Erdafitinib in Asian patients with advanced solid tumors: an open-label, single-arm, phase IIa trial.

BACKGROUND: FGFR genomic aberrations occur in approximately 5-10% of human cancers. Erdafitinib has previously demonstrated efficacy and safety in FGFR-altered advanced solid tumors, such as gliomas, thoracic, gastrointestinal, gynecological, and other rare cancers. However, its efficacy and safety in Asian patients remain largely unknown. We conducted a multicenter, open-label, single-arm phase IIa study of erdafitinib to evaluate its efficacy in Asian patients with FGFR-altered advanced cholangiocarcinoma, non-small cell lung cancer (NSCLC), and esophageal cancer. METHODS: Patients with pathologically/cytologically confirmed, advanced, or refractory tumors who met molecular and study eligibility criteria received oral erdafitinib 8 mg once daily with an option for pharmacodynamically guided up-titration to 9 mg on a 28-day cycle, except for four NSCLC patients who received erdafitinib 10 mg (7 days on/7 days off) as they were recruited before the protocol amendment. The primary endpoint was investigator-assessed objective response rate per RECIST v1.1. Secondary endpoints included progression-free survival, duration of response, disease control rate, overall survival, safety, and pharmacokinetics. RESULTS: Thirty-five patients (cholangiocarcinoma: 22; NSCLC: 12; esophageal cancer: 1) were enrolled. At data cutoff (November 19, 2021), the objective response rate for patients with cholangiocarcinoma was 40.9% (95% CI, 20.7-63.6); the median progression-free survival was 5.6 months (95% CI, 3.6-12.7) and median overall survival was 40.2 months (95% CI, 12.4-not estimable). No patient with RET/FGFR-altered NSCLC achieved objective response and the disease control rate was 25.0% (95% CI, 5.5-57.2%), with three patients with stable disease. The single patient with esophageal cancer achieved partial response. All patients experienced treatment-emergent adverse events, and grade ≥ 3 treatment-emergent adverse events were reported in 22 (62.9%) patients. Hyperphosphatemia was the most frequently reported treatment-emergent adverse event (all-grade, 85.7%). CONCLUSIONS: Erdafitinib demonstrated efficacy in a population of Asian patients in selected advanced solid tumors, particularly in those with advanced FGFR-altered cholangiocarcinoma. Treatment was tolerable with no new safety signals. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov (NCT02699606); study registration (first posted): 04/03/2016.

Prevalence of KRAS amplification in patients with metastatic cancer: Real-world next-generation sequencing analysis.

BACKGROUND: The Kirsten rat sarcoma virus (KRAS) is a prominent proto-oncogene. Several treatments for KRAS mutations have been developed. However, KRAS amplification, a KRAS alteration, is poorly understood, and there is currently no appropriate treatment other than conventional chemotherapy. This study aimed to elucidate the role of KRAS amplification in different types of cancers. METHODS: From October 2019 to June 2023, we performed next-generation sequencing using Trusight Oncology 500 on 3895 patients with 37 different cancer types at the Samsung Medical Center. We analyzed the distribution of KRAS amplification according to cancer type and its correlation with tumor mutation burden (TMB). Concomitant KRAS mutations were also identified. RESULTS: Of the total 3895 patients, 99 (2.5 %) had KRAS amplification. The highest frequency of KRAS amplification was detected in 2 % (27/1350) of patients with colorectal cancer, followed by 3.48 % (32/920) of patients with gastric cancer and 3.88 % (9/232) patients with of pancreatic cancer. MSI-High was not detected in patients with KRAS amplification. There was no correlation between KRAS copy number variation and TMB status. Among patients with KRAS amplification, 27.3 % (27/99) had a concomitant KRAS mutation. More than 50 % of patients had G12D or G12V mutations. In gastric cancer, patients with both KRAS amplification and mutation were extremely rare at 3.1 % (1/32); however, in colorectal cancer, more than half of the patients had KRAS amplification and mutation (51.9 %, 14/27). KRAS amplification and mutations are associated with mutations in tumor suppressor genes TP53, BRCA2, ARID1B, and PTCH1. CONCLUSIONS: Of the 3895 patients with metastatic solid tumors, 99 (2.5 %) had KRAS amplification, and next-generation sequencing analysis provided a deeper understanding of KRAS amplification.

