IL-17 Facilitates VCAM-1 Production and Monocyte Adhesion in Osteoarthritis Synovial Fibroblasts by Suppressing miR-5701 Synthesis.

Osteoarthritis (OA) is characterized by the infiltration and adhesion of monocytes into the inflamed joint synovium. Interleukin (IL)-17 is a critical inflammatory mediator that participates in the progression of OA, although the mechanisms linking IL-17 and monocyte infiltration are not well understood. Our analysis of synovial tissue samples retrieved from the Gene Expression Omnibus (GEO) dataset exhibited higher monocyte marker (CD11b) and vascular cell adhesion molecule 1 (VCAM-1) levels in OA samples than in normal, healthy samples. The stimulation of human OA synovial fibroblasts (OASFs) with IL-17 increased VCAM-1 production and subsequently enhanced monocyte adhesion. IL-17 affected VCAM-1-dependent monocyte adhesion by reducing miR-5701 expression through the protein kinase C (PKC)-α and c-Jun N-terminal kinase (JNK) signaling cascades. Our findings improve our understanding about the effect of IL-17 on OA progression and, in particular, VCAM-1 production and monocyte adhesion, which may help with the design of more effective OA treatments.

Ultrasound-guided L5/S1 intradiscal needle placement using biplanar approach with the patient in the lateral decubitus position: A report of three cases.

BACKGROUND: The use of ultrasound (US)-guided intradiscal injection has been described in the literature with the patient lying in the prone position; however, many patients are unable to lie in the prone position. Therefore, we describe an innovative technique of US-guided platelet-rich plasma (PRP) administration in the lumbar intervertebral disc (IVD) of 3 patients with chronic lower back pain who failed to improve with conservative management. CASE SERIES: For all the 3 patients, magnetic resonance imaging showed annular tears of the L5/S1 IVD with broad-based central posterior protrusions. PRP injection was performed with the patients in the lateral decubitus position or modified recovery position. With the transducer initially placed in the short axis to the lumbar spine, the needle was inserted in-plane to the IVD, with the needle trajectory clearly visualized. Once the needle entered the annulus fibrosus, placement of the needle was confirmed by turning the transducer along the long axis of the spine to validate the location of the needle tip inside the IVD. Discus stimulation was performed with contrast administered to elicit each patient's usual pain, and spread of the contrast was confirmed under fluoroscopy. Upon confirmation of the intradiscal location, 3 ml of PRP was administered. CONCLUSIONS: This report described a novel technique demonstrating that US-guided lumbar intradiscal needle placement for PRP administration in patients lying in the lateral decubitus position is feasible.

miR-144-3p ameliorates the progression of osteoarthritis by targeting IL-1ß: Potential therapeutic implications.

The pro-inflammatory cytokine interleukin 1 beta (IL-1ß) plays a critical role in osteoarthritis (OA) disease pathogenesis. MicroRNA (miRNA) activity is related to inflammation in OA and some miRNAs specifically regulate IL-mediated degradation of cartilage type II collagen. Previous studies have indicated that miR-144-3p is a useful target in the regulation of pro-inflammatory cytokines in different diseases. However, the role of miR-144-3p in OA is unclear. In this study, we observed a negative correlation between miR-144-3p and IL-1ß expression in OA. miR-144-3p mimic transfection of OA synovial fibroblasts downregulated levels of IL-1ß expression, while blocking the MAPK, PI3K/Akt, and NF-κB signaling pathways relating to IL-1ß production, and effectively increased miR-144-3p expression in OASFs. Findings from an anterior cruciate ligament transection rat model revealed that administration of miR-144-3p mimic effectively ameliorated OA progression and reduced the numbers of IL-1ß-positive cells in synovial tissue. This study suggests that miR-144-3p is a useful therapeutic target in OA disease.

An Integrative Index for Predicting Extubation Outcomes After Successful Completion of a Spontaneous Breathing Trial in an Adult Medical Intensive Care Unit.

