The effectiveness of acupuncture as an adjunctive therapy to oral pharmacological medication in patient with knee osteoarthritis: A systematic review and meta-analysis.

BACKGROUND: We aimed to find out whether the combined treatment of acupuncture and oral medication is more effective than sole oral medication in reducing pain and improving knee function at the end of treatment and after short-term period (4-6 weeks after treatment). Second, if it is effective, we investigated whether the effect surpasses the minimal clinically important difference. METHODS: Articles published between January 1, 1992, and August 31, 2022, were searched in PubMed, Cochrane, and Embase. The PICO (population, intervention, comparison, and outcome) of this study are as follows: Population: knee osteoarthritis patients; Intervention: acupuncture (non-sham acupuncture) + oral medication (analgesic or non-steroidal anti-inflammatory drugs); Comparison: oral medication (analgesic or non-steroidal anti-inflammatory drugs); Outcome: visual analog scale (VAS) or Western Ontario and McMaster University (WOMAC) osteoarthritis index. RESULTS: The combined treatment of oral medication and adjuvant acupuncture showed statistically significant improvement in VAS and WOMAC scores at the end of acupuncture treatment and short-term follow-up time (between 4 and 6 weeks after acupuncture). In addition, the degree of improvement of VAS and WOMAC index showed effects beyond minimal clinically important differences compared to pretreatment at both the end of acupuncture treatment and the short-term follow-up of acupuncture treatment. CONCLUSION: The existing evidence suggests that adjuvant acupuncture may play a role in the treatment of knee osteoarthritis. However, physicians should be aware of adverse effects such as hematoma in adjuvant acupuncture treatment.

CPR quality with rotation of every 1 versus 2 minutes as characteristics of rescuers: A randomized crossover simulation study.

BACKGROUND: Fatigue and rotation time are key factors affecting the quality of cardiopulmonary resuscitation (CPR). This study aimed to investigate the effects of rotation time on CPR duration, and sex on chest compression quality. METHODS: In this randomized crossover simulation study, we enrolled 100 paramedic students stratified by sex and randomly grouped into 28 male and 22 female pairs. In the 2- and 1-minute scenarios, 2 participants performed CPR for 20 minutes with a rotation cycle of 2 minutes and 1 minute, respectively. After taking a break, they changed over and performed CPR again for 20 minutes. The switching of roles was performed with the students positioned on opposite sides of the mannequin. For chest compression quality, a set was defined as CPR performed by 1 pair in a 2-minute scenario for 4 minutes. The quality of CPR in each set was compared between the 2 groups. RESULTS: The 1-minute group showed significantly higher chest compression depth than the 2-minute group (54.0 [51.5-57.0] vs 52.5 [48.5-56.5] mm, P = .001, respectively). The female 2-minute group showed decreased chest compression depth over time, and the 1-minute group showed significantly increased chest compression depth during all sets except the 2nd set (54.0 [51.9-55.1] vs 50.5 [48.5-53.8] mm [P = .030], 52.3 [49.4-54.5] vs 50.8 [47.0-53.1] mm [P = .080], 52.8 [49.8-54.5] vs 48.8 [45.4-51.6] mm [P = .002], 51.5 [48.5-53.3] vs 48.3 [44.5-50.6] mm [P = .004], and 50.8 [48.9-54.1] vs 47.5 [44.6-50.1] mm [P = .001], respectively). The fatigue scores in the 2-minute group were significantly higher during sets 4 and 5 than those in the 1-minute group. CONCLUSION: When rescuer fatigue increases during prolonged CPR owing to their physical strength and skill levels, the rotation of rescuers every minute would be helpful in maintaining high-quality CPR.

Impact of the COVID-19 Pandemic on Adolescent Self-Harm: Based on a National Emergency Department Information System.

