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Abstract Background Targeting the tumor microenvironment represents an emerging therapeutic strategy for cancer. Macrophages are an essential part of the tumor microenvironment. Macrophage polarization is modulated by mitochondrial metabolism, including oxidative phosphorylation (OXPHOS), the tricarboxylic acid (TCA) cycle, and reactive oxygen species content. Isocitrate dehydrogenase 2 (IDH2), an enzyme involved in the TCA cycle, reportedly promotes cancer progression. However, the mechanisms through which IDH2 influences macrophage polarization and modulates tumor growth remain unknown. Methods In this study, IDH2-deficient knockout (KO) mice and primary cultured bone marrow-derived macrophages (BMDMs) were used. Both in vivo subcutaneous tumor experiments and in vitro co-culture experiments were performed, and samples were collected for analysis. Western blotting, RNA quantitative analysis, immunohistochemistry, and flow cytometry were employed to confirm changes in mitochondrial function and the resulting polarization of macrophages exposed to the tumor microenvironment. To analyze the effect on tumor cells, subcutaneous tumor size was measured, and growth and metastasis markers were identified. Results IDH2-deficient macrophages co-cultured with cancer cells were found to possess increased mitochondrial dysfunction and fission than wild-type BMDM. Additionally, the levels of M2-associated markers decreased, whereas M1-associated factor levels increased in IDH2-deficient macrophages. IDH2-deficient macrophages were predominantly M1. Tumor sizes in the IDH2-deficient mouse group were significantly smaller than in the wild-type mouse group. IDH2 deficiency in macrophages was associated with inhibited tumor growth and epithelial–mesenchymal transition. Conclusions Our findings suggest that IDH2 deficiency inhibits M2 macrophage polarization and suppresses tumorigenesis. This study underlines the potential contribution of IDH2 expression in macrophages and tumor microenvironment remodeling, which could be useful in clinical cancer research.

Abstract Oxidative stress plays an essential role in the progression of Alzheimer’s disease (AD), the most common age-related neurodegenerative disorder. Streptozotocin (STZ)-induced abnormal brain insulin signaling and oxidative stress play crucial roles in the progression of Alzheimer’s disease (AD)-like pathology. Peroxiredoxins (Prxs) are associated with protection from neuronal death induced by oxidative stress. However, the molecular mechanisms underlying Prxs on STZ-induced progression of AD in the hippocampal neurons are not yet fully understood. Here, we evaluated whether Peroxiredoxin 1 (Prx1) affects STZ-induced AD-like pathology and cellular toxicity. Prx1 expression was increased by STZ treatment in the hippocampus cell line, HT-22 cells. We evaluated whether Prx1 affects STZ-induced HT-22 cells using overexpression. Prx1 successfully protected the forms of STZ-induced AD-like pathology, such as neuronal apoptosis, synaptic loss, and tau phosphorylation. Moreover, Prx1 suppressed the STZ-induced increase of mitochondrial dysfunction and fragmentation by down-regulating Drp1 phosphorylation and mitochondrial location. Prx1 plays a role in an upstream signal pathway of Drp1 phosphorylation, cyclin-dependent kinase 5 (Cdk5) by inhibiting the STZ-induced conversion of p35 to p25. We found that STZ-induced of intracellular Ca2+ accumulation was an important modulator of AD-like pathology progression by regulating Ca2+-mediated Calpain activation, and Prx1 down-regulated STZ-induced intracellular Ca2+ accumulation and Ca2+-mediated Calpain activation. Finally, we identified that Prx1 antioxidant capacity affected Ca2+/Calpain/Cdk5-mediated AD-like pathology progress. Therefore, these findings demonstrated that Prx1 is a key factor in STZ-induced hippocampal neuronal death through inhibition of Ca2+/Calpain/Cdk5-mediated mitochondrial dysfunction by protecting against oxidative stress.

Abstract Mitochondria are essential organelles in cellular energy metabolism and other cellular functions. Mitochondrial dysfunction is closely linked to cellular damage and can potentially contribute to the aging process. The purpose of this study was to investigate the subcellular structure of mitochondria and their activities in various cellular environments using super-resolution stimulated emission depletion (STED) nanoscopy. We examined the morphological dispersion of mitochondria below the diffraction limit in sub-cultured human primary skin fibroblasts and mouse skin tissues. Confocal microscopy provides only the overall morphology of the mitochondrial membrane and an indiscerptible location of nucleoids within the diffraction limit. Conversely, super-resolution STED nanoscopy allowed us to resolve the nanoscale distribution of translocase clusters on the mitochondrial outer membrane and accurately quantify the number of nucleoids per cell in each sample. Comparable results were obtained by analyzing the translocase distribution in the mouse tissues. Furthermore, we precisely and quantitatively analyzed biomolecular distribution in nucleoids, such as the mitochondrial transcription factor A (TFAM), using STED nanoscopy. Our findings highlight the efficacy of super-resolution fluorescence imaging in quantifying aging-related changes on the mitochondrial sub-structure in cells and tissues.

Abstract The CRISPR-Cas nickase system for genome editing has attracted considerable attention owing to its safety, efficiency, and versatility. Although alternative effectors to Cas9 have the potential to expand the scope of genome editing, their application has not been optimized. Herein, we used an enhanced CRISPR-Cas12a nickase system to induce mutations by targeting genes in a human-derived cell line. The optimized CRISPR-Cas12a nickase system effectively introduced mutations into target genes under a specific directionality and distance between nickases. In particular, the single-mode Cas12a nickase system can induce the target-specific mutations with less DNA double-strand breaks. By inducing mutations in the Thymine-rich target genes in single- or dual-mode, Cas12a nickase compensates the limitations of Cas9 nickase and is expected to contribute to the development of future genome editing technologies.

Abstract The primary hallmark of Parkinson's disease (PD) is the generation of Lewy bodies of which major component is α-synuclein (α-Syn). Because of increasing evidence of the fundamental roles of α-Syn oligomers in disease progression, α-Syn oligomers have become potential targets for therapeutic interventions for PD. One of the potential toxicities of α-Syn oligomers is their inhibition of SNARE-mediated vesicle fusion by specifically interacting with vesicle-SNARE protein synaptobrevin-2 (Syb2), which hampers dopamine release. Here, we show that α-Syn monomers and oligomers cooperatively inhibit neuronal SNARE-mediated vesicle fusion. α-Syn monomers at submicromolar concentrations increase the fusion inhibition by α-Syn oligomers. This cooperative pathological effect stems from the synergically enhanced vesicle clustering. Based on this cooperative inhibition mechanism, we reverse the fusion inhibitory effect of α-Syn oligomers using small peptide fragments. The small peptide fragments, derivatives of α-Syn, block the binding of α-Syn oligomers to Syb2 and dramatically reverse the toxicity of α-Syn oligomers in vesicle fusion. Our findings demonstrate a new strategy for therapeutic intervention in PD and related diseases based on this specific interaction of α-Syn.

