Determination of submicron aerosols effective density using two-stage low-pressure impactor and aerosol electrometer based on pre-measured particle size distribution.

A novel methodology was presented for determining the representative effective density of aerosols of a given size distribution, using a lab-made two-stage low-pressure impactor and an aerosol electrometer. Electrical currents upstream (Imeasured, up) and downstream (Imeasured, down) of the 2nd stage of the impactor were measured using a corona charger and the aerosol electrometer. In addition, the electrical currents upstream (Icalculated, up) and downstream (Icalculated, down) of the 2nd stage of the impactor were calculated using the aerosol charging theory. Then, the difference between the ratio of Imeasured,down to Imeasured,up and the ratio of Icalculated,down to Icalculated,up was iterated with varying the presumed effective density until the difference was smaller than 0.001. The methodology was validated using poly-disperse sodium chloride (NaCl) particles. The effective densities of ambient aerosols were then obtained from indoor and outdoor environments and compared with those calculated from a relation between mobility (scanning mobility particle sizer (SMPS) measurement) and aerodynamic (electrical low-pressure impactor (ELPI) measurement) diameters. Compared to the effective densities obtained with SMPS and ELPI measurements, the effective densities obtained using the methodology introduced in this paper differed within 10 % deviation, depending on measurement location. After an averaged effective density for given size distribution is obtained at a measurement location, the number-based size distribution can be easily converted to mass-based size distribution using the representative effective density.

Investigating the link between antipsychotic use and post-stroke infections in older people: multi-centre propensity score analysis.

BACKGROUND: The risk of stroke increases with age, and although previous reports have suggested that infection risk may increase with antipsychotic use, relevant studies after stroke are scarce. We aimed to investigate whether antipsychotics increase post-stroke infection risk in the acute stroke period. METHODS: This propensity score matching study included adults diagnosed with first-ever stroke between 2011 and 2020 at five university hospitals. In-hospital antipsychotic exposure was defined as any administration during hospitalisation for stroke. The primary outcome was post-stroke infection after the first 2 days of hospitalisation, and the secondary outcome was the presence of pneumonia, bacteraemia and/or bacteriuria. RESULT: Among 23,885 first-ever stroke patients, 2,773 antipsychotic users (age 71.6 ± 12.4, male 54.6%) and 2,773 non-users (age 71.2 ± 13.2, male 54.6%) were selected as matched cohorts. After adjusting for propensity score, antipsychotics were not associated with an increased risk of post-stroke infection (odds ratio 0.99, 95% confidence interval 0.87-1.14). CONCLUSION: While our study did not find conclusive evidence linking antipsychotic medication to an increased risk of post-stroke infection, prescribing these medications should still be approached with prudence. Until further research can provide more definitive insights, clinicians should carefully weigh the potential infection risks when considering antipsychotic treatment during the acute stroke care period.

Implications of anti-ganglioside antibodies in isolated dysphagia following COVID-19 infection: Case series.

BACKGROUND: There have been multiple reports about the occurrence of dysphagia after the contraction of coronavirus disease 2019 (COVID-19). However, a detailed pathology and epidemiologic relation between COVID-19 infection and dysphagia have yet to be established. Here, we report three cases of unexplained dysphagia after COVID-19 diagnosis, with atypical clinical presentations. CASE REPORT: All patients showed severe isolated lower cranial nerve involvement with dysphagia and aspiration, which required full tube feeding but showed no evidence of limb weakness or sensory symptoms. All tested positive for anti-ganglioside antibody tests, which all commonly (GD1b, GM1, and GQ1b) are known to have terminal NeuNAc(α2-3)Gal epitope. DISCUSSION: We report a series of cases featuring severe, isolated dysphagia post-COVID-19 infection, concomitant with positive anti-ganglioside antibodies. One potential etiology is a variant of Guillain-Barré syndrome. Because only isolated dysphagia with sparing of the facial and extraocular muscles was evident in these cases, we explore the association between anti-ganglioside antibodies specific to NeuNAc(α2-3)Gal, which has been frequently associated with the development of bulbar dysfunction. Given that NeuNAc(α2-3)Gal exhibits an affinity for the spike glycoprotein of SARS-CoV-2, a cross-reaction against NeuNAc(α2-3)Gal may possibly contribute to isolated dysphagia following COVID-19 infection.

