Feasibility and acceptability of wrist actigraph in assessing sleep quality and sleep quantity: A home-based pilot study in healthy volunteers

Purpose: This study aimed to determine the feasibility and acceptability of actigraphy to monitor sleep quality and quantity in healthy self-rated good sleeper adults at home-based settings. Method: Sixteen healthy volunteers (age > 18) were invited to participate. Each participant was provided with a wrist actigraph device to be worn for 24-hour/day for seven consecutive days to monitor their sleep-wake patterns. Actigraphy data were downloaded using-proprietary software to generate an individual-sleep report. Participants also completed a set of self-reported Health Related Quality of Life (HRQOL) using WHO (five) Well Being Index (WBI) questionnaires. Results: Actigraphy was well accepted by all participants. Only 43.8% of the participants achieved normal total sleep time (TST) and 62.5% had a mean sleep efficiency value below the normal range. Despite a reduced quality of sleep among the participants, the self-reported HRQOL scores produced by the WHO-5 WBI showed a “fair” to “good” among the participants. Conclusions: To maintain healthy well-being, it is vital to have efficient and quality sleep. Insufficient and poor sleep may contribute to various health problems and hazardous outcomes. People often believe they have normal and efficient sleep, not realising they may be developing poor sleep habits. This study found that actigraphy can be easily utilized to monitor sleep-wake patterns at home-based settings. We proposed that actigraphy could be adapted for use in the primary care settings (e.g. community pharmacy) to improve the sleep health management in the community.

Clonal Characterization of Bone Marrow Derived Stem Cells and Their Application for Bone Regeneration

Tissue engineering allows the design of functionally active cells within supportive bio-scaffolds to promote the development of new tissues such as cartilage and bone for the restoration of pathologically altered tissues. However, all bone tissue engineering applications are limited by a shortage of stem cells. The adult bone marrow stroma contains a subset of nonhematopoietic cells referred to as bone marrow mesenchymal stem cells （BMSCs）. BMSCs are of interest because they are easily isolated from a small aspirate of bone marrow and readily generate singlecell-derived colonies. These cells have the capacity to undergo extensive replication in an undifferentiated state ex vivo. In addition, BMSCs have the potential to develop either in vitro or in vivo into distinct mesenchymal tissues,including bone, cartilage, fat, tendon, muscle, and marrow stroma. Thus, BMSCs are an attractive cell source for tissue engineering approaches. However, BMSCs are not homogeneous and the quantity of stem cells decreases in the bone marrow in aged population. A sequential loss of lineage differentiation potential has been found in the mixed culture of bone marrow stromal cells due to a heterogenous popu- lation. Therefore, a number of studies have proposed that homogenous bone marrow stem cells can be generated from clonal culture of bone marrow cells and that BMSC clones have the greatest potential for the application of bone regeneration in vivo.

Dental pulp stem cells express tendon markers under mechanical loading and are a potential cell source for tissue engineering of tendon-like tissue

Postnatal mesenchymal stem cells have the capacity to differentiate into multiple cell lineages. This study explored the possibility of dental pulp stem cells （DPSCs） for potential application in tendon tissue engineering. The expression of tendon- related markers such as scleraxis, tenascin-C, tenomodulin, eye absent homologue 2, collagens I and VI was detected in dental pulp tissue. Interestingly, under mechanical stimulation, these tendon-related markers were significantly enhanced when DPSCs were seeded in aligned polyglycolic acid （PGA） fibre scaffolds. Furthermore, mature tendon-like tissue was formed after transplantation of DPSC-PGA constructs under mechanical loading conditions in a mouse model. This study demonstrates that DPSCs could be a ootential stem cell source for tissue enEineerin~ of tendon-like tissue.

