Ionogels: recent advances in design, material properties and emerging biomedical applications.

Ionic liquid (IL)-based gels (ionogels) have received considerable attention due to their unique advantages in ionic conductivity and their biphasic liquid-solid phase property. In ionogels, the negligibly volatile ionic liquid is retained in the interconnected 3D pore structure. On the basis of these physical features as well as the chemical properties of well-chosen ILs, there is emerging interest in the anti-bacterial and biocompatibility aspects. In this review, the recent achievements of ionogels for biomedical applications are summarized and discussed. Following a brief introduction of the various types of ILs and their key physicochemical and biological properties, the design strategies and fabrication methods of ionogels are presented by means of different confining networks. These sophisticated ionogels with diverse functions, aimed at biomedical applications, are further classified into several active domains, including wearable strain sensors, therapeutic delivery systems, wound healing and biochemical detections. Finally, the challenges and possible strategies for the design of future ionogels by integrating materials science with a biological interface are proposed.

Reversible Hydration Composite Films for Evaporative Perspiration Control and Heat Stress Management.

Donning of personal protective equipment (PPE) in the healthcare sector has been intensified by the on-going COVID-19 pandemic around the globe. While extensive PPE provides protection, it typically limits moisture permeability and severely hinders the sweat evaporation process, resulting in greater heat stress on the personnel. Herein, a zinc-poly(vinyl alcohol) (Zn-PVA) composite film is fabricated by embedding a super-hygroscopic zinc-ethanolamine complex (Zn-complex) in the PVA matrix. By attaching the Zn-PVA composite film, the relative humidity (RH) inside the protective suit decreases from 91.0% to 48.2%. The reduced RH level, in turn, enhances evaporative cooling, hence bringing down the heat index from 64.6 to 40.0 °C at an air temperature of 35 °C, remarkably lowering the likelihood of heat stroke. The American Society for Testing and Materials tests conducted on a sweating manikin have also proven that the Zn-PVA composite films can significantly reduce the evaporative resistance of the protective suit by 90%. The low material cost, facile fabrication process, and reusability allow the Zn-PVA composition films to be readily available for healthcare workers worldwide. This application can be further extended to other occupations that are facing severe thermal discomfort and heat stress.

Fatty Acid-Based Coacervates as a Membrane-free Protocell Model.

Membrane-less scenarios that involve liquid-liquid phase separation (coacervation) provide clues for how protocells might emerge. Here, we report a versatile approach to construct coacervates by mixing fatty acid with biomolecule dopamine as the protocell model. The coacervate droplets are easily formed over a wide range of concentrations. The solutes with different interaction characteristics, including cationic, anionic, and hydrophobic dyes, can be well concentrated within the coacervates. In addition, reversible self-assemblies of the coacervates can be controlled by concentration, pH, temperature, salinity, and bioreaction realizing cycles between compartmentalization and noncompartmentalization. Through in situ dopamine polymerization, the stability of coacervate droplets is significantly improved, leading to higher resistance toward external factors. Therefore, the coacervates based on fatty acid and dopamine could serve as a bottom-up membrane-less protocell model that provides the links between the simple (small molecule) and complex (macromolecule) systems in the process of cell evolution.

Excess mortality after hip fracture: fracture or pre-fall comorbidity?

Comorbidity and hip fracture independently increased mortality risk for 9 years in both sexes, with a significant additive interaction in the first year among women and through 6 years among men. INTRODUCTION: Hip fracture is associated with a persistently elevated mortality risk, but it is unknown whether the elevated risk is due to the fracture or to pre-fracture comorbidity. METHODS: In a population-based study in Singapore with 9 years of follow-up, patients age > 50 with first hip fracture from 2008 to 2017 were pair-matched to a cohort without hip fracture by age, sex, ethnicity, and pre-fracture Charlson Comorbidity Index (CCI). We investigated additive interaction using the relative excess risk due to interaction (RERI) and multiplicative interaction using the ratio of relative risks. RESULTS: Twenty-two thousand five hundred ninety of 22,826 patients with a first hip fracture in 2008-2017 were successfully matched. Hip fracture and comorbidity independently increased mortality risk for 9 years in both sexes. After adjustment for comorbidity, excess mortality risk continued to persist for 9 years post-fracture in both men and women. Women with a hip fracture and pre-fracture CCI > 4 had a higher relative risk (RR) of mortality at 9 years of 3.29 [95% confidence interval (CI) 3.01, 3.59] than those without comorbidity (RR 1.51, 95%CI 1.36, 1.68) compared to the referent without hip fracture or comorbidity. An additive interaction between hip fracture and pre-fracture CCI > 4 was observed in the first post-fracture year` [relative excess risk due to interaction (RERI) 1.99, 95%CI 0.97, 3.01]. For men with CCI ≥ 4, the positive additive interaction was observed through 6 years. CONCLUSIONS: Excess mortality risks post-fracture are attributable to both the fracture and pre-fracture comorbidity. Early interventions in hip fracture patients with high comorbidity could reduce their excess mortality.

