Deep electroacupuncture of neurogenic spots attenuates immobilization stress-induced acute hypertension in rats.

Background: Our previous studies proved that neurogenic inflammatory spots (or neurogenic spots) have the same physiological features as acupuncture points and that neurogenic spot stimulation generates therapeutic effects in various animal models. However, it is unclear how deeply the neurogenic spots should be stimulated to generate therapeutic effects. Methods: The effects of acupuncture at various needle depths below the neurogenic spot were examined in a rat immobilization stress-induced hypertension (IMH) model. Electroacupuncture was applied to a neurogenic spot at depths of 1, 2, or 3 mm using a concentric bipolar electrode. Results: Electrical stimulation of the neurogenic spot at a 3-mm depth most effectively lowered blood pressure compared with controls and stimulation at 1- and 2-mm depths, which was inhibited by pretreatment with a local anesthetic lidocaine. Electrical stimulation of the neurogenic spot or injection of substance P (SP) at a 3-mm depth significantly excited the rostral ventrolateral medulla (rVLM) compared with superficial stimulation. Electrical stimulation applied at a 3-mm depth on neurogenic spots dominantly caused c-fos expression from rVLM and ventrolateral periaqueductal gray (vlPAG) in IMH rats. Pretreatment with resiniferatoxin (RTX) injection into the neurogenic spot to ablate SP or calcitonin gene-related peptide (CGRP) prevented the effects of 3-mm neurogenic spot stimulation on blood pressure in IMH rats. Conversely, artificial injection of SP or CGRP generated anti-hypertensive effects in IMH rats. Conclusion: Our data suggest that neurogenic spot stimulation at a 3-mm depth generated anti-hypertensive effects through the local release of SP and CGRP and activation of rVLM and vlPAG.

A hypothalamus-habenula circuit regulates psychomotor responses induced by cocaine.

Administration of cocaine increases synaptic dopamine levels by blocking dopamine reuptake and leads to increased locomotor activity and compulsive drug-seeking behaviour. It has been suggested that the lateral hypothalamus (LH) or lateral habenula (LHb) is involved in drug-seeking behaviours. To explore the role of the LH and the LHb in cocaine-induced psychomotor responses, we tested whether modulation of the LH or the LH-LHb circuit affects cocaine-induced locomotion. Cocaine-induced locomotor activity and dopamine release were suppressed by the activation of the LH with 2-[2,6-difluoro-4-[[2-[(phenylsulfonyl)amino]ethyl]thio]phenoxy]acetamide (PEPA), an AMPA receptor agonist. When the LH was inhibited by microinjection of a GABA receptor agonists mixture prior to cocaine injection, the cocaine's effects were enhanced. Furthermore, optogenetic activation of the LH-LHb circuit attenuated the cocaine-induced locomotion, while optogenetic inhibition of the LH-LHb circuit increased it. In vivo extracellular recording found that the LH sent a glutamatergic projection to the LHb. These findings suggest that the LH glutamatergic projection to the LHb plays an active role in the modulation of cocaine-induced psychomotor responses.

Production of Feline Universal Erythrocytes with Methoxy Polyethylene Glycol.

Blood group mismatch in veterinary medicine is a significant problem in blood transfusion, sometimes leading to severe transfusion reactions and even patient death. Blood groups vary from species to species and there are three known blood groups in cats: A, B and AB. While A-type cats are most common, there is a shortage of feline B-type blood groups in cats. By using methoxy polyethylene glycol (mPEG) to protect antigenic epitopes on red blood cells (RBCs), we aimed to find the optimal conditions for the production of feline universal RBCs. The surfaces of feline A-type RBCs were treated with mPEG at various molecular weights and concentrations. Agglutination tests showed that the coating of feline A-type RBCs with mPEG of 20 kDa and 2 mM blocked hemagglutination to feline anti-A alloantibodies over 8 h. While no differences in RBC size and shape between intact and mPEG-treated RBCs were seen, coating RBCs with mPEG inhibited the binding of feline anti-A alloantibodies. Furthermore, the mPEG-treated RBCs did not cause spontaneous hemolysis or osmotic fragility, compared to control RBCs. According to a monocyte monolayer assay, mPEG treatment significantly reduced feline anti-A antibody-mediated phagocystosis of RBCs. These results confirm the potential of using activated mPEG on feline A-type RBC to create universal erythrocytes for transfusion to B-type cats.