Engineering osteoblastic metastases to delineate the adaptive response of androgen-deprived prostate cancer in the bone metastatic microenvironment

While stromal interactions are essential in cancer adaptation to hormonal therapies,the effects of bone stroma and androgen deprivation on cancer progression in bone are poorly understood.Here,we tissue-engineered and validated an in vitro microtissue model of osteoblastic bone metastases,and used it to study the effects of androgen deprivation in this microenvironment.The model was established by culturing primary human osteoprogenitor cells on melt electrowritten polymer scaffolds,leading to a mineralized osteoblast-derived microtissue containing,in a 3D setting,viable osteoblastic cells,osteocytic cells,and appropriate expression of osteoblast/osteocyte-derived mRNA and proteins,and mineral content.Direct co-culture of androgen receptordependent/ independent cell lines (LNCaP,C4-2B,and PC3) led cancer cells to display functional and molecular features as observed in vivo.Co-cultured cancer cells showed increased affinity to the microtissues,as a function of their bone metastatic potential.Cocultures led to alkaline phosphatase and collagen-I upregulation and sclerostin downregulation,consistent with the clinical marker profile of osteoblastic bone metastases.LNCaP showed a significant adaptive response under androgen deprivation in the microtissues,with the notable appearance of neuroendocrine transdifferentiation features and increased expression of related markers (dopa decarboxylase,enolase 2).Androgen deprivation affected the biology of the metastatic microenvironment with stronger upregulation of androgen receptor,alkaline phosphatase,and dopa decarboxylase,as seen in the transition towards resistance.The unique microtissues engineered here represent a substantial asset to determine the involvement of the human bone microenvironment in prostate cancer progression and response to a therapeutic context in this microenvironment.

Humanized bone facilitates prostate cancer metastasis and recapitulates therapeutic effects of zoledronic acid in vivo

Advanced prostate cancer(PCa)is known for its high prevalence to metastasize to bone,at which point it is considered incurable.Despite significant effort,there is no animal model capable of recapitulating the complexity of PCa bone metastasis.The humanized mouse model for PCa bone metastasis used in this study aims to provide a platform for the assessment of new drugs by recapitulating the human–human cell interactions relevant for disease development and progression.The humanized tissueengineered bone construct(hTEBC)was created within NOD-scid IL2rgnull(NSG)mice and was used for the study of experimental PC3-Luc bone metastases.It was confirmed that PC3-Luc cells preferentially grew in the hTEBC compared with murine bone.The translational potential of the humanized mouse model for PCa bone metastasis was evaluated with two clinically approved osteoprotective therapies,the non-species-specific bisphosphonate zoledronic acid(ZA)or the human-specific antibody Denosumab,both targeting Receptor Activator of Nuclear Factor Kappa-ΒLigand.ZA,but not Denosumab,significantly decreased metastases in hTEBCs,but not murine femora.These results highlight the importance of humanized models for the preclinical research on PCa bone metastasis and indicate the potential of the bioengineered mouse model to closely mimic the metastatic cascade of PCa cells to human bone.Eventually,it will enable the development of new effective antimetastatic treatments.

Independent effects of diet and exercise training on fat oxidation in non-alcoholic fatty liver disease

AIM To investigate the independent effects of 6-mo of dietary energy restriction or exercise training on wholebody and hepatic fat oxidation of patients with nonalcoholic fatty liver disease(NAFLD).METHODS Participants were randomised into either circuit exercise training(EX;n = 13;3 h/wk without changes in dietary habits),or dietary energy restriction(ER) without changes in structured physical activity(ER;n = 8).Respiratory quotient(RQ) and whole-body fat oxidation rates(Fatox) were determined by indirect calorimetry under basal,insulin-stimulated and exercise conditions.Severity of disease and steatosis was determined by liver histology;hepatic Fatox was estimated from plasma β-hydroxybutyrate co.ncentrations;cardiorespiratory fitness was expressed as VO2 peak.Complete-case analysis was performed(EX:n = 10;ER:n = 6).RESULTS Hepatic steatosis and NAFLD activity score decreased with ER but not with EX.β-hydroxybutyrate concentrations increased significantly in response to ER(0.08 ± 0.02 mmol/L vs 0.12 ± 0.04 mmol/L,P = 0.03) but remained unchanged in response to EX(0.10 ± 0.03 mmol/L vs 0.11 ± 0.07 mmol/L,P = 0.39).Basal RQ decreased(P = 0.05) in response.to EX,while this change was not significant after ER(P = 0.38).VO_(2peak)(P < 0.001) and maximal Fa_(tox) during aerobic exercise(P = 0.03) improved with EX but not with ER(P > 0.05).The increase in β-hydroxybutyrate concentrations was correlated with the reduction in hepatic steatosis(r =-0.56,P = 0.04).CONCLUSION ER and EX lead to specific benefits on fat metabolism of patients with NAFLD.Increased hepatic Fat_(ox) in response to ER could be one mechanism through which the ER group achieved reduction in steatosis.

