Women with estrogen deficiency are at the risk of suffering from neurological symptoms such as memory impairment. In the present study, we investigated the effect of garlic, Allium sativum L. ...(Asparagales: Amaryllidaceae), treated with subcritical water on memory impairment in ovariectomized (OVX) rats. OVX rats were administered garlic powder for 84d. Hippocampus-dependent spatial memory was assessed using the Morris water maze test. Escape latency of the OVX rats increased compared with that of sham-operated rats. The prolonged escape latency of the OVX rats decreased to the level of that of sham-operated rats upon the administration of garlic powder (0.5% in feed). The weights of the body, uterus, and brain were not affected by the garlic powder administration. These results suggest that garlic powder treated with subcritical water mitigates memory impairment in OVX rats.
Our previous studies found that an anti-placental growth factor (PlGF) antibody protected the retina in light-induced retinal damage model, a model of non-exudative age-related macular degeneration ...(AMD). Aflibercept is an inhibitor of vascular endothelial growth factor (VEGF) and PlGF. In present study, we revealed that the intravitreal injection of aflibercept lessens light-induced retinal damage, while anti-VEGF antibody has no effect on the light-exposed retina. Moreover, PlGF disrupted the tight junctions between the human retinal pigment epithelial cells in vitro, and aflibercept blocked the disruption. These data suggest that the aflibercept may be an effective treatment of non-exudative AMD.
Previously, we revealed that neurotensin (NTS) derived from the oviduct and uterus can function during fertilization. However, little is known about NTS actions on the pre-implantation embryo after ...fertilization. Here, we found that pro-Nts mRNA is expressed in the oviduct and uterus during when preimplantation embryos develop and an increase in mRNA level in the uterus is induced by human chorionic gonadotropin (hCG) treatment. Expression of mRNA for two NTS receptors, Ntr1 and Ntr3, was found throughout these stages, whereas Ntr2 mRNA was not detected, suggesting that NTS signaling occurred through NTR1 and NTR3. Supplementation of 1, 10, 100 or 1000 nM NTS to embryo culture medium after fertilization showed that 100 nM NTS significantly improved the blastocyst formation. In comparison, the total number of cells and inner cell mass ratio of blastocysts was not significant different between the 0 nM and 100 nM NTS treatment groups. These results indicate that NTS has a positive effect upon preimplantation embryo development in vitro.
We analyze Mars Atmosphere and Volatile EvolutioN (MAVEN) observations of magnetic flux ropes embedded in Martian magnetotail current sheets, in order to evaluate the role of magnetotail reconnection ...in their generations. We conduct a minimum variance analysis to infer the generation processes of magnetotail flux ropes from the geometrical configuration of the individual flux rope axial orientation with respect to the overall current sheet. Of 23 flux ropes detected in current sheets in the near‐Mars (∼1–3 Martian radii downstream) magnetotail, only 3 (possibly 4) can be explained by the magnetotail reconnection scenario, while the vast majority of the events (19 events) are more consistent with flux ropes that are originally generated in the dayside ionosphere and subsequently transported into the nightside magnetotail. The mixed origins of the detected flux ropes imply complex nature of generation and transport of Martian magnetotail flux ropes.
Key Points
Instances of magnetic flux ropes within near‐Mars magnetotail current sheets are observed that have a wide variety of orientations
Only 3 of the 23 flux ropes analyzed here have orientations within 30 degrees of the cross‐tail current direction
Majority has large angles to the cross‐tail current direction consistent with those formed in ionosphere and transported into magnetotail
To investigate the influence of perioperative antithrombotic agent (antiplatelet agents and anticoagulants) discontinuation in elective posterior spinal surgery in terms of bleeding complications, ...such as epidural hematoma and postoperative thromboembolism.
We enrolled patients undergoing elective posterior spinal surgery at 9 hospitals between April 2017 and August 2020. We collected data regarding patient baseline characteristics, surgical details, intraoperative estimated blood loss, and postoperative complication rates, including epidural hematoma and thromboembolism. We divided the patients into a discontinuation group, in which antithrombic agents were discontinued perioperatively, and a control group without antithrombic agents. Propensity scores for taking any antithrombic agents were calculated, with 1-to-1 matching based on the estimated propensity scores to adjust for patient baseline characteristics and surgical details. Intraoperative estimated blood loss and 30-day postoperative complication rates were compared between the groups.
