Cross-cultural adaptation of Cantonese (Hong Kong) Oswestry Disability Index version 2.1b.

PURPOSE: Oswestry Disability Index (ODI) was established by Fairbank in 1989 to assess functional disabilities in low back pain (LBP). It was last updated in 2019 as ODI version 2.1b (ODI AU_2.1b). ODI was first translated into Simplified Chinese Oswestry Disability Index (CODI) in 2008 by Lue. The construct validity, internal consistency, level of agreement and the floor and ceiling effects of CODI were found unclear by Yao in 2016. This study will verify how well the adapted Cantonese-Hong Kong Oswestry Disability Index version 2.1b (HKCODI) aligns with ODI AU_2.1b in the Southern Chinese population. METHODS: The translation of ODI AU_2.1b was performed according to guidelines from MAPI Research Trust and American Association of Orthopaedic Surgeons. Psychometric properties of HKCODI were tested statistically by Pearson's correlation, Cronbach's Alpha and Intraclass  Correlation  Coefficient (ICC). RESULTS: A total of 200 subjects (109 males, 91 females) aged from 15 to 85 (mean age = 58.91) with LBP scored from 3/10 to 10/10 in the Visual Analogue Scale (VAS) were recruited in the Occupational Therapy Department of a tertiary referral center. HKCODI demonstrated strong construct validity in comparing with Hong Kong Roland-Morris Disability Questionnaire (HKRMDQ) (r = 0.666, p = 0.000), Short Form Health Survey (SF-36)  Physical Composite Summary (- 0.700, p = 0.000) and VAS (0.487, p = 0.000). Excellent internal consistency and test-retest reliability were confirmed with Cronbach's Alpha of 0.997 and ICC of 0.993 at 95% confidence level. CONCLUSION: Cross-cultural adaptation of ODI AU_2.1b has been translated and validated as   HKCODI and Item-8 (Sex Life) was suggested to skip for patient older than 60. HKCODI is a fully self-administered and highly reliable tool in assessing the functional disability of patients with LBP in the Southern Chinese population.

Linking Stage-Specific Plasma Biomarkers to Gray Matter Atrophy in Parkinson Disease.

BACKGROUND AND PURPOSE: The shortcomings of synucleinopathy-based Parkinson disease staging highlight the need for systematic clinicopathologic elucidation and biomarkers. In this study, we investigated associations of proteinopathy and inflammation markers with changes in gray matter volume that accompany Parkinson disease progression. MATERIALS AND METHODS: We prospectively enrolled 42 patients with idiopathic Parkinson disease, subdivided into early-/late-stage groups and 27 healthy controls. Parkinson disease severity and participants' functional and cognitive performance were evaluated. Peripheral plasma α-synuclein, ß-amyloid42, and tau were quantified with immunomagnetic reduction assays, and nuclear DNA by polymerase chain reaction, and regional gray matter volumes were determined by MR imaging. Statistical tests identified stage-specific biomarkers and gray matter volume patterns in the early-stage Parkinson disease, late-stage Parkinson disease, and control groups. Correlations between gray matter volume atrophy, plasma biomarkers, Parkinson disease severity, and cognitive performance were analyzed. RESULTS: Patients with Parkinson disease had significantly elevated α-synuclein, tau, and ß-amyloid42 levels compared with controls; nuclear DNA levels were similar in early-stage Parkinson disease and controls, but higher in late-stage Parkinson disease (all P < .01). We identified 3 stage-specific gray matter volume atrophy patterns: 1) control > early-stage Parkinson disease = late-stage Parkinson disease: right midfrontal, left lingual, and fusiform gyri, left hippocampus, and cerebellum; 2) control > early-stage Parkinson disease > late-stage Parkinson disease: precentral, postcentral, parahippocampal, left superior-temporal, right temporal, right superior-frontal, and left cingulate gyri, occipital lobe, and bilateral parts of the cerebellum; 3) control = early-stage Parkinson disease > late-stage Parkinson disease: left midfrontal, superior-frontal and temporal, amygdala, and posterior cingulate gyri, caudate nucleus, and putamen. We discovered stage-specific correlations among proteinopathy, inflammation makers, topographic gray matter volume patterns, and cognitive performance that accompanied Parkinson disease progression. CONCLUSIONS: Identifying associations linking peripheral plasma biomarkers, gray matter volume, and clinical status in Parkinson disease may facilitate earlier diagnosis and improve prognostic accuracy.

Revisits after adenotonsillectomy in children with sleep-disordered breathing: A retrospective single-institution study.