Hispanic/Latino Ethnicity is an Independent Predictor of Worse Survival for Gastric Cancer in a Multicenter Safety-Net Patient Population.

BACKGROUND: Various population-based studies have shown Hispanic/Latino ethnicity is a risk factor for worse survival in patients with gastric cancer linked to disparate access to care. We aimed to address whether Hispanic patients treated within safety-net hospital systems continue to experience this survival deficit compared to non-Hispanic patients. METHODS: We performed a retrospective cohort study comparing survival between Hispanic and non-Hispanic patients diagnosed with gastric adenocarcinoma between January 1, 2016 to December 31, 2020 within Los Angeles County's safety-net hospital system. Gastric cancer-specific survival was compared between the two cohorts using the Kaplan-Meier estimate and Cox proportional-hazards regression model. RESULTS: 448 patients who received care from five medical centers were included. 348 (77.7%) patients self-identified as Hispanic and 100 (22.3%) as non-Hispanic. Mean follow-up time was 2.0 years (median 0.91 years, IQR, 0.34-2.5 years). Hispanic patients were found to be diagnosed at a younger age (55.6 vs 60.7 years, p <0.01), demonstrate higher state area deprivation index (6.4 vs 5.0, p <0.01), and present with metastatic disease (59.8% vs 45%, p =0.04). After adjusting social and oncologic variables, Hispanic ethnicity remained an independent risk factor for worse survival (HR 1.56, [95% CI 1.06-2.28], p = 0.02). CONCLUSIONS: Hispanic patients treated within a large, multi-center safety-net hospital system experience worse survival compared to non-Hispanic patients. This suggests ethnic disparities exist within safety-net hospital systems, independent of known clinicopathologic factors. IMPACT: Improving outcomes for Hispanic patients with gastric cancer requires future efforts aimed at defining and addressing these unidentified barriers to care.

The Different Associations of White Matter Hyperintensities With Severity of Dementia and Cognitive Impairment According to the Distance From the Lateral Ventricular Surface in Patients With Alzheimer's Disease.

OBJECTIVE: White matter hyperintensities (WMH) are common among the elderly. Although WMH play a key role in lowering the threshold for the clinical expression of dementia in Alzheimer's disease (AD)-related pathology, the clinical significance of their location is not fully understood. This study aimed to investigate the association between WMH and cognitive function according to the location of WMH in AD. METHODS: Subjects underwent clinical evaluations including volumetric brain magnetic resonance imaging study and neuropsychological tests using the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet. WMH were calculated using automated quantification method. According to the distance from the lateral ventricular surface, WMH within 3 mm, WMH within 3-13 mm, and WMH over 13 mm were classified as juxtaventricular WMH (JVWMH), periventricular WMH (PVWMH), and deep WMH (DWMH), respectively. RESULTS: Total WMH volume was associated with poor performance in categorical verbal fluency test (ß=-0.197, p=0.035). JVWMH volume was associated with poor performances on categorical verbal fluency test (ß=-0.201, p=0.032) and forward digit span test (ß= -0.250, p=0.012). PVWMH volume was associated with poor performances on categorical verbal fluency test (ß=-0.185, p=0.042) and word list memory test (ß=-0.165, p=0.042), whereas DWMH volume showed no association with cognitive tests. PVWMH volume were also related to Clinical Dementia Rating Scale Sum of Boxes score (ß=0.180, p=0.026). CONCLUSION: WMH appear to exhibit different associations with the severity of dementia and cognitive impairment according to the distance from ventricle surface in AD.

