Asthma admission among children in Hong Kong during the first year of the COVID-19 pandemic.

BACKGROUND: Multiple nonpharmaceutical interventions (NPIs) had been introduced in Hong Kong during coronavirus disease 2019 (COVID-19) pandemic. The impact on asthma admission, which was closely related to viral infection, was of concern. OBJECTIVE: The study aimed to identify the impact of NPIs on pediatric asthma admissions and their association with respiratory viruses. METHODS: We conducted a retrospective observational study to compare the difference in pediatric asthma hospital admission rates between pre-COVID-19 and COVID-19 periods. Information on demographics, nasopharyngeal specimen results, ventilatory support, intensive care admission, hospital stay duration, asthma control therapy, and previous admission episodes was collected. Weather parameters including temperature, rainfall, humidity, and air quality data that was reflected by the air quality health index were recorded. RESULTS: A total of 1808 pediatric asthma admissions were recorded during the pre-COVID-19 period while there were 62 admissions during COVID-19 period, among which 54 admissions from the pre-COVID-19 period and 4 admissions from COVID-19 period were excluded. Weekly pediatric asthma admissions per total pediatric admissions during COVID-19 was one-third of that during the pre-COVID-19 period (0.3% vs. 0.9%, p < 0.001). During COVID-19 period, a significantly lower percentage of respiratory virus isolates was noted (58.6% vs. 72.6%, p = 0.019). Poisson regression analysis showed that the COVID-19 period (odds ratio [OR] = 0.202, 95% confidence interval  [CI, 0.16-0.26]; p ≤ 0.001), summer vacation period (OR = 0.512, 95% CI [0.43-0.62]; p ≤ 0.001), and humidity (OR = 0.99, 95% CI [0.98-1.00]; p = 0.004) were independent protective factors for asthma admission. CONCLUSIONS: There was a significant reduction in pediatric asthma hospitalizations and respiratory virus isolates in the first year of COVID-19 pandemic in Hong Kong with the implementation of NPIs. Rhinovirus remained the key respiratory virus isolate. Incorporation of appropriate NPIs in long run could reduce virus infection-related pediatric asthma admission.

Mesenchymal stem cell exosomes in bone regenerative strategies-a systematic review of preclinical studies.

The ability of bone for regeneration has long been recognized. However, once beyond a critical size, spontaneous regeneration of bone is limited. Several studies have focused on enhancing bone regeneration by applying mesenchymal stromal/stem cells (MSCs) in the treatment strategies. Despite the therapeutic efficacy of MSCs in bone regeneration, cell-based therapies are impeded by several challenges in maintaining the optimal cell potency and viability during expansion, storage, and final delivery to patients. Recently, there has been a paradigm shift in therapeutic mechanism of MSCs in tissue repair from one based on cellular differentiation and replacement to one based on secretion and paracrine signaling. Among the broad spectrum of trophic factors, extracellular vesicles â€‹particularly the exosomes have been reported to be therapeutically efficacious in several injury/disease indications, including bone defects and diseases. The current systematic review aims to summarize the results of the existing animal studies which were conducted to evaluate the therapeutic efficacy of MSC exosomes for bone regeneration. Following the Preferred Reporting Items for Systematic Reviews and Meta-analysis â€‹guidelines, the PubMed and The Cochrane Library database were searched for relevant controlled preclinical animal studies. A total of 23 studies were identified, with the total sample size being 690 rats or mice and 38 rabbits. Generally, MSC exosomes were found to be efficacious for bone regeneration in animal models of bone defects and diseases such as osteonecrosis and osteoporosis. In these studies, MSC exosomes promoted new bone formation with supporting vasculature â€‹and displayed improved morphological, biomechanical, and histological outcomes, coupled with positive effects on cell survival, proliferation, and migration, osteogenesis, and angiogenesis. Unclear-to-low risk in bias and incomplete reporting in the primary studies highlighted the need for standardization in outcome measurements and reporting. Further studies in large animal models to establish the safety and efficacy would provide useful information on guiding the design of clinical trials.

Validation study of the Brief Medication Adherence Scale (BMAS) in patients with schizophrenia and related disorders in Hong Kong.