Mediation of mPFC-LHb pathway in acupuncture inhibition of cocaine psychomotor activity.

The medial prefrontal cortex (mPFC) and the lateral habenula (LHb) play roles in drug addiction and cognitive functions. Our previous studies have suggested that acupuncture at Shenmen (HT7) points modulates mesolimbic reward system in order to suppress drug-induced addiction behaviours. To explore whether an mPFC-LHb circuit mediates the inhibitory effects of acupuncture on addictive behaviours, we examined the projection from mPFC to LHb, excitation of mPFC neurons during acupuncture stimulation, the effects of optogenetic modulation of mPFC-LHb on HT7 inhibition of cocaine-induced locomotion and the effect of mPFC lesion on HT7 inhibition of nucleus accumbens (NAc) dopamine release. Acupuncture was applied at bilateral HT7 points for 20 s, and locomotor activity was measured in male Sprague-Dawley rats. Although cocaine injection significantly increased locomotor activity, HT7 acupuncture suppressed the cocaine-induced locomotion. The inhibitory effect of HT7 on cocaine-enhanced locomotion was blocked by optogenetic silencing of the mPFC-LHb circuit. In vivo extracellular recordings showed that HT7 acupuncture evoked an increase in the action potentials of mPFC neurons. Optopatch experiment proved glutamatergic projections from mPFC to LHb. HT7 acupuncture suppressed NAc dopamine release following cocaine injection, which was blocked by electrolytic lesion of mPFC. These results suggest the mediation of mPFC-LHb circuit in the inhibitory effects of acupuncture on cocaine psychomotor activity in rats.

Peptides derived from high voltage-gated calcium channel ß subunit reduce blood pressure in rats.

The ß subunits of high voltage-gated calcium channels (HGCCs) are essential for optimal channel functions such as channel gating, activation-inactivation kinetics, and trafficking to the membrane. In this study, we report for the first time the potent blood pressure-reducing effects of peptide fragments derived from the ß subunits in anesthetized and non-anesthetized rats. Intravenous administration of 16-mer peptide fragments derived from the interacting regions of the ß1 [cacb1(344-359)], ß2 [cacb2(392-407)], ß3 [cacb3(292-307)], and ß4 [cacb4(333-348)] subunits with the main α-subunit of HGCC decreased arterial blood pressure in a dose-dependent manner for 5-8 min in anesthetized rats. In contrast, the peptides had no effect on the peak amplitudes of voltage-activated Ca2+ current upon their intracellular application into the acutely isolated trigeminal ganglion neurons. Further, a single mutated peptide of cacb1(344-359)-cacb1(344-359)K357R-showed consistent and potent effects and was crippled by a two-amino acid-truncation at the N-terminal or C-terminal end. By conjugating palmitic acid with the second amino acid (lysine) of cacb1(344-359)K357R (named K2-palm), we extended the blood pressure reduction to several hours without losing potency. This prolonged effect on the arterial blood pressure was also observed in non-anesthetized rats. On the other hand, the intrathecal administration of acetylated and amidated cacb1(344-359)K357R peptide did not change acute nociceptive responses induced by the intradermal formalin injection in the plantar surface of rat hindpaw. Overall, these findings will be useful for developing antihypertensives.

Mediation of lateral hypothalamus orexin input to lateral habenula in the inhibitory effects of mechanical stimulation on psychomotor responses induced by cocaine.

Introduction: The lateral hypothalamus (LH) plays an important physiological role in brain function and also plays an important role in substance abuse. The neuropeptides called orexin (or hypocretins) have been identified as being located exclusively in the cell bodies of the LH. Our previous studies have demonstrated that mechanical stimulation (MS) of the ulnar nerve produces strong inhibitory effects on cocaine addiction-like behaviors through activation of LH projection to the lateral habenula (LHb). Methods: Therefore, the present study hypothesized that ulnar MS would suppress the psychomotor responses induced by cocaine through the orexinergic LH-to-LHb pathway. Results: Ulnar MS attenuated cocaine enhancement of locomotor activity and 50-kHz ultrasonic vocalizations, which was prevented by antagonism of orexin-receptor type 2 (OX2R) in the LHb. Injection of orexin-A into the LHb reduced the cocaine-induced psychomotor responses. MS of the ulnar nerve excited LH orexinergic neurons. In addition, the excitation of LHb neurons by MS was blocked by the systemic administration of an OX2R antagonist. Discussion: These findings suggest that MS applied to the ulnar nerve recruits an orexinergic LH-to-LHb pathway to suppress the psychomotor responses induced by cocaine.

