Non-loaded Group Research Articles

The Effect of a Loading Dose Regimen in the Switch to Brolucizumab for Patients with Aflibercept-Resistant nAMD.

To evaluate the one-year outcomes of switching to brolucizumab with and without a loading dose regimen (three monthly injections) in eyes with aflibercept-resistant neovascular age-related macular degeneration (nAMD). We retrospectively studied nAMD patients who had retinal exudate under bimonthly injections of aflibercept and were switched to brolucizumab from aflibercept. Patients were grouped into intravitreal brolucizumab injection (IVBr) with a loading dose regimen (loading group) and without a loading dose regimen (nonloading group). We assessed the best-corrected visual acuity (BCVA), central retinal thickness (CRT) at the fovea, subfoveal choroidal thickness (SFCT), IVBr status (number of injections and last injection interval), and retinal exudate status on optical coherence tomography. Overall, 52 eyes received ≥1 IVBr; 26 eyes received ≥3 IVBr with 12-month follow-up. A total of 13 eyes in the loading group and 13 eyes in the nonloading group were reviewed. One year after switching, BCVA changed from 0.28 ± 0.25 to 0.19 ± 0.28 in the loading group (P=0.28) and from 0.25 ± 0.20 to 0.23 ± 0.25 in the nonloading group (P=0.92). The mean CRT decreased from 263.6 ± 40.7 µm to 221.7 ± 54.6 µm in the loading group (P=0.03), while it only changed from 244.9 ± 77.2 µm to 221.0 ± 78.7 µm in the nonloading group (P=0.26). Both the loading and nonloading groups achieved 69% dry macula. The number of injections received was significantly higher in the loading group (7.6 ± 0.6 vs. 6.8 ± 0.4, P < 0.001). Two patients (4.2%) developed intraocular inflammation. Switching to brolucizumab from aflibercept for eyes with nAMD with resistance to bimonthly injections of aflibercept is a valuable treatment option with and without the loading regimen. This trial is registered with UMIN000023676.

Does high dose statin pretreatment affect global strains in patients undergoing valve replacement.

To study the effect of rosuvastatin 40mg (initiated 7days prior to surgery) in patients undergoing valve replacement (VR) for rheumatic mitral valve disease on left ventricular (LV) strain and biomarker release kinetics. In this randomized study, cardiac biomarkers viz. troponin I (TnI), Creatine kinase MB (CK-MB), N-terminal pro B-type natriuretic peptide (NTPBNP) were measured before surgery; and 8, 24 and 48h postoperatively. Global LV (circumferential, global circumferential strain (GCS); longitudinal, GLS; radial, global radial strain (GRS)) strains were measured preoperatively; and 48h and 30days postoperatively. Following VR, Global Longitudinal Strain (GLS), Global Circumferential Strain (GCS) and Global Radial Strain (GRS) declined at 48h in both statin loaded (SL) and non loaded (NL) groups. The %decline in strain was significantly lower in SL group (% change in GLS 35.8% vs 38.8%, GCS 34% vs 44.1%, GRS 45.7% vs 52.6%; p < 0.001).All strain values improved at 30days with higher improvement in SL group (GLS -15.92 ± 2.00% vs -12.6 ± 1.66%, GCS -15.12 ± 2.93% vs -13.04 ± 2.44%; GRS 22.12 ± 6.85% vs 19.32 ± 6.48%). While TnI, CKMB, NTPBNP increased following surgery, values at 8, 24 and 48h were lower in the SL vs. NL group. Mean change (baseline to peak biomarker value) was also significantly lower in SL group.The SL group had shorter hospital and Intensive Care Unit (ICU) stay. On Receiver Operating Characteristic Curve (ROC) analysis, baseline GCS ≤ 14% best predicted postoperative 30day Left Ventricular Ejection Fraction (LVEF) ≤ 50%. Pre-operative high dose rosuvastatin was "cardioprotective" with favorable effect on LV global strain and release kinetics of biomarkers. These cut-offs (described for the first time for rheumatic VR) can be used as prognostic predictors.

