Patient experience with bronchoscopy: topical versus monitored anesthesia.

BACKGROUND: This study aimed to compare patient experiences during bronchoscopy procedures using either topical anesthesia (TA) or monitored anesthesia care (MA). The goal was to identify circumstances where patients could achieve similar levels of tolerance and satisfaction using only TA, especially in resource-limited settings. METHODS: This study included consecutive patients who underwent bronchoscopy with either TA or MA. Data collected included demographics, indications for bronchoscopy, procedure time, and complications during the procedure. A quality assurance survey was administered to assess patient experience and satisfaction with both procedures. A pre-specified subgroup analysis was performed based on procedure invasiveness and time. RESULTS: This study enrolled 350 (TA 251; MA 99) patients, with an average age of 65 years. Main indications for bronchoscopy included tumor diagnosis (38%), esophageal cancer staging (18%), and pulmonary infection (17%). The average duration of the procedures was 20 min, with MA being associated with a significantly longer procedure time than TA (31 min vs. 16 min; P < 0.001). The overall satisfaction rating with bronchoscopy was significantly higher in the MA group (visual analogue scale, 8.9 vs. 8.2; P = 0.001). Subgroup analyses showed that when less invasive or shorter procedures were performed, TA patients reported tolerance and satisfaction levels comparable to MA patients. CONCLUSIONS: Bronchoscopy with MA offered patients a better experience and greater satisfaction; however, in settings with limited resources, TA alone may provide similar levels of patient tolerance and satisfaction during less invasive or shorter procedures.

Assessing the Clinical Effectiveness of an Exergame-Based Exercise Training Program Using Ring Fit Adventure to Prevent and Postpone Frailty and Sarcopenia Among Older Adults in Rural Long-Term Care Facilities: Randomized Controlled Trial.

BACKGROUND: Frailty and sarcopenia are geriatric syndromes of increasing concern and are associated with adverse health outcomes. They are more prevalent among long-term care facility (LTCF) users than among community dwellers. Exercise, especially multicomponent and progressive resistance training, is essential for managing these conditions. However, LTCFs, particularly in rural areas, face challenges in implementing structured exercise programs due to health care professional shortages. Moreover, older adults often become bored with repetitive exercise training and may lose interest over time. The Nintendo Switch Ring Fit Adventure (RFA) exergame is a novel exergame that combines resistance, aerobic, and balance exercises and offers a potential solution by boosting motivation in an immersive manner and reducing staff intervention needs. OBJECTIVE: We aimed to evaluate the clinical effectiveness of an exergame-based exercise training program delivered via RFA (exergame-RFA) in improving muscle mass and functional performance among older adult LTCF users. METHODS: This was a randomized controlled trial conducted from August 2022 to September 2023 and involved older adult LTCF users (aged ≥60 y) in rural southern Taiwan. Participants were randomized into an intervention group (exergame-RFA plus standard care) or a control group (standard care alone). The intervention, conducted seated with arm fit skills and trunk control exercises using the RFA, lasted 30 minutes twice weekly over 12 weeks. The primary outcomes measured were the Study of Osteoporotic Fractures index (serving as an indicator of frailty status) and the diagnostic criteria for sarcopenia (appendicular skeletal muscle mass index, handgrip strength, and gait speed). The secondary outcomes included functional performance (box and block test as well as maximum voluntary isometric contraction of the dominant upper extremity), muscle condition (muscle thickness measured using ultrasonography), activities of daily living (Kihon checklist), health-related quality of life (Short Form Health Survey-36), and cognitive function (brain health test). We used an intention-to-treat analysis, incorporating a simple imputation technique in statistical analysis. A mixed ANOVA, with time as a within-participant factor and intervention as a between-participant factor, was used to compare the training effects on outcomes. RESULTS: We recruited 96 individuals, of whom 60 (62%) underwent randomization. Of these 60 participants, 55 (92%) completed the study. Significant group×time interactions were observed in the intervention group in all primary outcomes (all P<.001, except P=.01 for handgrip strength) and most secondary outcomes, including maximum voluntary isometric contraction of the biceps (P=.004) and triceps brachii (P<.001) muscles, biceps muscle thickness measured using ultrasonography (P<.001), box and block test (P<.001), Kihon checklist (physical function: P=.01, mood status: P=.003, and total: P=.003), and brain health test (P<.001). CONCLUSIONS: The exergame-RFA intervention significantly improved muscle mass, strength, and functional performance among older adult users of rural LTCFs, offering a novel approach to addressing frailty and sarcopenia. TRIAL REGISTRATION: ClinicalTrials.gov NCT05360667; https://clinicaltrials.gov/study/NCT05360667. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.3389/fmed.2022.1071409.