Manifestations of type 2 diabetes in corneal endothelial cell density,corneal thickness and intraocular pressure

We sought to evaluate central corneal thickness（CCT）,corneal endothelial cell density（ECD）and intraocular pressure（IOP）in patients with type 2 diabetes mellitus（DM）and to associate potential differences with diabetes duration and treatment modality in a prospective,randomized study.We measured ECD,CCT and IOP of125 patients with type 2 DM（mean age 57.1±11.5 years）and compared them with 90 age-matched controls.Measured parameters were analyzed for association with diabetes duration and glucose control modalities（insulin injection or oral medication）while controlling for age.In the diabetic group,the mean ECD（2511±252 cells/mm^2）,mean CCT（539.7±33.6μm）and mean IOP（18.3±2.5 mmHg）varied significantly from those the control group[ECD：2713±132 cells/mm^2（P〈0.0001）,CCT：525.0±45.3μm（P=0.003）and IOP：16.7±1.8 mmHg（P〈0.0001）].ECD was significantly reduced by about 32 cell/mm^2 for diabetics with duration of〉10 years when compared with those with duration of〈10 years（P〈0.05）.CCT was thicker and IOP was higher for diabetics with duration of〉10 years than those with duration of〈10 years（P〉0.05）.None of the measured parameters was significantly associated with diabetes duration and treatment modality（P〉0.05）.In conclusion,subjects with type 2DM exhibit significant changes in ECD,IOP and CCT,which,however,are not correlated with disease duration or if the patients receive on insulin injection or oral medications.

Validity of a noninvasive estimation of deep body temperature when wearing personal protective equipment during exercise and recovery

Background:Deep body temperature is a critical indicator of heat strain.However,direct measures are often invasive,costly,and difficult to implement in the field.This study assessed the agreement between deep body temperature estimated from heart rate and that measured directly during repeated work bouts while wearing explosive ordnance disposal(EOD)protective clothing and during recovery.Methods:Eight males completed three work and recovery periods across two separate days.Work consisted of treadmill walking on a 1%incline at 2.5,4.0,or 5.5 km/h,in a random order,wearing EOD protective clothing.Ambient temperature and relative humidity were maintained at 24℃and 50%[Wet bulb globe temperature(WBGT)(20.9±1.2)℃]or 32℃and 60%[WBGT(29.0±0.2)℃]on the separate days,respectively.Heart rate and gastrointestinal temperature(TGI)were monitored continuously,and deep body temperature was also estimated from heart rate(ECTemp).Results:The overall systematic bias between TGI and ECTemp was 0.01℃with 95%limits of agreement(Lo A)of±0.64℃and a root mean square error of 0.32℃.The average error statistics among participants showed no significant differences in error between the exercise and recovery periods or the environmental conditions.At TGI levels of(37.0–37.5)℃,(37.5–38.0)℃,(38.0–38.5)℃,and>38.5℃,the systematic bias and±95%Lo A were(0.08±0.58)℃,(–0.02±0.69)℃,(–0.07±0.63)℃,and(–0.32±0.56)℃,respectively.Conclusions:The findings demonstrate acceptable validity of the ECTemp up to 38.5℃.Conducting work within an ECTemp limit of 38.4℃,in conditions similar to the present study,would protect the majority of personnel from an excessive elevation in deep body temperature(>39.0℃).

Effectiveness of in-office blood pressure measurement by eye care practitioners in early detection and management of hypertension