OBJECTIVE: To investigate emergency room (ER) revisits and hospital readmissions following adenotonsillectomy (T&A) in children with sleep-disordered breathing (SDB), and correlations between SDB severity and ER revisits. DESIGN: Retrospective chart review study. SETTING: Tertiary referral centre. PARTICIPANT: 610 consecutive children underwent T&A for treating SDB. MAIN OUTCOME MEASURES: Sleep-disordered breathing severity was defined according to the apnoea-hypopnoea index (AHI) (primary snoring = AHI < 1; mild = AHI 1-5; moderate = AHI 5-10; and severe = AHI > 10). Revisit and readmission patterns within 30 days of the surgery were extracted and analysed. RESULTS: Of these children (mean age = 7.2 years; males = 72%), 49 (8.0%) had first ER revisit, nine (1.5%) had second ER revisits, and one (0.2%) had third ER revisits. Reasons for ER revisits were bleeding related (46%) or non-bleeding related (54%). The timing for revisits was 6.9±1.9 postoperative days for bleeding-related revisits and 9.3±10.0 days for non-bleeding-related revisits. Treatment strategies during these revisits were treat and release in 44 children (74.6%), admission for observation in eight children (13.5%), and admission for surgery in seven children (11.9%). The incidence of ER revisit and hospital readmission was similar among children with all levels of SDB severity. Multivariable logistic regression analysis showed that young children (<3 years) experienced an increased risk of non-bleeding-related revisits (odds ratio [OR] = 4.1). CONCLUSIONS: Children with severe SDB do not experience increased risks of revisit or readmission; however, young children are at increased risk of non-bleeding-related revisits.

Cooling-evoked hemodynamic perturbations facilitate sympathetic activity with subsequent myogenic vascular oscillations via alpha2-adrenergic receptors.

This study extends our previous work by examining the effects of alpha2-adrenoceptors under cold stimulation involving the increase of myogenic vascular oscillations as increases of very-low-frequency and low-frequency of the blood pressure variability. Forty-eight adult male Sprague-Dawley rats were randomly divided into four groups: vehicle; yohimbine; hexamethonium+yohimbine; guanethidine+yohimbine. Systolic blood pressure, heart rate, power spectral analysis of spontaneous blood pressure and heart rate variability and spectral coherence at very-low-frequency (0.02 to 0.2 Hz), low-frequency (0.2 to 0.6 Hz), and high-frequency (0.6 to 3.0 Hz) regions were monitored using telemetry. Key findings are as follows: 1) Cooling-induced pressor response was attenuated by yohimbine and further attenuated by hexamethonium+yohimbine and guanethidine+yohimbine, 2) Cooling-induced tachycardia response of yohimbine was attenuated by hexamethonium+yohimbine and guanethidine+yohimbine, 3) Different patterns of power spectrum reaction and coherence value compared hexamethonium+yohimbine and guanethidine+yohimbine to yohimbine alone under cold stimulation. The results suggest that sympathetic activation of the postsynaptic alpha2-adrenoceptors causes vasoconstriction and heightening myogenic vascular oscillations, in turn, may increase blood flow to prevent tissue damage under stressful cooling challenge.

Integrative epigenome analysis identifies a Polycomb-targeted differentiation program as a tumor-suppressor event epigenetically inactivated in colorectal cancer.

Aberrant DNA hypermethylation in human cancer has been associated with Polycomb target genes in embryonic stem (ES) cells, but a functional link of the Polycomb-targeted differentiation program to tumorigenesis remains to be established. Here, through epigenome analysis correlating DNA hypermethylation in colon cancer with ES cell pluripotency and differentiation, we identified a set of DNA hypermethylated genes in cancer cells that are Polycomb targets strongly associated with ES cell differentiation, including HAND1, a developmental regulator. Intriguingly, HAND1 is silenced in over 90% of human primary colorectal tumors, and re-expression of HAND1 in colon cancer cells induces terminal differentiation, inhibits proliferation and prevents xenograft tumor formation. Moreover, hypermethylated HAND1 has a minimum enrichment of EZH2-H3K27me3 in cancer cells, but becomes EZH2 bound and bivalent upon the loss of DNA methylation, suggesting a sequential gene silencing event during oncogenesis. These findings established a functional role of Polycomb-targeted differentiation program as a tumor-suppressor event epigenetically inactivated in human cancer.

exomeSuite: Whole exome sequence variant filtering tool for rapid identification of putative disease causing SNVs/indels.