Efficacy of Treatment with and without Initial Clopidogrel Loading in Branch Atheromatous Disease.

Objective Despite aggressive therapeutic interventions during the acute phase of branch atheromatous disease (BAD)-type cerebral infarction, many patients, even those with a mild condition at the onset, experience neurological deterioration after hospitalization and develop serious deficits. We compared the therapeutic efficacy of multiple antithrombotic therapies for BAD between patients who received a clopidogrel loading dose (loading group; LG) and those without loading (non-loading group; NLG). Patients Between January 2019 and May 2022, patients with BAD-type cerebral infarction in the lenticulostriate artery admitted within 24 h of the onset were recruited. This study included 95 consecutive patients who received combination argatroban and dual antiplatelet therapy (aspirin and clopidogrel). Methods Patients were classified into the LG and NLG according to whether or not a loading dose of clopidogrel (300 mg) had been administered on admission. Changes in neurological severity [National Institutes of Health Stroke Scale (NIHSS) score] during the acute phase were retrospectively evaluated. Results There were 34 (36%) and 61 (64%) patients in the LG and NLG, respectively. On admission, the median NIHSS score was similar between the groups [LG: 2.5 (2-4) vs. NLG: 3 (2-4), p=0.771]. At 48 h following admission, the median NIHSS scores were 1 (0.25-4), and 2 (1-5) in the LG and NLG, respectively (p=0.045). Early neurological deterioration (END; defined as worsening of the NIHSS score by ≥4 points at 48 h after admission) occurred in 3% of LG and 20% of NLG patients (p=0.028). Conclusion Administration of a clopidogrel loading dose with combination antithrombotic therapy for BAD reduced END.

The necessity of a loading dose when prescribing intravenous colistin in critically ill patients with CRGNB-associated pneumonia: a multi-center observational study

BackgroundThe importance or necessity of a loading dose when prescribing intravenous colistin has not been well established in clinical practice, and approximate one-third to half of patients with carbapenem-resistant gram-negative bacteria (CRGNB) infection did not receive the administration of a loading dose. The aim of this study is to investigate the efficacy and risk of acute kidney injury when prescribing intravenous colistin for critically ill patients with nosocomial pneumonia caused by CRGNB.MethodsThis was a multicenter, retrospective study that recruited ICU-admitted patients who had CRGNB-associated nosocomial pneumonia and were treated with intravenous colistin. Then, we classified the patients into colistin loading dose (N = 85) and nonloading dose groups (N = 127). After propensity-score matching for important covariates, we compared the mortality rate, clinical outcome and microbiological eradication rates between the groups (N = 67).ResultsThe loading group had higher percentages of patients with favorable clinical outcomes (55.2% and 35.8%, p = 0.037) and microbiological eradication rates (50% and 27.3%, p = 0.042) at day 14 than the nonloading group. The mortality rates at days 7, 14 and 28 and overall in-hospital mortality were not different between the two groups, but the Kaplan–Meier analysis showed that the loading group had a longer survival time than the nonloading group. Furthermore, the loading group had a shorter length of hospital stay than the nonloading group (52 and 60, p = 0.037). Regarding nephrotoxicity, there was no significant difference in the risk of developing acute kidney injury between the groups.ConclusionsThe administration of a loading dose is recommended when prescribing intravenous colistin for critically ill patients with nosocomial pneumonia caused by CRGNB.

Effects of repetitive insertion/removal cycles and simulated occlusal loads on retention of denture retainers.

The purpose of this study was to investigate the effects of repetitive insertion/removal cycle tests on denture retainers with simulated occlusal loads on the retentive force and deformation of clasp. Abutment teeth in the form of mandibular secondary premolars and clasp in the form of Akers clasps were prepared. The retentive force of the clasp on the abutment teeth were evaluated before and after undergoing repetitive insertion/removal cycle tests with or without cyclic loading. Changes in the clasp shape were monitored using a 3D scanner and scanning electron microscope. The initial retentive force was approximately 10 N and this value later decreased due to deformation of the clasp tips. In contrast to the non-load group, the load group exhibited a reduction in retentive force during earlier stages. Therefore, cyclic loading was related to a decrease in retentive forces, specifically in the early stages of repetitive insertion/removal cycles.