The purpose of this study was to develop and test an original self-rating instrument known as Brief Medication Adherence Scale (BMAS) to assess antipsychotic adherence level of Hong Kong Chinese patients with schizophrenia. On the interview day, BMAS and three other validated rating scales were given to local patients with schizophrenia and related disorders for completion. BMAS was required to fill in a second time after two weeks for the study of test-retest reliability. Results of BMAS were matched with those of other scales and blood level of prescribed mood stabilizers to test for construct validity. Data analysis was performed for 84 patients. Median BMAS scores recorded at both times were identical at 89/100, and a cutoff score of 70 was considered medication adherent with a sensitivity of 98.61% (CI 92.50%-99.96%). BMAS was positively and significantly correlated with the established Medication Adherence Rating Scale -Taiwanese (Spearman's ρ = 0.56, p < 0.05) and with variation in serum mood stabilizer level (Pearson's r = 0.55, p < 0.05). On the other hand, correlations with scales measuring mental condition and medication side effects were weak. Principal component analysis found two components (i.e. medication taking behaviors and attitudes) for the 10-question BMAS. Test-retest BMAS total scores were significantly correlated (intraclass correlation alpha = 0.87, p < 0.05), and Cronbach's alpha measuring internal consistency was 0.68. The current study confirms that BMAS is a valid and reliable scale that assesses medication adherence in patients with schizophrenia.

Autofluorescence-Free Live-Cell Imaging Using Terbium Nanoparticles.

Fluorescent nanoparticles (NPs) have become irreplaceable tools for advanced cellular and subcellular imaging. While very bright NPs require excitation with UV or visible light, which can create strong autofluorescence of biological components, NIR-excitable NPs without autofluorescence issues exhibit much lower brightness. Here, we show the application of a new type of surface-photosensitized terbium NPs (Tb-NPs) for autofluorescence-free intracellular imaging in live HeLa cells. The combination of exceptionally high brightness, high photostability, and long photoluminecence (PL) lifetimes for highly efficient suppression of the short-lived autofluorescence allowed for time-gated PL imaging of intracellular vesicles over 72 h without toxicity and at extremely low Tb-NP concentrations down to 12 pM. Detection of highly resolved long-lifetime (ms) PL decay curves from small (∼10 µm2) areas within single cells within a few seconds emphasized the unprecedented photophysical properties of Tb-NPs for live-cell imaging that extend well beyond currently available nanometric imaging agents.

Hip fractures, preceding distal radius fractures and screening for osteoporosis: should we be screening earlier? A minimum 10-year retrospective cohort study at a single centre.

UNLABELLED: Both men and women who sustain a fracture of the distal forearm run an increased risk of sustaining a subsequent hip fracture. Our study implies that these patients may not necessarily constitute a group in which osteoporosis screening is warranted. INTRODUCTION: People who sustain a distal radius fracture run an increased risk of sustaining a subsequent hip fracture. However, many institutions only screen for osteoporosis at the time of a hip fracture. We aimed to determine the true incidence of preceding distal radius fractures in an Asian population of patients with a hip fracture aged 60 years or older and whether screening for osteoporosis earlier would be beneficial. METHODS: We reviewed 22 parameters of 572 patients aged 60 years or older admitted after sustaining a hip fracture over a 3-year period. This included the occurrence or absence of a distal radius fracture in the 10 years preceding their hip fracture. RESULTS: Twenty-nine patients (5 %) had a fracture of the distal radius in the preceding decade. Univariate analyses suggested that hip fracture patients who had preceding distal radius fractures were older, female, have lower mean haemoglobin levels, and right-sided hip fractures. Of these factors, only age was found to have significant predictive value in a multivariate analysis. CONCLUSIONS: A number of institutions have started to screen for osteoporosis when a patient presents with a fracture of the distal radius because these patients may have an increased risk of a subsequent hip fracture. Our study implies that this may not be warranted. Implementing such a screening service from both cost and resource utilization point of view must be studied prospectively and in greater detail considering earlier screening may only be beneficial to a very small percentage of patients.

Calcaneal fractures: selection bias is key.