Humans are continuously exposed to benzisothiazolinone (BIT), which is used as a preservative, through multiple routes. BIT is known to be a sensitizer; in particular, dermal contact or aerosol inhalation could affect the local toxicity. In this study, we evaluated the pharmacokinetic properties of BIT in rats following various routes of administration. BIT levels were determined in rat plasma and tissues after oral inhalation and dermal application. Although the digestive system rapidly and completely absorbed orally administered BIT, it underwent severe first-pass effects that prevented high exposure. In an oral dose escalation study (5–50 mg/kg), nonlinear pharmacokinetic properties showed that Cmax and the area under the curve (AUC) increased more than dose proportionality. In the inhalation study, the lungs of rats exposed to BIT aerosols had higher BIT concentrations than the plasma. Additionally, the pharmacokinetic profile of BIT after the dermal application was different; continuous skin absorption without the first-pass effect led to a 2.13-fold increase in bioavailability compared with oral exposure to BIT. The [14C]-BIT mass balance study revealed that BIT was extensively metabolized and excreted in the urine. These results can be used in risk assessments to investigate the relationship between BIT exposure and hazardous potential.

Abstract Chiral organic ligand‐incorporated low‐dimensional metal‐halide perovskites have received increasing attention for next‐generation photodetectors because of the direct detection capability of circularly polarized light (CPL), which overcomes the requirement for subsidiary optical components in conventional CPL photodetectors. However, most chiral perovskites have been based on low‐dimensional structures that confine chiroptical responses to the ultraviolet (UV) or short‐wavelength visible region and limit photocurrent due to their wide bandgap and poor charge transport. Here, chiroptical properties of 3D Cs0.05FA0.5MA0.45Pb0.5Sn0.5I3 polycrystalline films are achieved by incorporating chiral plasmonic gold nanoparticles (AuNPs) into the mixed PbSn perovskite, without sacrificing its original optoelectronic properties. CPL detectors fabricated using chiral AuNP‐embedded perovskite films can operate without external power input; they exhibit remarkable chirality in the near‐infrared (NIR) region with a high anisotropy factor of responsivity (gres) of 0.55, via giant plasmon resonance shift of chiral plasmonic AuNPs. In addition, a CPL detector array fabricated on a plastic substrate demonstrates highly sensitive self‐powered NIR detection with superior flexibility and durability.

The hemiparkinsonian nonhuman primate model induced by unilateral injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into the carotid artery is used to study Parkinson’s disease. However, there have been no studies that the contralateral distribution of MPTP via the cerebral collateral circulation is provided by both the circle of Willis (CoW) and connections of the carotid artery. To investigate whether MPTP-induced unilaterally damaged regions were determined by asymmetrical cerebral blood flow, the differential asymmetric damage of striatal subregions, and examined structural asymmetries in a circle of Willis, and blood flow velocity of the common carotid artery were observed in three monkeys that were infused with MPTP through the left internal carotid artery. Lower flow velocity in the ipsilateral common carotid artery and a higher ratio of ipsilateral middle cerebral artery diameter to anterior cerebral artery diameter resulted in unilateral damage. Additionally, the unilateral damaged monkey observed the apomorphine-induced contralateral rotation behavior and the temporary increase of plasma RANTES. Contrastively, higher flow velocity in the ipsilateral common carotid artery was observed in the bilateral damaged monkey. It is suggested that asymmetry of blood flow velocity and structural asymmetry of the circle of Willis should be taken into consideration when establishing more efficient hemiparkinsonian nonhuman primate models.

Transcription and translation are coupled in bacteria. Here, the authors show that the movement of a gene locus to the nucleoid periphery correlates with transcription, and the effect is potentiated by translation.

We studied the impact of grain boundary (GB) protrusion on the electrical properties of low temperature polycrystalline silicon thin film transistors. The analysis of atomic force microscopy and transmission electron microscopy images indicate the grain size of ~350 nm and a protrusion height of ~35 nm. The transfer and output characteristics are well fitted by technology computer-aided design using two different density of states for poly-Si grain and GB, respectively. From 2-D contour mapping, a drastic reduction of hole concentration (~5 x 1016 cm-3) at GB protrusion site was obtained as compared to the grain (~3 x 1018 cm-3). Trapping concentration at GB is much higher, which leads to the reduction in the mobility.

A 47-year-old nulliparous, virginal woman presented to the emergency department with acute abdominal pain. Emergency pelvic ultrasound and abdominal CT were taken, which showed a significant amount of hemoperitoneum and a bicornuate uterus with about 18cm x 10cm mass on left uterus. Since the mass had increased vascularity and irregular margins, we thought that the mass could be a uterine sarcoma. MRI and PET/CT were taken additionally for oncologic evaluation before surgery. Intra operative findings showed a ruptured bicornuate uterus with a large mass within the left uterine horn. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed. Pathologic analysis confirmed an undifferentiated uterine sarcoma. She was treated with 6 cycles of chemotherapy(etoposide, ifosfamide, cisplatin) postoperatively. Chest and abdomen CT for follow up after chemotherapy showed no sign of cancer recurrence. We suggest a bicornuate uterus with concomitant sarcoma should be concerned as a possible cause of uterine rupture by reviewing this case.

Non-alcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver disease globally. NAFLD—which can develop into liver fibrosis, nonalcoholic steatohepatosis, cirrhosis, and hepatocellular carcinoma—is defined as an excess accumulation of fat caused by abnormal lipid metabolism and excessive reactive oxygen species (ROS) generation in hepatocytes. Recently, we reported that Peroxiredoxin 5 (Prx5) plays an essential role in regulating adipogenesis and suggested the need to further investigation on the potential curative effects of Prx5 on obesity-induced fatty liver disease. In the present study, we focused on the role of Prx5 in fatty liver disease. We found that Prx5 overexpression significantly suppressed cytosolic and mitochondrial ROS generation. Additionally, Prx5 regulated the AMP-activated protein kinase pathway and lipogenic gene (sterol regulatory element binding protein-1 and FAS) expression; it also inhibited lipid accumulation, resulting in the amelioration of free fatty acid-induced hepatic steatosis. Silence of Prx5 triggered de novo lipogenesis and abnormal lipid accumulation in HepG2 cells. Concordantly, Prx5 knockout mice exhibited a high susceptibility to obesity-induced hepatic steatosis. Liver sections of Prx5-deletion mice fed on a high-fat diet displayed Oil Red O-stained dots and small leaky shapes due to immoderate fat deposition. Collectively, our findings suggest that Prx5 functions as a protective regulator in fatty liver disease and that it may be a valuable therapeutic target for the management of obesity-related metabolic diseases. Keywords: Peroxiredoxin 5, Hepatic steatosis, NAFLD, ROS, AMPK, SREBP-1

Hydrogels containing colorimetric nanoparticles have been used for ion sensing, glucose detection, and microbial metabolite analyses. In particular, the rapid chemical reaction owing to both the hydrogel form of water retention and the sensitive color change of nanoparticles enables the rapid detection of target substances. Despite this advantage, the poor dispersibility of nanoparticles and the mechanical strength of nanoparticle–hydrogel complexes have limited their application. In this study, we demonstrate a milliliter agarose gel containing homogeneously synthesized polyaniline nanoparticles (PAni-NPs), referred to as PAni-NP–hydrogel complexes (PNHCs). To fabricate the optimal PNHC, we tested various pH solvents based on distilled water and phosphate-buffered saline and studied the colorimetric response of the PNHC with thickness. The colorimetric response of the prepared PNHC to the changes in the pH of the solution demonstrated excellent linearity, suggesting the possibility of using PNHC as a pH sensor. In addition, it was verified that the PNHC could detect minute pH changes caused by the cancer cell metabolites without cytotoxicity. Furthermore, the PNHC can be stably maintained outside water for approximately 12 h without deformation, indicating that it can be used as a disposable patch-type wearable biosensing platform.