Impact of a computerised clinical decision support system on vancomycin loading and the risk of nephrotoxicity

BackgroundA vancomycin loading dose is recommended for the treatment of serious methicillin-resistant Staphylococcus aureus (MRSA) infections. However, clinicians often do not adhere to these recommendations, mainly due to nephrotoxicity risk, unfamiliarity with the guideline, or complexity of calculating an individual dose. Therefore, we introduced a computerised clinical decision support system (CDSS) for vancomycin loading (hereafter Vancomycin CDSS) to promote the use of vancomycin loading dose. MethodsWe describe a quasi-experimental study spanning 6 months before and 18 months after the deployment of a Vancomycin CDSS. The Vancomycin CDSS was integrated into the hospital’s electronic medical record system in the form of a vancomycin order set. Our primary endpoint was the incidence of nephrotoxicity; the secondary endpoint was mean initial vancomycin trough levels. We also conducted a survey to evaluate the reasons why clinicians opted not to utilise a vancomycin loading dose. ResultsAfter implementation of Vancomycin CDSS, 363 out of 746 patients (49 %) who were first administered vancomycin received a loading dose. We did not find significant differences in nephrotoxicity between the pre- and post-intervention groups, nor between the loading- and non-loading groups. In the pre-intervention group, the mean initial vancomycin trough level was 7.10 mg/L, which was significantly lower than that in the post-intervention group of 11.11 mg/L. In the vancomycin loading group, the mean initial trough level was 11.95 mg/L, compared to 7.55 mg/L in the non-loading group. The main reason stated for not prescribing a vancomycin loading dose was concern about nephrotoxicity. ConclusionIntroduction of the Vancomycin CDSS did not increase nephrotoxicity and increased the mean initial dose and trough level of vancomycin.

Effect of statin on perioperative myocardial injury in isolated valve surgery.

Statins have known pleiotropic effects that confer protection from ischemia-reperfusion injury. Because cardiopulmonary bypass is a potentially reversible ischemia-reperfusion sequence, we aimed to assess whether statin loading could help to limit myocardial injury in patients undergoing isolated heart valve replacement under cardiopulmonary bypass. One hundred patients with rheumatic valvular heart disease undergoing valve replacement received either a loading dose of rosuvastatin (40 mg initiated 7 days before surgery; loaded group) or no statins (non-loaded group). Cardiac troponin I, creatine kinase MB, and brain natriuretic peptide were measured at 8, 24, and 48 hours postoperatively. The primary endpoint was the extent of perioperative myocardial injury measured by the area under the curve for each biomarker. Despite similar baseline levels, all biomarkers at 8, 24, and 48 h were significantly lower in the loaded group. The area under the curve of each biomarker was significantly lower in the loaded group than in the non-loaded group (troponin I: 31.43 vs. 77.21 ng·h·mL-1, creatine kinase MB 309.31 vs. 429.12 ng·h·mL-1, brain natriuretic peptide 5176.11 vs. 16119.31 pg·h·mL-1, all p < 0.001). The mean changes from baseline to peak levels were also significantly lower in the loaded group. The loaded group had a shorter hospital stay but no significant difference was seen in ventilator time, inotrope time, aortic crossclamp time, cardiopulmonary bypass time, or intensive care unit stay. In patients undergoing valve replacement, high-dose statin loading before surgery had a favorable impact on the release kinetics of various cardiac biomarkers.

MiR-34a affects G2 arrest in prostate cancer PC3 cells via Wnt pathway and inhibits cell growth and migration.