Physical therapy intervention for breast symptoms in lactating women: a randomized controlled trial.

BACKGROUND: Therapeutic ultrasound, education, and massage are the most common physical therapy interventions provided to mothers with breast symptoms. However, there is insufficient evidence on the effectiveness of the combination of these interventions. This study aimed to explore the effects of the combination of therapeutic ultrasound, education, and massage on breast symptoms in lactating women. METHODS: This study was a single-blind randomized controlled trial. Postpartum lactating women aged from 21 to 45 with breast symptoms were recruited and randomly allocated to one of three groups (ultrasound group, sham group, and usual care group). The severity of breast symptoms (pain, redness, lump, general malaise), breast engorgement, breast hardness, body temperature, breast temperature, and milk volume were assessed at baseline (T1), immediately post-intervention (T2), and at 3 months following baseline (T3). RESULTS: A total of 37 participants were included in the study (ultrasound group n = 12; sham group n = 12; usual care n = 13). The severity of breast symptoms (i.e., pain, lump, and general malaise) as well as breast engorgement, were significantly improved in the ultrasound group at T2 when compared to T1, and these improvements were sustained at T3. The severity of breast engorgement was significantly lower in the ultrasound group when compared to the usual care group at T2. However, no statistically significant differences were found between the ultrasound and sham groups for all outcomes at any assessment time points. CONCLUSIONS: Physical therapy interventions may be beneficial in relieving breast symptoms in lactating women. Larger randomized controlled trials are needed to confirm the findings of this study. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04569136); Date of registration: 29/09/2020.

Physical therapists' experiences and perceptions of antepartum and postpartum care.

BACKGROUND: Little is known about the physical therapists' practice and perceptions toward management of pregnancy/postpartum-related disorders in Taiwan. The aim of this study was to document current practice of physical therapy in antepartum and postpartum care in Taiwan. METHODS: An exploratory, cross-sectional study was conducted in registered physical therapists living in Taiwan. An anonymized online survey was designed, piloted, and advertised widely from March 2020 to March 2021. Data were analyzed using descriptive statistics, Chi square analysis and multivariate logistic regression. RESULTS: Of the 364 respondents, 37.6% had experience of treating pregnant or postpartum women in clinical practice. The most commonly treated pregnancy/postpartum-related disorder in practice was low back pain (61.3%). All respondents reported little to moderate level of confidence in their ability to manage pregnancy/postpartum-related disorder. Being female (p < 0.01); working at a regional hospital (p = 0.01), district hospital or district teaching hospital (p < 0.01), clinic (p = 0.01) or physiotherapy clinic (p = 0.01); and having prior experience of treating antepartum or postpartum women (p < 0.01) were significantly associated with willingness to provide customer-oriented service or health education to patients/clients with pregnancy/postpartum-related disorder after controlling for other confounding variables. The most commonly reported barrier was "lack of available training" (81.3%). CONCLUSION: The majority of participating physical therapists indicated a positive attitude to antepartum and postpartum care but were not confident in management of various pregnancy/postpartum-related disorder in practices. The findings of this study highlight the educational needs related to antepartum and postpartum care in clinical practice for physical therapists in Taiwan.

Effect of Neferine on DNCB-Induced Atopic Dermatitis in HaCaT Cells and BALB/c Mice.