Abstract Background Mounting evidence shows that ROS regulation by various antioxidants is essential for the expression of enzymes involved in steroidogenesis and maintenance of progesterone production by the corpus luteum (CL). However, the underlying mechanisms of peroxiredoxin 1 (PRDX1), an antioxidant enzyme, in luteal function for progesterone production in mice have not been reported. The aim of this study was to evaluate the functional link between PRDX1 and progesterone production in the CL of Prdx1 knockout (K/O) mice in the functional stage of CL. Methods The expression pattern of the unfolded protein response (UPR) signaling pathways, endoplasmic reticulum (ER) stress-induced apoptosis related genes and peroxiredoxins 1 (PRDX1) were investigated by western blotting analysis in CL tissue of 10 weeks mice during functional stage of CL. The protein levels of these genes after ER-stress inducer tunicamycin (Tm), ER-stress inhibitor tauroursodeoxycholic acid (TUDCA) and ROS scavenger, N-acetylcysteine (NAC) stimulation by intraperitoneal (i.p) injection were also investigated in CL tissue of wild type (WT) mice. Finally, we examined progesterone production and UPR signaling related gene expression in CL tissue of Prdx1 K/O mice. Results We demonstrated that PRDX1 deficiency in the functional stage activates the UPR signaling pathways in response to ER stress-induced apoptosis. Interestingly, CL number, serum progesterone levels, and steroidogenic enzyme expression in Prdx1 K/O mice decreased significantly, compared to those in wild type mice. Levels of UPR signaling pathway markers (GRP78/BIP, P50ATF6, and phosphorylated (p)-eIF2) and ER-stress associated apoptotic factors (CHOP, p-JNK, and cleaved caspase-3) were dramatically increased in the CL tissue of Prdx1 K/O mice. In addition, administration of the NAC, reduced progesterone production and activated ER-stress-induced UPR signaling in the CL tissue obtained from the ovary of Prdx1 K/O mice. Taken together, these results indicated that reduction in serum progesterone levels and activation of ER-stress-induced UPR signaling are restored by NAC injection in the CL of Prdx1 K/O mice. Conclusion These observations provide the first evidence regarding the basic mechanisms connecting PRDX1 and progesterone production in the functional stage of CL.

Descending necrotizing mediastinitis (DNM) is a rare form of mediastinal infection. Most cases are associated with esophageal rupture. DNM after a trigger point injection in the upper trapezius has not been described previously. We present a case of DNM after a trigger point injection in the upper trapezius. A 70-year-old man visited the emergency department with chest discomfort and fever after a trigger point injection in the left upper trapezius. Chest computed tomography showed evidence of DNM, and antibiotic therapy was immediately administered intravenously. Because of the risk of sudden death, poor prognosis due to underlying disease, and his age, he declined surgical treatment and died of septic shock. Although trigger point injections are generally considered safe, caution should be used in patients with an underlying disease or in the elderly. Early diagnosis, broad-spectrum antibiotics, and aggressive surgical management are essential to improve the prognosis.

ObjectiveThis study aimed to show the epidemiological characteristics and the difference in the risk factors and types of collision between older and younger drivers in Korea.MethodsWe collected data from the Emergency Department-based Injury In-depth Surveillance retrieved by the Korea Centers for Disease Control and Prevention from 2011 to 2015. We included injured drivers aged ≥ 18 years who were registered in the database, who were limited to drivers of four-wheeled vehicles. The enrolled patients were divided according to age into older (≥ 65 years) and younger (< 65 years) drivers. The total number of enrolled drivers was 37,511; 2,361 (6.3%) of them were older drivers. The epidemiological characteristics (e.g., age, sex, fatality rate) of traffic collision victims for 5 years were determined, and the risk factors (e.g., seat belt use) and types of collision (single- vs. multi-vehicle) between the two groups were compared.ResultsThe median age and interquartile range (IQR; 25th and 75th percentiles) of all drivers were 41.0 (IQR, 32.0-52.0), and 24,544 (65.4%) of them were men. The median age increased from 40.0 (IQR, 31.0-50.0) to 43.0 (IQR, 33.0-54.0) between 2010 and 2015 (P < 0.001). The proportion of older drivers increased from 5.0% to 8.4% annually during the study period (P < 0.001). Between 2010 and 2015, the fatality rate decreased from 3.1% to 1.2% (P = 0.287) for older drivers and from 0.9% to 0.5% (P = 0.009) for younger drivers. The proportion of single-vehicle collision (25.9% vs. 20.3%) was higher in older than in younger drivers (P < 0.001). Older drivers had a lower rate of seat-belt use than younger drivers (79.0% vs. 83.0%, P < 0.001).ConclusionsThe proportion of older drivers increased annually during the study period, and older drivers experienced more single-vehicle collision and used seat belt less frequently than younger drivers. A national policy support to reduce traffic collision in older drivers and public relation activities to enhance their seat belt use should be strengthened in the future.

BackgroundNationwide and regional interventions can help improve bystander cardiopulmonary resuscitation (CPR) awareness, knowledge, and the willingness. Periodic community investigation will help monitor the effect. This study aimed to compare the experience of CPR education, CPR knowledge, and CPR willingness, during a 5-year interval.MethodsThis is a pre and post study. Two surveys were done in February 2012 and December 2016. National and regional intervention including legislation promoting public involvement, standardizing CPR education programs, training CPR instructors, and installing supporting organizations were done at the period. In both surveys, respondents were selected via quota sampling in Daegu Metropolitan City and answered the survey through face-to-face interview. Respondents' general demographic characteristics, CPR educational experience, CPR knowledge and CPR willingness were questioned.ResultsTotal of 2141 respondents (1000 in 2012, 1141 in 2016) were selected. The percentage of respondents who received CPR education itself and recent education were higher after intervention compared to before intervention (36.2% vs. 55.1%, 16.9% vs. 30.1%, respectively). Correct knowledge of performing CPR seems to be improved overall (1.6% vs. 11.7%, odd ratio 14.28, 95% confidence interval 5.68-35.94). However, less respondents were willing to perform CPR on strangers (54.5% vs 35.0%).ConclusionNationwide and regional interventions to promote bystander CPR and CPR education were associated with increased CPR education experience and improved correct CPR knowledge in performing bystander CPR. Willingness to perform bystander CPR on family did not increase significantly and CPR willingness to strangers was decreased. Additional legal and technological measures should be implemented to promote bystander CPR.

