the COVID-19 outbreak at the rate of 1.54 attempts per week (95% confidence interval 0.49-2.60; p = 0.004). Sex difference analysis revealed that, however, this increasing trend was observed only in females not in males. CONCLUSIONS: The COVID-19 pandemic has different impacts on suicides attempts and deaths during the early pandemic in New Taipei City, Taiwan. The COVID-19 outbreak drastically increased the trend of suicide attempts. In contrast, the number of suicide deaths had remained constant in the investigated periods.

Use and impact of a novel nurse-led consultation model in a palliative care consultation service for terminally ill cancer patients in Taiwan: an 11-year observational study.

PURPOSE: The early integration of palliative care for terminally ill cancer patients improves quality of life. We have developed a new nurse-led consultation model for use in a palliative care consultation service (PCCS) to initiate early palliative care for cancer patients. METHODS: In this 11-year observational study, data were collected from the Hospice-Palliative Clinical Database (HPCD) of Taichung Veterans General Hospital (TCVGH). Terminally ill cancer patients who had received PCCS during the years 2011 to 2021 were enrolled. Trend analysis was performed in order to evaluate differences in outcomes seen within the categories of either a nurse-led consultation model or ordinary consultation model throughout the study period. Analysis included studying the duration of PCCS and DNR declaration, as well as awareness of disease by both patients and families before and after PCCS. RESULTS: In total, 6923 cancer patients with an average age of 64.1 years received PCCS from 2011 to 2021, with the average duration of PCCS being 11.1 days. Three thousand four hundred twenty-one patients (49.4%) received both a nurse consultation and doctor consultation during PCCS. Being admitted to the Department of Hematology, a longer duration of hospitalization, a DNR declaration after PCCS, and having had a PCCS consultation by a nurse only or both with a nurse and a doctor were significant determinants of a PCCS duration of more than 7 days. CONCLUSION: This 11-year observational study shows that the number of terminal cancer patients receiving a novel nurse-led consultation during PCCS has increased significantly during the past decade, while a nurse-led consultation model during PCCS was effective in improving the duration of PCCS among terminally ill cancer patients.

Prognostic and Immune Infiltration Value of Proteasome Assembly Chaperone (PSMG) Family Genes in Lung Adenocarcinoma.

The complexity of lung adenocarcinoma (LUAD) including many interacting biological processes makes it difficult to find therapeutic biomarkers for treatment. Previous studies demonstrated that PSMG (proteasome assembly chaperone) family members regulate the degradation of abnormal proteins. However, transcript expressions of this gene family in LUAD still need to be more fully investigated. Therefore, we used a holistic bioinformatics approach to explore PSMG genes involved in LUAD patients by integrating several high-throughput databases and tools including The Cancer Genome Atlas (TCGA), and Kaplan-Meier plotter database. These data demonstrated that PSMG3 and PSMG4 were expressed at significantly higher levels in neoplastic cells than in normal lung tissues. Notably, increased expressions of these proteins were correlated with poor prognoses of lung cancer patients, which probably confirmed their fundamental roles in the staging of LUAD tumors. Meanwhile, it was also indicated that there were positive correlations between PSMG family genes and the immune response, metabolism of ubiquinone, cell cycle regulatory pathways, and heat shock protein 90 (HSP90)/phosphatidylinositol 3-kinase (PI3K)/Wnt signaling. Experimental data also confirmed that the knockdown of PSMG4 in LUAD cell lines decreased cell proliferation and influenced expressions of downstream molecules. Collectively, this study revealed that PSMG family members are novel prognostic biomarkers for LUAD progression, which also provide new therapeutic targets of LUAD patients.

Glutamine synthetase regulates the immune microenvironment and cancer development through the inflammatory pathway.