Marked differences in local bone remodelling in response to different marrow stimulation techniques in a large animal.

Marrow stimulation, including subchondral drilling and microfracture, is the most commonly performed cartilage repair strategy, whereby the subchondral bone plate is perforated to release marrow-derived cells into a cartilage defect to initiate repair. Novel scaffolds and therapeutics are being designed to enhance and extend the positive short-term outcomes of this marrow stimulation. However, the translation of these newer treatments is hindered by bony abnormalities, including bone resorption, intralesional osteophytes, and bone cysts, that can arise after marrow stimulation. In this study, three different marrow stimulation approaches - microfracture, subchondral drilling and needle-puncture - were evaluated in a translationally relevant large-animal model, the Yucatan minipig. The objective of the study was to determine which method of marrow access (malleted awl, drilled Kirschner wire or spring-loaded needle) best preserved the underlying subchondral bone. Fluorochrome labels were injected at the time of surgery and 2 weeks post-surgery to capture bone remodelling over the first 4 weeks. Comprehensive outcome measures included cartilage indentation testing, histological grading, microcomputed tomography and fluorochrome imaging. Findings indicated that needle-puncture devices best preserved the underlying subchondral bone relative to other marrow access approaches. This may relate to the degree of bony compaction occurring with marrow access, as the Kirschner wire approach, which consolidated bone the most, induced the most significant bone damage with marrow stimulation. This study provided basic scientific evidence in support of updated marrow stimulation techniques for preclinical and clinical practice.

Irisin promotes odontogenic differentiation and angiogenic potential in human dental pulp cells.

AIM: To determine whether irisin, a newly discovered myokine that links exercise-induced and metabolic homeostasis, is able to promote odontogenic differentiation and angiogenesis in human dental pulp cells (HDPCs). METHODOLOGY: Cell viability in the presence of irisin was measured. Real-time PCR and Western blot analysis were performed to evaluate the expression levels of irisin, odontogenic and angiogenic markers. The involvement of mitogen-activated protein kinase (MAPK) and the protein kinase B (Akt) signalling pathway was evaluated by Western blot. To evaluate mineralization nodule formation, alkaline phosphatase (ALP) staining and alizarin red S staining were performed. Scratch wound assays were performed to evaluate the effects of irisin on cell migration. The data were analysed using one-way analysis of variance (anova) followed by Tukey post hoc test and Student's t-test. Statistical significance was considered at P < 0.05. RESULTS: Irisin significantly promoted odontogenic differentiation as evidenced by formation of mineralized nodules, induction of ALP activity and upregulation of odontogenic and angiogenic markers (P < 0.05). Scratch wound assays revealed that irisin significantly increased migration of HDPCs (P < 0.05). Phosphorylation of both MAPK and Akt was increased by irisin. MAPK and Akt inhibitors inhibited mineralization, cell migration and the increased expression of odontogenic and angiogenic markers. CONCLUSIONS: Irisin promoted odontogenic differentiation and mineralization and has the potential for angiogenesis through activation of the MAPK and Akt signalling pathways in HDPCs.

Natural history of incomplete atypical femoral fractures in patients after a prolonged and variable course of bisphosphonate therapy-a long-term radiological follow-up.