Atopic dermatitis (AD) is a chronic and persistent inflammatory skin disease characterized by eczematous lesions and itching, and it has become a serious health problem. However, the common clinical treatments provide limited relief and are accompanied by adverse effects. Therefore, there is a need to develop novel and effective therapies to treat AD. Neferine is a small molecule compound isolated from the green embryo of the mature seeds of lotus (Nelumbo nucifera). It has a bisbenzylisoquinoline alkaloid structure. Relevant studies have shown that neferine has many pharmacological and biological activities, including anti-inflammatory, anti-thrombotic, and anti-diabetic activities. However, there are very few studies on neferine in the skin, especially the related effects on inflammatory skin diseases. In this study, we proved that it has the potential to be used in the treatment of atopic dermatitis. Through in vitro studies, we found that neferine inhibited the expression of cytokines and chemokines in TNF-α/IFN-γ-stimulated human keratinocyte (HaCaT) cells, and it reduced the phosphorylation of MAPK and the NF-κB signaling pathway. Through in vivo experiments, we used 2,4-dinitrochlorobenzene (DNCB) to induce atopic dermatitis-like skin inflammation in a mouse model. Our results show that neferine significantly decreased the skin barrier damage, scratching responses, and epidermal hyperplasia induced by DNCB. It significantly decreased transepidermal water loss (TEWL), erythema, blood flow, and ear thickness and increased surface skin hydration. Moreover, it also inhibited the expression of cytokines and the activation of signaling pathways. These results indicate that neferine has good potential as an alternative medicine for the treatment of atopic dermatitis or other skin-related inflammatory diseases.

Anti-Allergic and Anti-Inflammatory Effects of Neferine on RBL-2H3 Cells.

Mast cells play a very important role in skin allergy and inflammation, including atopic dermatitis and psoriasis. In the past, it was found that neferine has anti-inflammatory and anti-aging effects on the skin, but its effect on mast cells has not yet been studied in detail. In this study, we used mast cells (RBL-2H3 cells) and mouse models to study the anti-allergic and inflammatory effects of neferine. First, we found that neferine inhibits the degranulation of mast cells and the expression of cytokines. In addition, we observed that when mast cells were stimulated by A23187/phorbol 12-myristate-13-acetate (PMA), the elevation of intracellular calcium was inhibited by neferine. The phosphorylation of the MAPK/NF-κB pathway is also reduced by pretreatment of neferine. The results of in vivo studies show that neferine can improve the appearance of dermatitis and mast cell infiltration caused by dinitrochlorobenzene (DNCB). Moreover, the expressions of barrier proteins in the skin are also restored. Finally, it was found that neferine can reduce the scratching behavior caused by compound 48/80. Taken together, our results indicate that neferine is a very good anti-allergic and anti-inflammatory natural product. Its effect on mast cells contributes to its pharmacological mechanism.

Gastrointestinal complications are associated with a poor outcome in non-critically ill pneumonia patients.

BACKGROUND: Development of gastrointestinal (GI) complications is adversely associated with prognosis in the critically ill. However, little is known about their impact on the outcome of non-critically ill patients. In this study, we aimed to investigate the incidence of GI complications and their influence on prognosis of hospitalized pneumonia patients. METHODS: Adult patients admitted with a diagnosis of pneumonia from 2012 to 2014 were included. Medical records were reviewed to obtain patients' demographics, physical signs, comorbidities, laboratory results, clinical events, and the Confusion, Urea, Respiratory rate, Blood pressure and age ≥ 65 (CURB-65) score was calculated to assess the severity of pneumonia. GI complications, including bowel distension, diarrhea, GI bleeding and ileus, were evaluated during the first 3 days of hospitalization and their association with patient outcomes, such as hospital mortality and length of stay, was analyzed. RESULTS: A total of 1001 patients were enrolled, with a mean age of 73.7 years and 598 (59%) male. Among them, 114 (11%) patients experienced at least one GI complication and diarrhea (5.2%) was the most common. The hospital mortality was 14% and was independently associated with an increase in the CURB-65 score (odds ratio [OR] 1.952 per point increase; 95% confidence interval [CI] 1.516-2.514), comorbid malignancy (OR 1.943; 95% CI 1.209-3.123), development of septic shock (OR 25.896; 95% CI 8.970-74.765), and the presence of any GI complication (OR 1.753; 95% CI 1.003-3.065). CONCLUSIONS: Compared to a critical care setting, GI complications are not commonly observed in a non-critical care setting; however, they still have a negative impact on prognosis of pneumonia patients, including higher mortality and prolonged length of hospital stay.

Feasibility of Smartphone-Based Badminton Footwork Performance Assessment System.

