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.

Endoplasmic Reticulum Stress in Elderly Patients with COVID-19: Potential of Melatonin Treatment.

Aging processes, including immunosenescence, inflammation, inflammasome formation, genomic instability, telomeric attrition, and altered autophagy, are involved in viral infections and they may contribute to increased pathophysiological responses to the SARS-CoV-2 infection in the elderly; this poses additional risks of accelerated aging, which could be found even after recovery. Aging is associated with oxidative damage. Moreover, SARS-CoV-2 infections may increase the production of reactive oxygen species and such infections will disturb the Ca++ balance via an endoplasmic reticulum (ER) stress-mediated unfolded protein response. Although vaccine development and anti-inflammation therapy lower the severity of COVID-19, the prevalence and mortality rates are still alarming in some countries worldwide. In this review, we describe the involvement of viral proteins in activating ER stress transducers and their downstream signals and in inducing inflammation and inflammasome formation. Furthermore, we propose the potential of melatonin as an ER stress modulator, owing to its antioxidant, anti-inflammatory, and immunoregulatory effects in viral infections. Considering its strong safety profile, we suggest that additive melatonin supplementation in the elderly could be beneficial in treating COVID-19.

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.

Sitting Posture during Prolonged Computer Typing with and without a Wearable Biofeedback Sensor.

Prolonged sitting combined with an awkward posture might contribute to the increased risks of developing spinal pain. Maintaining an upright sitting posture is thus often suggested, especially nowadays when people spend longer periods in the sitting posture for occupational or leisure activities. Many types of assistive devices are commercially available to help computer users maintain an upright sitting posture. As the technology advances, wearable sensors that use microelectromechanical technology are designed to provide real-time biofeedback and promote adjusting posture actively. However, whether such wearable biofeedback sensors could assist adjusting sitting posture in computer users during prolonged typing remains unknown. This study aimed to investigate the effects of a wearable biofeedback sensor on maintaining an upright sitting posture. Twenty-one healthy young adults were recruited and performed a 1-h computer typing task twice, with and without using the active biofeedback device. The sagittal spinal posture during computer typing was measured using a three-dimensional motion analysis system. Using the wearable biofeedback sensor significantly decreased the neck flexion (p < 0.001), thoracic kyphotic (p = 0.033), and pelvic plane (p = 0.021) angles compared with not using the sensor. Computer users and sedentary workers may benefit from using wearable biofeedback sensors to actively maintain an upright sitting posture during prolonged deskwork.

Immediate effects of real-time postural biofeedback on spinal posture, muscle activity, and perceived pain severity in adults with neck pain.

BACKGROUND: Previous studies have investigated various types of postural biofeedback devices on different body regions to improve posture; however, they focused only on healthy adults without a history of chronic musculoskeletal disorders. In addition, those postural biofeedback devices used in previous studies are often designed for experimental research. The designs are usually bulky with many wires, which is not practical for everyday use. RESEARCH QUESTION: The aim of this study was to determine the immediate effect of a commercially available real-time postural biofeedback device on spinal posture, muscle activity, and perceived pain severity in adults with neck pain. METHODS: 21 adults who had chronic or recurrent nonspecific neck pain for more than 3 months and whose pain was induced or aggravated by prolonged computer work were enrolled in this study. Spinal posture (head tilt, neck flexion, cervical and thoracic angles), muscle activity (cervical erector spinae, upper trapezius, and thoracic erector spinae), and self-reported neck and shoulder pain were measured during computer typing tasks, with and without biofeedback. RESULTS: Compared with the non-biofeedback condition, the biofeedback condition significantly decreased neck flexion, upper cervical, and lower thoracic angles and lowered the activity of the cervical erector spinae. Self-reported neck pain was not influenced by the application of biofeedback, but significantly increased over the 1-hour typing task. SIGNIFICANCE: The application of a commercially available wearable real-time biofeedback device improves sitting posture and reduces muscular activity in adults with nonspecific neck pain during computer work. Future studies should examine the long-term effects of wearable real-time postural biofeedback devices for prevention and management of neck pain.

Validity of ICD9-CM codes to diagnose chronic obstructive pulmonary disease from National Health Insurance claim data in Taiwan.