Microsupercapacitors have attracted significant attention due to several of their advantageous characteristics such as lightweight, small volume, and planar structure that is favorable for high mechanical flexibility. Among the various micro supercapacitor forms, those with laser-induced graphene (LIG) electrodes are promising as flexible energy storage devices. While LIG microelectrodes can be fabricated simply by direct laser writing, the capacitance and energy density of these devices are limited because of the relatively low density of LIG, which leads to low surface areas. These limitations could be overcome by densifying the LIG. Here, we report the use of densified laser-induced graphene (d-LIG) to fabricate flexible micro supercapacitors. Interdigitated d-LIG electrodes were prepared by duplicate laser pyrolysis of a polyimide sheet by using a CO2 laser. A PVA-H2SO4 gel-type electrolyte was then applied to the d-LIG electrode surface to assemble a d-LIG micro supercapacitor. This d-LIG micro supercapacitor exhibited substantially increased capacitance and energy density versus conventional low-density LIG micro supercapacitors. While the d-LIG electrode exhibited a substantial change in resistance when subjected to bending at a radius of 3 mm, the change in the capacitance of the d-LIG micro supercapacitor was negligible at the same bending radius due to reinforcement by the infiltrated poly(vinyl alcohol) (PVA) electrolyte, demonstrating the potential application of d-LIG micro supercapacitors in wearable electronics.

Introduction: Increase in life expectancy across the globe has led to rise in geriatric population. Geriatric population is now living longer and healthier. This rise in geriatric population has also led to increase in the geriatric ailments leading to increased number of geriatric patients requiring intensive care including mechanical ventilation. Data on outcomes of geriatric patients requiring mechanical ventilation from India is scarce. Aim: To study the profile and outcome of geriatric patients more than equal to 60 years requiring mechanical ventilation in Intensive Care Unit (ICU). Materials and Methods: The data of all the geriatric patients, more than 60 years of age, admitted to ICU between January 2008 to August 2014 requiring mechanical ventilation for various reasons were extracted from the hospital records. Various reasons for ventilation, duration of ventilation/hospital stay, mortality and associated comorbidities were recorded and analysed. Results: Total 140 geriatric patients were mechanically ventilated in the study period, out of which 43.5% (61/140) were above 70 years of age and 67.8% (95/140) were above 65 years of age. Chronic Obstructive Pulmonary Disease (COPD) was the most common cause for mechanical ventilation constituting 20% of patients followed by severe sepsis (17.8%), cerebrovascular accident (12.8%), post-surgical patients (12.8%) and Coronary Artery Disease (CAD) in 10%. In our study, 44.28% of the geriatric patients requiring mechanical ventilation in the ICU were successfully weaned off the ventilator. Early tracheostomy helped in weaning off from ventilator as 83.33% (5/6) of patients requiring tracheostomy could be weaned off the ventilator suggesting that tracheostomy may help in improving the outcome. Reintubation carried a very poor prognosis and increased mortality, as 80% (4/5) of the patients who were reintubated in our study could not survive. Conclusion: Our study revealed that in appropriate intensive care setting and with standard protocol based therapy for primary ailments, outcomes with mechanical ventilation in geriatric population can be comparable to outcomes in younger population.

ObjectiveTherapeutic hypothermia (TH) has become the standard strategy for reducing brain damage in the postresuscitation period. The aim of this study was to investigate current TH performance and outcomes in out-of-hospital cardiac arrest (OHCA) survivors using data from the Korean Hypothermia Network (KORHN) registry. MethodsWe used the KORHN registry, a web-based multicenter registry that includes 24 participating hospitals throughout the Republic of Korea. Adult comatose OHCA survivors treated with TH between 2007 and 2012 were included. The primary outcomes were neurological outcome at hospital discharge and in-hospital mortality. The secondary outcomes were TH performance and adverse events during TH. ResultsA total of 930 patients were included, of whom 556 (59.8%) survived to discharge and 249 (26.8%) were discharged with good neurologic outcomes. The median time from return of spontaneous circulation (ROSC) to the start of TH was 101 minutes (interquartile range [IQR], 46 to 200 minutes). The induction, maintenance, and rewarming durations were 150 minutes (IQR, 80 to 267 minutes), 1,440 minutes (IQR, 1,290 to 1,440 minutes), and 708 minutes (IQR, 420 to 900 minutes), respectively. The time from the ROSC to coronary angiography was 1,045 hours (IQR, 121 to 12,051 hours). Hyperglycemia (46.3%) was the most frequent adverse event. ConclusionMore than one-quarter of the OHCA survivors (26.8%) were discharged with good neurologic outcomes. TH performance was appropriately managed in terms of the factors related to its timing, including cooling start time and rewarming duration.

Background: Anti-Program-Death-1 (PD-1) is a standard adjuvant therapy for patients with resected melanoma. We hypothesized that there are discrepancies in survival, recurrence pattern and toxicity to adjuvant PD-1 between different ethnicities and melanoma subtypes. Objective: We performed a multicenter cohort study incorporating 6 independent institutions in Australia, China, Japan, and the United States. The primary outcomes were recurrence free survival (RFS) and overall survival (OS). Secondary outcomes were disease recurrence patterns and toxicities. Results: In total 534 patients were included. East-Asian/Hispanic/African reported significantly poorer RFS/OS. Nonacral cutaneous or melanoma of unknown primary reported the best RFS/OS, followed by acral, and mucosal was the poorest. Within the nonacral cutaneous or melanoma of unknown primary subtypes, East-Asian/Hispanic/African reported significantly poorer RFS/OS than Caucasian. In the multivariate analysis incorporating ethnicity/melanoma-subtype/age/sex/stage/lactate dehydrogenase/BRAF (v-Raf murine sarcoma viral oncogene homolog B)-mutation/adjuvant radiotherapy, East-Asian/Hispanic/African had independently significantly poorer outcomes (RFS: HR, 1.71; 95% CI, 1.19-2.44 and OS: HR, 2.34; 95% CI, 1.39-3.95), as was mucosal subtype (RFS: HR, 3.25; 95% CI, 2.04-5.17 and OS: HR, 3.20; 95% CI, 1.68-6.08). Mucosal melanoma was an independent risk factor for distant metastasis, especially liver metastasis. East-Asian/Hispanic/African had significantly lower incidence of gastrointestinal/musculoskeletal/respiratory/other-rare-type-toxicities; but higher incidences of liver toxicities. Limitations: A retrospective study. Conclusions: Ethnicity and melanoma subtype are associated with survival and recurrence pattern in melanoma patients treated with adjuvant anti-PD-1. Toxicity profile differs by ethnicity and may require a precision toxicity surveillance strategy.