Footwork is the most fundamental skill in badminton, involving the ability of acceleration or deceleration and changing directions on the court, which is related to accurate shots and better game performance. The footwork performance in-field is commonly assessed using the total finished time, but does not provide any information in each direction. With the higher usage of the smartphones, utilizing their built-in inertial sensors to assess footwork performance in-field might be possible by providing information about body acceleration in each direction. Therefore, the purpose of this study was to evaluate the feasibility of a smartphone-based measurement system on badminton six-point footwork. The body acceleration during the six-point footwork was recorded using a smartphone fixed at the belly button and a self-developed application in thirty badminton players. The mean and maximum of the acceleration resultant for each direction of the footwork were calculated. The participants were classified into either the faster or slower group based on the finished duration of footwork. Badminton players who finished the footwork faster demonstrated a greater mean and maximum acceleration compared to those who finished slower in most directions except for the frontcourt directions. The current study found that using a smartphone's built-in accelerometer to evaluate badminton footwork is feasible.

Landing Kinematics, Sports Performance, and Isokinetic Strength in Adolescent Male Volleyball Athletes: Influence of Core Training.

CONTEXT: Core control and strength are important for reducing the risk of lower-extremity injury. Current evidence on the effect of core training in male adolescent athletes is limited, and other investigations into the effects of core training often emphasized core strength only. OBJECTIVE: To examine whether core training emphasizing both control and strength of the trunk and hip would improve joint kinematics during landing, sports performance, and lower-extremity muscle strength in adolescent male volleyball athletes. DESIGN: Single group pretest and posttest design. SETTING: University laboratory. PARTICIPANTS: Sixteen male participants (age: 13.4 [1] y, height: 167.8 [8.6] cm, mass: 58.6 [13.9] kg, and volleyball experience: 3.8 [1.5] y) from a Division I volleyball team at a junior high school. MAIN OUTCOME MEASUREMENTS: Kinematics of the trunk and lower-extremity during box landing and spike jump landing tasks, volleyball-related sports performance, and isokinetic strength of hip and knee muscles were assessed before and after a 6-week core training program. RESULTS: After training, the participants demonstrated decreased trunk flexion angle (P = .01, Cohen's d = 0.78) during the box landing task and reduced the maximum knee internal rotation angle (P = .04, Cohen's d = 0.56) during the spike jump landing task. The average isokinetic strength of hip flexors and external rotators, and knee flexors and extensors also significantly increased (P = .001, Cohen's d = 0.98; P = .04, Cohen's d = 0.57; P = .02, Cohen's d = 0.66; P = .003, Cohen's d = 0.87, respectively); however, sports performance did not show significant changes. CONCLUSIONS: A more erect landing posture following training suggests that the core training program may be beneficial for improving core stability. The long-term effect of core training for knee injury prevention needs further investigation.

Metformin use mitigates the adverse prognostic effect of diabetes mellitus in chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: Among patients with chronic obstructive pulmonary disease (COPD), diabetes mellitus (DM) is a common comorbidity and is probably associated with increased systemic inflammation and worse prognosis. Metformin, with its pleiotropic anti-inflammatory and antioxidant actions, may offer theoretical benefits in COPD patients with DM. Thus, this study aimed to investigate the effects of DM and metformin use on mortality in the clinical trajectory of COPD. METHODS: This was a retrospective cohort study comprising patients with spirometry-confirmed COPD and an age of ≥40 years from 2008 to 2014. The primary outcome of interest was all-cause mortality. We evaluated the effects of DM on mortality through the clinical course of COPD and we also assessed the impact of metformin use on survival of the COPD population. RESULTS: Among 4231 COPD patients, 556 (13%) had DM, and these patients had 1.62 times higher hazards of 2-year mortality than those without DM (95% confidence interval [CI], 1.15-2.28) after adjusting for age, gender, COPD stage, comorbidities and prior COPD hospitalization. Over a 2-year period, metformin users had a significantly lower risk of death (hazard ratio, 0.46; 95% CI, 0.23-0.92) compared with non-metformin users in patients with coexistent COPD and DM. Moreover, metformin users had similar survival to COPD patients without DM. CONCLUSIONS: This study shows that DM is associated with an increased risk of death in COPD patients and metformin use seems to mitigate the hazard. Our findings suggest a potential role of metformin in the management of DM in COPD.