In this paper, we critically appraise the recent publication of the United Kingdom Heel Fracture Trial, which concluded that when patients with an absolute indication for surgery were excluded, there was no advantage of surgical over non-surgical treatment in the management of calcaneal fractures. We believe that selection bias in that study did not permit the authors to reach a firm conclusion that surgery was not justified for most intra-articular calcaneal fractures.

Correlation of hormone receptor status between circulating tumor cells, primary tumor, and metastasis in breast cancer patients.

PURPOSE: Estrogen receptor (ER) and progesterone receptor (PR) status is prognostic and predictive in breast cancer. Because metastatic breast tumor biopsies are not routinely feasible, circulating tumor cells (CTCs) offer an alternative source of determining ER/PR tumor status. METHODS/PATIENTS: Peripheral blood was collected prospectively from 36 patients with metastatic breast cancer. CTCs were isolated using the microfluidic OncoCEE™ platform. Detection was accomplished with an expanded anti-cytokeratin (CK) cocktail mixture and anti-CD45. ER/PR protein expression was assessed by immunocytochemistry (ICC) on the CK+ cells and compared to the primary and/or metastatic tumor by immunohistochemistry (IHC). RESULTS: Among the 24 CK + CTC cases, a concordance of 68 % (15/22) in ER/PR status between primary breast tumor and CTCs and 83 % (10/12) between metastatic tumor and CTCs was observed. An overall concordance of 79 % (19/24) was achieved when assessing CTC and metastatic tumor (primary tumor substituted if metastatic breast biopsy not available). A test sensitivity of 72 % and specificity of 100 % was identified when comparing CTCs to tumor tissue. Of the 7 discordant cases between CTCs and primary tumor tissue, 2 were concordant with the metastatic biopsy. CONCLUSIONS: CTC ER/PR status using the OncoCEE™ platform is feasible, with high concordance in ER/PR status between tumor tissue (IHC) and CTCs (ICC). The prognostic and predictive significance of CTC ER/PR protein expression needs further evaluation in larger trials.

Development and selection of Asian-specific humeral implants based on statistical atlas: toward planning minimally invasive surgery.

PURPOSE: The commercial humeral implants based on the Western population are currently not entirely compatible with Asian patients, due to differences in bone size, shape and structure. Surgeons may have to compromise or use different implants that are less conforming, which may cause complications of as well as inconvenience to the implant position. The construction of Asian humerus atlases of different clusters has therefore been proposed to eradicate this problem and to facilitate planning minimally invasive surgical procedures [6,31]. According to the features of the atlases, new implants could be designed specifically for different patients. Furthermore, an automatic implant selection algorithm has been proposed as well in order to reduce the complications caused by implant and bone mismatch. METHODS: Prior to the design of the implant, data clustering and extraction of the relevant features were carried out on the datasets of each gender. The fuzzy C-means clustering method is explored in this paper. Besides, two new schemes of implant selection procedures, namely the Procrustes analysis-based scheme and the group average distance-based scheme, were proposed to better search for the matching implants for new coming patients from the database. Both these two algorithms have not been used in this area, while they turn out to have excellent performance in implant selection. Additionally, algorithms to calculate the matching scores between various implants and the patient data are proposed in this paper to assist the implant selection procedure. RESULTS: The results obtained have indicated the feasibility of the proposed development and selection scheme. The 16 sets of male data were divided into two clusters with 8 and 8 subjects, respectively, and the 11 female datasets were also divided into two clusters with 5 and 6 subjects, respectively. Based on the features of each cluster, the implants designed by the proposed algorithm fit very well on their reference humeri and the proposed implant selection procedure allows for a scenario of treating a patient with merely a preoperative anatomical model in order to correctly select the implant that has the best fit. Based on the leave-one-out validation, it can be concluded that both the PA-based method and GAD-based method are able to achieve excellent performance when dealing with the problem of implant selection. The accuracy and average execution time for the PA-based method were 100 % and 0.132 s, respectively, while those of the GAD- based method were 100 % and 0.058 s. Therefore, the GAD-based method outperformed the PA-based method in terms of execution speed. CONCLUSION: The primary contributions of this paper include the proposal of methods for development of Asian-, gender- and cluster-specific implants based on shape features and selection of the best fit implants for future patients according to their features. To the best of our knowledge, this is the first work that proposes implant design and selection for Asian patients automatically based on features extracted from cluster-specific statistical atlases.