AIM: To investigate the number of hypertensive patients, the optometrist is able to identify by routinely taking blood pressure(BP) measurements for patients in "at-risk" groups, and to sample patients’ opinions regarding in-office BP measurement. Many of the optometrists in Saudi Arabia practice in optical stores.These stores are wide spread, easily accessible and seldom need appointments. The expanding role of the optometrist as a primary health care provider(PHCP) and the increasing global prevalence of hypertension,highlight the need for an integrated approach towards detecting and monitoring hypertension.METHODS: Automated BP measurements were made twice(during the same session) at five selected optometry practices using a validated BP monitor(Omron M6) to assess the number of patients with high BP(HBP)- in at-risk groups-visiting the eye clinic routinely. Prior to data collection, practitioners underwent a two-day training workshop by a cardiologist on hypertension and how to obtain accurate BP readings. A protocol for BP measurement was distributed and retained in all participating clinics. The general,,.,attitude towards cardiovascular health of 480 patients aged 37.2(±12.4)y and their opinion towards in-office BP measurement was assessed using a self-administered questionnaire.RESULTS: A response rate of 83.6% was obtained for the survey. Ninety-three of the 443 patients(21.0%)tested for BP in this study had HBP. Of these,(62subjects) 67.7% were unaware of their HBP status. Thirty of the 105 subjects(28.6%) who had previously been diagnosed with HBP, still had HBP at the time of this study, and only 22(73.3%) of these patients were on medication. Also, only 25% of the diagnosed hypertensive patients owned a BP monitor.CONCLUSION: Taking BP measurements in optometry practices, we were able to identify one previously undiagnosed patient with HBP for every 8 adults tested.We also identified 30 of 105 previously diagnosed patients whose BP was poorly controlled, twenty-two of whom were on medication. The patients who participated in this study were positively disposed toward the routine measurement of BP by optometrists.

Combination curcumin and vitamin E treatment attenuates diet-induced steatosis in Hfe-/-mice

AIM To investigate the synergistic hepato-protective properties of curcumin and vitamin E in an Hfe^(-/-)high calorie diet model of steatohepatitis.METHODS Hfe^(-/-)C57BL/6J mice were fed either a high calorie diet or a high calorie diet with 1 mg/g curcumin; 1.5 mg/g vitamin E; or combination of 1 mg/g curcumin + 1.5 mg/g vitamin E for 20 wk. Serum and liver tissue were collected at the completion of the experiment. Liver histology was graded by a pathologist for steatosis, inflammation and fibrosis. RNA and protein was extracted from liver tissue to examine gene and protein expression associated with fatty acid oxidation, mitochondrial biogenesis and oxidative stress pathways.RESULTS Hfe^(-/-)mice fed the high calorie diet developed steatohepatitis and pericentral fibrosis. Combination treatment with curcumin and vitamin E resulted in a greater reduction of percent steatosis than either vitamin E or curcumin therapy alone. Serum alanine aminotransferase and non-alcoholic fatty liver disease(NAFLD) activity score were decreased following combination therapy with curcumin and vitamin E compared with high calorie diet alone. No changes were observed in inflammatory or fibrosis markers following treatment. Epididymal fat pad weights were significantly reduced following combination therapy, however total body weight and liver weight were unchanged. Combination therapy increased the m RNA expression of Adipo R2, Ppar-α, Cpt1 a, Nrf-1 and Tfb2 m suggesting enhanced fatty acid oxidation and mitochondrial biogenesis. In addition, combination treatment resulted in increased catalase activity in Hfe^(-/-)mice. CONCLUSION Combination curcumin and vitamin E treatment decreases liver injury in this steatohepatitis model, indicating that combination therapy may be of value in NAFLD.

Evaluation of visual stress symptoms in age-matched dyslexic, Meares-Irlen syndrome and normal adults