Optimized trans-cranial direct current stimulation for prolonged consciousness disorder in a patient with titanium mesh cranioplasty.

BACKGROUND: Transcranial direct current stimulation (tDCS) has been used for the restoration of awareness in patients with a minimal consciousness state (MCS). Most brains of patients in MCS may structurally and electrophysiologically differ from un-damaged brains. Moreover, tDCS is currently contraindicated for patients with craniotomy or skull with metallic implants. CASE PRESENTATION: We present a case with prolonged MCS over 1 year, who had severe brain damage, ventriculoperitoneal shunt, and cranioplasty with a titanium mesh, which was treated with tDCS which optimized with the simulation of the electric field based on the patient's brain MRI. The patient was resulting in emergence from MCS. Six months later, she ate meals orally and started walking with assistance. DISCUSSION AND PERSPECTIVE: This personalized simulation based on MRI would make the treatment available even to patients with severe brain structural changes and metallic instrumentation.

An Exercise Prescription for Patients with Stroke and Sarcopenia Based on the Modified Delphi Study.

BACKGROUND: We aimed to develop a consensus on the need for and priorities of exercise to treat preexisting sarcopenia with hemiplegic stroke. METHODS: A modified three-round Delphi study was conducted. The panelists responded to the questionnaire on a 7-point Likert scale. Responses were returned with descriptive statistics in the next round. Consensus was defined as >75% agreement (score of 5-7) with a median > 5. The percentage of strong agreement (score of 6-7) and Kendall's coefficient of concordance were calculated to demonstrate a more refined interpretation of the consensus. RESULTS: Fifteen panelists contributed to all rounds. The need for exercise was demonstrated. The consensus was reached on 53 of 58 items in the first round and all items in the second and final rounds. The percentage of strong agreement was high for all but eight items. CONCLUSIONS: This study is the first Delphi study to investigate the need for and priorities of exercise for treating preexisting sarcopenia in stroke hemiplegia. We present a standard recommendation including 57 priorities and a strong recommendation including 49 priorities. The eight items that were excluded reflected factors that are less important to hemiplegic patients with poor balance, cognitive decline, or mental vulnerability.

Safety and therapeutic effects of personalized transcranial direct current stimulation based on electrical field simulation for prolonged disorders of consciousness: study protocol for a multi-center, double-blind, randomized controlled trial.

Background: Disorders of consciousness (DOC) resulting from acquired brain injury (ABI) increase the mortality rate of patients, complicate rehabilitation, and increase the physical and economic burden that DOC imposes on patients and their families. Thus, treatment to promote early awakening from DOC is vital. Transcranial direct current stimulation (tDCS) has shown great potential for promoting neuro-electrochemical activity. However, previous tDCS studies did not consider structural damage or head and brain lesions, so the applicability of the results to all DOC patients was limited. In this study, to establish a patient-specific tDCS treatment plan considering the brain lesions of and damage sustained by DOC patients, we considered the electric field calculated by a the "finite electric" three-dimensional brain model based on magnetic resonance images. This protocol was developed to aid tDCS treatment of actual patients, and to verify its safety and effectiveness. Methods/design: Twenty-four patients with DOC after ABI will be enrolled in this cross-over trial. All participants will receive typical rehabilitation combined with sham tDCS and typical rehabilitation plus personalized tDCS (P-tDCS). Each interventional period will last 2 weeks (30 min/day, 5 days/week). The primary outcome [score on the Korean version of the Coma Recovery Scale-Revised (K-CRS-R)] will be assessed at baseline and the end of the first day of the intervention. Secondary outcomes (K-CRS-R at 1 week and 2 weeks after experimental session and quantitative EEG changes quantitative electroencephalography changes) will be measured at baseline and the end of week 4. Adverse events will be recorded during each treatment session. Discussion: For patients with neurological disorders, tDCS has served as a painless, non-invasive, easily applied, and effective therapy for several decades, and there is some evidence that it can improve the level of consciousness of patients with DOC. However, variability in the effects on consciousness among subjects have been reported and personalized strategies are lacking. This protocol is for a randomized controlled trial designed to validate the effectiveness and safety of P-tDCS combined with typical rehabilitation for DOC. Clinical trial registration: https://cris.nih.go.kr, identifier KCT0007157.