To investigate the effect and mechanism of miRNA-34a overexpression on proliferation and migration of PC3 prostate cancer cells. Benign prostatic hyperplasia tissue (30 cases), prostate cancer tissue (30 cases), and prostate paracancerous tissue (30 cases) were collected. Levels of miRNA-34a in these fresh tissues were measured by fluorescence quantitative PCR. PC3 cells were divided into non-loaded group and overexpression group. Cells in the non-loaded group were transfected with non-loaded plasmid. Cells in the overexpression group were transfected with miRNA-34a plasmid, and the miRNA-34a level was determined by fluorescence quantitative PCR to confirm the overexpression. Cell proliferation was analyzed by CCK-8 assay. Cell migration rate was measured by cell scratch assay. Flow cytometry was used to detect apoptosis and analyze cell cycle. Western blot was used to measure the expression levels of β-catenin, E-cadherin and Vimentin. The expression level of miRNA-34a in prostate cancer tissue was significantly lower than that in prostate paracancerous tissue. Dual-Luciferase reporter gene assay was used to analyze the transcriptional activity of Wnt1 gene. The proliferation and migration of PC3 cells were significantly decreased after overexpression of miRNA-34a, and the differences were statistically significant compared with those in the non-loaded group (p<0.05). Flow cytometry analysis showed that in the overexpression group, the apoptotic rate, as well as the proportion of cells in the G2 phase, was significantly higher than that in the non-loaded group (p<0.05). The β-catenin level in the nucleus of PC3 cells was significantly reduced after overexpression of miRNA-34a. The total protein levels of β-catenin and Vimentin were significantly decreased, whereas the level of E-cadherin in the overexpression group was apparently increased, compared with that in the non-loaded group. The Dual-Luciferase reporter gene showed a decrease in the relative fluorescence intensity of Wnt1 after overexpression of miR-34a (p<0.05). Overexpression of miRNA-34a inhibits Wnt/β-catenin pathway by regulating the transcriptional activity of Wnt1, thereby regulating the proliferation and migration of PC3 cells and promoting apoptosis.

Effects of immediately static loading on osteointegration and osteogenesis around 3D-printed porous implant: A histological and biomechanical study.

The 3D-printed porous implant is capable of achieving favorable osteointegration and osteogenesis in the absence of mechanical stimulation during the early healing period. The purpose of this study is to evaluate the impact of immediately static loading on bone osteointegration and osteogenesis around the 3D-printed porous implant. Thirty porous implants with optimal configuration were installed bilaterally into femurs of 15 rabbits. The Load group on the left side was applied the maximal initial load of 10 N offered by a diminutive and built-in loading device and the Non-load group was on the contralateral side. At 2, 4, and 8 weeks post-operatively, the explants were harvested for push-out test to measure the biological fixation strength. The quantity and quality of new bone were evaluated by the means of histological examination, Micro-CT and bone density analysis. Moreover, the animal data were integrated into finite element models to assess the biomechanics of peri-implant bone. The results indicated that the quantity, quality and biomechanical properties of the new bone increased and optimized along with the healing time. It also demonstrated that the immediately static loading increased the volume of new bone with inferior quality in 2 weeks after implantation and the adverse influence emerged gradually as time extended. Moreover, finite element results demonstrated that the early structures of new bone around porous implant were not suitable for functional loading. This study indicated the mineralization modes of distance osteogenesis and contact osteogenesis around the porous implant. Accordingly, the delay and progressive loading protocol was recommended.

Evaluating the optimal dose of teicoplanin with therapeutic drug monitoring: not too high for adverse event, not too low for treatment efficacy.