Despite the widespread use of the five major xanthophylls astaxanthin, β-cryptoxanthin, canthaxanthin, lutein, and zeaxanthin as dietary supplements, there have been no studies regarding their inhibitory effects on hepatic UDP-glucuronosyltransferases (UGTs). Here, we evaluated the inhibitory potential of these xanthophylls on the seven major human hepatic UGTs (UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, UGT2B7 and UGT2B15) in vitro by LC-MS/MS using specific marker reactions in human liver microsomes (except UGT2B15) or recombinant supersomes (UGT2B15). We also predicted potential dietary supplement-drug interactions for β-cryptoxanthin via UGT1A1 inhibition. We demonstrated that astaxanthin and zeaxanthin showed no apparent inhibition, while the remaining xanthophylls showed only weak inhibitory effects on the seven UGTs. β-Cryptoxanthin mildly inhibited UGT1A1, UGT1A3, and UGT1A4, with IC50 values of 18.8 ± 2.07, 28.3 ± 4.40 and 34.9 ± 5.98 μM, respectively. Canthaxanthin weakly inhibited UGT1A1 and UGT1A3, with IC50 values of 38.5 ± 4.65 and 41.2 ± 3.14 μM, respectively; and lutein inhibited UGT1A1 and UGT1A4, with IC50 values of 45.5 ± 4.01 and 28.7 ± 3.79 μM, respectively. Among the tested xanthophyll-UGT pairs, β-cryptoxanthin showed the strongest competitive inhibition of UGT1A1 (Ki, 12.2 ± 0.985 μM). In addition, we predicted the risk of UGT1A1 inhibition in vivo using the reported maximum plasma concentration after oral administration of β-cryptoxanthin in humans. Our data suggests that these xanthophylls are unlikely to cause dietary supplement-drug interactions mediated by inhibition of the hepatic UGTs. These findings provide useful information for the safe clinical use of the tested xanthophylls.

Abstract

Abstract Background Limited information is available regarding the effect of age on choice of surgical and oncological treatment for rectal cancer. The objective of this study was to assess the influence of age on treatment and outcome of rectal cancer. Methods We utilized data in the Swedish Rectal Cancer Registry (SRCR) from patients treated for rectal cancer in Sweden in 1995–2004. Results A total of 15,104 patients with rectal cancer were identified, 42.4% of whom were 75 years or older. Patients ≥75 years were less likely to have distant metastases than younger patients (14.8% vs. 17.8%, P < 0.001), and underwent abdominal tumor resection less frequently (68.5% vs. 84.4%, P < 0.001). Of 11,725 patients with abdominal tumor resection (anterior resection [AR], abdominoperineal excision [APE], and Hartmann's procedure [HA]), 37.4% were ≥75 years. Curative surgery was registered for 85.0% of patients ≥ 75 years and for 83.9% of patients < 75 years, P = 0.11. Choice of abdominal operation differed significantly between the two age groups for both curative and non-curative surgery, The frequency of APE was similar in both age groups (29.5% vs. 28.6%), but patients ≥75 years were more likely to have HA (16.9% vs. 4.9%) and less likely to have preoperative radiotherapy (34.3vs. 67.2%, P < 0.001). The relative survival rate at five years for all patients treated with curative intent was 73% (70–75%) for patients ≥75 years and 78% (77–79%) for patients < 75 years of age. Local recurrence rate was 9% (8–11%) for older and 8% (7–9%) for younger patients. Conclusion Treatment of rectal cancer is influenced by patient's age. Future studies should include younger and older patients alike to reveal whether or not age-related differences are purposive. Local recurrence following surgery for low tumors and quality of life aspects deserve particular attention.

Abstract Background Preoperative mechanical bowel preparation can be questioned as standard procedure in colon surgery, based on the result from several randomised trials. Methods As part of a large multicenter trial, 105 patients planned for elective colon surgery for cancer, adenoma, or diverticulitis in three hospitals were asked to complete a questionnaire regarding perceived health including experience with bowel preparation. There were 39 questions, each having 3 – 10 answer alternatives, dealing with food intake, pain, discomfort, nausea/vomiting, gas distension, anxiety, tiredness, need of assistance with bowel preparation, and willingness to undergo the procedure again if necessary. Results 60 patients received mechanical bowel preparation (MBP) and 45 patients did not (No-MBP). In the MBP group 52% needed assistance with bowel preparation and 30% would consider undergoing the same preoperative procedure again. In the No-MBP group 65 % of the patients were positive to no bowel preparation. There was no significant difference between the two groups with respect to postoperative pain and nausea. On Day 4 (but not on Days 1 and 7 postoperatively) patients in the No-MBP group perceived more discomfort than patients in the MBP group, p = 0.02. Time to intake of fluid and solid food did not differ between the two groups. Bowel emptying occurred significantly earlier in the No-MBP group than in the MBP group, p = 0.03. Conclusion Mechanical bowel preparation is distressing for the patient and associated with a prolonged time to first bowel emptying.

Chimeric antigen receptor (CAR)-modified natural killer (NK) cells show antileukemic activity against acute myeloid leukemia (AML) in vivo. However, NK cell-mediated tumor killing is often impaired by the interaction between human leukocyte antigen (HLA)-E and the inhibitory receptor, NKG2A. Here, we describe a strategy that overcomes CAR-NK cell inhibition mediated by the HLA-E-NKG2A immune checkpoint. We generate CD33-specific, AML-targeted CAR-NK cells (CAR33) combined with CRISPR/Cas9-based gene disruption of the NKG2A-encoding KLRC1 gene. Using single-cell multi-omics analyses, we identified transcriptional features of activation and maturation in CAR33-KLRC1 ko -NK cells, which are preserved following exposure to AML cells. Moreover, CAR33-KLRC1 ko -NK cells demonstrate potent antileukemic killing activity against AML cell lines and primary blasts in vitro and in vivo. We thus conclude that NKG2A-deficient CAR-NK cells have the potential to bypass immune suppression in AML., (© 2024. The Author(s).)

Purpose: Creating wax-ups of missing teeth for backward planning in implant surgery is a complex and time-consuming process. To facilitate implant-planning procedures, the automatic generation of a virtual wax-up would be useful. In the present study, the reconstruction of missing teeth in partially edentulous patients was performed automatically using newly developed software. The accuracy was investigated in order to test its clinical applicability., Materials and Methods: This study presents a new method for creating an automatic virtual wax-up, which could serve as a basic tool in modern implant-planning procedures. First, a statistical shape model (SSM) based on 76 maxillary and mandibular arch scans from dentally healthy individuals was generated. Then, artificially generated tooth gaps were reconstructed. The accuracy of the workflow was evaluated on a separate testing sample of 10 individuals with artificially created tooth gaps given as a median deviation, in millimeters. Scans of three clinical cases with partial edentulism were equally reconstructed using the SSM and compared with the final prosthodontic work., Results: The reconstruction of the artificial tooth gaps could be performed with the following median reconstruction accuracy: gap 21 with 0.15 mm; gap 27 with 0.20 mm; gap 34 with 0.22 mm: gap 36 with 0.22 mm; gaps 12 to 22 with 0.22 mm; gaps 34 to 36 with 0.22 mm. A scenario for an almost edentulous mandible with all teeth missing except teeth 33 and 43 could be reconstructed with a median reconstruction accuracy of 0.37 mm. The median tooth gap deviation of the SSM-based reconstruction in clinical cases differed from the final inserted prosthodontic teeth by 0.49 to 0.86 mm in median., Conclusion: A first feasibility of creating virtual wax-ups using an SSM could be shown. Artificially generated tooth gaps could be reconstructed close to the original with the proposed workflow. In the clinical cases, the SSM proposes an anatomical reconstruction, which does not yet consider prosthodontic aspects. To obtain clinical use, contact with antagonist teeth must be considered and more training data must be implemented. However, the presented method offers a fast and viable way for the approximate placement of missing crowns. This could be used in a digital planning workflow when implant position must be determined. (Int J Comput Dent 2022;25(4):349-0; doi: 10.3290/j.ijcd.b2599407).