Structural Integrity of the Cerebellar Outflow Tract Predicts Long-Term Motor Function After Middle Cerebral Artery Ischemic Stroke.

BACKGROUND: The cerebellum plays a crucial role in functional movement by influencing sensorimotor coordination and learning. However, the effects of cortico-cerebellar connectivity on the recovery of upper extremity motor function after stroke have not been investigated. We hypothesized that the integrity of the cortico-cerebellar connections would be reduced in patients with a subacute middle cerebral artery (MCA) stroke, and that this reduction may help to predict chronic upper extremity motor function. METHODS: We retrospectively analyzed the diffusion-tensor imaging of 25 patients with a subacute MCA stroke (mean age: 62.2 ± 2.7 years; 14 females) and 25 age- and sex-matched healthy controls. We evaluated the microstructural integrity of the corticospinal tract (CST), dentatothalamocortical tract (DTCT), and corticopontocerebellar tract (CPCT). Furthermore, we created linear regression models to predict chronic upper extremity motor function based on the structural integrity of each tract. RESULTS: In stroke patients, the affected DTCT and CST showed significantly impaired structural integrity compared to unaffected tracts and the tracts in controls. When all models were compared, the model that used the fractional anisotropy (FA) asymmetry indices of CST and DTCT as independent variables best predicted chronic upper extremity motor function (R2 = .506, P = .001). The extent of structural integrity of the CPCT did not significantly differ between hemispheres or groups and was not predictive of motor function. CONCLUSIONS: We found evidence that microstructural integrity of the DTCT in the subacute phase of an MCA stroke helped to predict chronic upper extremity motor function, independent of CST status.

Investigating the Impact of Voice Impairment on Quality of Life in Stroke Patients: The Voice Handicap Index (VHI) Questionnaire Study.

The Voice Handicap Index (VHI) is a patient-centered evaluation tool specifically designed for assessing voice-related quality of life. Although the VHI has been extensively used in patients with voice disorders, its applicability in stroke patients has not been fully established. This prospective cross-sectional study aimed to investigate the feasibility of using the VHI questionnaire in identifying stroke patients with voice problems. The study included a cohort of acute to subacute first-ever stroke patients (n = 48), with or without voice problems, as well as other non-stroke patients (n = 31) who agreed to complete the VHI questionnaire. Stroke patients with self-reported voice problems demonstrated significantly higher VHI scores and poorer life quality scores compared to the control groups. These patients also had lower Mini-Mental State Examination (MMSE), Modified Barthel Index (MBI), and Euro-QoL-5D-5L (EQ-5D-5L) scores. Spearman correlation analysis revealed an inverse association between VHI scores and EQ-5D-5L (rho = -0.77, p < 0.001), Korean Mann Assessment of Swallowing Ability (rho = -0.51, p < 0.001), and other functional parameters, including the National Institutes of Health Stroke Scale, MMSE, and MBI scores. Multiple regression analysis indicated that the VHI score was the biggest contributing factor to EQ scores. This is the first study to demonstrate that stroke patients with voice problems may experience reduced quality of life, even after controlling for other confounding factors such as dysphagia or neurological deficits. Future studies are needed whether addressing these issues by implementing the VHI may facilitate the improvement of patients' quality of life.

Post-Stroke Infections: Insights from Big Data Using Clinical Data Warehouse (CDW).