Non-invasive strategy: Developing a topical IL-4Rα-specific nanobody for the treatment of allergic airway diseases.

Inhibiting IL-4 and IL-13 are critical cytokines that induce the pathogenic responses of allergic airway diseases. Currently, monoclonal antibodies targeting IL-4Rα are administered subcutaneously to treat eosinophilic rhinosinusitis and allergic asthma. However, these treatments have several drawbacks. To address these issues, we have developed a novel IL-4Rα-targeting nanobody designed for non-invasive delivery to local inflammatory sites in allergic airway diseases. H5, selected via the ribosomal display applied screening from synthetic nanobody library, underwent dimerization and in-silico affinity maturation using AlphaFold2 and GROMACS resulting in a substantial/dramatic enhancement of its binding affinity. H5 effectively controlled inflammatory markers such as MUC5AC, CCL26, and FOXJ1 in human nasal epithelial cells (HNECs) by inhibiting IL-4 and IL-13 signaling. The bivalent form of H5 showed efficacy in easily accessible cells, such as multi-ciliated cells, while the monovalent variant targeted hard-to-reach cells, such as basal cells of HNECs. In summary, we developed a nanobody that could effectively inhibit inflammatory signaling in HNECs via intranasal administration, showing promise as a non-invasive rhinitis treatment.

Fate assessment of the ectatic common iliac artery using flared limb during endovascular aneurysm repair.

OBJECTIVES: This study aimed to evaluate the outcomes and anatomical predictors of the complications of flared limb (FL) use for ectatic common iliac arteries accompanied by abdominal aortic aneurysm treated with endovascular aneurysm repair (EVAR). METHODS: In this single-center retrospective study, we reviewed data from 391 patients (638 limbs) treated between 2005 and 2020. The cohort was divided into two groups. The standard limbs (SLs, n = 403) included stent graft (SG) of <20 mm in diameter and the FLs (n = 235) included stent graft of ≥20 mm in diameter. Complications within 30 days were investigated as the short-term outcome. Limb events during follow-up including type Ib endoleak (EL), type IIIa EL, and limb occlusion were compared between SLs and FLs using log-rank test. RESULTS: Early results indicated that the FL group had a significantly higher incidence of intraoperative type Ib EL at 5.1% (12), than 1.7% (7) in the SLs (p = .016). For 19 patients in whom intraoperative type Ib EL was discovered, SG extension alone or internal iliac artery embolization was all performed before completing the procedure. Overall, we noted one case of type Ib EL and two cases of limb events in each group at 30 days. Over a median follow-up of 39 months, 31 (4.9%) events (17 type Ib EL, 2 type IIIa EL, and 12 limb events), 13 (5.5%) in FLs and 18 (4.5%) in SLs (p = .984), were observed. The FLs had significantly higher rates of aortic sac enlargement, with 46 (19.6%) cases for FLs and 36 (8.9%) for SLs (p < .001). The Kaplan-Meier analysis revealed significant differences at 5 years in SLs versus FLs for freedom from type Ib EL (96.6% vs 82.4%, respectively; p < .001) and no difference in freedom from limb events (94.7% vs 84.5%, respectively; p = .519). Furthermore, no difference was observed for overall survival and aneurysm-related mortality. CONCLUSIONS: Although an FL for EVAR is used to treat dilated iliac arteries, there is an increased risk of intraoperative and late type Ib EL and aortic sac enlargement. Long-term close follow-up is mandatory, especially in the patients who undergo EVAR using FLs.

Exploring the usability of simulated patient methodology in dental clinics in Western Australia: A pilot survey.