AIM： To examine the prevalence of dyslexia and Meares-Irlen syndrome（MIS） among female students and determine their level of visual stress in comparison with normal subjects.·METHODS： A random sample of 450 female medical students of King Saud University Riyadh（age range, 18-30y） responded to a wide range of questions designed to accomplish the aims of this study. The detailed questionnaire consisted of 54 questions with 12 questions enquiring on ocular history and demography of participants while 42 questions were on visual symptoms. Items were categorized into critical and non-critical questions（CQ and NCQ） and were rated on four point Likert scale. Based on the responses obtained, the subjects were grouped into normal（control）, dyslexic with or without MIS（Group 1） and subjects with MIS only（Group 2）. Responses were analysed as averages and mean scores were calculated and compared between groups using one way analysis of variance to evaluate total visual stress score（TVSS =NCQ ＋CQ）, critical and non-critical visual stress scores. The relationship between categorical variables such as age, handedness and condition were assessed with Chi-square test.·RESULTS： The completion rate was 97.6% and majority of the respondents（92%） were normal readers, 2%dyslexic and 6% had MIS. They were age-matched. More than half of the participants had visited an eye care practitioner in the last 2y. About 13% were recommendedeye exercises and one participant experienced pattern glare. Hand preference was not associated with any condition but Group 1 subjects（3/9, 33%） were significantly more likely to be diagnosed of lazy eye than Group 2（2/27, 7%） and control（27/414, 7%） subjects. The mean±SD of TVSS responses were 63±14 and it was 44±9for CQ and 19 ±5 for NCQ. Responses from all three variables were normally distributed but the CQ responses were on the average more positive（82%） in Group 2 and less positive（46%） in Group 1 than control. With NCQ,the responses were equally less positive in Group 1 and2 than control. Group 2 subjects showed significantly higher TVSS（P =0.002）, NCQ（P =0.006） and CQ（P =0.008）visual stress scores than control but no difference between Group 1 and control subjects, was observed for all scores（P 〉0.05, for all comparisons）.·CONCLUSION： The prevalence of dyslexia and MIS among Saudi female students was 2% and 6%,respectively. Critical questions performed best for assessing visual stress symptoms in dyslexic and MIS subjects. Generally, students with MIS were more sensitive to visual stress than normal students but dyslexics were more likely to present with a lazy eye than MIS and normal readers.

Proximal Femoral Cortical Thickness and Medullary Canal Diameter in Soft and Hard Water Regions

This study compared proximal femoral morphology in patients living in soft and hard water regions. The proximal femoral morphology of two groups of 70 patients living in hard and soft water regions with a mean age of 72.29 (range: 50 to 87 years) was measured using an antero-posterior radiograph of the non-operated hip with magnification adjusted. The medullary canal diameter at the level of the lesser trochanter (LT) was significantly wider in patients living in the hard water region (mean width: 1.9 mm wider;p = 0.003). No statistical significant difference was found in the medullary canal width at 10 cm below the level of LT, Dorr index, or Canal Bone Ratio (CBR). In conclusion, the proximal femoral morphology does differ in patients living in soft and hard water areas. These results may have an important clinical bearing in patients undergoing total hip replacement surgery. Further research is needed to determine whether implant survivorship is affected in patients living in hard and soft water regions.

Speckle-type POZ protein mutations interrupt tumor suppressor function of speckle-type POZ protein in prostate cancer by affecting androgen receptor degradation

Large scale exome sequencing studies have ＇revealed regions of the genome, which contribute to the castrate resistant prostate cancer （CRPC） phenotype.1-3 Such studies have identified mutations in genes, which may have diagnostic/prognostic potential, or which may be targeted therapeutically. Two of these genes include the androgen receptor （AR） and speckle-type POZ protein （SPOP） genes. However, the findings from these exome sequencing studies can only be translated therapeutically once the functional consequences of these mutations have been determined. Here, we highlight the recent study by An et al.4 which investigated the functional effects of mutations in the SPOP gene that were identified in the aforementioned exome sequencing studies, particnlarly in the context of SPOP-mediated degradation of the AR.

自体骨髓间充质干细胞移植密度与Beagle犬牙Ⅱ度根分叉病变组织修复的关系(英文)