This study analyzed a digitized database of electronic medical records (EMRs) to identify risk factors for post-stroke infections. The sample included 41,236 patients hospitalized with a first stroke diagnosis (ICD-10 codes I60, I61, I63, and I64) between January 2011 and December 2020. Logistic regression analysis was performed to examine the effect of clinical variables on post-stroke infection. Multivariable analysis revealed that post-stroke infection was associated with the male sex (odds ratio [OR]: 1.79; 95% confidence interval [CI]: 1.49-2.15), brain surgery (OR: 7.89; 95% CI: 6.27-9.92), mechanical ventilation (OR: 18.26; 95% CI: 8.49-44.32), enteral tube feeding (OR: 3.65; 95% CI: 2.98-4.47), and functional activity level (modified Barthel index: OR: 0.98; 95% CI: 0.98-0.98). In addition, exposure to steroids (OR: 2.22; 95% CI: 1.60-3.06) and acid-suppressant drugs (OR: 1.44; 95% CI: 1.15-1.81) increased the risk of infection. On the basis of the findings from this multicenter study, it is crucial to carefully evaluate the balance between the potential benefits of acid-suppressant drugs or corticosteroids and the increased risk of infection in patients at high risk for post-stroke infection.

Single Nucleotide Polymorphisms May Increase the Risk of Aspiration Pneumonia in Post-Stroke Patients with Dysphagia.

This study aimed to evaluate whether genetic polymorphism is associated with an increased risk of infection, specifically post-stroke aspiration pneumonia. Blood samples were obtained from a total of 206 post-stroke participants (males, n = 136; mean age, 63.8 years). Genotyping was performed for catechol-O-methyltransferase (rs4680, rs165599), dopamine receptors (DRD1; rs4532, DRD2; rs1800497, DRD3; rs6280), brain-derived neurotrophic factor (rs6265), apolipoprotein E (rs429358, rs7412), and the interleukin-1 receptor antagonist gene (rs4251961). The subjects were stratified into two groups, aged < 65 (young) and ≥ 65 (elderly). Functional parameters and swallowing outcomes were measured at enrollment and at 3 months post-onset. The primary outcome was the incidence of aspiration pneumonia. Analysis of the association between genetic polymorphisms and aspiration pneumonia history showed that a minor C rs429358 allele was associated with the occurrence of aspiration pneumonia in the young group, both in the additive and the dominant models (odds ratio: 4.53; 95% CI: 1.60−12.84, p = 0.004). In the multivariable analysis, the minor C rs429358 allele increased the risk of post-stroke aspiration pneumonia in young stroke patients by 5.35 (95% CI: 1.64−20.88). In contrast, no such association was observed in the elderly group. Apolipoprotein E polymorphism may affect the risk of post-stroke aspiration pneumonia.

Neural correlates in the development of and recovery from dysphagia after supratentorial stroke: A prospective tractography study.

BACKGROUND: Swallowing impairment after stroke may be related to the state of the corticobulbar tract (CBT), which is the motor projection fiber responsible for deglutition, but evidence is still lacking regarding which parameter could relate to poststroke swallowing recovery as measured by videofluroscope findings. This prospective study evaluated diffusion tensor imaging (DTI) parameters among dysphagic stroke patients compared with those of nondysphagia stroke patients and age-matched healthy subjects and followed swallowing recovery in dysphagic patients as assessed with the Modified Barium Swallow Impairment Profile (MBSImP©). METHODS: Diffusion tractography was performed in 69 subjects, consisting of 27 S patients with dysphagia, 18 healthy subjects and 24 S patients with no evidence of dysphagia. DTI was performed within 14 days of stroke onset. Follow-up DTI was performed in the dysphagic group at three months. The tract volume (TV) of the CBT and frontal operculum as determined by fractional anisotropy (FA) was compared among the 3 groups. Correlations of these parameters with initial dysphagia severity and swallowing parameters at baseline and 3 months postonset were assessed. RESULTS: All stroke patients showed lower CBT TV on the affected and unaffected sides than those in the control group, even in those who showed no evidence of clinical dysphagia. The dysphagia group showed a greater reduction in CBT TV on the affected side (P < 0.001). Receiver operating characteristic analysis showed that cutoff values of 4.1 cm3 for TV and 0.24 for FA from the affected side could classify dysphagia with good accuracy (AUC = 0.77, 0.75, respectively) and specificity levels. FA values in the unaffected frontal operculum showed a significant correlation (rho = -0.40, P = 0.02) with swallowing outcome as observed by the total scores of MBSImP©. In addition, these values proved to be significant variables to predict swallowing outcome in multiple regression analysis (R2 = 0.6317, adjR2 = 0.5815, F = 12.58, p < 0.001, AIC = 203.65). CONCLUSIONS: Even when clinical dysphagia is not apparent, individuals with a supratentorial stroke may show reduced CBT parameters compared to healthy controls. Supratentorial stroke may manifest with dysphagia if a certain extent of CBT volume and white matter tract integrity is involved, with a greater degree of CBT injury in the affected sides determining poststroke dysphagia severity. In contrast, recovery was independent of the affected parameters, and an initial lower FA value in the unaffected frontal operculum was indicative of a poorer 3-month dysphagia outcome. DTI parameters obtained within two weeks of stroke onset may help classify those with dysphagia, predict recovery and help plain therapeutic strategies to maintain the adaptive role of the white matter tract, which is crucial in swallowing recovery.