Republic of Korea's suicide rate is the highest among Organization for Economic Co-operation and Development countries. In Republic of Korea, suicide is the leading cause of death among young people aged 10-19 years. This study aimed to identify changes in patients aged 10-19 years who visited the emergency department in Republic of Korea after inflicting self-harm over the past five years and to compare the situations before and after the outbreak of the COVID-19 pandemic. Analysis of government data revealed that the average daily visits per 100,000 were 6.25, 8.18, 13.26, 15.31, and 15.71 from 2016 to 2020, respectively. The study formed four groups for further analysis, with the population divided by sex and age (10-14 and 15-19 years old). The late-teenage female group showed the sharpest increase and was the only group that continued to increase. A comparison of the figures 10 months before and after the outbreak of the pandemic revealed a statistically significant increase in self-harm attempts by only the late-teenage female group. Meanwhile, visits (per day) in the male group did not increase, but the rates of death and ICU admission increased. Additional studies and preparations that account for age and sex are warranted.

Influence of meteorological factors on development of spontaneous pneumothorax.

This study investigated the correlation between spontaneous pneumothorax (SP) and meteorological factors during different seasons. Patients who visited emergency rooms (ERs) in large cities in Korea and were discharged with SP from 2014 to 2016 were included in this study. Data on temperature, air pressure, and wind speed for each region were collected to obtain each factor's daily maximum, minimum, average, and changes. Days with more than 1 case of SP per million were referred to as pneumothorax days (PD) and those with less than 1 case of SP per million were referred to as non-pneumothorax days (NPD). The environmental factors were assessed on the same day (Day 0), 1 day prior (Day-1), and 2 days prior (Day-2) to PD and NPD per season. A total of 17,846 patients were included in this study. During winter, 4080 patients with SP visited the ERs of large cities with low population densities. The maximum temperature (0.16°C vs 0.76°C, 0.04°C vs 0.87°C, and 0.09°C vs 0.91°C), change in temperature (0.24°C vs 0.90°C, 0.38°C vs 0.81°C, and 0.41°C vs 0.83°C), average atmospheric pressure (0.16 vs 0.52 hPa, 0.25 vs 0.42 hPa, 0.34 vs 0.40 hPa), and maximum atmospheric pressure (0.15 vs 0.53 hPa, 0.28 vs 0.49 hPa, 0.33 vs 0.71 hPa) were greater for Day 0, Day-1, and Day-2, respectively, in PD than in NPD. Meanwhile, the average (0.31 vs 0.48 m/s, 0.28 vs 0.46 m/s, 0.20 vs 0.40 m/s), minimum (0.20 vs 0.31 m/s, 0.18 vs 0.25 m/s, 0.16 vs 0.25 m/s), and maximum (0.44 vs 0.67 m/s, 0.36 vs 0.71 m/s, 0.26 vs 0.58 m/s) wind speeds were slower, and the changes in wind speed (0.44 vs 0.67 m/s, 0.36 vs 0.71 m/s, 0.16 vs 0.25 m/s) were lower for all 3 days in PD than in NPD. High average and change in temperature, slow and unchanging wind speed, and high average and maximum atmospheric pressure were associated with SP. Since many findings of this study were contradictory to previous studies, it is assumed that the interaction of various factors affects SP.

Unintentional fatal toxicity due to nicotine chewing gum: A case report.

RATIONALE: Since tobacco contains numerous harmful substances, besides nicotine, which is addictive, smoking cessation products and tobacco alternatives, such as electronic (e-) cigarettes, nicotine chewing gums, and patches, are being widely used. Nicotine gums are consumed orally. The nicotine from the gum is absorbed at a slower rate than that from e-cigarettes, and the former remains in the bloodstream for a longer period. In addition, the maximum number of daily doses is high, and it can be purchased without a doctor's prescription in many countries. PATIENT CONCERNS: A 29-year-old male patient consumed 5 2-mg nicotine gums at a time, twice a day, for 4 days (total amount: 70 mg). However, he visited the emergency unit with the chief complaint of involuntary limb movements after consuming an additional 15 gums 3 hour before the visit. At admission, his consciousness was clear, although 2 hour later, he experienced sudden loss of consciousness with worsening hypoxia and respiratory acidosis. DIAGNOSIS: The patient's vital signs were stable at the time of admission, and blood test results showed no specific findings other than a white blood cell count of 14,800/µL, lactate level of 6.4 mmol/L, and prolactin level of 119.02 ng/mL. In addition, chest radiography and head computed tomography scans showed no acute phase abnormalities. Two hours later, he experienced loss of consciousness and respiratory failure, and the results of blood tests performed at this time showed that his blood cotinine level was 3491 ng/mL. INTERVENTIONS: Supportive treatment, including endotracheal intubation followed by mechanical ventilation, was provided. OUTCOME: The patient's vital signs stabilized 3 days after treatment, and his consciousness and respiratory status had improved; therefore, mechanical ventilation was stopped. His condition was stable for the next 2 days, and he was discharged on the fifth day. LESSONS: Acute respiratory exacerbation due to nicotine poisoning (from levels exceeding the lethal dose of 30-60 mg) was observed, although the gums were consumed over several days. Patients with nicotine poisoning may show acute respiratory failure and should be monitored carefully. Further studies are required to determine the toxic effects of nicotine replacement therapies.