Atypical cells in pathology of endobronchial ultrasound-guided transbronchial biopsy of peripheral pulmonary lesions: incidence and clinical significance.

BACKGROUND: Atypical cells may occasionally be the only pathologic finding in radial-probe endobronchial ultrasound (EBUS)-guided transbronchial biopsy (TBB) of peripheral pulmonary lesions (PPLs); however, it is uncertain how often we encounter such a situation and what clinical features can be used to identify these ambiguous PPLs, which are more likely to be malignant. METHODS: From 2009 to 2016, consecutive patients referred for EBUS-guided TBB of PPLs and with pathology reports indicating atypical cells alone were included. Medical records were reviewed to extract patient demographics, clinical characteristics, procedural details and complications. The primary outcome was the final diagnosis of the PPLs on subsequent investigation. Multivariate logistic regression analysis was used to identify independent factors associated with a final malignant diagnosis. RESULTS: One hundred sixty-five (7.2%) of 2291 patients had non-diagnostic TBB showing atypical cells. Benign and malignant diagnoses were subsequently obtained in 45 (27%) and 120 (73%) patients, respectively. The leading malignancy was lung adenocarcinoma; of note, a variety of benign lesions revealed cellular atypia on pathology, in particular, chronic inflammation, tuberculosis and pneumonia. Multivariate analysis indicated lesion appearance [solid vs. others; odds ratio (OR) 7.93; 95% confidence interval (CI) 2.94-21.40; P < 0.001] and probe position (adjacent to vs. within; OR 3.36; 95% CI 1.11-10.15; P = 0.032) were two significant factors predictive of a final diagnosis of malignancy. CONCLUSIONS: One out of 14 EBUS-guided TBB procedures for PPLs exhibited atypical cells on pathology. Meticulous management strategies should be formulated to deal with these instances after taking into consideration lesion appearance, probe position and patient preferences.

Radial endobronchial ultrasound-guided transbronchial biopsy for peripheral pulmonary malignancy: biopsy- or brushing-first?

BACKGROUND: Radial endobronchial ultrasound (R-EBUS)-guided transbronchial biopsy (TBB) is a common diagnostic modality for peripheral pulmonary lesions; however, there is uncertainty about the optimal sequence of TBB and bronchial brushing during the procedure. Thus, we aimed to investigate whether a biopsy-first or brushing-first strategy confers a better diagnostic yield and safety signal for R-EBUS-guided procedures for peripheral pulmonary malignancy. METHODS: From January 2017 to June 2018, consecutive patients referred for R-EBUS-guided TBB and bronchial brushing of peripheral pulmonary lesions and with a final malignant diagnosis were included. Patients were placed in a biopsy-first (biopsy followed by brushing) or a brushing-first (brushing followed by biopsy) group. The outcomes of interest were the diagnostic yield and complication profile of the procedures. Multivariate logistic regression and subgroup analysis were used to assess the impact of the procedure strategy. RESULTS: A total of 438 patients were included and the diagnostic yield of R-EBUS-guided TBB plus brushing for peripheral pulmonary malignancy was 73%. The diagnostic yield was associated with the solid lesion appearance (odds ratio [OR] 2.01; 95% confidence interval [CI] 1.08-3.75) and R-EBUS probe position within the lesion (OR 1.92; 95% CI 1.08-3.42), and the yield rates were comparable between the biopsy-first and brushing-first strategies. Moreover, the safety signal did not differ between the two groups. CONCLUSIONS: The two procedure strategies were indistinguishable in terms of diagnostic efficacy and adverse events for patients with peripheral pulmonary malignancy. Current evidence indicates that in patients with peripheral pulmonary lesions suspected of being malignant, either biopsy-first or brushing-first is a viable and acceptable diagnostic strategy during R-EBUS-guided procedures.

Collegiate baseball players with more optimal functional movement patterns demonstrate better athletic performance in speed and agility.