PURPOSE: Claim data from Taiwan's National Health Insurance (NHI) database have previously been utilized in the study of COPD. However, there are limited data on the positive predictive value of claim data for COPD diagnosis. Therefore, this study aimed to characterize and validate the COPD cohort identified from the NHI research database. METHODS: This cross-sectional study compared records from claim data with those from a medical center. From 2007 to 2014, a COPD cohort was constructed from claim data using ICD9-CM codes for COPD. The diagnostic positive predictive value of these data was assessed with reference to physician-verified COPD. In addition, a multivariate logistic regression model was built to identify independent factors associated with the positive predictive value of COPD diagnosis by claim data. RESULTS: During the 8-year study period, a total of 12,127 subjects met the criterion of having two or more outpatient codes in 1 year or one or more inpatient COPD codes in their claim data. Of this total, the diagnosis of COPD was verified by physicians in 7,701 (63.5%) subjects. Applying a more stringent criterion - three or more outpatient codes or two or more inpatient codes - improved the diagnostic positive predictive value to 72.2%. Age ≥65 years and a claim for spirometry were the two most important factors associated with the positive predictive value of claim-data-defined COPD. Adding spirometry testing to diagnostic ICD9-CM codes for COPD increased the positive predictive value to 84.6%. CONCLUSION: This study emphasizes the importance of validation of disease-specific diagnosis prior to applying an administrative database in clinical studies. It also indicates the limitation of ICD9-CM codes alone in recognizing COPD patients within the NHI research database.

18ß-glycyrrhetinic acid derivative promotes proliferation, migration and aquaporin-3 expression in human dermal fibroblasts.

Licorice (Glycyrrhiza) species have been widely used as a traditional medicine and a natural sweetener in foods. The 18ß-glycyrrhetinic acid (18ß-GA) is a bioactive compound in licorice that exhibits potential anti-cancer, anti-inflammatory, and anti-microbial activities. Many synthesized derivatives of 18ß-GA have been reported to be cytotoxic and suggested for the treatment of malignant diseases. In this study, we explored the possible pharmacological roles of an 18ß-GA derivative in skin biology using primary human dermal fibroblasts and HaCaT keratinocytes as cell models. We found that this 18ß-GA derivative did not cause cell death, but significantly enhanced the proliferation of dermal fibroblasts and HaCaT keratinocytes. A scratch wound healing assay revealed that the 18ß-GA derivative promoted the migration of fibroblasts. Due to the important role of aquaporin-3 in cell migration and proliferation, we also investigated the expression of aquaporin-3 and found this compound up-regulated the expression of aquaporin-3 in dermal fibroblasts and HaCaT keratinocytes. In dermal fibroblasts, the 18ß-GA derivative induced the phosphorylation of Akt, ERK, and p38. The inhibitor of Akt predominantly suppressed the 18ß-GA derivative-induced expression of aquaporin-3. Collectively, this compound had a positive effect on the proliferation, migration, and aquaporin-3 expression of skin cells, implying its potential role in the treatment of skin diseases characterized by impaired wound healing or dermal defects.

Diabetes mellitus in patients with chronic obstructive pulmonary disease-The impact on mortality.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the leading cause of morbidity and mortality worldwide. There is evidence to support a connection between COPD and diabetes mellitus (DM), another common medical disorder. However, additional research is required to improve our knowledge of these relationships and their possible implications. In this study, we investigated the impact of DM on patient outcomes through the clinical course of COPD. METHODS: We conducted a cohort study in patients from the Taiwan Longitudinal Health Insurance Database between 2000 and 2013. Patients with COPD were identified and assessed for pre-existing and incident DM. A Cox proportional hazards model was built to identify factors associated with incident DM and to explore the prognostic effects of DM on COPD patients. A propensity score method was used to match COPD patients with incident DM to controls without incident DM. RESULTS: Pre-existing DM was present in 332 (16%) of 2015 COPD patients who had a significantly higher hazard ratio (HR) [1.244, 95% confidence interval (CI) 1.010-1.532] for mortality than that of the COPD patients without pre-existing DM. During the 10-year follow-up period, 304 (19%) of 1568 COPD patients developed incident DM; comorbid hypertension (HR, 1.810; 95% CI, 1.363-2.403), cerebrovascular disease (HR, 1.517; 95% CI, 1.146-2.008) and coronary artery disease (HR, 1.408; 95% CI 1.089-1.820) were significant factors associated with incident DM. Survival was worse for the COPD patients with incident DM than for the matched controls without incident DM (Log-rank, p = 0.027). CONCLUSIONS: DM, either pre-existing or incident, was associated with worse outcomes in COPD patients. Targeted surveillance and management of DM may be important in clinical care of the COPD population.