Role of Catechol-O-methyltransferase Val158Met Polymorphism on Transcranial Direct Current Stimulation in Swallowing.

Transcranial direct current stimulation (tDCS) is one of the latest post-stroke dysphagia treatment modalities, and the effect of tDCS is known to be affected by various factors including genetic polymorphisms. However, the role of catechol-O-methyltransferase (COMT) polymorphisms on tDCS in swallowing is unclear. In this prospective pilot study, we aim to explore the effect of tDCS on the swallowing cortex and subsequent swallowing motor function according to COMT polymorphism. Twenty-four healthy participants received either anodal tDCS or sham mode tDCS on the mylohyoid motor cortex at random order, after inhibitory repetitive transcranial magnetic stimulation (rTMS) for preconditioning. The primary outcome was the changes of mylohyoid-motor-evoked potentials (MH-MEP) amplitude in each COMT polymorphism group, from the post-inhibitory rTMS baseline state to immediate, 30, and 60 min after tDCS. The secondary outcomes were the changes in swallowing function. The results showed that COMT Val/Val polymorphism showed improvement across time in the MH-MEP amplitudes and triggering time of swallowing after tDCS, whereas COMT Met carrier group did not show significant changes of MH-MEP or swallowing function across time. This therapeutic response variability of tDCS in the mylohyoid motor system according to COMT polymorphism support the importance of genetic analysis in individualized dysphagia treatment.

A Risk Factor Analysis of Axillary Web Syndrome in Patients After Breast Cancer Surgery: A Single Center Study in Korea.

OBJECTIVE: To investigate the prevalence and risk factors of axillary web syndrome (AWS) in Korean patients. METHODS: This retrospective study included a total of 189 women who underwent breast cancer surgery and received physical therapy between September 2019 and August 2020. We analyzed AWS and the correlation between the patients' demographics, underlying disease, type of surgery and chemotherapy or radiation therapy, and lymphedema. RESULTS: The prevalence of AWS was found to be 30.6%. In the univariable analysis, age, chemotherapy, and hypertension were related to AWS. Finally, the multivariable logistic regression revealed that chemotherapy (odds ratio [OR]=2.84; 95% confidence interval [CI], 1.46-5.53) and HTN (OR=2.72; 95% CI, 1.18-6.30) were the strongest risk factors of AWS. CONCLUSION: To the best of our knowledge, this was the first study that explored the risk factors of AWS in a Korean population after breast cancer surgery. As almost one-third of patients suffer from AWS after breast cancer surgery, it is essential to closely monitor the development of AWS in patients with hypertension or undergoing chemotherapy.

Potential Prognostic Impact of Dopamine Receptor D1 (rs4532) Polymorphism in Post-stroke Outcome in the Elderly.