Therapeutic drug monitoring (TDM) of teicoplanin is aimed at minimizing the clinical impact of pharmacokinetic variability; however, its benefits are still being defined. We performed a retrospective study of teicoplanin TDM focusing on the dose-serum concentration relationship and clinical outcomes in a clinical setting. From January 2017 to December 2018, patients receiving teicoplanin ≥ 72h with TDM were enrolled. Patients were divided into three groups: non-loading (NL) group, low-dose loading (LD) group (loading dose < 9mg/kg), and high-dose loading (HD) group (≥ 9mg/kg). Serum teicoplanin trough concentration (Cmin) and adverse events (AEs) were evaluated in each regimen. A subgroup of patients with bacteremia was analyzed to evaluate clinical efficacy. Among 65 patients, 12, 18, and 35 were grouped in NL, LD, and HD, respectively. Achievement rates of Cmin > 20mg/L within 10days were significantly different among the groups (25.0%, 38.9%, and 68.6% in the NL, LD, and HD groups, respectively; P = 0.014). Fourteen patients (21.5%) had AEs, and higher Cmin over 10days (adjusted odds ratio 2.08 per every 20mg/L increases, 95% CI 1.13-3.84, P = 0.019) and age ≥ 65years (P = 0.009) were identified as independent risk factors. In the subgroup analysis, HD regimen (P = 0.050) and high mean Cmin over 10days (P = 0.025) were significantly associated with treatment success. Although HL regimen could achieve Cmin targets and improve clinical outcome during teicoplanin treatment, high Cmin was associated with AEs during treatment. Routine TDM can be helpful to optimize teicoplanin administration.

Ankle loading ameliorates bone loss from breast cancer-associated bone metastasis.

Breast cancer is a serious health problem that preferentially metastasizes to bone. We have previously shown that bone loss can be prevented by mechanical loading, but the efficacy of ankle loading for metastasis-linked bone loss has not been investigated. This study showed that body weight was decreased after inoculation of tumor cells, but ankle loading restored a rapid weight loss. The nonloading group exhibited a decrease in bone volume/tissue volume (BV/TV), trabecular thickness, and trabecular number (all P < 0.01) as well as an increase in trabecular separation (P < 0.001). However, ankle loading improved those changes (all P < 0.05). Furthermore, although the nonloading group increased the tumor bearing as well as expression of IL-8 and matrix metalloproteinase 9, ankle loading decreased them. Induction of tumor in the bone elevated the osteoclast number (P < 0.05) as well as the levels of nuclear factor of activated T-cells cytoplasmic 1, NF-κB ligand, cathepsin K, and serum tartrate-resistant acid phosphatase type 5b, but ankle loading reduced osteoclast activity and those levels (all P < 0.05). Tumor bearing was positively correlated with the osteoclast number (P < 0.01) and negatively correlated with BV/TV and the osteoblast number (both P < 0.01). Collectively, these findings demonstrate that ankle loading suppresses tumor growth and osteolysis by inhibiting bone resorption and enhancing bone formation.-Yang, S., Liu, H., Zhu, L., Li, X., Liu, D., Song, X., Yokota, H., Zhang, P. Ankle loading ameliorates bone loss from breast cancer-associated bone metastasis.

Abstract 17122: Cardioprotection With Proangiogenic Nanomaterials Formulated With CHIR99021 and FGF1

Introduction: We aimed at to investigate whether activation of both FGF1 and Wnt1 synergistically enhances angiogenesis and render the cardioprotection in hearts with post infarction LV remodeling. Materials and methods: CHIR99021 (a Wnt1 activator) and FGF1 were encapsulated into poly lactic-co-glycolic acid nanoparticles (CHIR99021/FGF1-NPs). Ischemic heart models were generated in C57BL/6 mice or Yorkshire swine by ligation of the left anterior descending coronary. The mice were randomly divided into 6 groups: Myocardial infarction (MI) Only (n=11), MI with nanoparticles (CHIR99021 or/and FGF1 loaded) injection (n=12, each), MI with non-loaded nanoparticles injection (n=11) and Sham group (n=10). The swine were divided into 3 groups: ischemic reperfusion injury (IRI) (n=4), IRI with CHIR99021/FGF-NPs injection (n=4) and Sham group (n=4). Left ventricle function 4 week after surgery were evaluated by Echocardiography. Cell proliferation was assessed via immunostaining in ischemic hearts and in cultivated human umbilical vein endothelial cells (HUVECs) and Human vascular smooth muscle cells (HVSMCs) using the following markers: Ki67, Brdu, PH3, and Aurora B. Apoptosis was determined with TUNEL staining. Cardiac fibrosis was evaluated via Sirius red and Fast green staining (mice) and magnetic resonance imaging (swine). Results: CHIR99021/FGF1-NPs treatment attenuated fibrosis and preserved heart contractile function in mice and swine models of postinfarction LV remodeling. The proportion of cells that expressed cell cycle markers (Ki67; BrdU; Aurora B and PH3) was significantly greater in CHIR99021+FGF1 treatment group than CHIR99021, FGF1 and PBS treatment group. The proportion of apoptotic cells was significantly smaller in CHIR99021+FGF1 treatment group than in groups of control, VEGF, CHIR99021, or FGF1 treatment alone. Conclusions: CHIR99021 and FGF synergistically activate cell cycle and reduce apoptosis, which accompanied by a significant improvement of cardiac function.