Low-voltage Activating K+ Channels in Cochlear Afferent Nerve Fiber Dendrites.

Cochlear afferent nerve fibers (ANF) are the first neurons in the ascending auditory pathway. We investigated the low-voltage activating K+ channels expressed in ANF dendrites using isolated rat cochlear segments. Whole cell patch clamp recordings were made from the dendritic terminals of ANFs. Outward currents activating at membrane potentials as low as -64 mV were observed in all dendrites studied. These currents were inhibited by 4-aminopyridine (4-AP), a blocker known to preferentially inhibit low-voltage activating K+ currents (IKL) in CNS auditory neurons and spiral ganglion neurons. When the dendritic IKL was blocked by 4-AP, the EPSP decay time was significantly prolonged, suggesting that dendritic IKL speeds up the decay of EPSPs and likely modulates action potentials of ANFs. To reveal molecular subtype of dendritic IKL, α-dendrotoxin (α-DTX), a selective inhibitor for Kv1.1, Kv1.2, and Kv1.6 containing channels, was tested. α-DTX inhibited 23±9% of dendritic IKL. To identify the α-DTXsensitive and α-DTX-insensitive components of IKL, immunofluorescence labeling was performed. Strong Kv1.1- and Kv1.2-immunoreactivity was found at unmyelinated dendritic segments, nodes of Ranvier, and cell bodies of most ANFs. A small fraction of ANF dendrites showed Kv7.2- immunoreactivity. These data suggest that dendritic IKL is conducted through Kv1.1and Kv1.2 channels, with a minor contribution from Kv7.2 and other as yet unidentified channels.

Changes in self-harm attempts after the COVID-19 pandemic based on pre-hospital medical records.

Although many concerns have been raised on increased self-harm or suicide attempts since the emergence of the coronavirus disease 2019 (COVID-19) pandemic, the numbers of studies reported no consistent increase. This study aimed to analyze the data on the request for emergency medical service (EMS) in Daegu Metropolitan City in Korea to investigate the effects of the COVID-19 pandemic on the incidence and types of suicidal patients. Data of 4480 cases requesting EMS related to self-harm or suicide 1 year before and after the COVID-19 pandemic were retrospectively comparatively analyzed (February 19, 2019-February 18, 2021). The number of EMS requests for self-harm and suicide increased after the pandemic compared to that before the pandemic (daily mean request 5.83 [±2.597] vs 6.43 [±2.918]). In particular, the number of female patients increased per day on average (2.61 [±1.717] vs 3.17 [±1.893]). With respect to the reasons for the request, committed self-harm and attempts to commit self-harm increased, whereas the presumption against suicide decreased. With respect to consciousness levels, the number of alert patients increased, whereas the number of transport cases decreased. For the method of the attempt, hanging and carbon monoxide/gas poisoning decreased, whereas jumping from a height and drowning increased. The number of patients with psychiatric history and those with other chronic illnesses increased. In multivariate regression analysis, women (OR 1.227, 95% CI = 1.072-1.405, P = .003), patients with psychiatric diseases (OR 1.223, 95% CI = 1.031-1.450, P = .021), patients with other chronic illnesses (OR 1.510, 95% CI = 1.127-2.023, P = .006), and CO or gas poisoning (not attempted) (OR 1.349, 95% CI = 1.038-1.753, P = .025) showed statistically significant differences. Among the request for EMS, requests for committed self-harm and attempts to commit suicide increased. Medical support and measures for mental health and emergency medical systems should be established for female patients and patients with psychiatric or other chronic diseases.