Exome and whole-genome analyses powered by next-generation sequencing (NGS) have become invaluable tools in identifying causal mutations responsible for Mendelian disorders. Given that individual exomes contain several thousand single nucleotide variants and insertions/deletions, it remains a challenge to analyze large numbers of variants from multiple exomes to identify causal alleles associated with inherited conditions. To this end, we have developed user-friendly software that analyzes variant calls from multiple individuals to facilitate identification of causal mutations. The software, termed exomeSuite, filters for putative causative variants of monogenic diseases inherited in one of three forms: dominant, recessive caused by a homozygous variant, or recessive caused by two compound heterozygous variants. In addition, exomeSuite can perform homozygosity mapping and analyze the variant data of multiple unrelated individuals. Here we demonstrate that filtering of variants with exomeSuite reduces datasets to a fraction of a percent of their original size. To the best of our knowledge this is the first freely available software developed to analyze variant data from multiple individuals that rapidly assimilates and filters large data sets based on pattern of inheritance.

The relationship between memory complaints, activity and perceived health status.

Subjective memory complaints (SMC) is a possible symptom of mild cognitive impairment which may progress to dementia. The present study examines the relationship of physical activity (PA), cognitive activity (CA), social activity (SA), and perceived health status (HS) with SMC for middle age and older adults. Participants were from the MIDUS II study (Midlife in the United States) recruited in 2004-2006 (Mean age = 55.99; N = 3030). Hierarchical multiple regression was performed with SMC as the dependent variable, along with PA, CA, SA, and HS as the independent variables. The study revealed that SMC was strongly related to PA, CA, and HS, while controlling covariates. Further, HS had the strongest link with SMC among these predictors while interaction effects (PA × HS, CA × HS, and SA × HS) were insignificant. In addition, different results were achieved in younger versus older groups. Participants with more CA, PA and perception of better health had lower frequency of memory complaints.

Central sleep apnea in obese children with sleep-disordered breathing.

OBJECTIVES: In contrast to obstructive sleep apnea (OSA), central sleep apnea (CSA) in obese children has received lesser attention. As pediatric CSA is more prevalent than expected and adversely impacts health, this study aims to elucidate the major factors associated with central apnea index (CAI) and compare CSA between obese and non-obese children. METHODS: Retrospective analysis was performed in a tertiary referral medical center. Children with sleep-disordered breathing (SDB) ranging from 2-18 years old were enrolled. All participants completed history taking, otolaryngological examination and overnight polysomnography. CSA was defined as having CAI exceeding 1 h(-1). CAI and the prevalence of CSA were analyzed in children of different age groups, weight statuses and adenotonsillar sizes. RESULTS: A total of 487 cases were included. The prevalence of CSA was 13.3% (65/487). CAI was negatively correlated with age (r=-0.32, P<0.001). Obese children had a significantly lower CAI than that of non-obese ones (0.20 ± 0.36 vs 0.48 ± 0.82 h(-1), P<0.001). Multiple linear regression analysis demonstrated a relationship between CAI, age and obesity as 'CAI=0.883-0.055 × Age -0.22 × (Obesity)'. CONCLUSIONS: In children with SDB, younger ones have a significantly higher CAI than older ones. Additionally, obese children had a lower CAI than non-obese ones.

BMP receptor-integrin interaction mediates responses of vascular endothelial Smad1/5 and proliferation to disturbed flow.

BACKGROUND: Vascular endothelial cells (ECs) are constantly exposed to blood flow-induced shear stress. Our previous study demonstrated that disturbed flow with low and oscillatory shear stress (OSS) induces bone morphogenetic protein receptor (BMPR)-specific Smad1/5 activation in ECs, but the underlying mechanisms and the in vivo functional role of Smad1/5 remain unclear. OBJECTIVES: Here we elucidated the molecular mechanisms by which OSS activates EC Smad1/5 and its in vivo functional role. METHODS: Lentiviral Smad5-specific short hairpin RNA (Lenti-shSmad5) was constructed and intra-arterially injected into the lumen of stenosed abdominal aorta in bromodeoxyuridine-infused rats. Co-immunoprecipitation and in situ proximity ligation assays were performed on ECs exposed to OSS (0.5 ± 4 dynes/cm(2) ) in a parallel-plate flow chamber to investigate BMPR-integrin interactions and their regulatory role in OSS-activation of EC Smad1/5. RESULTS: Intra-arterial administration of Lenti-shSmad5 inhibited bromodeoxyuridine uptake of ECs at post-stenotic sites, where disturbed flow with OSS occurs. OSS induced sustained BMPRIB-αv ß3 integrin association in ECs, which was mediated by the intracytoplasmic kinase domain of BMPRII and subsequently activated the Shc/focal adhesion kinase (FAK)/extracellular signal-regulated kinase (ERK) cascade, leading to Smad1/5 activation. This OSS-activation of Smad1/5 induced its association with and activation of runt-related transcription factor-2 (Runx2), leading to activations of mammalian target of rapamycin (mTOR) and p70S6 kinase (p70S6K), a pathway critical for EC proliferation in response to OSS. CONCLUSIONS: Oscillatory shear stress induces synergistic interactions between specific BMPRs and integrin to activate Smad1/5 through the Shc/FAK/ERK pathway, which leads to the activation of the Runx2/mTOR/p70S6K pathway to promote EC proliferation.