Background: Single-nucleotide polymorphisms (SNPs) may affect post-stroke motor recovery, and some SNPs have been implicated in swallowing disturbances after stroke. Certain SNPs may also have altered influences according to different age. Objective: This post-hoc study investigated whether SNPs have different effects on dysphagia recovery between the elderly vs. young stroke patients. Methods: Analysis was conducted from a previous study including 218 stroke subjects with dysphagia. They were stratified into two groups, aged <65 and aged ≥65 years. The primary outcome was persistence of nil per mouth (NPM) at 3 months post-stroke onset. Association between outcome and nine different SNPs were investigated. Results: The elderly group (50%, n = 103) showed poorer swallowing outcomes than the young group. The minor allele of the dopamine receptor D1 (DRD1, rs4532) polymorphism showed potential association (p = 0.022) with an increased risk of NPM at 12 weeks post-stroke in the elderly, both in the additive (OR, 2.94; 95% CI, 1.17-7.37) and dominant models (OR, 2.93; 95% CI, 1.04-8.23) but did not reach statistical significance after Bonferonni correction. Logistic regression analysis showed that in those aged ≥65 years, models including the minor allele of rs4532 predicted the risk of the poor outcome with good accuracies even after adjustment of clinical factors, such as previous pneumonia episodes (AUROC, 0.86; 95% CI, 0.79-0.93) or the National Institutes of Health Stroke Scale (AUROC, 0.82; 95% CI, 0.67-0.92). In contrast, those aged <65 years seemed not to be affected by the presence of the rs4532 polymorphism, and models that included intubation history (AUROC, 0.81; 95% CI, 0.73-0.90) or previous pneumonia episodes (AUROC, 0.77; 95% CI, 0.68-0.87) showed modest levels of accuracies in predicting NPM at 12 weeks poststroke. Conclusions: Our study suggests a possible association between the rs4532 and post-stroke swallowing recovery, primarily in those aged ≥65 years. Certain SNPs may lead to less favorable outcomes in the elderly. The gene-age interaction should be considered in post-stroke swallowing recovery. Clinical Trial Registration: https://www.clinicaltrials.gov, Unique identifier [NCT03577444].

Ultrasound Evaluation of the Rectus Femoris for Sarcopenia in Patients with Early Subacute Stroke.

We investigated the ultrasound characteristics of the rectus femoris for sarcopenia detected by dual-energy X-ray absorptiometry (DEXA) in the early subacute stroke phase. Physical features (age, sex, body mass index, and circumference of thigh) and performances (modified Barthel index in Korean, functional ambulation categories, and mini-mental state examination in Korean) were measured. The thickness of the fat layer, the thickness of the rectus femoris (TRF), echo intensity (EI), EI to TRF ratio, and strain ratio of elastography (SRE) were measured by ultrasound in 30 patients with first-ever stroke (male: n = 20). Appendicular lean body mass was measured by DEXA. Sarcopenia was defined according to the Foundation for the National Institutes of Health Sarcopenia Project. In total, 14 patients were in the sarcopenia group, and 16 were in the non-sarcopenia group. Clinical characteristics were similar between the two groups. In the sarcopenia group, TRF was significantly decreased in the paretic (p < 0.026) and non-paretic sides (p < 0.01), and the EI to TRF ratio on the paretic side was significantly increased (p < 0.049). Multivariate binary logistic regression showed that TRF on the non-paretic side was independently and significantly associated with sarcopenia (OR = 0.616, 95% CI: 0.381-0.996). The EI and SRE were not significant between the two groups. In the early subacute stroke phase, TRF on the non-paretic side is a key factor for quantitative evaluation of sarcopenia, and the EI to TRF ratio on the paretic side is also a meaningful qualitative evaluation of sarcopenia.