Effects of dynamic response to coronavirus disease outbreak in a regional emergency medical center: A retrospective study.

ABSTRACT: Emergency departments (EDs) are on the frontline of the coronavirus disease (COVID-19) outbreak. To resolve the abrupt overloading of COVID-19-suspected patients in a community, each ED needs to respond in various ways. In our hospital, we increased the isolation beds through temporary remodeling and by performing in-hospital COVID-19 polymerase chain reaction testing rather than outsourcing them. The aim of this study was to verify the effects of our response to the newly developed viral outbreak.The medical records of patients who presented to an ED were analyzed retrospectively. We divided the study period into 3: pre-COVID-19, transition period of response (the period before fully implementing the response measures), and post-response (the period after complete response). We compared the parameters of the National Emergency Department Information System and information about isolation and COVID-19.The number of daily ED patients was 86.8 ±â€Š15.4 in the pre-COVID-19, 36.3 ±â€Š13.6 in the transition period, and 67.2 ±â€Š10.0 in the post-response period (P < .001). The lengths of stay in the ED were significantly higher in transition period than in the other periods [pre-COVID-19 period, 219.0 (121.0-378.0) min; transition period, 301 (150.0-766.5) min; post-response period, 281.0 (114.0-575.0) min; P < .001]. The ratios of use of an isolation room and fever (≥37.5°C) were highest in the post-response period [use of isolation room: pre-COVID-19 period, 0.6 (0.7%); transition period, 1.2 (3.3%); post-response period, 16.1 (24.0%); P < .001; fever: pre-COVID-19 period, 14.8(17.3%); transition period, 6.8 (19.1%); post-response period, 14.5 (21.9%), P < .001].During an outbreak of a novel infectious disease, increasing the number of isolation rooms in the ED and applying a rapid confirmation test would enable the accommodation of more suspected patients, which could help reduce the risk posed to the community and thus prevent strain on the local emergency medical system.

Comparison of the effects of shortening rest intervals on the quality of cardiopulmonary resuscitation, physiological parameters, and hemodynamic parameters in well-trained rescuers: Randomized simulation study.

BACKGROUND: Cardiopulmonary resuscitation (CPR) performance depends on individual ability and training. Well-trained or professional rescuers can maintain high-quality CPR for longer than laypeople. This study aimed to examine the effects of reducing resting intervals on CPR performance, physiological parameters, and hemodynamic parameters during prolonged CPR in well-trained providers. METHODS: The study enrolled 90 volunteers from the paramedic students of our institution. They were randomly divided into 3 groups: 2 minutes, 1 minute 45 seconds, and 1 minute 30 seconds rest groups. Each participant performed 5 cycles of chest compression only CPR (2 min/cycle) with different resting intervals according to grouping. CPR quality, physiological variations, and hemodynamic variations were measured for each cycle and compared across the groups. RESULTS: Of the 90 volunteers, 79 well-trained providers were finally included. The variation of the average chest compression depth across the 5 cycles showed significant differences between the 3 groups: from cycle 1 to 2: 1.2 (3.1) mm, -0.8 (2.0) mm, and -2.0 (3.0) mm in the 2 minutes, 1 minute 45 seconds, and 1 minute 30 seconds groups, respectively (P < .001); from cycle 1 to 3: 0.0 (3.0) mm, -0.7 (3.2) mm, and -2.6 (3.9) mm, respectively (P = .030). However, all 3 groups maintained the recommended rate and chest compression depth for all 5 cycles. Physiological and hemodynamic parameters showed no significant differences between the groups. CONCLUSIONS: Well-trained providers were able to maintain high-quality CPR despite reducing rest intervals. Adjusting the rest interval may help maintain overall CPR quality in special situations or where layperson rescuers are involved.

Impact of the coronavirus disease 2019 outbreak on the transportation of patients requiring emergency care.