Mechanical Loading Improves Engineered Tendon Formation with Muscle-Derived Cells: An In Vivo Analysis.

The authors' previous study showed that muscle-derived cells could regenerate strong engineered tendon with better tissue structure. However, little was known about the mechanism of neotendon built by muscle-derived cells, and the development and maturation of the cells. The authors hypothesized that mechanical loading modulated this process. The aim of this study was to investigate whether mechanical loading could regulate muscle-derived cell-based engineered tendon formation and maturation. Muscle-derived cells were isolated, expanded, and seeded onto polyglycolic acid fibers that formed a cell-scaffold complex. After in vitro culture for 2 weeks, half of them were implanted without loading and the other half were sutured to mouse fascia that could provide a natural dynamic loading. At 12 and 24 weeks after implantation, histologic examinations, ultrastructure, and biomechanical characteristics were evaluated. Gross observation results showed that under mechanical loading, neotendon tissue could be generated with muscle-derived cells and the tissue structure became more mature with the increase of culture time. Well-organized aligned collagen fibers and elongated morphologic cells were observed on histologic examination under mechanical loading. In contrast, the nonload group failed to form neotendon, but formed disorganized fibrous tissue with significantly worse mechanical properties and poor collagen fibril structure. This study demonstrates that mechanical loading is indispensable in tendon tissue engineering with muscle-derived cells. Although muscle-derived cells have a potential advantage in neotendon regeneration, stress deprivation resulted in a distinctly inferior maturity level of engineered tendon.

Effects with and without clopidogrel loading treatment for acute ischemic cerebrovascular disease patients: A retrospective cohort study

Objectives We investigated the effectiveness of clopidogrel loading (CL) treatment compared with usual clopidogrel non-loading (NL) treatment for acute ischemic cerebrovascular disease. Methods We screened consecutive 1072 patients with ischemic cerebrovascular disease within 48 hours of symptom onset admitted to our hospital. Eligible patients were divided into the CL group (300 mg on day 1, followed by 50-75 mg once daily) and NL group (50-75 mg once daily). The incidence proportion of neurologic deterioration during hospitalization was compared between the 2 groups using logistic regression analysis. Results A total of 224 patients, 39 in CL group and 185 in NL group, were enrolled. The frequency of neurologic deterioration did not significantly differ between the 2 groups (risk ratio [95% confidence interval]: 1.47 [.88-2.46]). On the preset subgroup analysis according to stroke subtype, the frequency of neurologic deterioration in CL group was significantly higher in branch atheromatous disease (risk ratio: 2.44 [1.67-3.55]) and was not different statistically in transient ischemic attack (risk ratio: 0). The analysis adjusted by several confounders showed that the incidence proportion of neurologic deterioration was not significantly different in large artery atherosclerosis (adjusted odds ratio: 1.06 [.23-4.84]) as crude analysis. The incidence proportion of adverse events was not significantly different between the 2 groups. Conclusions The effect of CL therapy differed by stroke subtypes in preventing neurologic deterioration. CL therapy appeared to be ineffective in branch atheromatous disease. Therefore, the choice of CL therapy should carefully be made according to stroke subtypes.