Adding computed tomography and transcranial Doppler findings to the ABCD2 score to predict long-term risk of stroke after transient ischaemic attack or minor stroke.

BACKGROUND AND PURPOSE: The ABCD(2) score can predict the early risk of stroke after transient ischaemic attack or minor stroke. However, there is no simple and practical assessment method for the long-term risks. Computed tomography (CT) and transcranial Doppler (TCD) findings were added to the ABCD(2) score to build an ABCD(2) L(2) score and whether the new scoring system could improve the predictive value of the ABCD(2) score for the long-term risk of stroke was determined. METHODS: From January 2004 to December 2005, all patients with a definite diagnosis of transient ischaemic attack or minor stroke at the Prince of Wales Hospital were consecutively enrolled and followed up until August 2008. CT and TCD were performed. The areas under the curve were used to quantify the ABCD(2) and ABCD(2) L(2) scores and related items. RESULTS: All 481 patients completed the follow-up. The shortest follow-up time was 0.17 months (until death), the longest follow-up time was 55.60 months and the mean follow-up time was 40.3 ± 11.0 months. In total, 277 (57.6%) patients showed lesions on CT scans and 195 (40.6%) patients were found with intracranial large artery atherosclerosis. Further strokes occurred in 74 (15.4%) patients, including four (0.83%) patients who died of ischaemic stroke during the follow-up period. The area under the curve increased from 0.650 (0.586-0.715) for the ABCD(2) score to 0.700 (0.637-0.764) for the ABCD(2) L(2) score. CONCLUSION: Adding CT and TCD results to the ABCD(2) score to increase its predictability for long-term risk of stroke recurrence might be a meaningful exploration.

Statistical atlas-based morphological variation analysis of the asian humerus: towards consistent allometric implant positioning.

PURPOSE: Positioning existing humeral implants into Asian patients poses significant challenges due to the inconsistent statistical shapes between Western population and Asian population. Current humeral orthopedic fixation devices and implants have a generic shape and are not designed for Asian patients who exhibit different sizes and shapes compared to their Western counterparts for which present day designs have been based on. To address this problem, it is necessary to develop Asian-specific implants that accommodate the morphology of Asian humeri. Existing morphological studies of humeri in Asian populations are rare and most previous analyses are either based on the manual measurement of dry bones or the use of dual energy X-ray absorptiometry scans. The purpose of this pilot morphological study is to explore the characteristics of Asian humeri using statistical atlas-based analysis. METHODS: Forty-four CT scans of normal upper limbs were obtained from the National University Hospital, Singapore and used to construct statistical humerus atlases. The atlases were subsequently used to study the morphology of the humeri in an Asian population. Humeral shapes of different patient clusters were analyzed based on statistical shape models. Comparison between different clusters was conducted with regard to centerline, length, width and surface curvature. RESULTS: The statistical humerus atlases reflected the mean shape and modes of variation of humeri in an Asian population. Analyses based on these atlases indicated that curvature and shape of the internal humeral canal were similar in males and females while humeral length and width were greater in males. Most importantly, surface curvatures were explicitly different between clusters. CONCLUSION: Morphologic analysis based on statistical atlases is novel and useful to characterize the Asian humerus. The humerus demonstrates gender-specific morphology. This unique approach provides information that is useful to the clinician and biomedical engineer, not only in the modification of current or design of future humeral implants, but also in the precise dynamic positioning of Asian-specific humeral implants to Asian patients. Our findings support the need for further development of humeral implants, curvilinear robotics, and the questioning of whether gender-specific devices are necessary.

Consensus statements on adherence issues in schizophrenia for Hong Kong.