Understanding the natural history of lateral femoral stress fractures helps to guide their management. Improvement in their radiographic characteristics is rare. Progression was generally sequential, most developing an incomplete fracture line before fracture displacement. Stopping bisphosphonates decreased the fracture rate, a feasible management option for lesions without incomplete fracture lines. INTRODUCTION: Retrospective study evaluating the natural history of lateral femoral stress fractures (FSF) by serial radiography over a variable period of time in a cohort of patients treated for some time with bisphosphonates for osteoporosis, whilst also identifying the fracture response in cases where bisphosphonates were discontinued. METHODS: The radiographs of 76 consecutive patients (92 femurs) with 161 FSF were reviewed to document their change over time. Femurs were classified into the following: A-normal, B-focal cortical thickening, C-dreaded black line and D-displaced fracture. Bisphosphonate history was recorded. RESULTS: 66.5% FSF showed group stability between the first and last radiographs: group B (79.1%), group C (45.7%). 28.6% progressed, mostly following an ordered sequence starting from group A, progressing to B, then C, before culminating in D. Progression rate was as follows: A-100% (11/11), B-18.3% (21/115), C-40% (14/35). Regression in FSF was uncommon-5.6% (8/161). 34.8% (32/92) sustained displaced fractures. Kaplan-Meier analysis showed statistically significant difference between the groups; median survival (95% CI): A-4189 (-), B-3383.0 (-), C-1807 (0.0-3788.6) and progression to displaced fracture when bisphosphonate had been stopped for at least 6 months. The group without recent bisphosphonates had a lower group progression rate (17.1%, 12/70). Nevertheless, 10.9% (5/46) progressed to displaced fracture. This group also had the highest proportion of stable (77.1%, 54/70) and regressive lesions (5.7%, 4/70). CONCLUSIONS: In FSF, there is natural progression from normal bone, to focal cortical thickening, to dreaded black line and eventually to displaced fracture. Most lesions persist, remaining static or progressing, especially if a dreaded black line is present and bisphosphonates are continued. Regression is uncommon and more frequent when bisphosphonates are discontinued. Despite stopping bisphosphonates, there remains a 10.9% risk of progression to displaced fracture.

Pre-discharge prognostic factors of physical function among older adults with hip fracture surgery: a systematic review.

INTRODUCTION: To identify, organize, and assess the evidence level of pre-discharge prognostic factors of physical function beyond discharge after hip fracture surgery. METHODS: We performed a systematic search of four databases (PubMed, Embase, CINAHL, PsycINFO) for longitudinal studies of prognostic factors of physical function at ≥ 1 month among older adults ≥ 50 years old with surgically treated hip fracture, complemented with hand-searching. Two reviewers independently screened papers for inclusion and assessed the quality of all the included papers using the Quality in Prognosis Studies (QUIPS) tool. We assigned the evidence level for each prognostic factor based on consistency in findings and study quality. RESULTS: From 98 papers that met our inclusion criteria, we identified 107 pre-discharge prognostic factors and organized them into the following seven categories: demographic, physical, cognitive, psychosocial, socioeconomic, injury-related, and process of care. Potentially modifiable factors with strong or moderate evidence of an association included total length of stay, physical function at discharge, and grip strength. Factors with strong or moderate evidence of no association included gender, fracture type, and time to surgery. Factors with limited, conflicting, or inconclusive evidence included body-mass index, psychological resilience, depression, and anxiety. CONCLUSIONS: Our findings highlight potentially modifiable prognostic factors that could be targeted and non-modifiable prognostic factors that could be used to identify patients who may benefit from more intensive intervention or to advise patients on their expectations on recovery. Examining the efficacies of existing interventions targeting these prognostic factors would inform future studies and whether any of such interventions could be incorporated into clinical practice.

CD4 T cell count is inversely associated with lumbar spine bone mass in HIV-infected men under the age of 50 years.

HIV-infected men under the age of 50 years had a lower bone mass compared to that of HIV-uninfected men. Lower CD4 T cell counts, independent of whether antiretroviral therapy (ART) was used, were associated with lower BMD. HIV-infected patients with low CD4 T cell counts may need follow-up and intervention regarding bone health, including younger patients. INTRODUCTION: HIV-infected patients have a low bone mineral density (BMD) owing to multifactorial interaction between common osteoporosis risk factors and HIV-related factors, including chronic inflammation and ART. Although HIV infection and ART might affect bone metabolism, little data is available for patients aged under 50 years. We aimed to investigate the association of HIV infection-induced low CD4 T cell counts and ART with BMD in men aged under 50 years. METHODS: We performed an age- and body mass index-matched case-control study. BMD values of HIV-infected and HIV-uninfected men (< 50 years) were compared, and HIV-infected men were stratified by CD4 T cell counts and ART use. RESULTS: After adjusting confounders, HIV-infected men with CD4 T cell counts ≥ 500 cells/µL (n = 28) and < 500 cells/µL (n = 139) had lower BMD at the femoral neck (FN, p < 0.001) and total hip (TH, p < 0.001) than HIV-uninfected men (n = 167). HIV-infected men with CD4 T cell counts < 500/µL had lower BMD at the lumbar spine (LS, p = 0.034) than those with counts of ≥ 500 cells/µL, but not at FN and TH. The CD4 T cell count (γ = 0.169, p = 0.031) was positively correlated with BMD at LS. There was no significant difference in the BMD (p = 0.499-> 0.999) between the ART-naïve (n = 75) and ART-user group (n = 92). CONCLUSIONS: Despite their relatively younger age, HIV-infected men had a lower BMD than HIV-uninfected men. Lower CD4 T cell counts, irrespective of ART, might result in lower bone mass.