Activation of a hypothalamus-habenula circuit by mechanical stimulation inhibits cocaine addiction-like behaviors.

BACKGROUND: Mechanoreceptor activation modulates GABA neuron firing and dopamine (DA) release in the mesolimbic DA system, an area implicated in reward and substance abuse. The lateral habenula (LHb), the lateral hypothalamus (LH), and the mesolimbic DA system are not only reciprocally connected, but also involved in drug reward. We explored the effects of mechanical stimulation (MS) on cocaine addiction-like behaviors and the role of the LH-LHb circuit in the MS effects. MS was performed over ulnar nerve and the effects were evaluated by using drug seeking behaviors, optogenetics, chemogenetics, electrophysiology and immunohistochemistry. RESULTS: Mechanical stimulation attenuated locomotor activity in a nerve-dependent manner and 50-kHz ultrasonic vocalizations (USVs) and DA release in nucleus accumbens (NAc) following cocaine injection. The MS effects were ablated by electrolytic lesion or optogenetic inhibition of LHb. Optogenetic activation of LHb suppressed cocaine-enhanced 50 kHz USVs and locomotion. MS reversed cocaine suppression of neuronal activity of LHb. MS also inhibited cocaine-primed reinstatement of drug-seeking behavior, which was blocked by chemogenetic inhibition of an LH-LHb circuit. CONCLUSION: These findings suggest that peripheral mechanical stimulation activates LH-LHb pathways to attenuate cocaine-induced psychomotor responses and seeking behaviors.

Reducing the Volume of Upper Eyelids in East Asians Increases Vertical Palpebral Height.

BACKGROUND: Correcting puffy eyelids is important for improving the first impression. The puffiness is most predictable corrected by tissue resection and fat excision. Fold asymmetry, overcorrection, and recurrence can sometimes occur after levator aponeurosis manipulation. The objective of this study was to introduce a method of volume-controlled blepharoptosis correction (VC) without levator manipulation. METHODS: The medical records of patients who had undergone upper blepharoplasty between 2017 and 2022 were retrospectively reviewed. Questionnaires, digital photographs, and charts were used to evaluate the surgical outcomes and complications. The degree of levator function was graded as poor, fair, good, or very good. Levator function must be above good (>8 mm) to employ the VC method. Poor and fair grades of levator function were excluded because they require levator aponeurosis manipulation. The margin to reflex distance (MRD) 1 was assessed preoperatively, 2 weeks postoperatively, and at follow-up visits. RESULTS: Postoperative satisfaction was 4.3 ± 0.8 with no postoperative discomfort (0%), and the duration of swelling was 10.1 ± 2.0 days. Regarding other complications, no fold asymmetry (0%) was observed, although hematoma formation was observed in 1 (2.9%) patient in the VC group. Significant differences were observed in the changes in palpebral fissure height over time (p < 0.001). CONCLUSIONS: VC can effectively correct puffy eyelids and create natural-looking, beautiful, and thin eyelids. Thus, VC is associated with higher patient satisfaction and surgical longevity without serious complications. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A novel ultrasonic inspection method of the heat exchangers based on circumferential waves and deep neural networks.

The heat exchanger (HE) is an important component of almost every energy generation system. Periodic inspection of the HEs is particularly important to keep high efficiency of the entire system. In this paper, a novel ultrasonic water immersion inspection method is presented based on circumferential wave (CW) propagation to detect defective HE. Thin patch-type piezoelectric elements with multiple resonance frequencies were adopted for the ultrasonic inspection of narrow-spaced HE in an immersion test. Water-filled HE was used to simulate defective HE because water is the most reliable indicator of the defect. The HE will leak water no matter what the defect pattern is. Furthermore, continuous wavelet transform (CWT) was used to investigate the received CW, and inverse CWT was applied to separate frequency bands corresponding to the thickness and lateral resonance modes of the piezoelectric element. Different arrangements of intact and leaky HE were tested with several pairs of thin piezoelectric patch probes in various instrumental setups. Also, direct waveforms in the water without HE were used as reference signals, to indicate instrumental gain and probe sensitivity. Moreover, all filtered CW corresponding to resonance modes together with the direct waveforms in the water were used to train the deep neural networks (DNNs). As a result, an automatic HE state classification method was obtained, and the accuracy of the applied DNN was estimated as 99.99%.