AIM: In view of the clinical importance of the adherence issues in schizophrenia management, a consensus group of experienced local psychiatrists and nurse specialists gathered to outline a number of consensus statements for clinicians to consider enhancing adherence in their patients. PROCESS: Prior to the consensus group meeting, three core members drafted eight statements on the issue of adherence in schizophrenia. Using a modified Delphi method, published literature and published guidelines regarding the management of schizophrenia were reviewed by the full panel during the group meeting. After discussion and reflection from each individual member of the consensus group, the eight statements were reworded and electronically voted on anonymously in two steps: acceptance on quality of evidence and practicability in implementation. RESULTS: After modifications of the original statements, there was very high overall level of agreement and acceptance (reaching international standard) on all the five areas of adherence within the eight statements of the finalised statement. CONCLUSIONS: The present consensus statements are the first in Hong Kong to address systematically adherence issues in schizophrenia management. They include areas on adherence assessment and definition, treatment strategies in enhancing adherence, and treatment considerations at specific phases of schizophrenia. They are tailored to be of practical utility in the local Hong Kong setting.

Over-expression of astrocytic ET-1 attenuates neuropathic pain by inhibition of ERK1/2 and Akt(s) via activation of ETA receptor.

A differential role of endothelin-1 (ET-1) in pain processing has recently been suggested. However, the function of central ET-1 in neuropathic pain (NP) has not been fully elucidated to date. We report here the action of endogenous central ET-1 in sciatic nerve ligation-induced NP (SNL-NP) in a transgenic animal model that over-expresses ET-1 in the astrocytes (GET-1 mice). We hypothesized that the over-expression of astrocytic ET-1 would exert anti-allodynic and anti-hyperalgesic effects in NP, as demonstrated by mechanical threshold and plantar withdrawal latency using the von Frey filament and heat stimuli. In our animal model, GET-1 mice showed an increase in the withdrawal threshold and latency in response to the mechanical and thermal stimuli, respectively, in pain behavior tests after SNL. ET-1 and endothelin type A receptor (ETA-R) levels were increased significantly in L4-L6 segments of the spinal cord (ipsilateral to SNL) of GET-1 mice at 7 and 21days after surgery. Moreover, intrathecal administration of a specific ETA-R antagonist, BQ-123, attenuated the anti-allodynic and anti-hyperalgesic phenotype in GET-1 mice. The effects of BQ-123 on the mRNA expression of extracellular signal-regulated protein kinase 1/2 (ERK1/2) and protein kinase B/serine protein kinase (Akt(s)) were assessed in the ipsilateral L4-L6 segments harvested 30min after BQ-123 administration on day 7 after surgery. Phosphorylation of ERK1/2 and Akt(s) in the ipsilateral spinal cord of GET-1 mice was reduced following SNL, whereas no reduction was observed after intrathecal injection of BQ-123. In conclusion, our results showed that the xover-expression of astrocytic ET-1 reduced SNL-induced allodynia and hyperalgesia by inhibiting the activation of ERK1/2 and Akt(s) via the ETA-R-mediated pathway.

A strong two-photon induced phosphorescent Golgi-specific in vitro marker based on a heteroleptic iridium complex.

A new heteroleptic iridium complex demonstrated low cytotoxicity and near-infrared excitation (via two-photon absorption) for target-specific in vitro Golgi imaging in various cell lines (HeLa and A549 cells) with two-photon absorption cross section (~350 GM) in DMSO.

Differential effects of anti-metastatic mechanism of Tian-Xian liquid (TXL) and its bioactive fractions on human colorectal cancer models.