Correction to: CD4 T cell count is positively associated with lumbar spine bone mass in HIV-infected men under the age of 50 years.

Two sentences in the Discussion section were incorrect.

The effects of cortisol and adrenal androgen on bone mass in Asians with and without subclinical hypercortisolism.

Analyses using the largest Korean cohort of adrenal incidentaloma (AI) revealed that subtle cortisol excess in premenopausal women and reduced dehydroepiandrosterone-sulfate (DHEA-S) in postmenopausal women and men are associated with bone mineral density (BMD) reduction in Asian patients with subclinical hypercortisolism (SH). INTRODUCTION: Few studies evaluated bone metabolism in Asians with SH. We investigated associations of cortisol and DHEA-S, an adrenal androgen, with BMD in Asians with AI, with or without SH. METHODS: We used cross-sectional data of a prospective multicenter study from Korea. We measured BMD, bone turnover markers, cortisol levels after 1-mg dexamethasone suppression test (1-mg DST), DHEA-S, and baseline cortisol to DHEA-S ratio (cort/DHEA-S) in 109 AI patients with SH (18 premenopausal, 38 postmenopausal women, and 53 men) and 686 with non-functional AI (NFAI; 59 premenopausal, 199 postmenopausal women, and 428 men). RESULTS: Pre- and postmenopausal women, but not men, with SH had lower BMDs at lumbar spine (LS) than those with NFAI (P = 0.008~0.016). Premenopausal women with SH also had lower BMDs at the hip than those with NFAI (P = 0.009~0.012). After adjusting for confounders, cortisol levels after 1-mg DST demonstrated inverse associations with BMDs at all skeletal sites only in premenopausal women (ß = - 0.042~- 0.033, P = 0.019~0.040). DHEA-S had positive associations with LS BMD in postmenopausal women (ß = 0.096, P = 0.001) and men (ß = 0.029, P = 0.038). The cort/DHEA-S had inverse associations with LS BMD in postmenopausal women (ß = - 0.081, P = 0.004) and men (ß = - 0.029, P = 0.011). These inverse associations of cort/DHEA-S remained significant after adjusting for cortisol levels after 1-mg DST (ß = - 0.079~- 0.026, P = 0.006~0.029). In postmenopausal women, the odds ratios of lower BMD by DHEA-S and cort/DHEA-S was 0.26 (95% CI, 0.08-0.82) and 3.40 (95% CI, 1.12-10.33), respectively. CONCLUSION: Subtle cortisol excess in premenopausal women and reduced DHEA-S in postmenopausal women and men may contribute to BMD reduction in Asians with SH.

Association of blood n-3 fatty acid with bone mass and bone marrow TRAP-5b in the elderly with and without hip fracture.