We enrolled 9853 patients, including 1123 patients (11.4%) who discontinued antithrombic agents perioperatively. One-to-one propensity score matching yielded 1111 pairs with and without antithrombic agents. Intraoperative estimated blood loss per 10 minutes (8.2 mL vs. 8.9 mL) and the incidence of epidural hematoma requiring revision (0.97% vs. 0.72%) were similar between the groups. Although postoperative cardiac events and stroke were observed only in the discontinuation group (0.27% and 0.09%, respectively), these incidences were not significantly different between the groups.
Perioperative antithrombic agent discontinuation in elective posterior spinal surgery normalized the intraoperative bleeding tendency and the incidence of postoperative epidural hematoma and did not influence in a significative way the incidence of postoperative thromboembolism.
VGF nerve growth factor inducible (VGF) is a polypeptide that is induced by neurotrophic factors and is involved in neurite growth and neuroprotection. The mRNA of the Vgf gene has been detected in ...the adult rat retina, however the roles played by VGF in the retina are still undetermined. Thus, the purpose of this study was to determine the effects of VGF on the retinal ganglion cells (RGCs) of mice in the optic nerve crush (ONC) model, rat-derived primary cultured RGCs and human induced pluripotent stem cells (iPSCs)-derived RGCs. The mRNA and protein of Vgf were upregulated after the ONC. Immunostaining showed that the VGF was located in glial cells including Müller glia and astrocytes but not in the retinal neurons and their axons. AQEE-30, a VGF peptide, suppressed the loss of RGCs induced by the ONC, and it increased survival rat-derived RGCs and promoted the outgrowth of neurites of rat and human iPSCs derived RGCs in vitro. These findings indicate that VGF plays important roles in neuronal degeneration and has protective effects against the ONC on RGCs. Thus, VGF should be considered as a treatment of RGCs degeneration.
•Nivolumab efficacy is unknown in patients who are categorized into small subgroups.•This was a 15-center retrospective study of NSCLC patients who received nivolumab.•A total of 613 NSCLC patients ...who received nivolumab were included.•We showed efficacy data from previously underreported patient populations.•We described common frequency of pneumonitis and some of its key characteristics.
Nivolumab has been shown to be effective and safe in previously treated patients with advanced non-small cell lung cancer (NSCLC). However, little is known regarding its performance in real-world (i.e., non-trial) settings. Furthermore, nivolumab efficacy is unknown in patients who are ineligible for clinical trials or who are categorized into small subgroups in such trials.
We conducted a 15-center, observational, retrospective cohort study of patients with advanced NSCLC who received nivolumab monotherapy between January and December 2016.
Of 613 patients included in our study, 141 had poor performance status (PS) and 106 were EGFR mutation – or ALK rearrangement-positive. The response and disease control rates were 20% and 44%, respectively; the estimated 1-year progression-free survival (PFS) was 18%. Multivariate analysis identified never smoking, poor PS, and EGFR mutation/ALK rearrangement as independent negative predictors of PFS. The most frequently reported grade ≥3 adverse event was pneumonitis (5% of patients). Severe pneumonitis (grade ≥3) occurred significantly earlier than mild pneumonitis (1.6 vs. 2.3 months, P = 0.031). Patients with pneumonitis achieved higher response rates and longer PFS than those without (37% vs. 18%, and 5.8 vs. 2.1 months, respectively; P = 0.002).
Smoking status, PS, and EGFR mutation/ALK rearrangement were independent predictors of PFS. Our study elucidated nivolumab's efficacy in previously underreported patient populations; i.e., those with poor PS and/or with driver oncogenes. We also found that pneumonitis is not infrequent, and carries key implications for outcomes. These data should be useful for improving the clinical courses of nivolumab-treated patients with NSCLC.