The first confirmed community transmission of coronavirus disease 2019 in Daegu Metropolitan City, South Korea, occurred on February 18, 2020. In the following 70-day period, approximately 6000 new cases occurred, severely impacting the medical service system. This study investigated the crisis-impact on the local emergency transport system.Emergency medical service activity reports were retrospectively reviewed to determine patient demographics and initial vital signs. Delay in reaching the patient, transporting the patient to the hospital, and returning to the fire station were assessed and categorized based on patients' initial vital signs. The study period was divided into 4 groups (1/1-2/18, 2/19-3/3, 3/4-3/31, and 4/1-04/30) and intergroup differences were analyzed.When compared to Period 1, the time-difference between the request to attend a scene and arrival at the scene was delayed in Periods 2, 3, and 4 by 4 minute 58 s, 3  minute 24 seconds, and 2 minute 20 seconds, respectively; that between arriving at the scene and at the hospital was delayed by 7  minute 43 seconds, 6 minutes 59 seconds, and 4 minutes 30 seconds, respectively; and that between arriving at the hospital and returning to the fire station was delayed by 29  minute 3 second, 25  minute 55 second, and 18  minute 44 second, respectively. In Period 2, for patients with symptoms of severe illness when compared to patients lacking such symptoms, the time-difference between the request to attend the scene and arrival at a hospital and between arrival at the hospital and returning to the fire station were 6 to 23 minute and 12 to 48 minute longer, respectively. Most of the delays impacted patients with a fever. In terms of condition, the statistical effect size for delay in transport time was from large to small: fever, hypoxia, abnormal respiratory rate, respiratory symptom, and hypotension.Outbreaks of infectious disease cause a paradoxical state in emergency medical transport systems, inducing delays in the transport of severely ill patients. Therefore, maintenance and improvement of the medical service system for both patients with infectious disease and those with other severe illnesses is required.

Involvement of peroxiredoxin 2 in cumulus expansion and oocyte maturation in mice.

Peroxiredoxin 2 (Prdx2), an antioxidant enzyme, is expressed in the ovary during the ovulatory process. The aim of the present study was to examine the physiological role of Prdx2 during ovulation using Prdx2-knockout mice and mouse cumulus-oocyte complex (COC) from WT mice. Two days of treatment of immature mice (21-23 days old) with equine chorionic gonadotrophin and followed by treatment with human chorionic gonadotrophin greatly impaired cumulus expansion and oocyte maturation in Prdx2-knockout but not wild-type mice. Treatment of COCs in culture with conoidin A (50µM), a 2-cys Prdx inhibitor, abolished epiregulin (EPI)-induced cumulus expansion. Conoidin A treatment also inhibited EPI-stimulated signal molecules, including signal transducer and activator of transcription-3, AKT and mitogen-activated protein kinase 1/2. Conoidin A treatment also reduced the gene expression of EPI-stimulated expansion-inducing factors (hyaluronan synthase 2 (Has2), pentraxin 3 (Ptx3), TNF-α induced protein 6 (Tnfaip6) and prostaglandin-endoperoxide synthase 2 (Ptgs2)) and oocyte-derived factors (growth differentiation factor 9 (Gdf9) and bone morphogenetic protein 15 (Bmp15)). Furthermore, conoidin A inhibited EPI-induced oocyte maturation and the activity of connexins 43 and 37. Together, these results demonstrate that Prdx2 plays a role in regulating cumulus expansion and oocyte maturation during the ovulatory process in mice, probably by modulating epidermal growth factor receptor signalling.

MYO1D binds with kinase domain of the EGFR family to anchor them to plasma membrane before their activation and contributes carcinogenesis.