背景:目前临床上II度根分叉病变区牙周组织的再生仍是一项难题。目的:比较不同密度自体骨髓间充质干细胞修复II度牙根分叉病变区牙周组织缺损的能力。设计:随机对照观察实验。单位:福建医科大学附属口腔医院实验室和福州总医院动物实验科。材料:实验于2005-07/2006-09在解放军南京军区福州总医院动物实验科和福建医科大学附属口腔医院实验室完成。6只1岁半雄性Beagle犬由解放军南京军区福州总医院动物实验科提供,实验过程中对动物处置符合动物伦理学标准。实验中选用Bio-Gide胶原膜和BME-10X胶原膜。方法:在犬的下颌第2,3前磨牙和第1磨牙颊侧根分叉处制备慢性II度牙根分叉病变模型。从6只18月龄的Beagle犬抽取自体骨髓间充质干细胞。应用5×108L-1,5×109L-1,5×1010L-1的骨髓间充质干细胞复合BME-10X胶原膜移植治疗牙根分叉病变,表面覆盖Bi0-Gide胶原膜,单纯Bi0-Gide胶原膜组为对照组。采用OLYPUS IX71显微照相系统和OLYSIA BioAutoCell软件计算新生牙骨质长度的百分比和新生牙槽骨面积的百分比。主要观察指标:苏木精-伊红染色观察并测量牙周组织再生(新生牙骨质长度和新生牙槽骨面积的百分比)情况。结果:对照组的新生牙骨质长度和新生牙槽骨面积的百分比分别为:(51.5±5.6)%和(27.1±7.7)%;5×108L-1骨髓间充质干细胞组为:(84.8±8.9)%和(30.6±7.7)%;5×109L-1骨髓间充质干细胞组为:(91.8±5.2)%和(68.3±11.4)%;5×1010L-1骨髓间充质干细胞组为:(88.8±7.2)%和(78.5±12.7)%。细胞组的新生牙骨质量与对照组相比,差异有显著性意义(P<0.01),但各细胞组间相互比较差异无显著性意义;5×109L-1组和5×1010L-1组的新生牙槽骨量与5×108L-1组和对照组相比差异有显著性(P<0.05),但前两组间和后两组间比较则差异无显著性意义。结论:骨髓间充质干细胞移植能促进牙根分叉病变区的牙周组织再生,其作用与细胞的接种密度有关。

Why forefoot striking in minimal shoes might positively change the course of running injuries

It is believed that human ancestors evolved the ability to run bipedally approximately 2 million years ago. This form of locomotion may have been important to our survival and likely has influenced the evolution of our body form. As our bodies have adapted to run, it seems unusual that up to 79% of modern day runners are injured annually. The etiology of these injuries is clearly multifactorial. However, 1 aspect of running that has significantly changed over the past 50 years is the footwear we use. Modern running shoes have become increasingly cushioned and supportive, and have changed the way we run. In particular, they have altered our footstrike pattern from a predominantly forefoot strike(FFS) landing to a predominantly rearfoot strike(RFS) landing. This change alters the way in which the body is loaded and may be contributing to the high rate of injuries runners experience while engaged in an activity for which they were adapted. In this paper, we will examine the benefits of barefoot running(typically an FFS pattern),and compare the lower extremity mechanics between FFS and RFS. The implications of these mechanical differences, in terms of injury, will be discussed. We will then provide evidence to support our contention that FFS provides an optimal mechanical environment for specific foot and ankle structures, such as the heel pad, the plantar fascia, and the Achilles tendon. The importance of footwear will then be addressed, highlighting its interaction with strike pattern on mechanics. This analysis will underscore why footwear matters when assessing mechanics. Finally, proper preparation and safe transition to an FFS pattern in minimal shoes will be emphasized. Through the discussion of the current literature, we will develop a justification for returning to running in the way for which we were adapted to reduce running-related injuries.

Current pre-hospital traumatic brain injury management in China

BACKGROUND: Traumatic brain injury(TBI) is associated with most trauma-related deaths. Secondary brain injury is the leading cause of in-hospital deaths after traumatic brain injury. By early prevention and slowing of the initial pathophysiological mechanism of secondary brain injury, prehospital service can signifi cantly reduce case-fatality rates of TBI. In China, the incidence of TBI is increasing and the proportion of severe TBI is much higher than that in other countries. The objective of this paper is to review the pre-hospital management of TBI in China.DATA SOURCES: A literature search was conducted in January 2014 using the China National Knowledge Infrastructure(CNKI). Articles on the assessment and treatment of TBI in pre-hospital settings practiced by Chinese doctors were identified. The information on the assessment and treatment of hypoxemia, hypotension, and brain herniation was extracted from the identifi ed articles.RESULTS: Of the 471 articles identified, 65 met the selection criteria. The existing literature indicated that current practices of pre-hospital TBI management in China were sub-optimal and varied considerably across different regions.CONCLUSION: Since pre-hospital care is the weakest part of Chinese emergency care, appropriate training programs on pre-hospital TBI management are urgently needed in China.