Although adjuvant tamoxifen therapy is beneficial to estrogen receptor-positive (ER+) breast cancer patients, a significant number of patients still develop metastasis or undergo recurrence. Therefore, identifying novel diagnostic and prognostic biomarkers for these patients is urgently needed. Predictive markers and therapeutic strategies for tamoxifen-resistant ER+ breast cancer are not clear, and micro (mi)RNAs have recently become a focal research point in cancer studies owing to their regulation of gene expressions, metabolism, and many other physiological processes. Therefore, systematic investigation is required to understand the modulation of gene expression in tamoxifen-resistant patients. High-throughput technology uses a holistic approach to observe differences among expression profiles of thousands of genes, which provides a comprehensive level to extensively investigate functional genomics and biological processes. Through a bioinformatics analysis, we revealed that glutamine synthetase/glutamate-ammonia ligase (GLUL) might play essential roles in the recurrence of tamoxifen-resistant ER+ patients. GLUL increases intracellular glutamine usage via glutaminolysis, and further active metabolism-related downstream molecules in cancer cell. However, how GLUL regulates the tumor microenvironment for tamoxifen-resistant ER+ breast cancer remains unexplored. Analysis of MetaCore pathway database demonstrated that GLUL is involved in the cell cycle, immune response, interleukin (IL)-4-induced regulators of cell growth, differentiation, and metabolism-related pathways. Experimental data also confirmed that the knockdown of GLUL in breast cancer cell lines decreased cell proliferation and influenced expressions of specific downstream molecules. Through a Connectivity Map (CMap) analysis, we revealed that certain drugs/molecules, including omeprazole, methacholine chloride, ioversol, fulvestrant, difenidol, cycloserine, and MK-801, may serve as potential treatments for tamoxifen-resistant breast cancer patients. These drugs may be tested in combination with current therapies in tamoxifen-resistant breast cancer patients. Collectively, our study demonstrated the crucial roles of GLUL, which provide new targets for the treatment of tamoxifen-resistant breast cancer patients.

Attenuation of Ventilation-Enhanced Epithelial-Mesenchymal Transition through the Phosphoinositide 3-Kinase-γ in a Murine Bleomycin-Induced Acute Lung Injury Model.

Mechanical ventilation (MV) used in patients with acute lung injury (ALI) induces lung inflammation and causes fibroblast proliferation and excessive collagen deposition-a process termed epithelial-mesenchymal transition (EMT). Phosphoinositide 3-kinase-γ (PI3K-γ) is crucial in modulating EMT during the reparative phase of ALI; however, the mechanisms regulating the interactions among MV, EMT, and PI3K-γ remain unclear. We hypothesized that MV with or without bleomycin treatment would increase EMT through the PI3K-γ pathway. C57BL/6 mice, either wild-type or PI3K-γ-deficient, were exposed to 6 or 30 mL/kg MV for 5 h after receiving 5 mg/kg AS605240 intraperitoneally 5 days after bleomycin administration. We found that, after bleomycin exposure in wild-type mice, high-tidal-volume MV induced substantial increases in inflammatory cytokine production, oxidative loads, Masson's trichrome staining level, positive staining of α-smooth muscle actin, PI3K-γ expression, and bronchial epithelial apoptosis (p < 0.05). Decreased respiratory function, antioxidants, and staining of the epithelial marker Zonula occludens-1 were also observed (p < 0.05). MV-augmented bleomycin-induced pulmonary fibrogenesis and epithelial apoptosis were attenuated in PI3K-γ-deficient mice, and we found pharmacological inhibition of PI3K-γ activity through AS605240 (p < 0.05). Our data suggest that MV augmented EMT after bleomycin-induced ALI, partially through the PI3K-γ pathway. Therapy targeting PI3K-γ may ameliorate MV-associated EMT.

Efficacy of free gingival grafting to augment keratinized mucosa around dental implants in posterior regions after restorative procedures: A retrospective clinical study.