BACKGROUND: Among respiratory predictors, rapid shallow breathing index (RSBI) has been a commonly used respiratory parameter to predict extubation outcomes. However, the outcome of prediction remains inconsistent. Regarding nonrespiratory predictors, serum albumin, hemoglobin, bicarbonate, and patients' alertness have been reported to be associated with successful weaning or extubation. We aimed to develop an integrative index combining commonly used predictors in the adult medical intensive care units (MICUs) and to compare the predictability of the index with RSBI. METHODS: This prospective observational study with retrospective data collection of planned extubations was conducted in a 14-bed adult MICU. We enrolled patients who received mechanical ventilation via an endotracheal tube in the adult MICU for >24 hours and passed a 2-hour spontaneous breathing trial and underwent extubation. Extubation failure was defined as reinstitution of invasive mechanical ventilation within 48 hours of extubation. Respiratory parameters and Glasgow Coma Scale (GCS) scores of patients were recorded prospectively. Nonrespiratory parameters were recorded retrospectively. Logistic regression was used to determine significant predictors of extubation outcomes. RESULTS: Fifty-nine patients comprising 70 extubations were enrolled. Extubation failure was significantly and positively associated with lower serum albumin (albumin < 2.6 g/dL, odds ratio [OR] = 5.1; 95% confidence interval [CI], 1.04-24.66), lower hemoglobin (hemoglobin < 10.0 g/dL, OR = 10.8; 95% CI, 2.00-58.04), and lower GCS scores (GCS score ≤ 8, OR = 6.1; 95% CI = 1.15-32.34). By using an integrative index combining the 3 parameters together, the sensitivity and specificity to predict extubation outcomes were 78.6% and 75.9%, respectively. The area under the receiver operating characteristic curve of the index was significantly higher than RSBI (0.84 vs 0.61, P = .026). CONCLUSION: The integrative index combining serum albumin, hemoglobin, and GCS scores could predict extubation outcomes better than RSBI in an adult MICU.

Glucose enhances aggrecan expression in chondrocytes via the PKCα/p38-miR141-3p signaling pathway.

Aggrecan is a high molecular weight proteoglycan that plays a critical role in cartilage structure and the function of joints, providing intervertebral disc and cartilage with the ability to resist compressive loads. Aggrecan degradation in articular cartilage is a significant event in early-stage osteoarthritis (OA). Currently, no effective treatment exists for OA other than pain relief. Dextrose (D-glucose) prolotherapy has shown promising activity in the treatment of different musculoskeletal disorders, including OA. However, little is known about the molecular mechanism of the glucose effect in OA and on the regulation of chondrogenesis. We show for the first time that glucose upregulates aggrecan expression and subsequent chondrogenesis in ATDC5 cells. Moreover, we found that glucose-induced aggrecan expression is mediated through the protein kinase Cα (PKCα)- and p38-dependent pathway. As demonstrated by microRNA (miR) and luciferase analyses, the glucose-induced PKCα/p38 signaling axis is responsible for downregulating miR141-3p which targets to the 3'untranslated region of aggrecan. In summary, we show that glucose enhances chondrogenesis by upregulating aggrecan expression via the PKCα-p38-miR141-3p signaling pathway. This result provides new insights into the mechanism of glucose on chondrogenesis.

Glucose suppresses IL-1ß-induced MMP-1 expression through the FAK, MEK, ERK, and AP-1 signaling pathways.