Effects With and Without Clopidogrel Loading Treatment for Acute Ischemic Cerebrovascular Disease Patients: A Retrospective Cohort Study

We investigated the effectiveness of clopidogrel loading (CL) treatment compared with usual clopidogrel non-loading (NL) treatment for acute ischemic cerebrovascular disease. We screened consecutive 1072 patients with ischemic cerebrovascular disease within 48 hours of symptom onset admitted to our hospital. Eligible patients were divided into the CL group (300 mg on day 1, followed by 50-75 mg once daily) and NL group (50-75 mg once daily). The incidence proportion of neurologic deterioration during hospitalization was compared between the 2 groups using logistic regression analysis. A total of 224 patients, 39 in CL group and 185 in NL group, were enrolled. The frequency of neurologic deterioration did not significantly differ between the 2 groups (risk ratio [95% confidence interval]: 1.47 [.88-2.46]). On the preset subgroup analysis according to stroke subtype, the frequency of neurologic deterioration in CL group was significantly higher in branch atheromatous disease (risk ratio: 2.44 [1.67-3.55]) and was not different statistically in transient ischemic attack (risk ratio: 0). The analysis adjusted by several confounders showed that the incidence proportion of neurologic deterioration was not significantly different in large artery atherosclerosis (adjusted odds ratio: 1.06 [.23-4.84]) as crude analysis. The incidence proportion of adverse events was not significantly different between the 2 groups. The effect of CL therapy differed by stroke subtypes in preventing neurologic deterioration. CL therapy appeared to be ineffective in branch atheromatous disease. Therefore, the choice of CL therapy should carefully be made according to stroke subtypes.

Alignment of Biological Apatite c-Axis Under Functional Loading: A Preliminary Report.

To understand the bone modeling/remodeling process of functionally loaded implants by observing the alignment of the biological apatite (BAp) c-axis. Commercially available titanium implants with TiO2 grit-blasted surfaces were placed in the fourth premolar and the first molar of the beagle dog and were functionally loaded with casted crowns and were compared to the non-loaded controls. After being killed, the samples were subjected to histological observation and to a microbeam x-ray diffraction (μXRD) analysis with a transmission optical system to evaluate the preferential BAp c-axis alignment. The non-loaded group presented mostly nonoriented BAp c-axis around the implant, whereas for the loaded group, preferential alignment of BAp c-axis was observed along the loading direction of the implant suggesting that the Bap aligned itself based on the direction of the functional mechanical loading. The μXRD revealed that the c-axis orientation was perpendicular to the implant thread working against the functional loaded direction, which may contribute in designing an optimal implant macrogeometry.

In vitro mechanical analysis of complete-arch mandibular implant-supported fixed prostheses abutment screws after cyclic loading

Statement of problemClinicians question when to evaluate for worn or loose implant-supported retainer screws to prevent possible clinical complications. PurposeThe purpose of this study was to compare differences among initial and postdynamically loaded detorque values and identify physical structural changes of prosthetic retaining screws in a simulated implant-supported mandibular complete fixed prosthesis. Material and methodsNine groups and nonloaded controls comprising a 5-implant-supported, milled titanium framework were fabricated and assembled (screw torque 35 Ncm). Dynamic loading (20 to 220 N) was applied to simulate 2 years of oral function. After testing, screw detorque values were measured (ΔT, initial-detorque value). A scanning electron microscopic analysis of screw threads was used to assess physical changes. Data were analyzed by 2-way ANOVA to determine the influence of loading and implant position on ΔT (α=.05). ResultsΔT values of loaded and nonloaded groups were compared separately at each implant position and showed a significant difference only for the implant in the central position (P=.002). All positions were compared in terms of ΔT values separately for loaded and nonloaded conditions. A significantly higher ΔT was found in 1 cantilever area of the loaded group, whereas a significantly lower ΔT value was found in the central position in the nonloaded group. No statistically significant differences were found in physical changes between loading and nonloading or among implant positions. ConclusionsWhen delivering a multiimplant supported prosthesis, the application of dynamic loading and the sequence in which implant screws are tightened could influence the subsequent detorque value of a screw; they have no effect on the physical appearance of screws after extended function.