STATEMENT OF PROBLEM: Data on the shrinkage of free gingival grafts (FGGs) vary. Most studies have analyzed grafts in nonmolar sites because of measurement limitations and have addressed the changes in grafts and keratinized mucosa width (KMW) only in the early healing phase. PURPOSE: The purpose of this retrospective clinical study was to assess the dimensional changes of an FGG in the posterior regions and their influencing factors, with the aim of obtaining sufficient and stable KMW after restoration. MATERIAL AND METHODS: A total of 77 implants in 40 participants who had undergone an FGG surgery were recruited. Graft sizes during surgery and the surface areas of keratinized mucosa at the follow-up visit after restorations were compared by digital analysis and verified by clinical measurements and photographs. The association between shrinkage and the graft sizes, implant location, and sex and age of the participants was evaluated. The influence of the shrinkage of FGG on the KMW after restoration was analyzed by multivariable linear regression with generalized estimating equation (GEE) models. RESULTS: The mean ±standard deviation shrinkage of FGG around implants in the posterior regions was 24.76 ±14.77%, and the mean ±standard deviation KMW was 4.16 ±1.77 mm at the follow-up visit. Larger grafts had a statistically higher shrinkage ratio (P<.001). No statistically significant difference was found regarding the effect of implant location, sex, and age on the shrinkage of FGG and final KMW (P>.05). The mean ±standard deviation follow-up period after restoration was 12.45 ±7.73 months CONCLUSIONS: Free gingival grafting was found to be a predictable treatment approach for augmentation of KMW around implants in the posterior region after the fabrication of prostheses as long as grafts of sufficient size were placed. Stable outcomes were shown in the study participants in the follow-up period of up to 3 years.

A Socket Seal Technique With the Use of Autologous Dental Roots for Socket Seal: A Case Series.

The literature identified variations in socket seal surgery, each with limitations. This case series aimed to observe the outcome of using autologous dental root (ADR) for socket sealing on socket preservation (SP). A total of 9 patients with 15 extraction sockets were documented. After flapless extraction, the xenograft or alloplastic grafts were placed in the sockets. Autologous dental roots were prepared extraorally and applied to seal the socket entrance. All SP sites healed uneventfully. Cone-beam computed tomography (CBCT) scan was performed after 4-6 months of healing to evaluate ridge dimensions. The preserved alveolar ridge profiles were verified on CBCT scans and during implant surgery. Implants were placed successfully with a reduced need for guided bone regeneration. Histological biopsy specimens were examined in 3 cases. The histological examination demonstrated vital bone formation and osseointegration of graft particles. All patients completed the final restorations and were monitored for 15.56 ± 9.08 months after functional loading. The favorable clinical outcomes support the use of ADR for SP procedures. It was not only accepted to patients but also easy to perform with low complication rates. The ADR technique is thus a feasible method for socket seal surgery.

Increased Production of Interleukin-10 and Tumor Necrosis Factor-Alpha in Stimulated Peripheral Blood Mononuclear Cells after Inhibition of S100A12.

Sepsis may induce immunosuppression and result in death. S100A12 can bind to the receptor for advanced glycation end-products (RAGE) and Toll-like receptor (TLR)4 following induction of various inflammatory responses. It is unclear whether S100A12 significantly influences the immune system, which may be associated with sepsis-related mortality. We measured plasma S100A12 levels and cytokine responses (mean ± standard error mean) of lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) after S100A12 inhibition in healthy controls and patients with sepsis on days one and seven. Day one plasma soluble RAGE (sRAGE) and S100A12 levels in patients with sepsis were significantly higher than those in controls (2481.3 ± 295.0 vs. 1273.0 ± 108.2 pg/mL, p < 0.001; 530.3 ± 18.2 vs. 310.1 ± 28.1 pg/mL, p < 0.001, respectively). Day seven plasma S100A12 levels in non-survivors were significantly higher than those in survivors (593.1 ± 12.7 vs. 499.3 ± 23.8 pg/mL, p = 0.002, respectively). In survivors, plasma sRAGE levels were significantly decreased after 6 days (2297.3 ± 320.3 vs. 1530.1 ± 219.1 pg/mL, p = 0.009, respectively), but not in non-survivors. Inhibiting S100A12 increased the production of tumor necrosis factor (TNF)-α and interleukin (IL)-10 in stimulated PBMCs for both controls and patients. Therefore, S100A12 plays an important role in sepsis pathogenesis. S100A12 may competitively bind to TLR4 and RAGE, resulting in decreased IL-10 and TNF-α production.

