Vertebrate gastrulation entails massive cell movements that establish and shape the germ layers. During gastrulation, the individual cell behaviors are strictly coordinated in time and space by ...various signaling pathways. These pathways instruct the cells about proliferation, shape, fate and migration into proper location. Convergence and extension (C&E) movements during vertebrate gastrulation play a major role in the shaping of the embryonic body. In vertebrates, the Wnt/Planar Cell Polarity (Wnt/PCP) pathway is a key regulator of C&E movements, essential for several polarized cell behaviors, including directed cell migration, and mediolateral and radial cell intercalation. However, the molecular mechanisms underlying the acquisition of Planar Cell Polarity by highly dynamic mesenchymal cells engaged in C&E are still not well understood. Here we review new evidence implicating the Wnt/PCP pathway in specific cell behaviors required for C&E during zebrafish gastrulation, in comparison to other vertebrates. We also discuss findings on the molecular regulation and the interaction of the Wnt/PCP pathway with other signaling pathways during gastrulation movements.
There is still no consensus on the analgesic range and mechanisms of action of modified thoracoabdominal nerve block through perichondrial approach (M-TAPA). This cadaveric study aimed to determine ...the spread of an injectate following simulated M-TAPA.
Simulated M-TAPA injections (n=8) were administered on both sides of soft embalmed Thiel cadavers with 25 mL of a saline-soluble dye. Anatomic dissection was performed to document staining (deeply, faintly, or not stained) of the anterior cutaneous branches of the thoracoabdominal nerves and determine the extent of the injectate spread of the dye to the intercostal space in the thoracic cage following a simulated M-TAPA.
The median (IQR) dermatome of the stained segmental nerve was T10 (T8-T11) and the median (IQR) number of stained segmental nerves was 3 (4-2). The T9, T10 and T11 segmental nerves were stained in 75%, 100% and 62.5% of simulated M-TAPA, respectively. Conversely, the T8 segmental nerve was stained in only 25% of simulated M-TAPA. No injectate spread of dye to the intercostal space in the thoracic cage was observed in eight simulated injections of M-TAPA.
Our findings suggest that M-TAPA most likely involves the T9, T10 and T11 segmental nerves and that the local anesthetic may not spread to the intercostal space in the thoracic cage in M-TAPA. Further studies are required to confirm the precise mechanism of action and efficacy of M-TAPA in a large sample of human participants.
Background
Neuromodulation by magnetic field through the AT-04 (ait® (AT-04); Peace of Mind Co., Ltd., Kumamoto, Japan) has improved allodynia in neuropathic pain model rats. This report focuses on ...neuromodulation through magnetic field exposure using the AT-04 that provided an analgesic effect in a patient with neuropathic pain.
Case presentation
A 47-year-old man presented with flaccid paralysis and extensive neuropathic pain and scored 7 on the 11-point Numerical Rating Scale (NRS) for his left upper limb. The patient was treated with neuromodulation by magnetic field exposure using the AT-04. Baseline NRS scores were obtained three times daily during the baseline period (days 1–5). Magnetic field exposure was then performed for 30 min three times daily (morning, noon, and evening) at home for 36 days, which was termed the intervention period (days 6–41). During the baseline period, the median NRS score was 7 and the baseline NRS score for calculating the percentage of nonoverlap data (PND) was 6. During the intervention period, the median NRS score was 4 and the PND value of the NRS score was 77.8% (28/36). Neuromodulation by magnetic field exposure using the AT-04 effectively decreased the patient’s NRS score. The patient had no adverse effects during the intervention period.
Conclusions
Neuromodulation by magnetic field exposure using the AT-04 was effective in decreasing the NRS score in a patient with neuropathic pain. The AT-04 portable magnetic field-generating device shows potential as a therapeutic option for refractory neuropathic pain.
Purpose
Immobilization of the cervical spine after trauma is recommended as standard care to prevent secondary injury. We tested the hypothesis that a two-handed airway maneuver, consisting of ...mandibular advancement and mouth opening in the neutral neck position, would minimize changes in the angle of the cervical vertebrae at the C0/4 level and tidal volume in non-obese patients under anesthesia with neuromuscular blockade.
Methods
Twenty consecutive patients without cervical spine injury undergoing general anesthesia were enrolled and evaluated. The primary variable was change in the angle of the cervical vertebrae at the C0/4 level during mask ventilation using the modified two-handed technique. Secondary variables included changes in the angles of the cervical vertebrae at each level between C0 and C4, anterior movement of the vertebral bodies, change in the angle between the head and neck, change in the pharyngeal airway space, and tidal volume during mask ventilation.
Results
The two-handed airway maneuver of mandibular advancement and mouth opening resulted in statistically significant changes in the angle of the cervical spine at the C0/4 level (3.2 ± 3.0 degrees,
P
< 0.001) and the C3/4 level (1.4 ± 2.2 degrees,
P
= 0.01). The two-handed airway maneuver provided adequate mask ventilation without anterior movement of the vertebral bodies.
Conclusion
Our study suggests that a two-handed airway maneuver of mandibular advancement and mouth opening in the neutral neck position results in only slight change in the cervical vertebral angle at the C0/4 level in non-obese patients under general anesthesia with neuromuscular blockade.