Activation of a hypothalamus-habenula circuit by mechanical stimulation inhibits cocaine addiction-like behaviors

BACKGROUND: Mechanoreceptor activation modulates GABA neuron firing and dopamine (DA) release in the mesolimbic DA system, an area implicated in reward and substance abuse. The lateral habenula (LHb), the lateral hypothalamus (LH), and the mesolimbic DA system are not only reciprocally connected, but also involved in drug reward. We explored the effects of mechanical stimulation (MS) on cocaine addiction-like behaviors and the role of the LH-LHb circuit in the MS effects. MS was performed over ulnar nerve and the effects were evaluated by using drug seeking behaviors, optogenetics, chemogenetics, electrophysiology and immunohistochemistry. RESULTS: Mechanical stimulation attenuated locomotor activity in a nerve-dependent manner and 50-kHz ultrasonic vocalizations (USVs) and DA release in nucleus accumbens (NAc) following cocaine injection. The MS effects were ablated by electrolytic lesion or optogenetic inhibition of LHb. Optogenetic activation of LHb suppressed cocaine-enhanced 50 kHz USVs and locomotion. MS reversed cocaine suppression of neuronal activity of LHb. MS also inhibited cocaine-primed reinstatement of drug-seeking behavior, which was blocked by chemogenetic inhibition of an LH-LHb circuit. CONCLUSION: These findings suggest that peripheral mechanical stimulation activates LH-LHb pathways to attenuate cocaine-induced psychomotor responses and seeking behaviors.

An Increase in Peripheral Temperature following Cocaine Administration Is Mediated through Activation of Dopamine D2 Receptor in Rats.

Drug addiction has become a worldwide problem, affecting millions of people across the globe. While the majority of mechanistic studies on drug addiction have been focused on the central nervous system, including the mesolimbic dopamine system, the peripheral actions of drugs of abuse remain largely unknown. Our preliminary study found that the systemic injection of cocaine increased peripheral skin temperature. This led us to our present study, which investigated the mechanisms underlying the increase in peripheral temperature following cocaine injection. Male Sprague Dawley rats were anesthetized with pentobarbital sodium, and peripheral skin temperature measurements were taken using a thermocouple needle microprobe and an infrared thermal camera. Cocaine injection caused an acute rise in peripheral body temperature, but not core body temperature, about 10 min after injection, and the temperature increases were occluded by systemic injection of dopamine D2 receptor antagonist L741,626, but not D1 receptor antagonist SCH23390. In addition, systemic administration of bromocriptine, a dopamine D2 receptor agonist, significantly increased peripheral temperature. Infrared thermal imaging showed that the thermal increases following cocaine injection were predominantly in the distal areas of the forelimbs and hindlimbs, relative to core body temperature. Treatment with cocaine or bromocriptine decreased the size of skin blood vessels without affecting the expression of dopamine D2 receptors. These results suggest that increased peripheral temperature in skin following cocaine injection is associated with the activation of the dopamine D2 receptor.

Establishment and characterization of two human cutaneous angiosarcoma cell lines, KU-CAS3 and KU-CAS5.

BACKGROUND: Cutaneous angiosarcoma (CAS) is a rare but fatal cancer. Established CAS cell lines are necessary for the investigation of their properties and treatment options. METHODS: Two cell lines, KU-CAS3 and KU-CAS5, were established from human angiosarcoma specimens obtained from the scalp. Flow cytometric assay, tube formation assay, low-density lipoprotein (LDL) uptake assay, immunofluorescence analysis, real-time PCR, tumorigenesis assay, and STR analysis were conducted. RESULTS: The cells showed endothelial cell properties, based on the cobblestone appearance upon reaching confluence, CD31 positivity, tube-formation activity, active uptake of acetylated LDL, and vWF expression. The two cell lines expressed relatively high levels of adrenergic ß2 receptor, and the VEGF1 and VEGF2 receptors. In the in vivo study, the growing neoplasms, confirmed as CAS, were identified as subcutaneous dark papules. KU-CAS cell lines were considered authentic based on STR profiling. CONCLUSIONS: KU-CAS3 and KU-CAS5 are the first human CAS cell lines having tumorigenic potential in vivo.