OBJECTIVES: This study aimed to explore the dental staff knowledge of simulated patient methodology and support for its use to investigate dental staffs' triaging ability. MATERIAL AND METHODS: Staff at dental practices in Western Australia were invited to participate in a cross-sectional online questionnaire, consisting of demographic questions, questions on triaging, and knowledge of simulated patient methodology. Descriptive and parametric tests were undertaken for quantitative data; qualitative responses were thematically analyzed. RESULTS: Of the 100 participants, most were female (71%), aged 25-39 years (57%), dentists (46%), and worked in private practices (60%). While 82% of participants triaged dental appointment enquiries, only 26% had heard of simulated patient studies. The majority (66%) of participants spent 1-5 min when triaging appointments and less than half (29%) asked about medical history, aggravating or alleviating factors. Although there was a general positive attitude toward use of simulated patient methodology to investigate practice, some concerns were identified. CONCLUSIONS: The findings of our exploratory study suggests that there may be a potential for utilizing simulated patient studies to improve the care of patients by dental receptionists in general dental practices.

Emerging role of local treatment in the era of advanced systemic treatment in pancreatic cancer with liver metastasis: A systematic review and meta-analysis.

BACKGROUND: Approximately 50% of pancreatic cancer cases are diagnosed with distant metastases, commonly in the liver, leading to poor prognosis. With modern chemotherapy regimens extending patient survival and stabilizing metastasis, there has been a rise in the use of local treatments. However, the effectiveness for local treatment remains unclear. METHODS: PubMed, Embase, and Cochrane databases were searched for studies reporting the survival outcomes of pancreatic cancer cases with isolated synchronous or metachronous liver metastases who underwent curative-intent local treatment. Hazard ratios were combined using a random-effects model. RESULTS: The full texts of 102 studies were screened, and 14 retrospective studies were included in the meta-analysis. Among patients with synchronous liver metastases, overall survival was significantly better in those who underwent curative-intent local treatment than in those who did not (hazard ratio [HR]: 0.35, 95% confidence interval [CI]: 0.24-0.52). Among patients with metachronous liver metastases, overall survival was also significantly better in those who underwent curative-intent local treatment than in those who did not (HR 0.37, 95% CI: 0.19-0.73). CONCLUSIONS: Curative-intent local treatment may be a feasible option for highly selected pancreatic cancer cases with liver metastases. However, the optimal strategy for local treatments should be explored in future studies.

Temporal changes in microalgal biomass and species composition on different plastic polymers in nutrient-enriched microcosm experiments.

Marine plastic debris (MPD) is a potential threat to marine ecosystems, but its function as a vector for the transportation of harmful microalgae and its impact on the habitats of other marine organisms are uncertain. To address this gap in knowledge, we performed month-long experiments in 30 L microcosms that contained plates made of six different plastic polymers (polypropylene [PP], low-density polyethylene [LDPE], high-density polyethylene [HDPE], polyvinyl chloride [PVC], polyethylene terephthalate [PET], and polystyrene [PS]), and examined the time course of changes in planktonic and periphytic microalgae. There were no significant differences in the composition of periphytic microalgae or biomass among the different plastic polymers (p > 0.05). Nutrient depletion decreased the abundance of planktonic microalgae, but increased the biomass of attached periphytic microalgae (p < 0.05). In particular, analysis of the plastic plates showed that the abundance of benthic species that are responsible for harmful algal blooms (HABs), such as Amphidinium operculatum and Coolia monotis, significantly increased over time (days 21-28; p < 0.05). Our findings demonstrated that periphyton species, including benthic microalgae that cause HABs, can easily attach to different types of plastic and potentially spread to different regions and negatively impact these ecosystems. These observations have important implications for understanding the potential role of MPD in the spread of microalgae, including HABs, which pose a significant threat to marine ecosystems.

Re-evaluation of risk and oncological outcomes of resection of veins and arteries in the resection of pancreatic cancer.