Objectives: To determine the diagnostic value of resonance frequency analysis (RFA) in predicting palatal implant (PI) loss ., Materials and Methods: RFA values of 32 patients (study center at Mainz and Dresden) were evaluated in a prospective randomized controlled trial addressing clinical performance of two loading concepts on PI (Orthosystem, Straumann, Basel, Switzerland). Group 1: conventional loading after a 12-week healing period vs group 2: immediate loading within one week after insertion. Stability was assessed by RFA after surgical insertion (T1), one week (T2), and 12 weeks (T3) later., Results: All 32 PI were clinically stable after surgical insertion; 14 PI were loaded conventionally and 18 immediately. One implant in group 1 was lost 6 weeks after insertion. One drop-out was registered in group 2. One false positive and three false negative implant stability quotients (ISQ) were observed. ISQ values of clinically stable PI in group 1 were 67.2 (SD ± 9.5) at T1, 62.3 (SD ± 11.7) at T2, and 68.2 (SD ± 5.5) at T3. Group 2 showed 67.1 (SD ± 11.7) at T1, 65.4 (SD ± 10.4) at T2, and 72.3 (SD ± 5.6) at T3. Differences between groups were not statistically significant for starting time ( P = .88) and change from T1 to T2: 0.08 but were significant from T1 to T3: P = .04; (regression analysis)., Conclusions: RFA had no sensitivity for prediction of stability. General decrease after primary stability and increase with secondary stability gives support for specificity. Within the limits of the study, only the diagnostic value of RFA identifying stable palatal implants could be confirmed.

Background: Prolonged repolarization is the hallmark of long QT syndrome (LQTS), which is associated with subclinical mechanical dysfunction. We aimed at elucidating mechanical cardiac function in LQTS type 1 (loss of I Ks ) and its modification upon further prolongation of the action potential (AP) by I Kr -blockade (E-4031)., Methods: Transgenic LQT1 and wild type (WT) rabbits (n = 12/10) were subjected to tissue phase mapping MRI, ECG, and epicardial AP recording. Protein and mRNA levels of ion channels and Ca 2+ handling proteins (n = 4/4) were determined. In silico single cell AP and tension modeling was performed., Results: At baseline, QT intervals were longer in LQT1 compared to WT rabbits, but baseline systolic and diastolic myocardial peak velocities were similar in LQT1 and WT. E-4031 prolonged QT more pronouncedly in LQT1. Additionally, E-4031 increased systolic and decreased diastolic peak velocities more markedly in LQT1 - unmasking systolic and diastolic LQT1-specific mechanical alterations. E-4031-induced alterations of diastolic peak velocities correlated with the extent of QT prolongation., Conclusion: While baseline mechanical function is normal in LQT1 despite a distinct QT prolongation, further prolongation of repolarization by I Kr -blocker E-4031 unmasks mechanical differences between LQT1 and WT with enhanced systolic and impaired diastolic function only in LQT1. These data indicate an importance of the extent of QT prolongation and the contribution of different impaired ion currents for conveying mechanical dysfunction., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Biomechanical strain induces activation of the transcriptional co-activator yes-associated protein (YAP) by nuclear re-distribution. Recent findings indicate that the mechanically responsive mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase (ERK) 1/2 is involved in the amount of nuclear YAP, reflecting its activation. In this context, we conducted experiments to detect how biomechanical strain acts on the subcellular localization of YAP in periodontal cells. To this end, cells were subjected to 2.5% static equiaxial strain for different time periods. Western blot and fluorescence imaging-based analyses revealed a clear modulation of nuclear YAP localization. This modulation fairly coincided with the altered course of the KI-67 protein amount in conjunction with the percentage of KI-67-positive and thus proliferating cells. The inhibition of the ERK1/2 activity via U0126 yielded an unchanged strain-related modulation of nuclear YAP localization, while YAP amount in whole cell extracts of strained cells was decreased. Administration of the YAP-inhibiting drug Verteporfin evoked a clear reduction of KI-67-positive and thus proliferating cells by approximately 65%, irrespective of strain. Our data reveal YAP as a regulator of strain-modulated proliferation which occurs in a MAPK-independent fashion., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Regional dispersion of prolonged repolarization is a hallmark of long QT syndrome (LQTS). We have also revealed regional heterogeneities in mechanical dysfunction in transgenic rabbit models of LQTS., Objective: In this clinical pilot study, we investigated whether patients with LQTS exhibit dispersion of mechanical/diastolic dysfunction., Methods: Nine pediatric patients with genotyped LQTS (12.2 ± 3.3 years) and 9 age- and sex-matched healthy controls (10.6 ± 1.5 years) were subjected to phase-contrast magnetic resonance imaging to analyze radial (Vr) and longitudinal (Vz) myocardial velocities during systole and diastole in the left ventricle (LV) base, mid, and apex. Twelve-lead electrocardiograms were recorded to assess the heart rate-corrected QT (QTc) interval., Results: The QTc interval was longer in patients with LQTS than in controls (469.1 ± 39.4 ms vs 417.8 ± 24.4 ms; P < .01). Patients with LQTS demonstrated prolonged radial and longitudinal time-to-diastolic peak velocities (TTP), a marker for prolonged contraction duration, in the LV base, mid, and apex. The longer QTc interval positively correlated with longer time-to-diastolic peak velocities (correlation coefficient 0.63; P < .01). Peak diastolic velocities were reduced in LQTS in the LV mid and apex, indicating impaired diastolic relaxation. In patients with LQTS, regional (TTPmax-min) and transmural (TTPVz-Vr) dispersion of contraction duration was increased in the LV apex (TTPVz&#95;max-min: 38.9 ± 25.5 ms vs 20.2 ± 14.7 ms; P = .07; TTPVz-Vr: -21.7 ± 14.5 ms vs -8.7 ± 11.3 ms; P < .05). The base-to-apex longitudinal relaxation sequence was reversed in patients with LQTS compared with controls (TTPVz&#95;base-apex: 14.4 ± 14.9 ms vs -10.1 ± 12.7 ms; P < .01)., Conclusion: Patients with LQTS exhibit diastolic dysfunction with reduced diastolic velocities and prolonged contraction duration. Mechanical dispersion is increased in LQTS with an increased regional and transmural dispersion of contraction duration and altered apicobasal longitudinal relaxation sequence. LQTS is an electromechanical disorder, and phase-contrast magnetic resonance imaging Heterogeneity in mechanical dysfunction enables a detailed assessment of mechanical consequences of LQTS., (Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objectives: During orthodontic tooth movement (OTM), human periodontal ligament fibroblasts (hPDLFs) sense, and respond to mechanical forces. Since the molecular constituents involved in these processes are not fully elucidated, the objective of the present study was to identify further key molecules of the cellular strain response., Materials and Methods: Primary hPDLFs were strained with a static equiaxial strain of 2.5 per cent for 15 minutes, 1 hour, 6 hours, and 24 hours. Western blot (WB) and indirect immunofluorescence (IIF) analyses were performed to investigate the quantity and activation state of proteins involved in mechanotransduction, namely extracellular signal-regulated kinase (ERK) 1/2 and yes-associated protein (YAP). On the cell behavioural level, proliferation was assessed by the marker of proliferation KI-67., Results: In response to the applied strain, an early decline of phosphorylated and thus activated ERK1/2 was observed, followed by a mild recovery. Furthermore, both WB and IIF analyses revealed a modulation of nuclear YAP localisation. Concomitant with the modulation of YAP, the applied strain evoked an early increase in nuclear KI-67 amount, followed by a continuous decrease., Limitations: Consecutive studies will focus on scrutinising the suggested relationship between YAP and proliferation in response to static strain., Conclusions: Our findings provide evidence of ERK1/2 and YAP being biomechanically responsive molecular players in the context of OTM, among which YAP rather than ERK1/2 seems to be mechanistically interrelated with proliferation. Furthermore, the molecular and cell behavioural strain-induced early modulations may point to an involvement of the investigated molecules in the initial and the following lag phase of OTM., (© The Author 2017. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com)