Chemical Sterilization of Lipoplasty Cannula and Nontuberculous Mycobacteria Disinfection: An Experimental Study.

BACKGROUND: Nontuberculous mycobacteria are commonly found pathogens; however, skin and soft tissue infections due to nontuberculous mycobacteria are often associated with surgical procedures, particularly after lipoplasty. Although nontuberculous mycobacteria are resistant to some chemical disinfectants, glutaraldehyde, peracetic acid, povidone iodine, alcohol, and chlorine are still used for the sterilization of medical instruments. This study investigated the efficacy of various disinfectants in a fatty environment with adipose and a bloody environment without adipose. In addition, this study was also used to identify the most effective disinfectant against nontuberculous mycobacteria. METHODS: Three nontuberculous mycobacteria (Mycobacterium avium, M. abscessus, and M. fortuitum), pathogens frequently found in skin and soft tissue infections, were used. Seven chemical disinfectants were tested in both fatty and bloody environments. The disinfectants used were considered to have a sterilization effect when the log10 reduction factor exceeded 5. RESULTS: Most disinfectants had some sterilizing effects against nontuberculous mycobacteria; however, glutaraldehyde was the most effective against all 3. Chlorhexidine and povidone iodine also displayed sterilizing effects. Of the disinfectants tested, only alkyldiaminoethylglycine hydrochloride showed a diminished effect with statistical significance, specifically against M. fortuitum in a fatty environment, whereas it had effective results in a bloody environment. CONCLUSIONS: Glutaraldehyde showed the greatest sterilizing effect on nontuberculous mycobacteria with a log10 reduction factor >5 in both fatty and bloody environments. However, some chemical disinfectants did not show sufficient sterilizing effects in a fatty environment and, therefore, should be used with caution for the sterilization of nontuberculous mycobacteria. LEVEL OF EVIDENCE: Level II.

Vascularized lymph node transfer for surgical treatments of upper versus lower extremity lymphedema.

OBJECTIVE: The purpose of this study was to compare clinical outcomes after vascularized lymph node transfer (VLNT) for the treatment of lymphedema performed on the upper and lower extremities. METHODS: Between April 2015 and January 2020, 71 patients with advanced-stage lymphedema, categorized as International Society of Lymphology late stage 2 or 3, who underwent VLNT in upper and lower extremities were included in this study. Thirty-seven and 34 patients underwent VLNT in upper and lower extremities, respectively. The circumference of the affected and unaffected extremities was measured at baseline, follow-up visits, and at the last visit. The circumference was measured in six places on the extremities, and the circumference and volume percent differences between the affected and unaffected extremities were calculated. First, we compared preoperative and postoperative extremity circumferences in the overall, upper, and lower extremity groups. Second, we compared circumference and volume percent differences between the affected and unaffected extremities calculated at the last visit to identify the degree of improvement by VLNT in the upper and lower extremity groups. RESULTS: The results of the comparative analysis between the preoperative and postoperative extremity circumferences showed that all postoperative extremity circumferences measured at the last visit were decreased compared with the preoperative values in the overall, upper, and lower extremity groups. In the upper extremity group, the circumference percent difference measured at the elbow was 23.1% before surgery and decreased to 13.4% at the last visit (P < .001). In the lower extremity group, the circumference percent difference measured at the knee was 24.4% before surgery and decreased to 17.4% at the last visit (P = .003). In the results of comparative analysis between the upper and lower extremity groups, there was a statistically significant difference in the postoperative circumference percent differences at the elbow/knee calculated at the last visit (P = .048). Similarly, there were statistically significant differences in circumference percent differences in two of six measurement sites at the last visit between the upper and lower extremity groups. However, there was no statistically significant difference in the volume percent difference calculated at the last visit between the upper and lower extremity groups. CONCLUSIONS: These results demonstrate that VLNT may be effective in treating patients with advanced-stage lymphedema. However, patients with upper extremity lymphedema demonstrate superior outcomes compared with those with lower extremity lymphedema.