AIM OF STUDY: This study aimed to elucidate and compare the anti-metastatic mechanism of Tian-Xian liquid (TXL) and its bioactive components namely butanol (BU), ethyl-acetate (EA) and aqueous (WA) fractions on human colorectal cancer in vitro (HT-29 cancer cells) and in vivo (nude mouse xenografts). MATERIALS AND METHODS: The anti-proliferative effects of TXL and its bioactive components in HT-29 cells were determined by MTT assay. Their modulations on the potential angiogenic and metastatic marker expressions on HT-29 cells and xenografts were investigated by real-time PCR and Western blot at transcriptional and translational levels, respectively. For the in vitro study, migration abilities of HT-29 cells were determined using wound healing assay. For the in vivo study, daily measurements of the tumor size and volume of the xenografts were also performed. RESULTS: TXL, BU, EA and WA effectively inhibited the proliferation of HT-29 cells in a dose- and time-dependent manner. The IC(50) value of TXL on HT-29 cells was obtained after incubation with 1% (v/v) TXL for 4h; whereas IC(50) values were obtained for the following bioactive components: BU at 1.25% (v/v); EA at 5% (v/v); and WA at 0.3125% (v/v). It was found that 1% (v/v) TXL significantly down-regulated MMP2 and MMP7 expression at both transcriptional and translational levels and it reduced MMP9 and VEGF protein expression in vitro. TXL decreased the metastatic ability of HT-29 cells as demonstrated by wound healing assay. TXL and its bioactive fractions caused no significant changes in the body weight indicating lack of toxicity to the xenografts. CONCLUSIONS: In summary, TXL multi-targeted to down-regulate the metastatic markers in both in vitro and in vivo models. However, the effects of its bioactive fractions were not obvious. This study profoundly elucidated the anti-proliferative mechanism of TXL, which is vital for the development of future anti-cancer regime in Chinese medicinal formulations.

In Vitro characterization of low modulus linoleic acid coated strontium-substituted hydroxyapatite containing PMMA bone cement.

Poly (methyl methacrylate) (PMMA) bone cement is widely used in vertebral body augmentation procedures such as vertebroplasty and balloon kyphoplasty. Filling high modulus PMMA increases the modulus of filled verterbra, increasing the risk of fracture in the adjacent vertebra. On the other hand, in porous PMMA bone cements, wear particle generation and deterioration of mechanical performance are the major drawbacks. This study adopts a new approach by utilizing linoleic acid coated strontium substituted hydroxyapatite nanoparticle (Sr-5 HA) and linoleic acid as plasticizer reducing bone cement's modulus with minimal impact on its strength. We determined the compressive strength (UCS) and modulus (Ec), hydrophobicity, injectability, in vitro bioactivity and biocompatibility of this bone cement at different filler and linoleic acid loading. At 20 wt % Sr5-HA incorporation, UCS and Ec were reduced from 63 ± 2 MPa, 2142 ± 129 MPa to 58 ± 2 MPa, 1785 ± 64 MPa, respectively. UCS and Ec were further reduced to 49 ± 2 MPa and 774 ± 70 MPa respectively when 15 v/v of linoleic acid was incorporated. After 7 days of incubation, pre-osteoblast cells (MC3T3-E1) attached on 20 wt % Sr5-HA and 20 wt % Sr5-HA with 15 v/v of linoleic acid group were higher (3.73 ± 0.01 x 104, 2.27 ± 0.02 x 104) than their PMMA counterpart (1.83 ± 0.04 x 104). Incorporation of Sr5-HA with linoleic acid in monomer phase is more effective in reducing the bone cement's stiffness than Sr5-HA alone. Combination of low stiffness and high mechanical strength gives the novel bone cement the potential for use in vertebroplasty cement applications.

Usefulness of resistant gene markers for predicting treatment outcome on second-line anti-tuberculosis drugs.

AIM: Mutations in rrs [nucleotide (nt) 1401], gyrA gene (codons 90, 91 or 94), tlyA, ethA and thyA genes of Mycobacterium tuberculosis (MTB) were evaluated for their usefulness in predicting treatment outcome of kanamycin (KM), capreomycin (CPM), ofloxacin (OFX), ethionamide (ETH) and para-aminosalicylic acid (PAS). METHODS AND RESULTS: DNA sequence analyses of these genes were performed against 188 MTB isolates obtained from patients put on second-line anti-TB drugs (SLDs) with well-documented clinical history and treatment outcome. Mutations in rrs and gyrA have 100% positive predictive value (PPV) in predicting treatment failure for KM and OFX, while 88·9 and 80% were obtained, respectively, when tlyA and rrs mutations were considered in CPM. For ETH and PAS, the PPV of using ethA and thyA mutations to predict treatment failure was 82·5 and 89·3%, respectively. CONCLUSIONS: Our study demonstrated high specificities of gene mutations in predicting poor treatment outcome; however, further technical advancement is required to make the molecular detection of resistances to other SLDs feasible in clinical laboratories. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study to correlate different polymorphisms of major SLD resistance gene markers with predicted treatment outcome, using an international set of well-documented clinical MTB strains.