BACKGROUND: Advances in chemotherapy have led to increasing major vascular resection during pancreatectomy which has been contraindicated due to high morbidity. This study aimed to verify the safety and oncological outcomes of vascular resection during pancreatectomy in the era of neoadjuvant therapy. METHODS: Data from patients who underwent surgery for pancreatic cancer at Seoul National University Hospital between 2001 and 2021 were reviewed. Clinicopathological outcomes were analyzed according vessel resection. A propensity-score-matched (PSM) analysis was performed to evaluate survival outcomes. RESULTS: Of 1596 patients, the proportion of those who underwent vascular resection increased from 9.2% to 23.4% over time divided into 5-year intervals. There were no differences in major complications (15.6% vs. 13.0%; p = .266) and 30-day mortality rate (0.3% vs. 0.6%; p = .837) between the vascular and nonvascular resection groups. After PSM, the vascular resection group demonstrated comparable survival outcome with the nonvascular resection group (5 year-survival-rate 20.4 vs. 23.7%; p = .194). Arterial resection yielded comparable survival outcome with nonvascular resection (5 year-survival-rate 38.1% vs. 23.7%; p = .138). CONCLUSIONS: Appropriate vascular resection-even arterial-is safe and effective in patients carefully selected for radical surgery in the era of neoadjuvant therapy. Further studies are needed to determine the optimal indication and method for vascular resection in patients with pancreatic cancer.

The utilisation of teledentistry in Australia: A systematic review and meta-analysis.

BACKGROUND: Teledentistry is the usage of information-based technologies to deliver healthcare services remotely. It is used to deliver care in regional, rural and remote regions and was particularly useful to deliver care during the COVID-19 pandemic. OBJECTIVE: This systematic review and meta-analysis aimed to determine teledentistry utilisation in Australia. METHODS: The databases PubMed, Google Scholar, EMBASE and Web of Science were searched from inception to June-2024. The phrases "Dental" AND "Telehealth" AND "Australia" and "Teledentistry" AND "Australia" were used. Two authors completed the study selection and data extraction. The Joanna Briggs Institute Critical Appraisal Tools were used to assess quality and bias. RESULTS: Eighteen articles met the inclusion criteria. There were six diagnostic tests, six cross-sectional studies, 4 economic evaluations, one qualitative study and one expert opinion. Teledentistry was accurate for screening caries (average sensitivity=69.7 %, average specificity=97.4 %). There also appeared to be a non-significant negative correlation between specificity and sensitivity (r = 0.432). Opinions regarding teledentistry were mixed from clinicians but positive from patients. Teledentistry may also lead to savings for patients and healthcare providers. CONCLUSION: Teledentistry increases healthcare access especially for people in regional, rural and remote areas. It is an effective screening tool for caries. Whilst the opinions of clinicians were mixed, potential implementation barriers were identified which could improve opinions of clinicians and increase implementation. CLINICAL IMPORTANCE: This study demonstrates teledentistry as a satisfactory tool for screening caries. This could be beneficial to those with difficulties visiting dentists in-person, particularly if they live in regional, rural or remote areas.

Resistance Training Using VAriable Resistance Suit (VARS) Increased Isometric and Isokinetic Muscle Strength.

While resistance training promotes muscle hypertrophy and strength, accessibility of equipment is a barrier. This study evaluated a wearable VAriable Resistance Suit (VARS) as a novel and alternative method to achieve muscle strength improvement. It was hypothesized that by providing adjustable, bi-directional and speed dependent resistance, VARS can target specific muscles to improve muscle strength via an accessible and portable device. Twelve untrained healthy male adults (22.08 ± 4.1 years old) participated in an 8-week long resistance training using VARS to strengthen four muscles (biceps brachii, triceps brachii, biceps femoris, rectus femoris) of their non-dominant arm and leg using VARS. The results showed significant improvements in the muscle strength measured by isokinetic dynamometer - 49.9±9.6% increase in isokinetic force and 30.6±7.6% increase in isometric force. Muscle size and body composition were also assessed using ultrasound imaging and bioelectrical impedance analysis, which did not show significant changes. The study demonstrates the efficacy and feasibility of VARS as a resistance training tool to achieve muscle strength improvement and its potential extension to clinical populations.

Tricaprylin-based drug crystalline suspension for intramuscular long-acting delivery of entecavir with alleviated local inflammation.

