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Synaptic excitation and inhibition are essential for neuronal communication. However, the variables that regulate synaptic excitation and inhibition in the intact brain remain largely unknown. Here, we examined how spike transmission and suppression between principal cells (PCs) and interneurons (INTs) are modulated by activity history, brain state, cell type, and somatic distance between presynaptic and postsynaptic neurons by applying cross-correlogram analyses to datasets recorded from the dorsal hippocampus and medial entorhinal cortex (MEC) of 11 male behaving and sleeping Long Evans rats. The strength, temporal delay, and brain-state dependency of the spike transmission and suppression depended on the subregions/layers. The spike transmission probability of PC-INT excitatory pairs that showed short-term depression versus short-term facilitation was higher in CA1 and lower in CA3. Likewise, the intersomatic distance affected the proportion of PC-INT excitatory pairs that showed short-term depression and facilitation in the opposite manner in CA1 compared with CA3. The time constant of depression was longer, while that of facilitation was shorter in MEC than in CA1 and CA3. During sharp-wave ripples, spike transmission showed a larger gain in the MEC than in CA1 and CA3. The intersomatic distance affected the spike transmission gain during sharp-wave ripples differently in CA1 versus CA3. A subgroup of MEC layer 3 (EC3) INTs preferentially received excitatory inputs from and inhibited MEC layer 2 (EC2) PCs. The EC2 PC-EC3 INT excitatory pairs, most of which showed short-term depression, exhibited higher spike transmission probabilities than the EC2 PC-EC2 INT and EC3 PC-EC3 INT excitatory pairs. EC2 putative stellate cells exhibited stronger spike transmission to and received weaker spike suppression from EC3 INTs than EC2 putative pyramidal cells. This study provides detailed comparisons of monosynaptic interaction dynamics in the hippocampal-entorhinal loop, which may help to elucidate circuit operations., (© 2024 The Author(s). Hippocampus published by Wiley Periodicals LLC.)

Skin-sparing mastectomy (SSM) with immediate reconstruction is standard surgical treatment for early breast cancer with widespread ductal carcinoma in situ (DCIS). The local recurrence rate after SSM is up to 7.0%. We investigated prediction of the pathological margin using contrast-enhanced MRI, and evaluated the cut-off point to obtain the safety margin. We performed SSM with immediate reconstruction in 216 early breast cancer patients with widespread DCIS and/or invasive cancer from January 2014 to December 2015. Forty cases were retrospectively reviewed after excluding those with >15 mm between skin and tumor, determined by preoperative contrast-enhanced MRI, or involving reconstructive surgery for local recurrence, immeasurable lesion by preoperative contrast-enhanced MRI, or neoadjuvant chemotherapy. We defined a positive pathological margin as <1 mm from the cancer nest. We reviewed the distance between skin and tumor by MRI and pathological examination. To identify the cut-off for predicting a positive pathological margin, we performed sensitivity analysis using an ROC curve. The margin-positive rate by pathological examination was 27.5% (n = 11/40), with a moderate correlation of MRI margin and pathological margin (r = 0.44). The best cut-off point for margin positivity was 5 mm of MRI margin, with sensitivity and specificity of 54% and 86%, respectively (P = 0.009). This is the first prediction of pathological margin by preoperative contrast-enhanced MRI in early breast cancer patients with SSM. Care is required for SSM if the MRI margin is less than 5 mm due to pathological margin positivity., (© 2019 Wiley Periodicals, Inc.)