ObjectivesTo investigate the effect of the COVID-19 pandemic on surgical volume and outcomes in spine surgery.DesignA retrospective cohort study using prospectively collected data.Setting and ...participantsA total of 9935 patients who underwent spine surgery between January 2019 and December 2021 at eight high-volume spine centres in the Greater Tokyo metropolitan area were included.Outcome measuresThe primary outcome measures were the number of surgical cases, perioperative complications and patient-reported outcomes, including numerical rating scales for each body part, Euro quality of life 5-dimension (EQ5D), Neck Disability Index and Oswestry Disability Index (ODI).ResultsThe total number of surgeries in 2020 and 2021 remained lower than that of 2019, with respective percentages of 93.1% and 95.7% compared with the prepandemic period, with a marked reduction observed in May 2020 compared with the same period in 2019 (56.1% decrease). There were no significant differences between the prepandemic and postpandemic groups in the incidence of perioperative complications, although the frequency of reoperation tended to be higher in the postpandemic group (3.04% vs 3.76%, p=0.05). Subgroup analysis focusing on cervical spine surgery revealed significantly worse preoperative EQ5D scores in the postpandemic group (0.57 vs 0.54, p=0.004). Similarly, in lumbar spine surgery, the postpandemic group showed higher levels of leg pain (5.7 vs 6.1 to 0.002) and worse ODI scores (46.2 vs 47.7 to 0.02). However, postoperative outcomes were not different between pre and post-pandemic groups.ConclusionsThe COVID-19 pandemic has significantly impacted spinal surgeries in Japan, leading to a decrease in surgical volumes and changes in patient characteristics and surgical procedures. However, surgical outcomes remained comparable between the pre and postpandemic periods, indicating the resilience and adaptability of healthcare systems.
The impact of body mass index (BMI) on outcomes after lumbar spine surgery is currently unknown. Previous studies have reported conflicting evidence for patients with high BMI, while little research ...has been conducted on outcomes for underweight patients. This study aims to examine the impact of BMI on outcomes after lumbar spine surgery. This prospective cohort study enrolled 5622 patients; of which, 194, 5027, and 401 were in the low (< 18.5 kg/m
), normal (18.5-30), and high (≥ 30) BMI groups, respectively. Pain was assessed via the numerical pain rating scale (NPRS) for the lower back, buttock, leg, and plantar area. Quality of life was assessed via the EuroQol 5 Dimension (EQ-5D) and Oswestry Disability Index (ODI). Inverse probability weighting with propensity scores was used to adjust patient demographics and clinical characteristics between the groups. After adjustment, the 1-year postoperative scores differed significantly between groups in terms of leg pain. The proportion of patients who achieved a 50% decrease in postoperative NPRS score for leg pain was also significantly different. Obese patients reported less improvement in leg pain after lumbar spine surgery. The outcomes of patients with low BMI were not inferior to those of patients with normal BMI.
Pancreatic solid pseudopapillary neoplasm (SPN) is a low-grade malignant neoplasm with a good prognosis. Clinically aggressive SPNs have rarely been reported but have not been analyzed in detail. In ...this study, we referred to this highly malignant type of SPN as high-grade SPN (HG-SPN) and compared its clinicopathological and genetic characteristics with conventional SPN (C-SPN) using immunohistochemistry and gene panel analyses. Five HG-SPNs and 15 C-SPNs were evaluated in this study. HG-SPNs share many pathologic characteristics: macroscopically, solid/cystic appearances, microscopically, pseudopapillary/pseudorosette pattern (100%), tumor cell loose cohesiveness (100%), thin/delicate vasculature (100%), tumor cell cytoplasmic vacuolization (100%), immunohistochemical positivity for β-catenin (nuclear expression) (100%), CD10 (80%), CD56 (80%), and vimentin (100%). Conversely, HG-SPNs showed distinct malignant features compared with C-SPNs: mean tumor size (11.7 vs. 2.9 cm, P <0.001); true necrosis (100% vs. 0%, P <0.001); high-grade nuclear atypia (100% vs. 0%, P <0.001); lymphatic and/or venous invasion (100% vs. 20%, P =0.004); mean mitotic count (4.38 vs. 0.05/high-power field, P <0.001); and mean Ki-67 labeling index (33.9% vs. 3.4%, P <0.001). All HG-SPN patients died of primary disease 3 to 36 months after surgery, while all C-SPN patients were alive without disease. Genetic studies have shown that all analyzed HG-SPNs have CTNNB1 mutations. Two HG-SPN cases showed RB1 mutations with altered immunohistochemical findings for RB1 and p16. Two HG-SPN cases had TP53 mutation and/or p53 overexpression. In conclusion, HG-SPNs show distinct malignant features and some genetic alterations that differ from C-SPNs, indicating the importance of differentiating between these 2 subtypes.
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