Comparison of event-related modulation index and traditional methods for evaluating phase-amplitude coupling using simulated brain signals.

The investigation of brain oscillations and connectivity has become an important topic in the recent decade. There are several types of interactions between neuronal oscillations, and one of the most interesting among these interactions is phase-amplitude coupling (PAC). Several methods have been proposed to measure the strength of PAC, including the phase-locking value, circular-linear correlation, and modulation index. In the current study, we compared these traditional PAC methods with simulated electroencephalogram signals. Further, to assess the PAC value at each time point, we also compared two recently established methods, event-related phase-locking value and event-related circular-linear correlation, with our newly proposed event-related modulation index (ERMI). Results indicated that the ERMI has better temporal resolution and is more tolerant to noise than the other two event-related methods, suggesting the advantages of utilizing ERMI in evaluating the strength of PAC within a brain region.

Fish Oil and Selenium with Doxorubicin Modulates Expression of Fatty Acid Receptors and Selenoproteins, and Targets Multiple Anti-Cancer Signaling in Triple-negative Breast Cancer Tumors.

Omega-3 fatty acids from fish oil (FO) and selenium (Se) potentiate some conventional therapies and have anticancer immune potential. This study aims to determine whether FO/Se modulates G-protein-coupled polyunsaturated fatty acid receptors (GPR-40 and GPR-120) and selenoproteins (Sel-H, Sel-W, and GPx4), and increases the therapeutic effect of doxorubicin in a dose-dependent manner on triple-negative breast cancer (TNBC) mouse. Mice were randomized into 5 groups (n = 7/group) and treated with physiological saline (control), low-dose doxorubicin, and doxorubicin in combination with low, medium, or high doses of FO/Se. The expression of signaling molecules in tumors was determined by measuring either mRNA or protein expression. Compared with doxorubicin alone, combination treatment resulted in lower tumor sizes and fewer overall metastasis, lower GPR-40 mRNA levels, and higher expression of all selenoproteins. Doxorubicin-FO/Se combination treatment decreased expression of membrane EGFR and FGFR, down-regulated downstream PI3K/AKT/mTOR, MAPK/ERK, and JAK2/c-Src/STAT3 signaling, increased tumor suppressor PTEN/TSC1/TSC2 expression and P53 activation, and suppressed oncogenic transcription factor expression. Dose-dependent inhibition of proliferation index Ki-67, cell cycle, and stem-cell-related markers were observed. Decreased immune check-points PD-L1/CTLA-4/Foxp3/CD86 and increased PD-1/CD28/IL-2 expression was also found. These observations suggest that the nutritional supplements FO/Se increase the chemotherapeutic efficacy of doxorubicin against TNBC by modulating GPR-40 and selenoprotein and targeting multiple signaling pathways in tumor tissues.

High-flow nasal cannula compared with continuous positive airway pressure in the treatment of obstructive sleep apnea.

PURPOSE: Continuous positive airway pressure (CPAP) is a standard treatment for obstructive sleep apnea (OSA). However, CPAP has limitations. High-flow nasal cannula (HFNC) is already in use for various types of respiratory diseases. As HFNC generates positive airway pressure, it may be a potential candidate for OSA treatment. This prospective study compared the therapeutic effects of HFNC to CPAP in patients with OSA. METHODS: Patients whose apnea-hypopnea index (AHI) was > 5 events/h were enrolled in this study. All participants were randomly divided into two groups. The first group underwent CPAP the first night and HFNC the second night. Conversely, the second group received HFNC the first night and CPAP the second night. Their respiratory events and sleep quality were compared using baseline polysomnography, CPAP, and HFNC. RESULTS: In total, 28 participants completed this study. Median [interquartile range] AHI (35.0 [20.0-48.6] vs. 10.8 [5.5-20.6] events/h; p < 0.001) was significantly improved by the HFNC. However, sleep quality was not improved. When CPAP was compared directly with HFNC, CPAP demonstrated a more favorable effect for respiratory events (AHI 5.0 [2.0-7.0] vs. 10.8 [5.5-20.6] events/h; p < 0.001) and sleep efficiency (88.1 [79.9-92.5] vs. 77.9 [69.2-86.6] %; p = 0.001). CONCLUSION: The efficacy of CPAP was superior to HFNC for both respiratory events and sleep quality. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03843372; URL: www. CLINICALTRIALS: gov ; Date of registration: November 2, 2019.