The cell surface receptor tyrosine kinase (RTK) exists in a dynamic state, however, it remains unknown how single membrane-spanning RTK proteins are retained in the plasma membrane before their activation. This study was undertaken to investigate how RTK proteins are anchored in the plasma membrane before they bind with their respective extracellular ligands for activation through protein-protein interaction, co-localization, and functional phenotype studies. Here we show that unconventional myosin-I MYO1D functions to hold members of the EGFR family (except ErbB3) at the plasma membrane. MYO1D binds only with unphosphorylated EGFRs and anchors them to underlying actin cytoskeleton at the plasma membrane. The C-terminal end region of the MYO1D tail domain containing a ß-meander motif is critical for direct binding with kinase domain of the EGFR family, and expression of the tail domain alone suppresses the oncogenic action of full-length MYO1D. Overexpressed MYO1D increases colorectal and breast cancer cell motility and viability through upregulating EGFR level, and thereby promotes colorectal tumor progression in a syngeneic mouse model. MYO1D is upregulated in human colorectal cancer tissues from advanced stages. Collectively, molecular motor MYO1D plays a distinct role in the dynamic regulation of EGFR family levels by holding them at the plasma membrane before their activation. Overexpressed MYO1D contributes to colorectal carcinogenesis possibly as a novel oncogene and thus may serve as an additional target for suppression of RTK signaling in cancer treatment.

Noxa mitochondrial targeting domain induces necrosis via VDAC2 and mitochondrial catastrophe.

Noxa, a Bcl-2 homology 3 (BH3)-only protein of the Bcl-2 family, is responsive to cell stresses and triggers apoptosis by binding the prosurvival Bcl-2-like proteins Mcl1, BclXL, and Bcl2A1. Although the Noxa BH3 domain is necessary to induce apoptosis, the mitochondrial targeting domain (MTD) of Noxa functions as a pronecrotic domain, an inducer of mitochondrial fragmentation, and delivery to mitochondria. In this study, we demonstrate that the extended MTD (eMTD) peptide induces necrotic cell death by interaction with the VDAC2 protein. The eMTD peptide penetrates the cell membrane, causing cell membrane blebbing, cytosolic calcium influx, and mitochondrial swelling, fragmentation, and ROS generation. The MTD domain binds VDACs and opens the mitochondrial permeability transition pore (mPTP) in a CypD-independent manner. The opening of mPTP induced by eMTD is inhibited either by down-regulation of VDAC2 or by the VDACs inhibitor DIDS. These results indicate that the MTD domain of Noxa causes mitochondrial damage by opening mPTP through VDACs, especially VDAC2, during necrotic cell death.

Acute dystonic reaction induced by a single dose of clebopride: A case report.

RATIONALE: Clebopride is known as a dopamine antagonist used for alleviating emetic symptoms with minimal side effects. Herein, we report a case of acute dystonic reaction possibly caused by administration of clebopride in a young male. PATIENT CONCERNS: A 19-year-old with no special medical conditions, visited a local clinic complaining of abdominal discomfort, associated with nausea and vomiting. The patient was prescribed with tiropramide, clebopride, simethicone, and mosapride citrate, only to visit the emergency department for abrupt neck pain followed with dystonic reactions upon oral administration of the drugs. The patient suffered involuntary movements of the neck to the right, while maintaining voluntary motor controls of the neck to the left. DIAGNOSIS: Vital signs and neurological exams showed no obscurity and the preliminary blood workup (a complete blood count and measurement of electrolytes, inflammatory marker levels, copper concentration, etc) were all within normal ranges. Additional imagery tests including brain computed tomography (CT), neck contrast-enhanced CT, and magnetic resonance imaging failed to prove any focal lesion pertinent to the condition. Drug screening was done and then clebopride was suspected to be the cause of the dystonic reactions. INTERVENTIONS: Benztropine (1 mg) was administered orally. OUTCOMES: The patient's symptoms improved after 1 hour, and he was observed for 6 more hours for possible recurrences before he was discharged. The patient was referred to an outpatient neurology department for 1 month, during which he had no recurrence or other extrapyramidal symptoms. LESSONS: Although it is uncommon to experience extrapyramidal symptoms by clebopride, its chemical closeness to metoclopramide may induce such symptoms under certain clinical situations. Therefore, physicians should take in consideration of this effect and dwell in caution upon prescribing the drug.

Improved memory and reduced anxiety in δ-catenin transgenic mice.