The plasma n-3 fatty acid level was 26.2% lower in patients with osteoporotic hip fracture than in those with osteoarthritis. In all patients, n-3 fatty acid was positively associated with bone mineral density and inversely associated with tartrate-resistant acid phosphatase-5b level in bone marrow aspirates, reflecting the bone microenvironment. INTRODUCTION: Despite the potential beneficial role of n-3 fatty acid (FA) on bone metabolism, the specific mechanisms underlying these effects in humans remain unclear. Here, we assessed whether the plasma n-3 level, as an objective indicator of its status, is associated with osteoporosis-related phenotypes and bone-related markers in human bone marrow (BM) samples. METHODS: This was a case-control and cross-sectional study conducted in a clinical unit. n-3 FA in the blood and bone biochemical markers in the BM aspirates were measured by gas chromatography/mass spectrometry and immunoassay, respectively. BM fluids were collected from 72 patients who underwent hip surgery because of either osteoporotic hip fracture (HF; n = 28) or osteoarthritis (n = 44). RESULTS: After adjusting for confounders, patients with HF had 26.2% lower plasma n-3 levels than those with osteoarthritis (P = 0.006), and each standard deviation increment in plasma n-3 was associated with a multivariate-adjusted odds ratio of 0.40 for osteoporotic HF (P = 0.010). In multivariate analyses including all patients, a higher plasma n-3 level was associated with higher bone mass at the lumbar spine (ß = 0.615, P = 0.002) and total femur (ß = 0.244, P = 0.045). Interestingly, the plasma n-3 level was inversely associated with the tartrate-resistant acid phosphatase-5b level (ß = - 0.633, P = 0.023), but not with the bone-specific alkaline phosphatase level, in BM aspirates. CONCLUSIONS: These findings provide clinical evidence that n-3 FA is a potential inhibitor of osteoclastogenesis that favors human bone health.

Robust Oil-Fouling Resistance of Amorphous Cellulose Surface Underwater: A Wetting Study and Application.

The antioil-fouling characteristic of an amorphous cellulose (a-cellulose) surface was elucidated using the sessile droplet method (static) and a modified Wilhelmy plate technique (dynamic). As compared to other hydrophilic surfaces (cellulose acetate, poly(vinyl alcohol), and glass), the oil (poly(dimethylsiloxane)) contact angle on the a-cellulose surface underwater shows the largest value (170.5 ± 5.0°), having the smallest deviation from its theoretical value (180.0°) as estimated by Young's equation. Also, the a-cellulose surface demonstrates the strongest affinity with water in an oil medium (stable hydrophilicity). Moreover, the work of adhesion between the receding oil phase and a-cellulose underwater is quantified to be 10.3 mN/m, approximately one-fourth of that in air (42.0 mN/m). The overall wetting study suggests a rather low oil/solid/water three-phase contact line (TPL) friction in the direction that water displaces oil. A proposed mechanism attributes these phenomena to the water-accessible rigid cellulose chains and supramolecular structure of a-cellulose. The former hinders molecular rearrangement during processing or upon exposure to oil, such that its polar hydroxyl groups are readily accessible to water, thereby retaining its hydrophilicity. The latter allows water to diffuse across the TPL, forming the hydration shells that weaken the van der Waals interactions between oil and cellulose chains. Such findings of the a-cellulose surface can be exploited to fabricate mesh membranes with high water permeation flux (375.4 ± 13.5 L m-2 h-1 Pa-1), high oil/water separation efficiency (93-98%), and long-lasting stability, which is suitable for offshore oil spill remediation.

Phenotypic features and predictors of the clinical severity of keratoconjunctivitis sicca and salivary gland dysfunction in patients with Sjögren's syndrome: a longitudinal analysis of the Korean Initiative of primary Sjögren's Syndrome (KISS) cohort.

OBJECTIVE: The aim was to investigate prevalence and degree of ocular and oral involvement in patients with primary Sjögren's syndrome (PSS). METHOD: We analysed 134 participants from the Korean Initiative of PSS cohort who completed a 2 year follow-up oral and ocular sign test. The severity of keratoconjunctivitis sicca (KCS) was determined with the Schirmer I test value (STV) [abnormal (AB) ≤ 5 mm/5 min; normal (N) > 5 mm/5 min]. Salivary gland dysfunction (SGD) was determined by unstimulated whole salivary (UWS) flow rate [moderate to severe (MS) < 0.1 mL/min; mild (Mi) ≥ 0.1 mL/min]. Subgroups were divided into three groups according to STV and severity of SGD: AB-STV/MS-SGD, AB-STV/Mi-SGD, and N-STV/MS-SGD groups. We analysed the changes in STV and SGD during the follow-up period. RESULTS: Among the 134 participants enrolled in this study, 105 (78%) were placed in the AB-STV/MS-SGD group, 16 (12%) in the AB-STV/Mi-SGD, and 13 (10%) in the N-STV/MS-SGD at the 2 year follow-up. The AB-STV/Mi-SGD group was younger than the other two groups, and had a lower Xerostomia Inventory score and lower level of ß2-microglobulin. Participants in the N-STV/MS-SGD group had less hyperimmunoglobulinaemia, rheumatoid factor (RF), and antinuclear antibodies (ANAs). Patients and those with positive RF or ANA ≥ 1:320 at baseline were more likely to have abnormal STV at the 2 year follow-up. CONCLUSIONS: Patients with PSS and positive RF or ANA ≥ 1:320 at baseline may benefit from regular ophthalmology examinations, even if they do not have KCS at baseline or dry eye symptoms.