Osteoarthritis (OA) commonly affects the synovial joint and is characterized by degradation of articular cartilage. Increased matrix metalloproteinase (MMP) activity plays a major role in this degradation. Dextrose (D-glucose) prolotherapy has shown promising activity in the treatment of different musculoskeletal disorders, including OA. However, little is known about the role of glucose on MMP inhibition in OA therapy. We found that stimulating chondrocytes with the proinflammatory cytokine interleukin-1ß (IL-1ß) increased the expression of MMP-1, MMP-3, and MMP-13. Glucose reduced this increase in MMP-1 expression, but had no effect upon MMP-3 or MMP-13 expression. Analyses using a focal adhesion kinase (FAK) inhibitor, MEK inhibitors (U0126 and PD98059), an ERK inhibitor, AP-1 inhibitors (curcumin and tanshinone), or siRNAs demonstrated that the FAK, MEK, ERK, and AP-1 pathways mediate IL-1ß-induced increases in MMP-1 expression. Glucose antagonized IL-1ß-promoted phosphorylation of FAK, MEK, ERK, and c-Jun. Thus, glucose decreased IL-1ß-induced MMP-1 expression through the FAK, MEK, ERK, and AP-1 signaling cascades. These findings may provide a better understanding of the mechanisms of prolotherapy on inhibiting MMP expression.

Age of asthma onset and vulnerability to ambient air pollution: an observational population-based study of adults from Southern Taiwan.

BACKGROUND: Late-onset asthma (onset > 12 years) is pathologically distinct from early-onset asthma. The mechanism of air pollution is not a classic allergic inflammation and could have differential effect on late-onset and early-onset asthma. However, there is little known about the association of onset-age phenotype and air pollution. In this population-based study, we aimed to determine the association of asthma severity outcomes and air pollution regarding age at onset of asthma. METHODS: In 2004, we conducted a cross-sectional questionnaire survey about respiratory health among schoolchildren's parents randomly selected from 94 of 816 elementary and middle schools in southern Taiwan. Participants ever having typical asthma symptoms were enrolled. We used kriging method to estimate individual exposure to ambient air pollution in the preceding year before the year of asthma severity survey. Ordered logistic regression was used to determine the association of exposure and asthma severity scores. Age at asthma onset of 12 years was used as a cut-off to define early- or late-onset asthma. RESULTS: The study surveyed 35,682 participants. Data from 23,551 participants remained satisfactory with a response rate of 66 %. Among 20,508 participants aged 26-50 years, 703 questionnaire-determined asthmatics were identified and included for analysis. Using the median of PM10 (66 µg/m(3)) as a cut-off, those exposed to higher PM10 were more likely to have higher severity scores (OR = 1.74; 95 % CI, 1.13 - 2.70) only for asthmatics with asthma onset at > 12 years. CONCLUSIONS: In adulthood, exposure to PM10 has a greater effect on late-onset asthma than early-onset asthma and deserves greater attention among ambient air pollutants.

Different Severity and Severity Predictors in Early-Onset and Late-Onset Asthma: A Taiwanese Population-Based Study.

BACKGROUND: Late-onset asthma has been shown to be more severe than early-onset asthma in clinic-based studies. However, population-based studies are scarce, and the predictors of severity have been less studied. OBJECTIVES: To determine asthma severity and severity predictors regarding age at onset. METHODS: A cross-sectional questionnaire survey was conducted among parents of children from 94 schools in Taiwan in 2004. Asthma severity was defined as short-acting ß2-agonist (SABA), inhaled corticosteroid (ICS) and health care use in the last year. Information on age at onset, demographics, heredity and home exposure was collected. Ordered logistic or logistic regression was used for determining the associations between risk factors and severity. RESULTS: Participants aged 26-50 years were included, resulting in 21,057 (67.8%) participants. Among them, 449 reported ever having had physician-diagnosed asthma, and 381 of those subjects answered the question on age at asthma onset. The risks of rescue SABA, ICS and health care use were generally higher among late-onset (13-50 years) than early-onset (0-12 years) asthmatics. Use of SABA and health care increased from childhood-onset, adolescent- or young adult-onset to adult-onset asthma. Allergic rhinitis was positively associated with SABA use (OR, 9.08; 95% CI, 1.06-77.99) and ICS use (OR, 5.08; 95% CI, 1.47-17.52) in early-onset asthma. Dehumidifier use was negatively associated with SABA use (OR, 0.50; 95% CI, 0.29-0.87) and ICS use (OR, 0.38; 95% CI, 0.19-0.78) in late-onset asthma. CONCLUSIONS: In adults, late-onset asthma was more severe than early-onset asthma. Severity, as indicated by SABA and ICS use, was positively associated with allergic rhinitis in early-onset asthma and negatively associated with dehumidifier use in late-onset asthma.