Sleep deprivation aggravates median nerve injury-induced neuropathic pain and enhances microglial activation by suppressing melatonin secretion.

STUDY OBJECTIVES: Sleep deprivation is common in patients with neuropathic pain, but the effect of sleep deprivation on pathological pain remains uncertain. This study investigated whether sleep deprivation aggravates neuropathic symptoms and enhances microglial activation in the cuneate nucleus (CN) in a median nerve chronic constriction injury (CCI) model. Also, we assessed if melatonin supplements during the sleep deprived period attenuates these effects. DESIGN: Rats were subjected to sleep deprivation for 3 days by the disc-on-water method either before or after CCI. In the melatonin treatment group, CCI rats received melatonin supplements at doses of 37.5, 75, 150, or 300 mg/kg during sleep deprivation. Melatonin was administered at 23:00 once a day. PARTICIPANTS: Male Sprague-Dawley rats, weighing 180-250 g (n = 190), were used. MEASUREMENTS: Seven days after CCI, behavioral testing was conducted, and immunohistochemistry, immunoblotting, and enzyme-linked immunosorbent assay were used for qualitative and quantitative analyses of microglial activation and measurements of proinflammatory cytokines. RESULTS: In rats who underwent post-CCI sleep deprivation, microglia were more profoundly activated and neuropathic pain was worse than those receiving pre-CCI sleep deprivation. During the sleep deprived period, serum melatonin levels were low over the 24-h period. Administration of melatonin to CCI rats with sleep deprivation significantly attenuated activation of microglia and development of neuropathic pain, and markedly decreased concentrations of proinflammatory cytokines. CONCLUSIONS: Sleep deprivation makes rats more vulnerable to nerve injury-induced neuropathic pain, probably because of associated lower melatonin levels. Melatonin supplements to restore a circadian variation in melatonin concentrations during the sleep deprived period could alleviate nerve injury-induced behavioral hypersensitivity.

Melatonin reduces median nerve injury-induced mechanical hypersensitivity via inhibition of microglial p38 mitogen-activated protein kinase activation in rat cuneate nucleus.

In this study, we examined the relationships between p38 mitogen-activated protein kinase (MAPK) activation in the cuneate nucleus (CN) and behavioral hypersensitivity after chronic constriction injury (CCI) of the median nerve. We further investigated effects of melatonin administration and pinealectomy on p38 MAPK activation and development of hypersensitivity. Using immunohistochemistry and immunoblotting, low levels of phosphorylated p38 (p-p38) MAPK were detected in CN of normal rats. As early as 1 day after CCI, p-p38 MAPK levels in the ipsilateral CN were significantly increased (1.4 ± 0.2-fold, P < 0.05), which reached a maximum at 7 days (5.1 ± 0.4-fold, P < 0.001). Double immunofluorescence labeling with cell-specific markers showed that p-p38 MAPK immunoreactive cells co-expressed OX-42, a microglia activation maker, suggesting the expression of p-p38 MAPK in microglia. Microinjection of SB203580, a p38 MAPK inhibitor, into the CN 1 day after CCI attenuated injury-induced behavioral hypersensitivity in a dose-dependent manner. Furthermore, animals received melatonin treatment at daily doses of 37.5, 75, 150, or 300 mg/kg from 30 min before until 3 days after CCI. Melatonin treatment dose-dependently attenuated p-p38 MAPK levels, release of pro-inflammatory cytokines, and behavioral hypersensitivity following CCI; conversely, pinealectomy that resulted in a reduction in endogenous melatonin levels exacerbated these effects. In conclusion, median nerve injury-induced microglial p38 MAPK activation in the CN modulated development of behavioral hypersensitivity. Melatonin supplementation eased neuropathic pain via inhibition of p38 MAPK signaling pathway; contrarily, reducing endogenous blood melatonin levels by pinealectomy promoted phosphorylation of p38 MAPK and made rats more vulnerable to nerve injury-induced neuropathic pain.