Predictors for psychological distress of young burn survivors across three years: A cohort study of a burn disaster in Taiwan.

PURPOSE: The study aims to investigate long-term psychological distress and its risk factors in the burn survivors. DESIGN: A longitudinal study with follow-up interviews was conducted from November 2015-June 2018. A post-burn baseline interview was conducted 6 months after the event, followed by annual surveys for three years. METHODS: The burn survivors received structured assessment through telephone in the four-wave interviews, including the five-item Brief Symptom Rating Scale (BSRS-5); two-item Patient Health Questionnaire (PHQ-2); four-item Startle, Physiological Arousal, Anger, and Numbness Scale (SPAN-4); and six-item Impact of Event Scale (IES-6) alongside demographic data and other health-related assessment. FINDINGS: A total of 180 respondents with the mean age of 23 years old completed the four waves of interview. Using the BSRS-5 as the outcome, each variable had different input in psychological distress during the follow-up years. The main finding was that the SPAN-4 score could predict more than 62% of psychological distress between 6 months and 3 years after the disaster. The generalized estimating equation demonstrated that SPAN-4, IES-6, family functioning impairment, hypnotics use, adaptation to the event, and PHQ-2 could predict psychological distress. However, the variable of follow-up year did not exemplify significant estimation in the model. CONCLUSIONS: The results indicated that different factors had various influences on psychological distress across the four follow-up stages. PTSD-like symptoms, depression, and anxiety were the most common psychological problems experienced by the young burn cohort in the longitudinal post-traumatic period. CLINICAL RELEVANCE: Healthcare providers should be aware of psychological consequences of traumatic events within up to a 3-year post-burn period, particularly post-traumatic stress, depression, and anxiety symptoms.

Reduction in Ventilation-Induced Diaphragmatic Mitochondrial Injury through Hypoxia-Inducible Factor 1α in a Murine Endotoxemia Model.

Mechanical ventilation (MV) is essential for patients with sepsis-related respiratory failure but can cause ventilator-induced diaphragm dysfunction (VIDD), which involves diaphragmatic myofiber atrophy and contractile inactivity. Mitochondrial DNA, oxidative stress, mitochondrial dynamics, and biogenesis are associated with VIDD. Hypoxia-inducible factor 1α (HIF-1α) is crucial in the modulation of diaphragm immune responses. The mechanism through which HIF-1α and mitochondria affect sepsis-related diaphragm injury is unknown. We hypothesized that MV with or without endotoxin administration would aggravate diaphragmatic and mitochondrial injuries through HIF-1α. C57BL/6 mice, either wild-type or HIF-1α-deficient, were exposed to MV with or without endotoxemia for 8 h. MV with endotoxemia augmented VIDD and mitochondrial damage, which presented as increased oxidative loads, dynamin-related protein 1 level, mitochondrial DNA level, and the expressions of HIF-1α and light chain 3-II. Furthermore, disarrayed myofibrils; disorganized mitochondria; increased autophagosome numbers; and substantially decreased diaphragm contractility, electron transport chain activities, mitofusin 2, mitochondrial transcription factor A, peroxisome proliferator activated receptor-γ coactivator-1α, and prolyl hydroxylase domain 2 were observed (p < 0.05). Endotoxin-stimulated VIDD and mitochondrial injuries were alleviated in HIF-1α-deficient mice (p < 0.05). Our data revealed that endotoxin aggravated MV-induced diaphragmatic dysfunction and mitochondrial damages, partially through the HIF-1α signaling pathway.

Characteristics of the convergent angles of tapered implants based on a premolar root model.