Asthma incidence, remission, relapse and persistence: a population-based study in southern Taiwan.

BACKGROUND: In western countries, late-onset asthmatics are more severe than early-onset asthmatics in clinic-based studies. However, whether asthma occurrence rates were higher in late ages than in younger ages was inconclusive. This information is essentially lacking in Asian population. METHODS: The participants were schoolchildren's parents recruited from 94 elementary and middle schools in 2004. A cross-sectional self-administered questionnaire was sent through the children to their parents to survey their respiratory health. We investigated typical asthma symptoms occurring at different ages and subsequent remission or relapse after the first asthma event. Person-years of the participants from birth to the time of survey were used as the denominator. RESULTS: Among the 25,377 participants consisting of 949,807 total person-years, 860 reported ever having asthma. Highest incidences occurred at ages 0-12 and 36-40 years. The incidence of asthma was higher in males before puberty, and higher in females after puberty, with overall incidences 1.00 and 0.77 per 1000 person-years for females and males, respectively. Participants with late-onset asthma (onset age >12 years) comprised a large portion of adult current asthmatics. More than 52% of persistence or relapse was observed in early-onset asthma (onset age ≤12 years). The younger birth cohort had a more prominent later peak of asthma incidence than the older one. CONCLUSIONS: In Asian population, asthma occurrence showed a U-shape age distribution with a prominent second peak in the thirties. A high proportion of early-onset asthma relapsed and most of late-onset asthma persisted or relapsed in adulthood.

Novel Ultrasound-Guided Cervical Intervertebral Disc Injection of Platelet-Rich Plasma for Cervicodiscogenic Pain: A Case Report and Technical Note.

Ultrasound-guided needle placement into the cervical intervertebral discs using a lateral-to-medial approach is reportedly possible. Clinically, however, patients commonly present with very high uncovertebral joints or narrowed intervertebral spaces, making the method difficult or impossible. This report presents a novel ultrasound-guided needle placement technique to the cervical intervertebral discs using a more medial approach between the trachea/thyroid gland and the carotid sheath. A patient presented with neck pain radiating to the right shoulder and right-sided interscapular regions that affected his sleep and daily functioning. Physiotherapy, selective nerve root block, and percutaneous endoscopic right C7 laminotomy did not sufficiently improve his condition, which progressed to bilateral interscapular and bilateral shoulder pain. Provocative discography was performed with injection of leukocyte-poor and red blood cell-poor platelet-rich plasma to provoke the discogenic pain, which was treated with platelet-rich plasma mixed with lidocaine. The patient recovered well. A month later, there was a significant decrease in the neck disability index score from the initial 28/50 to 14, and there was a further decrease to 5 after 2 months. In conclusion, this medial approach of ultrasound-guided cervical disc needle placement is feasible, even in patients where disc access by previously described approaches is impossible.

A novel Doppler spectral index for differentiating benign from malignant lung tumors.

PURPOSE: It has been reported that the resistance index (RI) and pulsatility index (PI) are of limited value in differentiating lung cancers from benign lesions. We hypothesized that a vascular work index (VWI), derived from Doppler spectral waveforms, would yield better results. METHODS: Forty-one patients were enrolled, 20 of them having malignancies and 21 having benign lesions. The VWI was defined as the square of peak systolic velocity times the time-velocity integral. Maximal VWI, minimal RI, and minimal PI of each tumor were used for analysis. RESULTS: Significantly higher VWI values were found in malignant tumors compared with benign lesions (p < 0.0001). VWI was shown by analysis of the receiver operating characteristic curve to be a best predictor of lung malignancies than PI and RI (p < 0.05), with a 0.89 (95% confidence interval, 0.80-0.98) area under the receiver operating characteristic curve. CONCLUSIONS: VWI may be a useful index to help differentiate malignant from benign lung tumors.