Chronic neuropathic pain causes abnormal sensitivities such as hyperalgesia and allodynia, and emotional abnormalities such as anxiety and depression. Although spinal cord microglia are involved in ...abnormal sensitivity to neuropathic pain, no previous studies have examined the mechanism of neuropathic pain-induced anxiety. Here, we examined the involvement of bone marrow (BM)-derived microglia aggregated in the amygdalae of mice with chronic neuropathic pain in the development of anxiety-like behavior. We prepared partial sciatic nerve ligations (PSNL) in mice that received bone marrow transplantation from green fluorescent protein (GFP)-Tg mice after irradiation with head protection, and examined GFP-positive microglia in the central nuclei of the amygdalae (CeA). On day 28 after PSNL, BM-derived microglia aggregated in the CeA concurrent with anxiety-like behavior. BM-derived microglia in the CeA highly expressed interleukin (IL)-1β and C-C chemokine receptor type 2 (CCR2). In addition, neurons in the CeA highly expressed monocyte chemotactic protein-1 (MCP-1), a ligand for CCR2, in PSNL-treated mice compared to sham-operated mice, suggesting that the MCP-1/CCR2 axis is involved in the recruitment of BM-derived microglia. Oral administration of a CCR2 antagonist decreased the number of BM-derived microglia in the CeA, and successfully reversed the anxiety-like behavior and hypersensitivity to mechanical stimuli in PSNL-treated mice. Microinjections of an IL-1β receptor antagonist directly into the CeA successfully reversed the anxiety-like behavior in the PSNL-treated mice even though the neuropathic pain persisted. These results suggest that the recruitment of BM-derived microglia to the CeA via the MCP-1/CCR2 axis and neuron-microglia interactions might be important in the pathogenesis of neuropathic pain-induced anxiety.
Purpose
The newly introduced erector spinae plane block (ESPB) has given anesthesiologists an alternative regional anesthetic technique for thoracic analgesia. Although ESPB and retrolaminar block ...(RLB) have similar puncture sites, no clinical study comparing ESPB and RLB has been reported. The aim of this study was to compare ESPB and RLB in terms of analgesic efficacy in the context of multimodal analgesia following breast surgery.
Methods
Fifty female patients undergoing breast surgery under general anesthesia were randomly allocated to receive either ultrasound-guided ESPB or RLB with 20 mL of 0.375% levobupivacaine for postoperative analgesia. The primary outcome was analgesic efficacy in terms of time to first postoperative rescue analgesic after the block procedure. The secondary outcomes were consumption of remifentanil during anesthesia, pain intensity at rest for 24 h postoperatively, and occurrence of postoperative nausea and vomiting (PONV).
Results
After excluding five patients, 45 patients (22 and 23 patients in the ESPB and RLB group, respectively) were analyzed. Median time until the first postoperative rescue analgesic after the block procedure in the ESPB group was not significantly longer than that in the RLB group (8.6 range 2.7–24 vs. 4.8 3.0–24 h;
P
= 0.83). There was no significant difference in the consumption of remifentanil during anesthesia, pain intensity at rest for 24 h postoperatively, and occurrence of PONV between the two groups.
Conclusion
ESPB is equivalent, and not superior, to RLB for postoperative analgesia after breast surgery when 20 mL of 0.375% levobupivacaine is injected at the fourth thoracic vertebra.
Background
Cigarette smoking, alcohol consumption, and Lugol-voiding lesions (LVLs) are the major causative risk factors of esophageal squamous cell carcinoma (ESCC); however, reports on ESCC cases ...unrelated to these risk factors are very limited. Here, we investigated the clinicopathological features and etiology of such cases.
Methods
We retrospectively analyzed 704 consecutive superficial ESCC tumors of 512 patients who were treated with endoscopic submucosal dissection. The enrolled patients were divided into two groups—the very low-risk (VLR)-group and risk (R)-group—based on the presence of the abovementioned risks. Clinical, endoscopic, and pathological characteristics and genetic findings were assessed in both groups.
Results
The VLR-group consisted of 21 (4.1%) patients, who were characteristically female. Patients in the VLR-group presented gastroesophageal reflux disease (GERD), hiatal hernia, and non-open-type atrophic gastritis, and were negative for
Helicobacter pylori
. We found unique endoscopic features—frequently observed in the posterior wall of the middle thoracic esophagus—with a linear shape that closely resembled the erosion-like form of GERD. Additionally, histopathological examination showed that these tumors presented atypical nuclei limited to the basal and parabasal layer, sequential to the surrounding changes that presented pathological chronic inflammation of esophagitis. Evaluation of somatic mutations in cancer-related genes using next-generation sequencing revealed that the positive carcinogenic potential (
TP53
mutation) of the tumors was relatively frequent in the VLR-group.
Conclusions
Our study suggests that ESCC without major causative factors is related to GERD, with no remarkable oncogenic difference.
Microglia of the central nervous system act as sentinels and rapidly react to infection or inflammation. The pathophysiological role of bone marrow-derived microglia is of particular interest because ...they affect neurodegenerative disorders and neuropathic pain. The hypothesis of the current study is that chronic psychological stress (chronic PS) induces the infiltration of bone marrow-derived microglia into hypothalamus by means of chemokine axes in brain and bone marrow.
Here we show that bone marrow-derived microglia specifically infiltrate the paraventricular nucleus (PVN) of mice that received chronic PS. Bone marrow derived-microglia are CX3CR1(low)CCR2(+)CXCR4(high), as distinct from CX3CR1(high)CCR2(-)CXCR4(low) resident microglia, and express higher levels of interleukin-1β (IL-1β) but lower levels of tumor necrosis factor-α (TNF-α). Chronic PS stimulates the expression of monocyte chemotactic protein-1 (MCP-1) in PVN neurons, reduces stromal cell-derived factor-1 (SDF-1) in the bone marrow and increases the frequency of CXCR4(+) monocytes in peripheral circulation. And then a chemokine (C-C motif) receptor 2 (CCR2) or a β3-adrenoceptor blockade prevents infiltration of bone marrow-derived microglia in the PVN.
Chronic PS induces the infiltration of bone marrow-derived microglia into PVN, and it is conceivable that the MCP-1/CCR2 axis in PVN and the SDF-1/CXCR4 axis in bone marrow are involved in this mechanism.
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