STATEMENT OF PROBLEM: Developing tapered implants with the most appropriate angular characteristics requires an improved analysis of the anatomy of premolar roots. PURPOSE: The purpose of this observational study was to analyze the 3D anatomy of premolar roots by determining the tapered slope and convergent angle (TS/CA), to transform the TS/CA patterns into those in which the tapered implants mimic natural tooth roots, and to provide TS/CA references for future investigations. MATERIAL AND METHODS: A total of 73 human single-rooted premolars were surveyed and analyzed by microcomputed tomography and an associated software program. The 3D root surface area (RSA), the radius/diameter (R/D) at the planned first to tenth millimeter levels apical to the cementoenamel junction (CEJ), and the TS/CA at corresponding levels were calculated. The results were statistically analyzed by using an independent samples t test to assess the general differences of tested parameters between maxillary and mandibular premolars. A paired t test was used to examine the significant intragroup TS/CA differences between sequential coronoapical levels. One-way ANOVA was applied to study the general significance of developmental patterns in maxillary and/or mandibular groups. Two-way ANOVA was used to inspect the TS/CA significance at various measurements coronoapically between the maxillary and mandibular premolars (α=.05). RESULTS: Generally, the RSA, root length, R/D, and TS/CA parameters examined for the maxillary premolar roots differed significantly from those for the mandibular roots at the evaluated levels (P<.05). According to the measurements, the maxillary premolar roots generally exhibited nonsignificant RSA and R/D reduction patterns, with a decreasing angle of TS=13.44 degrees and CA=24.53 degrees coronoapically. However, mandibular premolar roots exhibited a significant reduction pattern, with TS=11.25 degrees and CA=21.06 degrees coronoapically according to both individual and general evaluations. CONCLUSIONS: Based on the developmental patterns of the evaluated TSs/CAs, tapered implants imitating premolar root anatomy should have a conical rather than a cylindrical shape, and the R/D of these models should be reduced to half at the apical third. However, further studies are warranted to identify more TS/CA characteristics related to the tapered implants, including the TSs/CAs of other tooth types.

Morphology of Peri-Implant Tissues Around Permanent Prostheses With Various Emergence Angles Following Free Gingival Grafting.

PURPOSE: To analyze the tissue morphology around implant-supported prostheses by digital technology and to evaluate the effect of prosthetic contours on the changes in tissues following the free gingiva graft procedure. MATERIAL AND METHODS: A total of 53 implants in 32 patients receiving free gingiva grafts were selected. These had previously presented insufficient keratinized mucosa width (KMW). At the follow-up visits (mean: 16.66 ± 9.97 months), the implant position and tissue condition were documented with an oral scanner. Vertical soft tissue thickness (VT), measured from the implant-abutment connection to the marginal tissues, and horizontal soft tissue thickness (HT), at the level of the platform, were calculated. The VT, HT, and emergence angle (EA) of prostheses were assessed by 3Shape analyzing software. The final KMW was measured by clinical assessment. Marginal bone loss (MBL) was calculated in the follow-up bitewing radiographs. RESULTS: The mean VT in the study was 2.65 ± 0.75 mm at the mid-buccal sites, 3.74 ± 1.22 mm at the mesial, 3.16 ± 1.08 mm at the distal, and 2.53 ± 0.92 at the mid-lingual aspects. The mid-buccal HT was 1.45 ± 0.53 mm while the mid-lingual was 1.05 ± 0.43 mm (p = 0.008). Interestingly, prostheses with mid-buccal EA > $\; > \;$ 30° exhibited slightly lower VT, but higher HT, than the ones with EA ≤ $\; \le \;$ 30°. Prostheses with proximal EA > 30° displayed slightly more MBL, compared to prostheses with EA ≤ $\; \le \;$ 30°. The mean KMW was 4.08 ± 1.10 mm. CONCLUSIONS: Free gingival grafting is a predictable treatment approach to augmenting soft tissue 3-dimensionally. Prostheses with EA ≤ $\; \le \;$ 30° were preferable for preserving the maximal VT and maintaining crestal bone stability.

Decreased Monocyte HLA-DR Expression in Patients with Sepsis and Acute Kidney Injury.