Ultrasound-Guided Cervical Intradiscal Injection with Platelet-Rich Plasma with Fluoroscopic Validation for the Treatment of Cervical Discogenic Pain: A Case Presentation and Technical Illustration.

Chronic neck pain has a high incidence and prevalence in urban society. Cervical disc-related chronic neck pain with its referred pain is one of the most common causes. Traditionally, pain caused by a cervical disc is diagnosed by fluoroscopy-guided provocative discography. In this report, we presented a patient with chronic neck and shoulder pain and a technique of using ultrasound to guide the needle entry to the cervical discs which were suspected to be the cause of the patient's chronic neck and shoulder pain. The needle placement was then validated by contrast fluoroscopy. The patient's symptoms significantly improved three weeks after the procedure. In conclusion, US can serve as a good imaging guiding tool for cervical intradiscal injections.

Ambient air pollution and asthma onset in Taiwanese adults.

BACKGROUND: Ambient nitrogen dioxide is associated with asthma occurrence in adults in Western countries. However, two recent large-scale studies have provided inconclusive results regarding this association. Moreover, the association remains unknown in an Asian population. OBJECTIVE: We aimed to investigate the association between ambient air pollution exposure and incident adult asthma. METHODS: From 2016 to 2017, we conducted a cross-sectional self-administered questionnaire survey with retrospective follow-up of incident asthma cases among schoolchildren's parents from 41 schools within 1 km of air monitoring stations distributed throughout the main island of Taiwan. To estimate participants' exposure, air pollution data of air monitoring stations within 1 km of schools from where participants were sampled were inputted into the proximity model. We used mixed logistic regression models to determine the association between air pollution exposure and asthma onset within five years prior to the survey. RESULTS: The questionnaire was completed for a total of 11 585 participants out of 13 424 candidates (response rate, 86.3%). Among 9131 participants aged from 26 to 50 years, 101 were diagnosed with asthma within the five years prior to the survey. The prevalence of incident asthma cases was 2.2 per 1000 person-years. Those exposed to higher ambient nitrogen dioxide (odds ratio = 1.20 per interquartile [5.7 ppb] of nitrogen dioxide, 95% CI = 1.02-1.42) were more likely to develop adult-onset asthma. CONCLUSION: In an Asian population, exposure to higher ambient nitrogen dioxide is associated with increased prevalence of incident asthma cases among adults aged 26-50 years.

Ultrasound-Guided Lumbar Intradiscal Injection for Discogenic Pain: Technical Innovation and Presentation of Two Cases.

We described two cases and the techniques for using the ultrasound (US) to guide lumbar intradiscal injection with platelet-rich plasma (PRP). The two cases suffered from chronic low back pain. Magnetic resonance imaging revealed posterior annular tear of the L5/S1 intervertebral disc (IVD) in the first case and L4/5 and L5/S1 IVDs in the second case. For the US-guided lumbar intradiscal injection, the patient was placed in a prone position. By placing the transducer in the axial plane at the interlaminar space, the needle was directed toward the center of the aimed IVD. The needle tip was ensured inside the IVD by using the end-feel of sudden reduction of resistance and the poking technique with the transducer oriented in the paramedian sagittal oblique plane. At the follow-up, both patients had significant improvement after the intradiscal PRP injections (visual analogue scale from 7.5 to 1.5 on average). The report indicated US-guided lumbar intradiscal PRP injection to be a feasible approach for treatments of low back pain. Familiarization of the anatomy and sonoanatomy of the lumbar spine is fundamental to achieve the success of intradiscal injection.

Potential risk of malposition of nasogastric tube using nose-ear-xiphoid measurement.