Sports injuries are common among baseball players and may result in abnormal movement patterns, increased risks of future injury, and unsatisfactory performance. The Functional Movement Screen (FMS™) has been developed to detect abnormal functional movement patterns and can be used for predicting risks of sports injury. However, whether FMS™ scores are associated with athletic performance remains unclear. The goal of this study was to determine the association between functional movements and athletic performance in elite baseball players. Core stability, muscular strength and flexibility of the lower extremities, and FMS™, as well as athletic performance in sprinting, agility, and balance tests were assessed in 52 male collegiate Division I baseball players placed into two groups based on FMS™ scores. The high-scoring group demonstrated better athletic performance than the low-scoring group, with a shorter duration of the agility test. No group differences were found in core stability, muscular strength, or muscle flexibility, except for rectus femoris flexibility. Thus, the FMS™ score is associated with sprinting and agility performance in elite baseball players. These findings indicate that the FMS™ may have a role in predicting athletic performance and thereby help determine the goals of training regimens or return-to-play strategies.

Erythropoietin reduces nerve demyelination, neuropathic pain behavior and microglial MAPKs activation through erythropoietin receptors on Schwann cells in a rat model of peripheral neuropathy.

Neuroprotective effects of erythropoietin (EPO) on peripheral nerve injury remain uncertain. This study investigated the efficacy of EPO in attenuating median nerve chronic constriction injury (CCI)-induced neuropathy. Animals received an intraneural injection of EPO at doses of 1,000, 3,000, or 5,000 units/kg 15 min before median nerve CCI. Afterwards, the behavioral and electrophysiological tests were conducted. Immunohistochemistry and immunoblotting were used for qualitative and quantitative analysis of microglial and mitogen-activated protein kinases (MAPKs), including p38, JNK, and ERK, activation. Enzyme-linked immunosorbent assay and microdialysis were applied to measure pro-inflammatory cytokine and glutamate responses, respectively. EPO pre-treatment dose-dependently ameliorated neuropathic pain behavior, decreased microglial and MAPKs activation, and diminished the release of pro-inflammatory cytokines and glutamate in the ipsilateral cuneate nucleus after CCI. Moreover, EPO pre-treatment preserved myelination of the injured median nerve on morphological investigation and suppressed injury-induced discharges. We also observed that EPO receptor (EPOR) expression was up-regulated in the injured nerve after CCI. Double immunofluorescence showed that EPOR was localized to Schwann cells. Furthermore, siRNA-mediated knockdown of EPOR expression eliminated the therapeutic effects of EPO on attenuating the microglial and MAPKs activation, pro-inflammatory cytokine responses, injury discharges, and neuropathic pain behavior in CCI rats. In conclusion, binding of EPO to its receptors on Schwann cells maintains myelin integrity and blocks ectopic discharges in the injured median nerve, that in the end contribute to attenuation of neuropathic pain via reducing glutamate release from primary afferents and inhibiting activation of microglial MAPKs and production of pro-inflammatory cytokines.

The value of repeat radial-probe endobronchial ultrasound-guided transbronchial biopsy after initial non-diagnostic results in patients with peripheral pulmonary lesions.

BACKGROUND: Radial-probe endobronchial ultrasound (rEBUS)-guided transbronchial biopsy (TBB) is invaluable in the diagnosis of peripheral pulmonary lesions (PPLs); however, in certain instances, the procedure has to be repeated because of initial non-diagnostic procedure(s). Little if any literature has been published on this issue. Therefore, the aim of this study was to investigate the utility of repeat rEBUS-guided TBB in achieving a definitive diagnosis of PPLs. METHODS: All patients who underwent rEBUS-guided TBB of PPLs at National Taiwan University Hospital between 2011 and 2015 and had a repeat procedure after non-diagnostic initial procedures were identified as the study subjects. The primary outcome of interest was the diagnostic yield of repeat rEBUS-guided TBB for PPLs. Also, we sought to discover features associated with the yield of repeat procedures. RESULTS: Forty-three (11%) out of 384 patients with initial non-diagnostic TBB were included for analysis. A diagnosis of PPLs was able to be confirmed with repeat TBB in 23(53%) patients. The pathology of the first TBB was significantly associated with the yield of repeat procedures (P = 0.011). Further, patients with normal lung tissue in initial pathology rarely (2/12, 17%) had a definite diagnosis on repeat TBB. Yet, patients with pathology showing atypical cells and other non-specific findings were more likely (21/31, 68%) to obtain a confirmed diagnosis. The diagnostic yield of repeat procedures was not affected by the size, location or CT appearance of the lesions, or position of the rEBUS probe. No death or other serious adverse events occurred with the repeat rEBUS-guided procedures. CONCLUSIONS: If clinically indicated, it is reasonable to repeat rEBUS-guided TBB after an initial non-diagnostic procedure as the diagnostic yield will be at least 50% and the side effect profile is favorable.