Background and objectives: Acute kidney injury (AKI) is common in critically ill patients, especially those with sepsis. Persistently low human leukocyte antigen (HLA)-DR expression in monocytes reflects the decreased function of antigen-presenting cells, contributing to poor outcomes in sepsis. This study aimed to establish an association between AKI and HLA-DR expression in monocytes of patients with sepsis. Materials and Methods: We detected HLA-DR expression in monocytes and measured plasma levels of S100A12, high-mobility group box 1 (HMGB1), advanced glycation end products (AGE), and soluble receptor for AGE (sRAGE) from septic patients and healthy controls. Results: HLA-DR expression in monocytes was decreased in patients with AKI than in those without AKI (29.8 ± 5.0% vs. 53.1 ± 5.8%, p = 0.005). Compared with AKI patients, the mean monocyte HLA-DR expression in patients with end-stage renal disease was increased without statistical significance. There were no differences in the AGE/sRAGE ratio and plasma levels of S100A12, HMGB1, AGE, and sRAGE between patients with and without AKI. Conclusions: Compared with septic patients without AKI, patients with AKI had significantly lower HLA-DR expression in monocytes. The role of hemodialysis in monocyte HLA-DR expression needs further studies to explore.

Effects of physical driving experience on body movement and motion sickness among passengers in a virtual vehicle.

Virtual vehicles (e.g., driving video games) can give rise to visually induced motion sickness. Typically, people drive virtual vehicles. In the present study, we investigated motion sickness among participants who were exposed to virtual vehicles as passengers; that is, they observed vehicle motion, but did not control it. We also asked how motion sickness and the postural precursors of motion sickness might be influenced by participants' previous experience of driving physical vehicles. Participants viewed a recording of a virtual automobile in a driving video game. Drivers were young adults with several years of experience driving physical automobiles, while non-drivers were individuals in the same age group who did not have a driver's license and had never driven an automobile. During exposure to the virtual vehicle, we monitored movement of the head and torso. The independent measures included the incidence and severity of motion sickness. After exposure to the virtual vehicle, the incidence and severity of motion sickness did not differ between Drivers and Non-Drivers. By contrast, postural movement differed between participants who later became motion sick and those who did not. In addition, during exposure to the virtual vehicle, physical driving experience was related to patterns of postural activity that preceded motion sickness. The results are consistent with the postural instability theory of motion sickness, and illuminate relations between the control of physical and virtual vehicles.

Increased Death of Peripheral Blood Mononuclear Cells after TLR4 Inhibition in Sepsis Is Not via TNF/TNF Receptor-Mediated Apoptotic Pathway.

BACKGROUND: Apoptosis is one of the causes of immune depression in sepsis. Pyroptosis also occurs in sepsis. The toll-like receptor (TLR) 4 and receptor for advanced glycation end products (RAGE) have been shown to play important roles in apoptosis and pyroptosis. However, it is still unknown whether TLR4 inhibition decreases apoptosis in sepsis. METHODS: Stimulated peripheral blood mononuclear cells (PBMCs) with or without lipopolysaccharides (LPS) and high-mobility group box 1 (HMGB1) were cultured with or without TLR4 inhibition using monoclonal antibodies from 20 patients with sepsis. Caspase-3, caspase-8, and caspase-9 activities were measured. The expression of B cell lymphoma 2 (Bcl2) and Bcl2-associated X (Bax) was measured. The cell death of PBMCs was detected using a flow cytofluorimeter. RESULTS: After TLR4 inhibition, Bcl2 to Bax ratio elevated both in LPS and HMGB1-stimulated PBMCs. The activities of caspase-3, caspase-8, and caspase-9 did not change in LPS or HMGB1-stimulated PBMCs. The cell death of LPS and HMGB1-stimulated CD8 lymphocytes and monocytes increased after TLR4 inhibition. The cell death of CD4 lymphocytes was unchanged. CONCLUSION: The apoptosis did not decrease, while TLR4 was inhibited. After TLR4 inhibition, there was an unknown mechanism to keep cell death in stimulated PBMCs in patients with sepsis.