BACKGROUND: Correct placement of nasogastric tubes provide proper functionality and maximize benefit and minimize risk. The Nose-Ear-Xiphoid (NEX) body surface estimate method is a long-lasting technique, and this study was conducted to evaluate the correlation between NEX method and the secure insertion depth of nasogastric tube. MATERIALS AND METHODS: Thirty patients with nasogastric tube insertion who received whole body positron emission tomography with computerized tomography scan (PET-CT) were recruited. All data were gathered in the image center, which included Nose-Ear (NE), Ear-Xiphoid (EX), Nose-Ear-Xiphoid (NEX), glabella-xiphoid (GX) and glabella-umbilicus (GU) lengths. The distances of the inserted portion of the nasogastric tube between the cardiac and the nostril were measured by multiplanar reconstruction algorithm. RESULTS: Only one patient successfully placed all side-holes into the stomach while using NEX method to estimate inserting depth. Twenty-nine patients (96.7%) failed to place correctly. Fourteen participants had one or more side-holes in both the esophagus and the stomach sides. Fifteen patients could not pass through any side-hole across the gastroesophageal junction. They had shorter EX distances (p = 0.02), but no difference among the NE distances. Body height had the highest statistical correlation with nasogastric tube length (adjusted R(2) = 0.459), as compared with the NEX, GX and GU body surface methods. CONCLUSION: This study suggests that NEX method is inappropriate for adult patients to estimate the ideal inserting length of nasogastric tube. Physicians should realize these underinsertions with any side-hole above the gastroesophageal junctions may increase the potential risk of complications.

Computer-aided diagnosis of mass-like lesion in breast MRI: differential analysis of the 3-D morphology between benign and malignant tumors.

This study aimed to evaluate the value of using 3-D breast MRI morphologic features to differentiate benign and malignant breast lesions. The 3-D morphological features extracted from breast MRI were used to analyze the malignant likelihood of tumor from ninety-five solid breast masses (44 benign and 51 malignant) of 82 patients. Each mass-like lesion was examined with regards to three categories of morphologic features, including texture-based gray-level co-occurrence matrix (GLCM) feature, shape, and ellipsoid fitting features. For obtaining a robust combination of features from different categories, the biserial correlation coefficient (|r(pb)|)≧0.4 was used as the feature selection criterion. Receiver operating characteristic (ROC) curve was used to evaluate performance and Student's t-test to verify the classification accuracy. The combination of the selected 3-D morphological features, including conventional compactness, radius, spiculation, surface ratio, volume covering ratio, number of inside angular regions, sum of number of inside and outside angular regions, showed an accuracy of 88.42% (84/95), sensitivity of 88.24% (45/51), and specificity of 88.64% (39/44), respectively. The AZ value was 0.8926 for these seven combined morphological features. In conclusion, 3-D MR morphological features specified by GLCM, tumor shape and ellipsoid fitting were useful for differentiating benign and malignant breast masses.

Feasibility of a novel two-piece nasogastric feeding tube for patients with dysphagia.

INTRODUCTION: The exposed section of a traditional nasogastric (NG) tube can interfere with patients' social activities and thereby result in distress. This study was conducted to evaluate the feasibility and safety of a novel two-piece NG tube for patients with dysphagia. METHODS: Ten patients with dysphagia were recruited between November 2011 and May 2012. Patients who were unconscious or in critical condition, had a traditional NG tube < 50 cm or > 60 cm in fixed length, or were unable to follow instructions or sign consent forms were excluded. The two-piece NG tube, which was placed in the patients for one week, comprised a removable external tube that can be joined to an internal tube via a T-connector, which was placed close to the naris. Events related to safety (e.g. nasal pressure sores, number of unplanned extubation, displacement and spontaneous migration of the NG tube, other unpredictable injuries) and effectiveness (e.g. liquid food spills, tube obstruction, perfusion rate, other adverse circumstances) were assessed daily. RESULTS: All patients received feeding without complication using the two-piece NG tube and none experienced premature removal of the tube. No serious NG tube complications or malfunctions were observed. CONCLUSION: The results of this study indicate that the two-piece NG feeding tube is a feasible option for patients with dysphagia. Future improvements to the connector may help enhance its performance. A rigorous randomised controlled trial to examine the effects of the two-piece NG tube on patients' quality of life and quality of medical care is being planned.