EFFECTS OF CULTURE PERIODS AND LOADING ON BIOMECHANICAL PROPERTIES OF SHEEP COLLAGEN FASCICLES

Soft tissues (e.g., tendon, skin, cartilage) change their dimensions and properties in response to applied mechanical stress/strain, which is called remodeling. Experimental studies using tissue cultures were performed to understand the biomechanical properties of collagen fascicles under mechanical loads. Collagen fascicles were dissected from sheep Achilles tendons and loaded under 1, 2, and 3 kg for 2, 4, and 6 days under culture. The mechanical properties of collagen fascicles after being loaded into the culture media were determined using tensile tester, and resultant stress–strain curves, tangent modulus, tensile strength, and strain at failure values were compared with those in a non-loaded and non-cultured control group of fascicles. The tangent modulus and tensile strength of the collagen fascicles increased with the increasing remodeling load after two days of culture. However, these values gradually decreased with the increasing culture period compared with the control group. According to the results obtained in this study, the mechanical properties of collagen fascicles were improved by loading at two days of culture, most likely due to the remodeling of collagen fibers. However, after a period of remodeling, local strains on the collagen fibrils increased, and finally, the collagen fibrils broke down, decreasing the mechanical properties of the tissue.

The effect of mechanical loading on osteogenesis of human dental pulp stromal cells in a novel in vitro model.

Tooth loss often results in alveolar bone resorption because of lack of mechanical stimulation. Thus, the mechanism of mechanical loading on stem cell osteogenesis is crucial for alveolar bone regeneration. We have investigated the effect of mechanical loading on osteogenesis in human dental pulp stromal cells (hDPSCs) in a novel in vitro model. Briefly, 1 × 10(7) hDPSCs were seeded into 1 ml 3% agarose gel in a 48-well-plate. A loading tube was then placed in the middle of the gel to mimic tooth-chewing movement (1 Hz, 3 × 30 min per day, n = 3). A non-loading group was used as a control. At various time points, the distribution of live/dead cells within the gel was confirmed by fluorescence markers and confocal microscopy. The correlation and interaction between the factors (e.g. force, time, depth and distance) were statistically analysed. The samples were processed for histology and immunohistochemistry. After 1-3 weeks of culture in the in-house-designed in vitro bioreactor, fluorescence imaging confirmed that additional mechanical loading increased the viable cell numbers over time as compared with the control. Cells of various phenotypes formed different patterns away from the reaction tube. The cells in the middle part of the gel showed enhanced alkaline phosphatase staining at week 1 but reduced staining at weeks 2 and 3. Additional loading enhanced Sirius Red and type I collagen staining compared with the control. We have thus successfully developed a novel in-house-designed in vitro bioreactor mimicking the biting force to enhance hDPSC osteogenesis in an agarose scaffold and to promote bone formation and/or prevent bone resorption.

Randomized controlled trial comparing efficacy between a vaginal misoprostol loading and non‐loading dose regimen for second‐trimester pregnancy termination

The aim of this study was to compare the efficacy of vaginal misoprostol loading dose regimen with non-loading dose regimen for termination of second-trimester pregnancy with live fetuses. A randomized controlled trial was conducted on pregnant women with a live fetus at 14-28 weeks. The patients were randomly allocated to receive either the vaginal misoprostol loading dose regimen (600 mcg, then 400 mcg every 6 h) or the non-loading dose regimen (400 mcg every 6 h). Failure to abort within 48 h was considered to be a failure. Of 157 recruited women, 77 were assigned to be in group 1 (loading group) and 80 were in group 2 (non-loading group). The median abortion time was not statistically different between the groups (14.08; 95% confidence interval: 12.45-17.77 h and 14.58; 95% confidence interval: 12.8-17.27 h, P > 0.05). The rates of abortion within 24 h and 48 h were also comparable between the groups. Fever and chills were more common in the loading group. No other serious complications, such as postpartum hemorrhage and uterine rupture, were found. Vaginal misoprostol in the loading dose regimen had a similar efficacy to the non-loading dose regimen but was associated with more adverse maternal effects.