Role of Lateral Hypothalamus in Acupuncture Inhibition of Cocaine Psychomotor Activity.

Acupuncture modulates the mesolimbic dopamine (DA) system; an area implicated in drug abuse. However, the mechanism by which peripheral sensory afferents, during acupuncture stimulation, modulate this system needs further investigation. The lateral hypothalamus (LH) has been implicated in reward processing and addictive behaviors. To investigate the role of the LH in mediating acupuncture effects, we evaluated the role of LH and spinohypothalamic neurons on cocaine-induced psychomotor activity and NAc DA release. Systemic injection of cocaine increased locomotor activity and 50 kHz ultrasonic vocalizations (USVs), which were attenuated by mechanical stimulation of needles inserted into HT7 but neither ST36 nor LI5. The acupuncture effects were blocked by chemical lesions of the LH or mimicked by activation of LH neurons. Single-unit extracellular recordings showed excitation of LH and spinohypothalamic neurons following acupuncture. Our results suggest that acupuncture recruits the LH to suppress the mesolimbic DA system and psychomotor responses following cocaine injection.

Role of the central amygdala in acupuncture inhibition of methamphetamine-induced behaviors in rats.

Methamphetamine (METH) enhances dopamine (DA) transmission in the mesolimbic system implicated in its reinforcing effects. Our previous studies have shown that acupuncture attenuates drug-seeking behaviors by modulating GABAergic transmission in the ventral tegmental area and DA release in the nucleus accumbens (NAc) of the striatum. The effects of acupuncture on METH-induced behaviors and its mediation by neural pathways remain a relatively understudied area of research. The central amygdala (CeA) plays a critical role in physiological and behavioral responses to somatosensory and drug stimuli and has been implicated in negative reinforcement. Thus, we evaluated the role of the CeA in acupuncture effects on locomotor activity, positive affective states, and DA release in the NAc following acute administration of METH. Acupuncture at acupoint HT7 reduced locomotor activity, 50-kHz ultrasonic vocalizations (USVs), and NAc DA release following systemic injection of METH, which was prevented by electrolytic lesions or optogenetic inhibition of the CeA. Acupuncture alone excited CeA neurons and reversed the suppression of CeA neurons induced by METH. These results suggest that acupuncture can relieve psychomotor responses and positive affective states following METH by inhibiting NAc DA release and this effect is mediated by activation of CeA neurons.

Aesthetic Comparison of Abdominal Donor Site Scar Between Absorbable Dermal Staple and Subcutaneous Suture after Autologous Breast Reconstruction: A Prospective Randomized Controlled, Double-Blinded Study.

BACKGROUND: Abdominal tissue transfer has become the most commonly used tool for breast reconstruction. However, a secondary operator is often responsible for donor closure, which leaves dissatisfaction to patients due to inconsistent donor scars. Now, an absorbable dermal stapler is popularized worldwide and currently used for wound closure in many surgical fields. In this study, we aim to evaluate the abdominal donor site scar in using an absorbable dermal staple compared to a conventional suture. METHODS: This is a prospective, randomized controlled and double-blinded study. Between January 2018 and April 2019, a total of 30 patients who underwent breast reconstruction using abdominal flap were included. Donor sites were divided into equal halves, and the each dermal layer was sutured with either dermal staples or traditional suturing, respectively. At 1, 3 and 6 months after operation, the scar was evaluated by two blinded plastic surgeons by using the modified Manchester scar scale (MSS). RESULTS: An averaged sum of modified MSS was lower for the side sutured with a dermal stapler at the first month (11.76 ± 2.12 vs. 12.28 ± 2.03, p = 0.097), third month (12.17 ± 1.86 vs. 12.62 ± 2.31, p = 0.301) and sixth month (11.28 ± 2.63 vs. 12.14 ± 2.76, p = 0.051). Also, the dermal stapler side scored significantly higher for patient satisfaction than did the suture side (4.03 ± 0.98 vs 3.66 ± 0.97, p < 0.05). CONCLUSION: The objective outcome of the scar closed by an absorbable dermal stapler was not statistically superior to conventional suturing. (p > 0.05) In the subjective outcome, however, it showed a significantly higher patients' satisfaction (p < 0.05). LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Voltage-dependent calcium channel ß subunit-derived peptides reduce excitatory neurotransmission and arterial blood pressure.