In order to ensure prolonged pharmacokinetic profile along with local tolerability at the injection site, tricaprylin-based drug crystalline suspension (TS) was designed and its local distribution, pharmacokinetics, and inflammatory response, were evaluated with conventional aqueous suspension (AS). As model drug particles, entecavir 3-palmitate (EV-P), an ester lipidic prodrug for entecavir (EV), was employed. The EV-P-loaded TS was prepared by ultra-sonication method. Prepared TS and conventional AS exhibited comparable morphology (rod or rectangular), median diameter (2.7 and 2.6 µm), crystallinity (melting point of 160-165°C), and in vitro dissolution profile. However, in vivo performances of drug microparticles were markedly different, depending on delivery vehicle. At AS-injected site, drug aggregates of up to 500 µm were formed upon intramuscular injection, and were surrounded with inflammatory cells and fibroblastic bands. In contrast, no distinct particle aggregation and adjacent granulation was observed at TS-injected site, with >4 weeks remaining of the oily vehicle in micro-computed tomographic observation. Surprisingly, TS exhibited markedly alleviated local inflammation compared to AS, endowing markedly lessened necrosis, fibrosis thickness, inflammatory area, and macrophage infiltration. The higher initial systemic exposure was observed with TS compared to AS, but TS provided prolonged delivery of EV for 3 weeks. Therefore, we suggest that the novel TS system can be a promising tool in designing parenteral long-acting delivery, with improved local tolerability.

Clinical outcomes of neoadjuvant chemoradiotherapy followed by total mesorectal excision in locally advanced rectal cancer with mesorectal fascia involvement.

PURPOSE: For the treatment of locally advanced rectal cancer (LARC), research on primary lesions with mesorectal fascia (MRF) involvement is lacking. This study analyzed the clinical outcomes and efficacy of dose-escalated neoadjuvant concurrent chemoradiotherapy (NCRT) to patients with LARC involving MRF. MATERIALS AND METHODS: We retrospectively reviewed 301 patients who were diagnosed with LARC involving MRF and underwent NCRT followed by total mesorectal excision (TME). Patients who received radiotherapy (RT) doses of ≤50.4 Gy were defined as the non-boost group, while ≥54.0 Gy as the boost group. Pathological tumor response and survival outcomes, including intrapelvic recurrence-free survival (IPRFS), distant metastases-free survival (DMFS) and overall survival (OS), were analyzed. RESULTS: A total of 269 patients (89.4%) achieved a negative pathological circumferential resection margin and 104 (34.6%) had good pathological tumor regression grades. With a median follow-up of 32.4 months, IPRFS, DMFS, and OS rates at 5-years were 88.6%, 78.0%, and 91.2%, respectively. In the subgroup analysis by RT dose, the boost group included more advanced clinical stages of patients. For the non-boost group and boost group, 5-year IPRFS rates were 90.3% and 87.0% (p = 0.242), 5-year DMFS rates were 82.0% and 71.3% (p = 0.105), and 5-year OS rates were 93.0% and 80.6% (p = 0.439), respectively. Treatment related toxicity was comparable between the two groups (p = 0.211). CONCLUSION: Although this retrospective study failed to confirm the efficacy of dose-escalated NCRT, favorable IPRFS and pathological complete response was achieved with NCRT followed by TME. Further studies combining patient customized RT dose with systemic therapies are needed.

Postoperative distress and influencing factors in patients with pancreatobiliary cancer.