Impact of Temperature on Mortality in Three Major Chinese Cities

Objective To study the relation between temperature and mortality by estimating the temperature-related mortality in Beijing, Shanghai, and Guangzhou. Methods Data of daily mortality, weather and air pollution in the three cities were collected. A distributed lag nonlinear model was established and used in analyzing the effects of temperature on mortality. Current and future net temperature-related mortality was estimated. Results The association between temperature and mortality was J-shaped, with an increased death risk of both hot and cold temperature in these cities. The effects of cold temperature on health lasted longer than those of hot temperature. The projected temperature-related mortality increased with the decreased cold-related mortality. The mortality was higher in Guangzhou than in Beijing and Shanghai. Conclusion The impact of temperature on health varies in the 3 cities of China, which may have implications for climate policy making in China.

Lipopolysaccharide mouse models for Parkinson's disease research:a critical appraisal

Parkinson's disease,the most common movement disorder,has a strong neuroinflammatory aspect.This is evident by increased pro-inflammatory cytokines in the serum,and the presence of activated microglial cells,and inflammatory cytokines in the substantia nigra of post-mortem brains as well as cerebrospinal fluid of Parkinson's disease patients.The central and peripheral neuroinflammatory aspects of Parkinson's disease can be investigated in vivo via administration of the inflammagen lipopolysaccharide,a component of the cell wall of gram-negative bacteria.In this mini-review,we will critically evaluate different routes of lipopolysaccharide administration(including intranasal systemic and ste reotasic),their relevance to clinical Parkinson's disease as well as the recent findings in lipopolysaccharide mouse models.We will also share our own expe riences with systemic and intrastriatal lipopolysaccharide models in C57BL/6 mice and will discuss the usefulness of lipopolysaccharide mouse models for future research in the field.

Combined VEGF/PDGF improves olfactory regeneration after unilateral bulbectomy in mice

The olfactory receptor neurons lining the nasal cavity have a remarkable capacity to regenerate throughout life. They are replenished continuously and their axons make new connections within the olfactory bulb. However, some factors such as head trauma and skull base surgery damage the olfactory nerve which lead to olfactory dysfunction. Losing the sense of smell has considerable effects on quality of life and life-expectancy. Therefore, there is a clear need to find a treatment for olfactory dysfunction. One such potential treatment is growth factor therapy which showed promising results in the spinal cord and brain injuries. The aim of the present study was to investigate whether combined delivery of two growth factors, vascular endothelial growth factor and platelet-derived growth factor treatment can improve the olfactory neurons regeneration in mice. The degeneration of the olfactory neurons was induced by unilateral bulbectomy. The treatment group received 1.5 μg of the combined growth factors intranasally, while the control injured group received saline. Growth factor treatment significantly increased the number of immature neurons at 5 and 7 days post injury and also the number of mature olfactory neurons at 10 and 14 days post bulbectomy. Regenerating axons extended over a larger volume in the operated cavity in the treatment group compared to control group at 14 days post bulbectomy. The growth factor treatment also significantly reduced astrocytic glia scar in the operated cavity. The results indicate that the combined delivery of the growth factors has the potential to improve olfactory dysfunction.

RANKL-induced M1 macrophages are involved in bone formation

The activation of M1 macrophages can be achieved by stimulating them with lipopolysaccharide （LPS） and interferon-γ （IFN-γ）. However, M1 can be found under physiological conditions without any pathological stimuli. This study aimed to understand the involvement of RANKL-induced M1 macrophages in bone formation compared with pathologically induced macrophages. Fischer rats were used to investigate macrophage distribution in normal and injured femoral condyles in vivo. Bone marrow-derived macrophages （BMDMs） were activated with LPS＋IFN-γ and RANKL to achieve M1 activation in vitro. Gene expression related to inflammation, osteoclastogenesis, angiogenesis, and migration was determined by reverse transcription-quantitative polymerase chain reaction （RT-qPCR） and fluorescence-activated cell sorting （FACS）. Tissue macrophages showed distinct expression patterns at different bone regions. RANKL was found in close proximity to inducible nitric oxide synthase-positive （iNOS＋） cells in vivo, suggesting an association between RANKL expression and iNOS＋ cells, especially in trabecular bone. RANKL-induced macrophages showed a different cytokine secretion profile compared with pathologically induced macrophages. Both osteoclasts and M1 macrophages peaked on day 7 during bone healing. RANKL could trigger Ml-like macrophages with properties that were different from those of LPS＋IFN-γ-induced macrophages. These RANKL-activated M1 macrophages were actively involved in bone formation.