Does a Commercially Available Augmented Reality-based Portable Hip Navigation System Improve Cup Positioning During THA Compared With the Conventional Technique? A Randomized Controlled Study.

BACKGROUND: Portable hip navigation systems have been developed to combine the accuracy of cup positioning by large console navigation systems with the ease of use and convenience of conventional surgical techniques. Although a novel augmented reality-based portable hip navigation system using a smartphone (AR navigation) has become available recently, no studies, to our knowledge, have compared commercially available AR navigation with the conventional technique. Additionally, no studies, except for those from designer-surgeon series, have demonstrated the results of AR navigation. QUESTIONS/PURPOSES: (1) Does intraoperative use of commercially available AR navigation improve cup positioning compared with the conventional technique? (2) Are operative factors, clinical scores, and postoperative course different between the two groups? METHODS: In this randomized trial, 72 patients undergoing THA were randomly assigned to undergo either commercially available AR navigation or a conventional technique for cup placement. All patients received the same cementless acetabular cups through a posterior approach in the lateral decubitus position. The primary outcome of the present study was cup positioning, including the absolute differences between the intended target and angle achieved, as well as the number of cups inside the Lewinnek safe zone. Our target cup position was 40° abduction and 20° anteversion. Secondary outcomes were operative factors, between-group difference in improvement in the Hip Disability and Osteoarthritis Outcome Score (HOOS), and the postoperative course, including the operative time (between the start of the surgical approach and skin closure), procedure time (between the first incision and skin closure, including the time to insert pins, registration, and transfer and redrape patients in the navigation group), time taken to insert pins and complete registration in the navigation group, intraoperative and postoperative complications, and reoperations. The minimum follow-up period was 6 months, because data regarding the primary outcome-cup positioning-were collected within 1 week after surgery. The between-group difference in improvement in HOOS, which was the secondary outcome, was much lower than the minimum clinically important difference for the HOOS. No patients in either group were lost to follow-up, and there was no crossover (the randomized treatment was performed in all patients, so there was no difference between an intention-to-treat and a per-protocol analysis). RESULTS: The use of the commercially available AR navigation slightly improved cup positioning compared with the conventional technique in terms of the absolute difference between the desired and achieved amounts of cup abduction and anteversion (which we defined as "absolute differences"; median 1° [IQR 0° to 4.0°] versus median 5° [IQR 3.0° to 7.5°], difference of medians 4°; p < 0.001 and median 2° [IQR 1.9° to 3.7°] versus median 5° [IQR 3.2° to 9.7°], difference of medians 2°; p = 0.001). A higher proportion of cups were placed inside the Lewinnek safe zone in the navigation group than in the control group (94% [34 of 36] compared with 64% [23 of 36]; p < 0.001). Median operative times were not different between the two groups (58 minutes [IQR 49 to 72 minutes] versus 57 minutes [IQR 49 to 69 minutes], difference of medians 1 minute; p = 0.99). The median procedure time was longer in the navigation group (95 minutes [IQR 84 to 109 minutes] versus 57 minutes [IQR 49 to 69 minutes], difference of medians 38 minutes; p < 0.001). There were no differences between the two groups in improvement in HOOS (27 ± 17 versus 28 ± 19, mean difference -1 [95% CI -9.5 to 7.4]; p = 0.81). In the navigation group, no complications occurred in the pin sites; however, one anterior dislocation occurred. In the conventional group, one hip underwent reoperation because of a deep infection. CONCLUSION: Although the use of commercially available AR navigation improved cup positioning in THA, the improvement in clinical scores and postoperative complication rates were not different between the two groups, and the overall magnitude of the difference in accuracy was small. Future studies will need to determine whether the improvement in the percentage of hips inside the Lewinnek safe zone results in differences in late dislocation or polyethylene wear, and whether such benefits-if any-justify the added costs and surgical time. Until or unless more compelling evidence in favor of the new system emerges, we recommend against widespread use of the system in clinical practice. LEVEL OF EVIDENCE: Level Ⅱ, therapeutic study.

Nutrient Signaling via the TORC1-Greatwall-PP2AB55δ Pathway Is Responsible for the High Initial Rates of Alcoholic Fermentation in Sake Yeast Strains of Saccharomyces cerevisiae.

Saccharomyces cerevisiae sake yeast strain Kyokai no. 7 (K7) and its relatives carry a homozygous loss-of-function mutation in the RIM15 gene, which encodes a Greatwall family protein kinase. Disruption of RIM15 in nonsake yeast strains leads to improved alcoholic fermentation, indicating that the defect in Rim15p is associated with the enhanced fermentation performance of sake yeast cells. In order to understand how Rim15p mediates fermentation control, we here focused on target-of-rapamycin protein kinase complex 1 (TORC1) and protein phosphatase 2A with the B55δ regulatory subunit (PP2AB55δ), complexes that are known to act upstream and downstream of Rim15p, respectively. Several lines of evidence, including our previous transcriptomic analysis data, suggested enhanced TORC1 signaling in sake yeast cells during sake fermentation. Fermentation tests of the TORC1-related mutants using a laboratory strain revealed that TORC1 signaling positively regulates the initial fermentation rate in a Rim15p-dependent manner. Deletion of the CDC55 gene, encoding B55δ, abolished the high fermentation performance of Rim15p-deficient laboratory yeast and sake yeast cells, indicating that PP2AB55δ mediates the fermentation control by TORC1 and Rim15p. The TORC1-Greatwall-PP2AB55δ pathway similarly affected the fermentation rate in the fission yeast Schizosaccharomyces pombe, strongly suggesting that the evolutionarily conserved pathway governs alcoholic fermentation in yeasts. It is likely that elevated PP2AB55δ activity accounts for the high fermentation performance of sake yeast cells. Heterozygous loss-of-function mutations in CDC55 found in K7-related sake strains may indicate that the Rim15p-deficient phenotypes are disadvantageous to cell survival.IMPORTANCE The biochemical processes and enzymes responsible for glycolysis and alcoholic fermentation by the yeast S. cerevisiae have long been the subject of scientific research. Nevertheless, the factors determining fermentation performance in vivo are not fully understood. As a result, the industrial breeding of yeast strains has required empirical characterization of fermentation by screening numerous mutants through laborious fermentation tests. To establish a rational and efficient breeding strategy, key regulators of alcoholic fermentation need to be identified. In the present study, we focused on how sake yeast strains of S. cerevisiae have acquired high alcoholic fermentation performance. Our findings provide a rational molecular basis to design yeast strains with optimal fermentation performance for production of alcoholic beverages and bioethanol. In addition, as the evolutionarily conserved TORC1-Greatwall-PP2AB55δ pathway plays a major role in the glycolytic control, our work may contribute to research on carbohydrate metabolism in higher eukaryotes.