AIMS: Voltage-dependent calcium channels (VDCCs) play an important role in various physiological functions in the nervous system and the cardiovascular system. In L-, N-, P/Q-, and R-type VDCCs, ß subunit assists the channels for membrane targeting and modulates channel properties. In this study, we investigated whether an inhibition of the ß subunit binding to α subunit, the pore-forming main subunit of VDCCs, have any effect on channel activation and physiological functions. MAIN METHODS: Peptides derived from the specific regions of ß subunit that bind to the α-interaction domain in I-II linker of α subunit were manufactured, presuming that the peptides interrupt α-ß subunit interaction in the channel complex. Then, they were tested on voltage-activated Ca2+ currents recorded in acutely isolated trigeminal ganglion (TG) neurons, excitatory postsynaptic currents (EPSCs) in the spinal dorsal horn neurons, and arterial blood pressure (BP) recorded from the rat femoral artery. KEY FINDINGS: When applied internally through patch pipettes, the peptides decreased the peak amplitudes of the voltage-activated Ca2+ currents. After fusing with HIV transactivator of transcription (TAT) sequence to penetrate cell membrane, the peptides significantly decreased the peak amplitudes of Ca2+ currents and the peak amplitudes of EPSCs upon the external application through bath solution. Furthermore, the TAT-fused peptides dose dependently reduced the rat BP when administered intravenously. SIGNIFICANCE: These data suggest that an interruption of α-ß subunit association in VDCC complex inhibits channel activation, thereby reducing VDCC-mediated physiological functions such as excitatory neurotransmission and arterial BP.

Cartilage tissue engineering for craniofacial reconstruction.

Severe cartilage defects and congenital anomalies affect millions of people and involve considerable medical expenses. Tissue engineering offers many advantages over conventional treatments, as therapy can be tailored to specific defects using abundant bioengineered resources. This article introduces the basic concepts of cartilage tissue engineering and reviews recent progress in the field, with a focus on craniofacial reconstruction and facial aesthetics. The basic concepts of tissue engineering consist of cells, scaffolds, and stimuli. Generally, the cartilage tissue engineering process includes the following steps: harvesting autologous chondrogenic cells, cell expansion, redifferentiation, in vitro incubation with a scaffold, and transfer to patients. Despite the promising prospects of cartilage tissue engineering, problems and challenges still exist due to certain limitations. The limited proliferation of chondrocytes and their tendency to dedifferentiate necessitate further developments in stem cell technology and chondrocyte molecular biology. Progress should be made in designing fully biocompatible scaffolds with a minimal immune response to regenerate tissue effectively.

Acupuncture Improves Comorbid Cognitive Impairments Induced by Neuropathic Pain in Mice.

Growing evidence indicates that neuropathic pain is frequently accompanied by cognitive impairments, which aggravate the quality of life of chronic pain patients. Here, we investigated whether acupuncture treatments can improve cognitive dysfunction as well as allodynia induced by neuropathic pain in mice. One week after the left partial sciatic nerve ligation (PSNL), acupuncture treatments on the acupoints GB30-GB34 (AP1), HT7-GV20 (AP2), or control points (CP) were performed for 4 weeks. Notably, the significant attenuations of mechanical allodynia and cognitive impairment were observed in the AP1 group, but not in PSNL, AP2, or CP groups. A random decision forest classifier based on the pain and cognitive functions displayed that the acupuncture group was clearly segregated from the other groups. We also demonstrated that acupuncture restored the reduced field excitatory post-synaptic potentials and was able to elevate the expression levels of glutamate receptors (NR2B and GluR1) in the hippocampus. Moreover, the expressions of Ca2+/calmodulin-dependent protein kinase II and synaptic proteins (pPSD-95 and pSyn-1) were enhanced by acupuncture treatment. These results suggest that acupuncture can enhance hippocampal long-term action through the regulation of the synaptic efficacy and that acupuncture may provide a viable option for managing both pain and cognitive functions associated with chronic neuropathic pain.