This study aimed to investigate distress levels, using the distress thermometer (DT), and the factors associated with distress in postoperative patients with pancreatobiliary cancer. This study retrospectively investigated 155 patients who underwent surgery for pancreatobiliary cancer between December 1, 2019 and September 30, 2021. The DT and problem list were used to measure distress. Descriptive statistics, t-test, and multivariate logistic regression analysis were used to analyze the data. Of the 155 patients, 16.8% (n = 26) and 83.2% (n = 129) were in the mild-distress and moderate-to-severe distress groups, respectively. The average DT score was 6.21; that for the mild-distress and moderate-to-severe distress groups was 2.46 and 6.97, respectively. More patients in the moderate-to-severe distress group reported having problems of "sadness" (χ2 = 4.538, P < 0.05), "indigestion" (χ2 = 10.128, P < 0.001), "eating" (χ2 = 6.147, P < 0.013), and "getting around" (χ2 = 4.275, P < 0.039) than in the mild-distress group. In addition, occupation status (odds ratio [OR] = 0.342, 95% confidence interval [CI] = 0.133-0.879, P = 0.026) and indigestion (OR = 5.897, 95% CI = 1.647-21.111, P = 0.006) were independent risk factors for the presence of severe distress. Patients with pancreatobiliary cancer demonstrated elevated levels of psychological distress. Healthcare providers should therefore be vigilant when evaluating patients for distress and providing appropriate referrals, particularly those who are unemployed or have indigestion.

Proposal regarding horizontal and vertical positioning of single implants placed in healed sites: Effect on cervical crown form and the need for bone grafting.

STATEMENT OF PROBLEM: When single implants are placed in healed sites, guidelines are lacking on the horizontal and vertical implant positions that optimize cervical crown form and the implant locations that would require bone grafting to develop the optimal crown form. PURPOSE: The purpose of this clinical study was to evaluate the cervical contour of wax patterns formed on casts of single implants placed in healed sites and to determine which horizontal and vertical implant positions produced the best cervical crown form and which indicated the need for bone grafting. MATERIAL AND METHODS: Fifty-eight wax patterns were fabricated on casts where implants had been placed in healed sites without bone grafting. The wax patterns were subjectively assessed by 5 dental faculty members and 5 graduate students as having good, fair, or poor cervical crown form. Horizontal measurements were made between the facial surface of the implant and a round metal wire connecting the gingival zeniths of the adjacent teeth. Vertical measurements were also made between the wire and implant platform. The subjective assessments along with the horizontal and vertical implant position measurements were used to propose guidelines for optimal implant placement in healed sites. RESULTS: Horizontal distances of 2.0 to 3.0 mm produced good cervical crown contours, with distances >3.0 mm and <2.0 mm resulting in fair or poor assessments. Vertical distances of 3.0 to 4.0 mm were judged to have good cervical crown contour, whereas depths of 1.0 mm or less were assessed as poor. CONCLUSIONS: Based on the subjective assessment of wax patterns formed on casts of single implants placed in healed sites, a guideline of 2.0 to 3.0 mm is proposed for the horizontal distance between a line connecting the adjacent gingival zeniths and the facial surface of the implant. A vertical distance guideline of 3.0 to 4.0 mm is proposed between the adjacent gingival zeniths and the implant platform.

Atractylodes macrocephala Koidz Alleviates Symptoms in Zymosan-Induced Irritable Bowel Syndrome Mouse Model through TRPV1, NaV1.5, and NaV1.7 Channel Modulation.

(1) Background: Irritable bowel syndrome (IBS) is a common disease in the gastrointestinal (GI) tract. Atractylodes macrocephala Koidz (AMK) is known as one of the traditional medicines that shows a good efficacy in the GI tract. (2) Methods: We investigated the effect of AMK in a network pharmacology and zymosan-induced IBS animal model. In addition, we performed electrophysiological experiments to confirm the regulatory mechanisms related to IBS. (3) Results: Various characteristics of AMK were investigated using TCMSP data and various analysis systems. AMK restored the macroscopic changes and weight to normal. Colonic mucosa and inflammatory factors were reduced. These effects were similar to those of amitriptyline and sulfasalazine. In addition, transient receptor potential (TRP) V1, voltage-gated Na+ (NaV) 1.5, and NaV1.7 channels were inhibited. (4) Conclusion: These results suggest that AMK may be a promising therapeutic candidate for IBS management through the regulation of ion channels.