δ-Catenin is abundant in the brain and affects its synaptic plasticity. Furthermore, loss of δ-catenin is related to the deficits of learning and memory, mental retardation (cri-du-chat syndrome), and autism. A few studies about δ-catenin deficiency mice were performed. However, the effect of δ-catenin overexpression in the brain has not been investigated as yet. Therefore we generated a δ-catenin overexpressing mouse model. To generate a transgenic mouse model overexpressing δ-catenin in the brain, δ-catenin plasmid having a Thy-1 promotor was microinjected in C57BL/6 mice. Our results showed δ-catenin transgenic mice expressed higher levels of N-cadherin, ß-catenin, and p120-catenin than did wild type mice. Furthermore, δ-catenin transgenic mice exhibited better object recognition, better sociability, and lower anxiety than wild type mice. However, both mice groups showed a similar pattern in locomotion tests. Although δ-catenin transgenic mice show similar locomotion, they show improved sociability and reduced anxiety. These characteristics are opposite to the symptoms of autism or mental retardation, which are caused when δ-catenin is deficient. These results suggest that δ-catenin may alleviate symptoms of autism, Alzheimer's disease and mental retardation.

p300/CBP-associated factor promotes autophagic degradation of δ-catenin through acetylation and decreases prostate cancer tumorigenicity.

δ-Catenin shares common binding partners with ß-catenin. As acetylation and deacetylation regulate ß-catenin stability, we searched for histone acetyltransferases (HATs) or histone deacetylases (HDACs) affecting δ-catenin acetylation status and protein levels. We showed that p300/CBP-associated factor (PCAF) directly bound to and acetylated δ-catenin, whereas several class I and class II HDACs reversed this effect. Unlike ß-catenin, δ-catenin was downregulated by PCAF-mediated acetylation and upregulated by HDAC-mediated deacetylation. The HDAC inhibitor trichostatin A attenuated HDAC1-mediated δ-catenin upregulation, whereas HAT or autophagy inhibitors, but not proteasome inhibitors, abolished PCAF-mediated δ-catenin downregulation. The results suggested that PCAF-mediated δ-catenin acetylation promotes its autophagic degradation in an Atg5/LC3-dependent manner. Deletions or point mutations identified several lysine residues in different δ-catenin domains involved in PCAF-mediated δ-catenin downregulation. PCAF overexpression in prostate cancer cells markedly reduced δ-catenin levels and suppressed cell growth and motility. PCAF-mediated δ-catenin downregulation inhibited E-cadherin processing and decreased the nuclear distribution of ß-catenin, resulting in the suppression of ß-catenin/LEF-1-mediated downstream effectors. These data demonstrate that PCAF downregulates δ-catenin by promoting its autophagic degradation and suppresses δ-catenin-mediated oncogenic signals.

Differential Expression of Ca2+-buffering Protein Calretinin in Cochlear Afferent Fibers: A Possible Link to Vulnerability to Traumatic Noise.

The synaptic contacts of cochlear afferent fibers (CAFs) with inner hair cells (IHCs) are spatially segregated according to their firing properties. CAFs also exhibit spatially segregated vulnerabilities to noise. The CAF fibers contacting the modiolar side of IHCs tend to be more vulnerable. Noise vulnerability is thought to be due to the absence of neuroprotective mechanisms in the modiolar side contacting CAFs. In this study, we investigated whether the expression of neuroprotective Ca2+-buffering proteins is spatially segregated in CAFs. The expression patterns of calretinin, parvalbumin, and calbindin were examined in rat CAFs using immunolabeling. Calretinin-rich fibers, which made up ~50% of the neurofilament (NF)-positive fibers, took the pillar side course and contacted all IHC sides. NF-positive and calretinin-poor fibers took the modiolar side pathway and contacted the modiolar side of IHCs. Both fiber categories juxtaposed the C-terminal binding protein 2 (CtBP2) puncta and were contacted by synaptophysin puncta. These results indicated that the calretinin-poor fibers, like the calretinin-rich ones, were afferent fibers and probably formed functional efferent synapses. However, the other Ca2+-buffering proteins did not exhibit CAF subgroup specificity. Most CAFs near IHCs were parvalbumin-positive. Only the pillar-side half of parvalbumin-positive fibers coexpressed calretinin. Calbindin was not detected in any nerve fibers near IHCs. Taken together, of the Ca2+-buffering proteins examined, only calretinin exhibited spatial segregation at IHC-CAF synapses. The absence of calretinin in modiolar-side CAFs might be related to the noise vulnerability of the fibers.