Heat shock protein 70 and AMP-activated protein kinase contribute to 17-DMAG-dependent protection against heat stroke.

Heat shock protein 70 (Hsp70) preconditioning induces thermotolerance, and adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays a role in the process of autophagy. Here, we investigated whether 17-dimethylaminoethylamino-17-demethoxy-geldanamycin (17-DMAG) protected against heat stroke (HS) in rats by up-regulation of Hsp70 and phosphorylated AMPK (pAMPK). To produce HS, male Sprague-Dawley rats were placed in a chamber with an ambient temperature of 42°C. Physiological function (mean arterial pressure, heart rate and core temperature), hepatic and intestinal injury, inflammatory mediators and levels of Hsp70, pAMPK and light chain 3 (LC3B) in hepatic tissue were measured in HS rats or/and rats pre-treated with 17-DMAG. 17-DMAG pre-treatment significantly attenuated hypotension and organ dysfunction induced by HS in rats. The survival time during HS was also prolonged by 17-DMAG treatment. Hsp70 expression was increased, whereas pAMPK levels in the liver were significantly decreased in HS rats. Following pre-treatment with 17-DMAG, Hsp70 protein levels increased further, and pAMPK levels were enhanced. Treatment with an AMPK activator significantly increased the LC3BII/LC3BI ratio as a marker of autophagy in HS rats. Treatment with quercetin significantly suppressed Hsp70 and pAMPK levels and reduced the protective effects of 17-DMAG in HS rats. Both of Hsp70 and AMPK are involved in the 17-DMAG-mediated protection against HS. 17-DMAG may be a promising candidate drug in the clinical setting.

Neurosteroid Allopregnanolone Suppresses Median Nerve Injury-induced Mechanical Hypersensitivity and Glial Extracellular Signal-regulated Kinase Activation through γ-Aminobutyric Acid Type A Receptor Modulation in the Rat Cuneate Nucleus.

BACKGROUND: Mechanisms underlying neuropathic pain relief by the neurosteroid allopregnanolone remain uncertain. We investigated if allopregnanolone attenuates glial extracellular signal-regulated kinase (ERK) activation in the cuneate nucleus (CN) concomitant with neuropathic pain relief in median nerve chronic constriction injury (CCI) model rats. METHODS: We examined the time course and cellular localization of phosphorylated ERK (p-ERK) in CN after CCI. We subsequently employed microinjection of a mitogen-activated protein kinase kinase (ERK kinase) inhibitor, PD98059, to clarify the role of ERK phosphorylation in neuropathic pain development. Furthermore, we explored the effects of allopregnanolone (by mouth), intra-CN microinjection of γ-aminobutyric acid type A receptor antagonist (bicuculline) or γ-aminobutyric acid type B receptor antagonist (phaclofen) plus allopregnanolone, and allopregnanolone synthesis inhibitor (medroxyprogesterone; subcutaneous) on ERK activation and CCI-induced behavioral hypersensitivity. RESULTS: At 7 days post-CCI, p-ERK levels in ipsilateral CN were significantly increased and reached a peak. PD98059 microinjection into the CN 1 day after CCI dose-dependently attenuated injury-induced behavioral hypersensitivity (withdrawal threshold [mean ± SD], 7.4 ± 1.1, 8.7 ± 1.0, and 10.3 ± 0.8 g for 2.0, 2.5, and 3.0 mM PD98059, respectively, at 7 days post-CCI; n = 6 for each dose). Double immunofluorescence showed that p-ERK was localized to both astrocytes and microglia. Allopregnanolone significantly diminished CN p-ERK levels, glial activation, proinflammatory cytokines, and behavioral hypersensitivity after CCI. Bicuculline, but not phaclofen, blocked all effects of allopregnanolone. Medroxyprogesterone treatment reduced endogenous CN allopregnanolone and exacerbated nerve injury-induced neuropathic pain. CONCLUSIONS: Median nerve injury-induced CN glial ERK activation modulated the development of behavioral hypersensitivity. Allopregnanolone attenuated glial ERK activation and neuropathic pain via γ-aminobutyric acid type A receptors. Reduced endogenous CN allopregnanolone after medroxyprogesterone administration rendered rats more susceptible to CCI-induced neuropathy.