Parental perception on the effects of early exposure to anaesthesia on neurodevelopment.

Several studies have investigated the effects of general anaesthesia on neurodevelopment in children, with conflicting results. The potential for early general anaesthesia exposure to impact neurodevelopment in children may cause significant concern for parents. Administering a questionnaire in 200 parents, we aimed to explore their knowledge, concerns and perceptions, and determine factors which influence parents' willingness for their children to participate in relevant research studies. A significant proportion of parents (40%) were concerned that general anaesthesia may affect their child's neurodevelopment. Generally these concerns arose from the parents' own beliefs or preconceived ideas and only 25.5% had encountered prior information in this domain. Parents with children aged 2 years or younger, those whose children had previous general anaesthesia exposure, and those who had encountered information about potential neurodevelopmental effects were most likely to be concerned. The majority of parents (68%) would agree to participate in research studies, especially if they were able to receive the test results. Anaesthetists should pre-emptively initiate discussions to address any potential misconceptions regarding the effects of general anaesthesia on neurodevelopment in children.

Effect of the Lactobacillus rhamnosus strain GG and tagatose as a synbiotic combination in a dextran sulfate sodium-induced colitis murine model.

Synbiotics, a combination of prebiotics and probiotics, produce synergistic effects to promote gastrointestinal health. Herein, we investigated the synbiotic interaction between the Lactobacillus rhamnosus strain GG (LGG; a probiotic strain) and tagatose (a prebiotic) in a dextran sulfate sodium (DSS)-induced colitis murine model. Initially, body weight, food intake, and clinical features were dramatically decreased after treatment with DSS, and the addition of LGG, tagatose, or both ameliorated these effects. In our pyrosequencing analysis of fecal microbiota, DSS treatment increased the abundance of Proteobacteria and decreased that of Firmicutes. When LGG and tagatose were administered as synbiotics, the gut microbiota composition recovered from the dysbiosis caused by DSS treatment. In particular, the abundance of Bacteroides, Lactobacillus, and Akkermansia was significantly associated with probiotic, prebiotic, and synbiotic treatments. Taken together, our results suggest that LGG and tagatose as synbiotics can alleviate colitis, and synbiotics could be applied as dietary supplements in dairy foods such as yogurt and cheese.

TLR5 activation induces expression of the pro-inflammatory mediator Urokinase Plasminogen Activator via NF-κB and MAPK signalling pathways in human dental pulp cells.

AIM: To explore the involvement of TLR5 in pulp inflammation and to examine the effects of TLR5 activation with its ligand, FlaB protein, on pro-inflammatory gene expression. METHODOLOGY: TLR5 expression in dental pulp tissues and human dental pulp cells (hDPCs) were determined by immunohistochemistry, immunocytochemistry, Western blots and RT-PCR analyses. To examine the role of TLR5, hDPCs were treated with recombinant FlaB protein (500 ng mL-1 ) to activate the receptor or with a small interfering RNA against TLR5 (si-TLR5) to downregulate the receptor. After exposure to FlaB, the expression of inflammation-related proteins was screened using a protein array kit. Western blots or qRT-PCR analyses were performed to identify changes in the expression of uPA (urokinase plasminogen activator), TIMPs (tissue inhibitor of metalloproteinases), and IL-6 and to determine their signalling pathways. Statistical analysis was performed using one-way analysis of variance (anova) with Tukey post hoc test; P < 0.05 was considered statistically significant. RESULT: TLR5 expression was identified in pulp tissues and hDPCs. In the protein array analysis, treatment with FlaB significantly increased uPA expression (P < 0.01) and significantly decreased TIMP1/4 (P < 0.05). FlaB treatment also significantly increased expression of the inflammatory marker IL-6 (P < 0.01). FlaB treatment increased phosphorylation of the NF-κB p65 subunit, JNK, p38 and ERK. Chemical inhibitors of NF-κB (Bay11-7082), p38 (SB202190) or ERK (U0126) decreased the FlaB induction of uPA expression. Downregulation of TLR5 expression by siRNA decreased the FlaB induction of uPA protein and p65 phosphorylation. CONCLUSION: TLR5 activation with FlaB treatment induced the expression of uPA via the NF-κB and MAPK signalling pathways. Flagellin-bearing oral bacteria may cause pulp inflammation through TLR5. The findings provide new clues to control pulpal diseases by targeting TLR5 signalling pathways.