Inhibitory Role of Greatwall-Like Protein Kinase Rim15p in Alcoholic Fermentation via Upregulating the UDP-Glucose Synthesis Pathway in Saccharomyces cerevisiae.

The high fermentation rate of Saccharomyces cerevisiae sake yeast strains is attributable to a loss-of-function mutation in the RIM15 gene, which encodes a Greatwall-family protein kinase that is conserved among eukaryotes. In the present study, we performed intracellular metabolic profiling analysis and revealed that deletion of the RIM15 gene in a laboratory strain impaired glucose-anabolic pathways through the synthesis of UDP-glucose (UDPG). Although Rim15p is required for the synthesis of trehalose and glycogen from UDPG upon entry of cells into the quiescent state, we found that Rim15p is also essential for the accumulation of cell wall ß-glucans, which are also anabolic products of UDPG. Furthermore, the impairment of UDPG or 1,3-ß-glucan synthesis contributed to an increase in the fermentation rate. Transcriptional induction of PGM2 (phosphoglucomutase) and UGP1 (UDPG pyrophosphorylase) was impaired in Rim15p-deficient cells in the early stage of fermentation. These findings demonstrate that the decreased anabolism of glucose into UDPG and 1,3-ß-glucan triggered by a defect in the Rim15p-mediated upregulation of PGM2 and UGP1 redirects the glucose flux into glycolysis. Consistent with this, sake yeast strains with defective Rim15p exhibited impaired expression of PGM2 and UGP1 and decreased levels of ß-glucans, trehalose, and glycogen during sake fermentation. We also identified a sake yeast-specific mutation in the glycogen synthesis-associated glycogenin gene GLG2, supporting the conclusion that the glucose-anabolic pathway is impaired in sake yeast. These findings demonstrate that downregulation of the UDPG synthesis pathway is a key mechanism accelerating alcoholic fermentation in industrially utilized S. cerevisiae sake strains.

A randomized phase 3 trial evaluating antithrombin gamma treatment in Japanese patients with early-onset severe preeclampsia (KOUNO-TORI study): Study protocol.

INTRODUCTION: Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality. Several studies have demonstrated the beneficial effects of antithrombin replacement in patients with preeclampsia. Here, we describe the study protocol of KOUNO-TORI (KW-3357 randOmized, mUlti-center, double-bliNd, placebO-controlled phase 3 sTudy in patients with early Onset pReeclampsIa) to evaluate recombinant human antithrombin gamma (rhAT-gamma) for the treatment of early-onset severe de novo preeclampsia. MATERIAL AND METHODS: Patients with early-onset severe de novo preeclampsia who are ≥24 to <32 weeks pregnant at the time of registration and have an antithrombin activity of ≤100% at screening are included. The target population is selected based on a reanalysis of the data of a previous plasma-derived antithrombin phase 3 study. Primary endpoint is the prolongation of pregnancy from the initiation of rhAT-gamma treatment to the pregnancy termination. Secondary endpoints include gestational age in terms of achievement of 32- and 34-weeks'gestation, and gestational age in terms of achievement of 28 weeks' gestation for patients enrolled at <28 weeks' gestation. Maternal, fetal, and neonatal outcomes will be assessed. DISCUSSION: As we have selected a specifically defined target population based on reanalysis of data of a previous plasma-derived antithrombin phase 3 study, the results of our study are expected to provide efficacy and safety data concerning rhAT-gamma treatment in Japanese patients. This study could help identify an effective novel treatment for such patients with early-onset severe preeclampsia for whom appropriate treatment is unavailable.

New cholestane glycosides and sterols from the underground parts of Chamaelirium luteum and their cytotoxic activity.

Six new cholestane glycosides (1, 5, 6, 10, 12, and 13) and two new sterols (9 and 11), along with five known compounds (2-4, 7, and 8), were isolated from the underground parts of Chamaelirium luteum (Liliaceae). The structures of these new compounds were determined by spectroscopic analysis and the results of hydrolytic cleavage. The isolated compounds and aglycones were evaluated for their cytotoxic activity against HL-60 human leukemia cells. Compounds 6a, 10a, 12a, 13, and 13a were cytotoxic to HL-60 cells, with IC50 values of 12.8, 9.8, 15.3, 6.2, and 10.2 µM, respectively.