Quantitative electrochemical metalloimmunoassay for TFF3 in urine using a paper analytical device.

We report a paper-based assay platform for the detection of the kidney disease marker Trefoil Factor 3 (TFF3) in human urine. The sensor is based on a quantitative metalloimmunoassay that can determine TFF3 concentrations via electrochemical detection of environmentally stable silver nanoparticle (AgNP) labels attached to magnetic microbeads via a TFF3 immunosandwich. The paper electroanalytical device incorporates two preconcentration steps that make it possible to detect concentrations of TFF3 in human urine at the low end of the target TFF3 concentration range (0.03-7.0 µg mL(-1)). Importantly, the paper device provides a level of accuracy for TFF3 determination in human urine equivalent to that of a commercial kit. The paper sensor has a dynamic range of ∼2.5 orders of magnitude, only requires a simple, one-step incubation protocol, and is fast, requiring only 10 min to complete. The cost of the materials at the prototypic laboratory scale, excluding reagents, is just US$0.42.

Runx1-deficient afferents impair visceral nociception, exacerbating dextran sodium sulfate-induced colitis.

Colitis is a group of inflammatory and auto-immune disorders that affect the tissue lining of the gastrointestinal (GI) system. Studies of chemically-induced animal models of colitis have indicated that nociceptive afferents or neuropeptides have differing effects on GI inflammation. However, the molecular mechanisms involved in visceral pain and the role of visceral sensory afferents involved in the modulation of colitis remains unclear. A previous study demonstrated that Runx1, a Runt domain transcription factor, is restricted to nociceptors. In these neurons, Runx1 regulates the expression of numerous ion channels and receptors, controlling the lamina-specific innervation patterns of nociceptive afferents in the spinal cord. Moreover, mice that lack Runx1 exhibit specific defects in thermal and neuropathic pain. To examine the function of Runx1 in visceral nociception, we employed double-transgenic mice (WntCre: Runx1(F/F)), in which the expression of Runx1 was specifically disrupted in the sensory neurons. To determine the role of Runx1 in visceral pain sensation, the WntCre: Runx1(F/F) mice and their control littermates (Runx1(F/F)) were treated using dextran sodium sulfate (DSS) to induce colitis. The results indicated that disrupted Runx1 in the sensory afferents resulted in: (1) impairment of the visceral pain sensation in murine DSS-induced colitis; (2) exacerbating the phenotypes in murine DSS-induced colitis; (3) a differential effect on the production of pro- and anti-inflammatory cytokines in the colon tissues isolated from mice treated using DSS and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis; and (4) alteration of the distribution of lymphocytes and mast cells in mucosa. These results show that the function of Runx1 in sensory afferents is vital for modulating visceral pain and the neuro-immune axis.

Application of heart-rate variability in patients undergoing weaning from mechanical ventilation.

INTRODUCTION: The process of weaning may impose cardiopulmonary stress on ventilated patients. Heart-rate variability (HRV), a noninvasive tool to characterize autonomic function and cardiorespiratory interaction, may be a promising modality to assess patient capability during the weaning process. We aimed to evaluate the association between HRV change and weaning outcomes in critically ill patients. METHODS: This study included 101 consecutive patients recovering from acute respiratory failure. Frequency-domain analysis, including very low frequency, low frequency, high frequency, and total power of HRV was assessed during a 1-hour spontaneous breathing trial (SBT) through a T-piece and after extubation after successful SBT. RESULTS: Of 101 patients, 24 (24%) had SBT failure, and HRV analysis in these patients showed a significant decrease in total power (P = 0.003); 77 patients passed SBT and were extubated, but 13 (17%) of them required reintubation within 72 hours. In successfully extubated patients, very low frequency and total power from SBT to postextubation significantly increased (P = 0.003 and P = 0.004, respectively). Instead, patients with extubation failure were unable to increase HRV after extubation. CONCLUSIONS: HRV responses differ between patients with different weaning outcomes. Measuring HRV change during the weaning process may help clinicians to predict weaning results and, in the end, to improve patient care and outcome.