The Effect of Extracorporeal Shock Wave Therapy on Pain Intensity and Neck Disability for Patients With Myofascial Pain Syndrome in the Neck and Shoulder: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: The aim of the study was to investigate the efficacy of extracorporeal shock wave therapy on myofascial pain syndrome in the neck and shoulder compared with that of other treatments. DATA SOURCES: PubMed, Embase, and Web of Science were systematically searched until May 30, 2019, to select randomized controlled trials. REVIEW METHODS: The randomized controlled trials comparing extracorporeal shock wave therapy with sham extracorporeal shock wave therapy or other treatments for patients with myofascial pain syndrome in the neck and shoulder patients were included. Two reviewers independently identified eligible studies. The Cochrane Handbook was used to evaluate the methodological quality of the included randomized controlled trials. Main outcomes associated with pain intensity, pressure pain threshold, and neck disability were selected. The study was registered with PROSPERO (Registration Number CRD 42019137459). RESULTS: A total of 11 randomized controlled trials were finally included. The results indicated that extracorporeal shock wave therapy had a large effect size on improving pain intensity (standardized mean difference [SMD] = 0.67, 95% confidence interval = 0.11 to 1.23, P = 0.02) and pressure pain threshold (SMD = 1.19, 95% confidence interval = 0.27 to l2.12, P = 0.01) at postintervention. However, there was no significant effect on neck disability at postintervention (SMD = 0.03, 95% confidence interval = -0.76 to 0.83, P = 0.93). After the subgroup analyses on the type of extracorporeal shock wave therapy, focused extracorporeal shock wave therapy had a significant effect on improving pain intensity (SMD = 0.75, 95% confidence interval = 0.13 to 1.36, P = 0.02) and pressure pain threshold (SMD = 1.70, 95% confidence interval = 0.21 to 3.18, P = 0.03) at postintervention in comparison with that of other treatments. CONCLUSIONS: Extracorporeal shock wave therapy is superior to other treatments in terms of alleviating the pain intensity and pressure pain threshold of patients with myofascial pain syndrome in the neck and shoulder at postintervention. In particular, focused extracorporeal shock wave therapy shows significant improvement in pain relief. However, radical extracorporeal shock wave therapy for myofascial pain syndrome treatment still remains unclear.

Epithelial-stromal communication via CXCL1-CXCR2 interaction stimulates growth of ovarian cancer cells through p38 activation.

PURPOSE: Paracrine interactions with the stromal environment, including fibroblasts, may be important in the pathogenesis of ovarian cancer. Here, we evaluated the effect of conditioned media derived from ovarian fibroblasts (fibroblast-CMs) and their major cytokines on the growth of ovarian cancer cells, as well as the involvement of mitogen-activated protein kinases (MAPKs) and AKT in mediating this effect. METHODS: Ovarian cancer cells were cultured in serum-free media (SF), or conditioned media of fibroblasts derived from normal ovary (CM1) and ovarian tumor tissue (CM2). Cell proliferation was measured by MTT assay. Phosphorylation of MAPKs and AKT was evaluated by Western blotting. Specific inhibitors of MAPKs and AKT were used to evaluate their respective involvement in mediating increased cell growth. Cytokine levels in fibroblast-CMs were measured using Luminex assays. Immunohistochemical staining was conducted for CXCL1, CXCR2 and phosphorylated p38 in primary ovarian tumors. RESULTS: CM1 and CM2 significantly increased the growth of ovarian cancer cells relative to SF. In OVCAR3 and OVCAR4 cells, p38 phosphorylation was strongly induced by fibroblast-CMs, and pre-treatment with a p38 inhibitor prevented the growth increase induced by fibroblast-CMs. Fibroblasts secreted high levels of IL-6, IL-8, MCP1 and CXCL1. Treatment with only CXCL1 (1 µg/ml) increased cell growth and p38 phosphorylation. Treatment with a CXCR2 inhibitor effectively prevented p38 activation and cell growth induced by fibroblast-CMs. High expression of both CXCL1 and CXCR2 correlated with high expression of phosphorylated p38 in primary ovarian tumors. CONCLUSIONS: From our data, we conclude that CXCL1 is a key factor derived from ovarian fibroblasts that is responsible for increased ovarian cancer cell growth in part through p38 activation. Phosphorylated p38 can be used as a biomarker to predict CXCL1-CXCR2 interaction in vivo.