Orthopedic trauma surgeons often encounter Smith's fracture in patients who report that they have fallen on the palms of their hands. The aim of this study was to clarify the pathogenesis of Smith's fracture in basic clinical aspects. First, a survey was conducted for investigating the mechanism of injury and arm position at the time of injury among patients with Smith's fractures who consulted at our outpatient clinic. Second, we created three-dimensional finite element models (FEMs) to predict the influence of arm position on the type of injury resulting from a fall. These predictions were then used in ten freshly frozen cadavers to provide experimental proof of Smith's fractures resulting from the impact on the palmar side. Twenty-six patients (5 males and 21 females) with Smith's fractures were enrolled in this study. Injury resulting from a fall on the palm of the hand, the dorsum, or ulno-dorsum of the hand, and fisting handle was observed in 16 cases (61%), 3 cases (12%), and 1 case (4%), respectively. Six patients were uncertain of their arm position at the time of injury. FEM analysis showed that Smith's fractures occurred when the angle between the long axis of the forearm and the ground was 30°-45° in the sagittal plane and 75°-90° in the coronal plane. Smith's fractures occurred in 7 of 10 wrists in the experimental study, whereas no Colles' fractures were observed. This study demonstrated that Smith's fracture results from falling on the palm of the hand. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2435-2441, 2017., (© 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Background and Purpose: Secretory phospholipase A2 (sPLA2) is implicated in atherosclerosis, although the effects of specific sPLA2 inhibitors have not been studied. We investigated the effects of the indole analogue indoxam on low-density lipoprotein (LDL) modification by sPLA2 enzymes of different types and on the associated inflammatory responses in human umbilical vein endothelial cells (HUVEC)., Experimental Approach: LDL modification was assessed by measuring the contents of two major molecular species of lysophosphatidylcholine (LPC) using electrospray ionization-liquid chromatography/mass spectrometry. The proinflammatory activity of the modified LDL was evaluated by determining monocyte chemoattractant protein-1 (MCP-1) mRNA expression and transcriptional factor nuclear factor-kappaB (NF-kappaB) activity in HUVEC., Key Results: Indoxam dose-dependently inhibited palmitoyl- and stearoyl-LPC production in LDL incubated with snake venom sPLA2 (IC50 1.2 microM for palmitoyl-LPC, 0.8 microM for stearoyl-LPC). MCP-1 mRNA expression and NF-kappaB activity were enhanced by venom sPLA2-treated LDL, which was completely suppressed by indoxam but not by thioetheramide-PC, a competitive sPLA2 inhibitor. Indoxam also suppressed LPC production in LDL treated with human synovial type IIA sPLA2. Tumour necrosis factor alpha (TNFalpha) increased type V sPLA2 expression in HUVEC. Indoxam dose-dependently suppressed LPC production in native and glycoxidized LDL treated with TNFalpha-stimulated HUVEC. Indoxam suppressed MCP-1 mRNA expression and NF-kappaB activity in TNFalpha-stimulated HUVEC incubated with native or glycoxidized LDL., Conclusions and Implications: Indoxam prevented sPLA2-induced LPC production in native and glycoxidized LDL as well as LDL-induced inflammatory activity in HUVEC. Our results suggest that indoxam may be a potentially useful anti-atherogenic agent.

This study examined the inhibitory effect of a new bisphosphonate (TRK-530) on wear debris-mediated bone resorption in a rat osteolysis model involving continuous infusion of high density polyethylene (HDPE) particles. TRK-530 (TRK) is a novel synthetic bisphosphonate that has been shown to decrease the level of tumor necrosis factor alpha (TNF-alpha) in the bone marrow of rats with adjuvant arthritis. Forty Wistar rats were randomized to two groups (n = 20 each). In each rat, a Kirshner (K) wire was inserted into the femur and HDPE particles were continuously infused into the knee joint. Thereafter, the animals were subcutaneously injected with saline (control group) or 1 mg/kg of TRK (TRK group) every second day, and were sacrificed at 4 or 8 weeks after surgery. Radiographs obtained at the time of sacrifice were evaluated for periprosthetic osteolysis. We also examined the thickness of the reactive membrane as well as the number of osteoclast-like cells around the K-wire. In addition, we examined the expression of genes for bone-resorbing cytokines in the reactive membrane. Radiographic peri-implant osteolysis was more frequent in the control group compared with the TRK group at each time of assessment (p < 0.01). The interfacial membrane was significantly thinner in the TRK group compared with the control group (p < 0.01) and the average number of osteoclast-like cells around the K-wire was significantly fewer in the TRK group (p < 0.01). In addition, the expression of interleukin 1-alpha messenger ribonucleic acid (IL-1alpha mRNA) and TNF-alpha mRNA was suppressed in the TRK group at each time of assessment. We conclude that the TRK can inhibit the formation of inflammatory peri-implant osteolysis induced by HDPE particles.

The Rvs161p and Rvs167p proteins of Saccharomyces cerevisiae, homologues of higher eukaryotes' amphiphysins, associate with actin and appear to be involved in several functions related to the actin cytoskeleton. In order to identify partners of the Rvsp proteins, yeast libraries constructed in two-hybrid vectors were screened using either Rvs167p or Rvs161p as a bait. The selected candidates, representing 34 ORFs, were then tested against both Rvsp proteins, as well as domains of Rvs167p or Rvs161p. Among the most significant ones, 24 ORFs were specific preys of Rvs167p only and two gave interactions with Rvs161p only. Interestingly, five ORFs were preys of both Rvs161p and Rvs167p (RVS167, LAS17, YNL094w, YMR192w and YPL249c). Analysis of putative functions of the candidates confirm involvement of the Rvsp in endocytosis/vesicle traffic, but also opens possible new fields, such as nuclear functions., (Copyright 2000 John Wiley & Sons, Ltd.)