Objective: The objectives of the present study are the following: (a) to investigate limitations (bone height, proximity to nasopalatine nerve and roots) in juvenile patients, (b) to review the recommended site for surgical insertion (level of the maxillary first premolars), and (c) to reassess the rationale behind the manufacturer's age limitation (12 years)., Patients and Methods: Cone beam CT images of 100 patients aged 10 to 20 years were analyzed. Vertical bone heights were measured in the median plane as well as 3- and 6-mm paramedian along the prospective axis of insertion, at the level of the first premolars (level 0), 3 mm anterior (level 1) and 3 mm posterior (level 2). The Mann-Whitney U test was used to compare bone heights between gender groups., Results: The risk of damage to the nasopalatine nerve is highest in the median region on level 1 (46 %). The risk was lowest in the midsagittal region on level 0 (recommended insertion site; 3 %) and level 2 (0 %), as well as paramedian on levels 0 and 2. The risk of damaging roots was irrelevant for median insertion at all levels; the only critical region was 6-mm paramedian on level 1., Conclusions: The recommendation of surgical insertion at the level of the maxillary first premolars is still justified, but a slightly more posterior implant position might improve safety. We found no relevant growth-related changes in the vertical bone heights in the median palatal area. Thus, our data do not support the strict 12-year age restriction for palatal implants.

Background: Echocardiographic examinations have revealed functional cardiac abnormalities in children with chronic kidney disease., Objective: To assess the feasibility of MRI tissue phase mapping in children and to assess regional left ventricular wall movements in children with chronic kidney disease., Materials and Methods: Twenty pediatric patients with chronic kidney disease (before or after renal transplantation) and 12 healthy controls underwent tissue phase mapping (TPM) to quantify regional left ventricular function through myocardial long (Vz) and short-axis (Vr) velocities at all 3 levels of the left ventricle., Results: Patients and controls (age: 8 years-20 years) were matched for age, height, weight, gender and heart rate. Patients had higher systolic blood pressure. No patient had left ventricular hypertrophy on MRI or diastolic dysfunction on echocardiography. Fifteen patients underwent tissue Doppler echocardiography, with normal z-scores for mitral early diastolic (V E ), late diastolic (V A ) and peak systolic (V S ) velocities. Throughout all left ventricular levels, peak diastolic Vz and Vr (cm/s) were reduced in patients: Vz base -10.6 ± 1.9 vs. -13.4 ± 2.0 (P < 0.0003), Vz mid -7.8 ± 1.6 vs. -11 ± 1.5 (P < 0.0001), Vz apex -3.8 ± 1.6 vs. -5.3 ± 1.6 (P = 0.01), Vr base -4.2 ± 0.8 vs. -4.9 ± 0.7 (P = 0.01), Vr mid -4.7 ± 0.7 vs. -5.4 ± 0.7 (P = 0.01), Vr apex -4.7 ± 1.4 vs. -5.6 ± 1.1 (P = 0.05)., Conclusion: Tissue phase mapping is feasible in children and adolescents. Children with chronic kidney disease show significantly reduced peak diastolic long- and short-axis left ventricular wall velocities, reflecting impaired early diastolic filling. Thus, tissue phase mapping detects chronic kidney disease-related functional myocardial changes before overt left ventricular hypertrophy or echocardiographic diastolic dysfunction occurs.

Long QT syndrome (LQTS) is a congenital arrhythmogenic channelopathy characterized by impaired cardiac repolarization. Increasing evidence supports the notion that LQTS is not purely an "electrical" disease but rather an "electro-mechanical" disease with regionally heterogeneously impaired electrical and mechanical cardiac function. In the first part, this article reviews current knowledge on electro-mechanical (dys)function in LQTS, clinical consequences of the observed electro-mechanical dysfunction, and potential underlying mechanisms. Since several novel imaging techniques - Strain Echocardiography (SE) and Magnetic Resonance Tissue Phase Mapping (TPM) - are applied in clinical and experimental settings to assess the (regional) mechanical function, advantages of these non-invasive techniques and their feasibility in the clinical routine are particularly highlighted. The second part provides novel insights into sex differences and sex hormone effects on electro-mechanical cardiac function in a transgenic LQT2 rabbit model. Here we demonstrate that female LQT2 rabbits exhibit a prolonged time to diastolic peak - as marker for contraction duration and early relaxation - compared to males. Chronic estradiol-treatment enhances these differences in time to diastolic peak even more and additionally increases the risk for ventricular arrhythmia. Importantly, time to diastolic peak is particularly prolonged in rabbits exhibiting ventricular arrhythmia - regardless of hormone treatment - contrasting with a lack of differences in QT duration between symptomatic and asymptomatic LQT2 rabbits. This indicates the potential added value of the assessment of mechanical dysfunction in future risk stratification of LQTS patients., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Initial rehabilitation in juvenile patients with oligodontia is a major challenge for the dentist. Conventional permanent prosthetic and/or implantological treatment options alongside permanent natural teeth are contraindicated in growing patients, because their skeletal development is still in progress., Case Report: A non-invasive temporary-fixed treatment option for an adolescent patient is presented by the use of adhesively cemented (non-prep) all-ceramic onlays of primary teeth. The outcome of treatment was monitored over a period of 4 years., Conclusion: Long-term preservation of persistent primary teeth may be a meaningful alternative to removable dentures in growing patients with oligodontia. Intermediate rehabilitation should cause no more than mild psychological stress for the patient and improve quality of life, especially when extensive orthodontic and/or implantological treatment is planned at the end of the patient's skeletal growth., (© 2014 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Oligodontia has a substantial oral functional and psychosocial impact on the quality of life of children. The treatment of oligodontia in adolescence is an interdisciplinary approach which can include extraction of the primary teeth with orthodontic space closure, or prosthodontic rehabilitation. This case report describes a conservative approach for the rehabilitation of a 12-year-old patient with 19 ageneses (excluding third molars) of permanent teeth, infraocclusion of the persisting primary teeth, deep overbite, and reduced mesiodistal dimension of the maxillary incisors with a central diastema. The treatment plan to restore esthetics and function included an initial noninvasive prosthetic rehabilitation for deep bite correction with additive leucite-reinforced glass-ceramic onlays/veneers until definitive orthodontic and implant therapy are reevaluated and determined in adulthood. Esthetics, functional occlusion, and crown-to-root ratio remained stable over a follow-up period of 3 years. No signs of fractures within the all-ceramic restorations or symptoms of a temporomandibular disorder were evident.