5-(Dimethylamino)-N-(4-ethynylphenyl)-1-naphthalenesulfonamide as a novel bifunctional antitumor agent and two-photon induced bio-imaging probe.

A novel compound, (5-(dimethylamino)-N-(4-ethynylphenyl)-1-naphthalenesulfonamide), was prepared and characterized; it shows dual functional roles as an effective antitumor and a two-photon induced bio-imaging agent.

Preconditioning with Porphyromonas gingivalis lipopolysaccharide may confer cardioprotection and improve recovery of the electrically induced intracellular calcium transient during ischemia and reperfusion.

BACKGROUND AND OBJECTIVE: Porphyromonas gingivalis lipopolysaccharide (LPS) is a ligand for cell surface toll-like receptors (TLR), TLR2 and TLR4 while stimulation of either leads to cardioprotection. We hypothesized that: (1) pretreatment with P. gingivalis LPS at appropriate concentrations would induce cardioprotection against injury induced by ischemia and reperfusion; and (2) P. gingivalis LPS pretreatment at cardioprotective concentrations may reduce Ca(2+) overload, which is a precipitating cause of injury, and improve recovery of contractile function. MATERIAL AND METHODS: Male Sprague-Dawley rats were randomly selected to receive intraperitoneal saline or hot phenol-water-extracted P. gingivalis LPS at 0.2, 0.5, 1.0, 2.0 or 4.0 mg/kg 24 h before the experiment. The hearts were isolated and subjected to regional ischemia by coronary artery ligation followed by reperfusion. In isolated rat ventricular myocytes, the cytosolic Ca(2+) level and the electrically induced intracellular calcium (E[Ca(2+)](i)) transient, which reflects contractile function, were determined after pretreatment with a cardioprotective dose of P. gingivalis LPS. RESULTS: Pretreatment with 0.5 mg/kg P. gingivalis LPS significantly reduced, while pretreatment with 1.0-4.0 mg/kg significantly increased infarct size. The Ca(2+) overload induced by ischemia-reperfusion was attenuated in myocytes from rats pretreated with 0.5 mg/kg P. gingivalis LPS. Pretreated myocytes also showed an increased amplitude of the E[Ca(2+)](i) transient, no prolongation of the time to reach the peak E[Ca(2+)](i) transient and shorter 50% decay time during reperfusion. CONCLUSION: At a dosage of 0.5 mg/kg, P. gingivalis LPS confers cardioprotection against ischemia-reperfusion-induced injury and improved intracellular E[Ca(2+)](i) transient recovery, hence improving myocyte contractile recovery.

The CD14(+/low)CD16(+) monocyte subset is more susceptible to spontaneous and oxidant-induced apoptosis than the CD14(+)CD16(-) subset.

Human monocytes can be classified into two subsets with distinctive characteristics. In this study, we report a difference in apoptotic potential between these two subsets with CD14(+/low)CD16(+) monocytes being more susceptible than CD14(+)CD16(-) monocytes to undergo spontaneous apoptosis and apoptosis induced by reactive oxygen species (ROS). By global transcriptomic and proteomic approaches, we observed that CD14(+/low)CD16(+) monocytes expressed higher levels of pro-apoptotic genes and proteins such as TNFα, caspase 3, Bax and cytochrome c and showed more caspases 3 and 7 activities. They also exhibited greater aerobic respiration resulting in a higher production of ROS from the mitochondria. CD14(+)CD16(-) monocytes, in contrast, showed higher expression of glutathione (GSH)-metabolizing genes such as GSH peroxidase and microsomal GSH S-transferase and were more resistant to oxidative stress than CD14(+/low)CD16(+) monocytes. The apoptosis of CD14(+/low)CD16(+) monocytes was ROS dependent as reducing ROS levels significantly reduced cell death. This is the first report of a differential apoptotic propensity of human monocyte subsets, and gaining a better understanding of this process may help to provide a better understanding of the roles of these subsets during homeostasis and under pathological conditions, particularly in situations in which high levels of oxidants are present.