The positive association of total protein intake with femoral neck strength (KNHANES IV).

Data gathered from a nationally representative cohort demonstrate that higher dietary protein intake was positively associated with the composite indices of femoral neck strength in both men and women, suggesting that higher protein intake may contribute to lower risk of hip fracture through the improvement of bone strength. INTRODUCTION: Despite the general belief that higher protein intake may be helpful for bone homeostasis, its impact on human bone health is still debated. Furthermore, the association of dietary protein intake with femoral neck (FN) strength, which can predict fracture risk independently of bone mineral density (BMD), has not been thoroughly studied. METHODS: This is a population-based, cross-sectional study from Korea National Health and Nutrition Examination Surveys, including 592 men aged 50 years or older and 590 postmenopausal women. The composite indices of FN strength, such as the compression strength index (CSI), bending strength index (BSI), and impact strength index (ISI), were generated by combining BMD, body weight, and height with the femoral axis length and width, which were measured by dual-energy X-ray absorptiometry. RESULTS: After adjustment for confounders, total protein intake (g/kg/day) positively correlated with all three FN composite indices in both genders (P = 0.006 to 0.035), except for BSI showing marginal significance in postmenopausal women (P = 0.093). Consistently, compared with subjects in lowest total protein intake quartile, those in the highest quartile showed markedly higher CSI, BSI, and ISI values (P = 0.043 to < 0.001), with a dose-response manner across increasing total protein intake quartile categories in both men and women (P for trend = 0.028 to < 0.001). CONCLUSIONS: These findings provide the clinical evidence that higher dietary protein intake can play a beneficial role on bone health through the increase of FN strength relative to load in adults.

The association of cortisol and adrenal androgen with trabecular bone score in patients with adrenal incidentaloma with and without autonomous cortisol secretion.

Despite ethnic differences in cortisol sensitivity, only one study in Caucasians has assessed trabecular bone score (TBS) in patients with subclinical hypercortisolism (SH). We showed that both subtle cortisol excess and reduced adrenal androgen may contribute to impaired bone quality in Asian women with SH. INTRODUCTION: One study in Caucasians has assessed trabecular bone score (TBS), an index of bone microstructure, in adrenal incidentaloma (AI) patients with subclinical hypercortisolism (SH). There are ethnic differences in cortisol sensitivities between Caucasian and Asian populations. We investigated the associations of cortisol and the adrenal androgen dehydroepiandrosterone-sulfate (DHEA-S) with TBS in AI patients with SH, adrenal Cushing's syndrome (CS), and nonfunctional AI (NFAI). METHODS: We measured TBS, cortisol levels after the overnight 1 mg dexamethasone suppression test (1 mg DST), and cortisol/DHEA-S in 61 patients with SH (30 men; 31 women), 19 with adrenal CS (4 men; 15 women), and 355 with NFAI (213 men; 142 women). RESULTS: After adjusting for confounders, the serum cortisol level after 1 mg DST was inversely correlated with TBS in men (ß = -0.133, P = 0.045) and women (ß = - 0.140, P = 0.048). Higher cortisol/DHEA-S ratio was associated with lower TBS in women (ß = - 0.252, P < 0.001), but not men. This inverse association of cortisol/DHEA-S ratio in women remained statistically significant after adjusting for the serum cortisol level after 1 mg DST (ß = - 0.221, P = 0.008). Compared with women with NFAI, women with SH had 2.2% lower TBS (P = 0.040). Deteriorated bone microstructure (TBS < 1.230) was associated with the serum cortisol level after 1 mg DST (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.04-4.53) and cortisol/DHEA-S ratio (OR, 2.05; 95% CI, 1.03-4.08). CONCLUSIONS: Subtle cortisol excess in both genders and reduced DHEA-S, especially in women, may contribute to impaired bone quality in Asian patients with SH.