Purpose: The measurement of velocities based on phase contrast MRI can be subject to different phase offset errors which can affect the accuracy of velocity data. The purpose of this study was to determine the impact of these inaccuracies and to evaluate different correction strategies on three-dimensional visualization., Methods: Phase contrast MRI was performed on a 3 T system (Siemens Trio) for in vitro (curved/straight tube models; venc: 0.3 m/s) and in vivo (aorta/intracranial vasculature; venc: 1.5/0.4 m/s) data. For comparison of the impact of different magnetic field gradient designs, in vitro data was additionally acquired on a wide bore 1.5 T system (Siemens Espree). Different correction methods were applied to correct for eddy currents, Maxwell terms, and gradient field inhomogeneities., Results: The application of phase offset correction methods lead to an improvement of three-dimensional particle trace visualization and count. The most pronounced differences were found for in vivo/in vitro data (68%/82% more particle traces) acquired with a low venc (0.3 m/s/0.4 m/s, respectively). In vivo data acquired with high venc (1.5 m/s) showed noticeable but only minor improvement., Conclusion: This study suggests that the correction of phase offset errors can be important for a more reliable visualization of particle traces but is strongly dependent on the velocity sensitivity, object geometry, and gradient coil design., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: The aim of this study was to investigate the efficacy of orthodontic treatment using the Invisalign® system. Particularly, we analyzed the influence of auxiliaries (Attachment/Power Ridge) as well as the staging (movement per aligner) on treatment efficacy., Methods: We reviewed the tooth movements of 30 consecutive patients who required orthodontic treatment with Invisalign®. In all patients, one of the following tooth movements was performed: (1) Incisor Torque >10°, (2) Premolar derotation >10° (3) Molar distalization >1.5 mm. The groups (1)-(3) were subdivided: in the first subgroup (a) the movements were supported with the use of an attachment, while in the subgroup (b) no auxiliaries were used (except incisor torque, in which Power Ridges were used). All tooth movements were performed in a split-mouth design. To analyze the clinical efficacy, pre-treatment and final plaster cast models were laser-scanned and the achieved tooth movement was determined by way of a surface/surface matching algorithm. The results were compared with the amount of tooth movement predicted by ClinCheck®., Results: The overall mean efficacy was 59% (SD = 0.2). The mean accuracy for upper incisor torque was 42% (SD = 0.2). Premolar derotation showed the lowest accuracy with approximately 40% (SD = 0.3). Distalization of an upper molar was the most effective movement, with efficacy approximately 87% (SD = 0.2)., Conclusion: Incisor torque, premolar derotation and molar distalization can be performed using Invisalign® aligners. The staging (movement/aligner) and the total amount of planned movement have an significant impact on treatment efficacy.

Introduction: The exact force systems as well as their progressions generated by removable thermoplastic appliances have not been investigated. Thus, the purposes of this experimental study were to quantify the forces and moments delivered by a single aligner and a series of aligners (Invisalign; Align Technology, Santa Clara, Calif) and to investigate the influence of attachments and power ridges on the force transfer., Methods: We studied 970 aligners of the Invisalign system (60 series of aligners). The aligners came from 30 consecutive patients, of which 3 tooth movements (incisor torque, premolar derotation, molar distalization) with 20 movements each were analyzed. The 3 movement groups were subdivided so that 10 movements were supported with an attachment and 10 were not. The patients' ClinCheck (Align Technology, Santa Clara, Calif) was planned so that the movements to be investigated were performed in isolation in the respective quadrant. Resin replicas of the patients' intraoral situation before the start of the investigated movement were taken and mounted in a biomechanical measurement system. An aligner was put on the model, the force systems were measured, and the calculated movements were experimentally performed until no further forces or moments were generated. Subsequently, the next aligners were installed, and the measurements were repeated., Results: The initial mean moments were about 7.3 N·mm for maxillary incisor torque and about 1.0 N for distalization. Significant differences in the generated moments were measured in the premolar derotation group, whether they were supported with an attachment (8.8 N·mm) or not (1.2 N·mm). All measurements showed an exponential force change., Conclusions: Apart from a few maximal initial force systems, the forces and moments generated by aligners of the Invisalign system are within the range of orthodontic forces. The force change is exponential while a patient is wearing removable thermoplastic appliances., (Copyright © 2014 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.)

Objective: Obtaining new details of radial motion of left ventricular (LV) segments using velocity-encoding cardiac MRI., Methods: Cardiac MR examinations were performed on 14 healthy volunteers aged between 19 and 26 years. Cine images for navigator-gated phase contrast velocity mapping were acquired using a black blood segmented κ-space spoiled gradient echo sequence with a temporal resolution of 13.8 ms. Peak systolic and diastolic radial velocities as well as radial velocity curves were obtained for 16 ventricular segments., Results: Significant differences among peak radial velocities of basal and mid-ventricular segments have been recorded. Particular patterns of segmental radial velocity curves were also noted. An additional wave of outward radial movement during the phase of rapid ventricular filling, corresponding to the expected timing of the third heart sound, appeared of particular interest., Conclusion: The technique has allowed visualization of new details of LV radial wall motion. In particular, higher peak systolic radial velocities of anterior and inferior segments are suggestive of a relatively higher dynamics of anteroposterior vs lateral radial motion in systole. Specific patterns of radial motion of other LV segments may provide additional insights into LV mechanics., Advances in Knowledge: The outward radial movement of LV segments impacted by the blood flow during rapid ventricular filling provides a potential substrate for the third heart sound. A biphasic radial expansion of the basal anteroseptal segment in early diastole is likely to be related to the simultaneous longitudinal LV displacement by the stretched great vessels following repolarization and their close apposition to this segment.

Background: The concept of scalloped implants to maintain the natural contour of the alveolar ridge has been a source of controversy for many years., Purpose: This study examined the long-term clinical performance of the scalloped NobelPerfect implant in a one-stage procedure (immediate loading in the esthetic zone)., Materials and Methods: In 20 patients, immediate prosthetic restorations were placed on 31 NobelPerfect implants in a private practice and followed for up to 78 months. Twenty-one implants were placed immediately after extraction, seven implants were placed after osseous consolidation of the extraction sockets, and three implants were placed secondary to extended alveolar ridge augmentation procedures. All implants were provisionalized on the day of implant placement and adjusted to clear all contacts in centric occlusion and during eccentric movements. Outcome variables were success rates, marginal bone levels, and pink esthetic score (PES) assessed per implant., Results: One implant failed after 1.4 months. Five patients with six implants in total were scored in the 5-year follow-up as dropouts. Mean follow-up period of remaining 24 implants was 65 months (range, 55-78 months). Cumulative success rates according to the criteria specified by Smith and Zarb were 96.8%. Marginal bone levels averaged 1.1 mm above the first thread. Mean PES ratings were 10.5 (range, 3-13)., Conclusions: Survival rates, marginal bone levels, and esthetic results suggest proof of principle for the preservation of the interproximal bony lamella with a scalloped implant design in long-term data., (© 2012 Wiley Periodicals, Inc.)