Impacts of body weight after surgery for obstructive sleep apnea in children.

OBJECTIVE: To investigate the impacts of body weight status on surgical outcomes and shifts of body weight status after adenotonsillectomy(T&A) in children with obstructive sleep apnea (OSA). METHODS: From 2009 to 2011, 161 children (mean age, 7.0 ± 3.4 years; 78% boys) were included. All the children had clinical symptoms and preoperative polysomnographic evaluations diagnosis of OSA. Children were divided into four weight status groups (underweight, normal weight, overweight and obese), based on age and gender corrected body mass index (BMI). RESULTS: Following T&A, the four different weight status groups significantly improved in apnea/hypopnea index (AHI) and minimum oxygen saturation. However, 49.1% of the children (79/161) had residual OSA (AHI ≥ 1). The incidence of residual OSA (AHI ≥ 1) in the obese group was 75%, which was significantly higher than the other three groups (P<0.01). Weight status changes after T&A were documented, and 54% (13/24) of the underweight children shifted to normal weight status within 6 months after surgery. CONCLUSION: Although sleep parameters improved in all weight statuses, obese children had a higher incidence of residual OSA postoperatively. About half of the underweight children shifted to normal weight status after T&A.

Body weight status and obstructive sleep apnea in children.

OBJECTIVE: The relationship between weight status, adenotonsillar hypertrophy and obstructive sleep apnea (OSA) in children has not yet been well studied. As the sleep parameters may show a disparity in different weight statuses, this study examined the relationship between the data of over-night polysomnography and different weight statuses, as well as the impact of adenotonsillar hypertrophy on children with OSA. METHODS: Children with sleep disturbances were recruited from our clinics. Standard physical examinations, history taking, lateral neck roentgenography, and full-night polysomnography were obtained. Children were divided into four groups based on the age- and gender-corrected body mass index (BMI): underweight, normal weight, overweight and obese. An adenoidal/nasopharyngeal ratio of more than 0.67 was considered adenoidal hypertrophy. Tonsillar hypertrophy was defined as having Grade III tonsils or above. RESULTS: From July 2006 to January 2009, 197 children were included in this study. Obese children had a significantly higher apnea-hypopnea index (AHI), obstructive apnea index and lower minimum oxygen saturation (MinSaO(2)) than those of the other groups. Underweight children had the second highest AHI. A negative correlation was also found between BMI z scores and MinSaO(2) (r = -0.194; P = 0.007). Children with tonsillar hypertrophy (P = 0.001) were associated with a higher risk of having OSA. The risk of having OSA was significantly higher in obese children (P = 0.001) and underweight children (P = 0.043) than in those with a normal weight. CONCLUSION: Obesity, underweight status and tonsillar hypertrophy are associated with children having OSA, and obese children have a significantly higher risk than children with underweight status.

Polycomb protein EZH2 regulates cancer cell fate decision in response to DNA damage.

Polycomb protein histone methyltransferase enhancer of Zeste homologe 2 (EZH2) is frequently overexpressed in human malignancy and is implicated in cancer cell proliferation and invasion. However, it is largely unknown whether EZH2 has a role in modulating DNA damage response. Here, we show that EZH2 is an important determinant of cell fate decision in response to genotoxic stress. EZH2 depletion results in abrogation of both cell cycle G1 and G2/M checkpoints, directing DNA damage response toward predominant apoptosis in both p53-proficient and p53-deficient cancer cells, but not in normal cells. Mechanistically, EZH2 regulates DNA damage response in p53 wild-type cells mainly through transcriptional repression of FBXO32, which binds to and directs p21 for proteasome-mediated degradation, whereas it affects p53-deficient cells through regulating Chk1 activation by a distinct mechanism. Furthermore, pharmacological depletion of EZH2 phenocopies the effects of EZH2 knockdown on cell cycle checkpoints and apoptosis. These data unravel a crucial role of EZH2 in determining the cancer cell outcome following DNA damage and suggest that therapeutic targeting oncogenic EZH2 might serve as a strategy for improving conventional chemotherapy in a given malignancy.

Inspiratory muscle dysfunction in patients with severe obstructive sleep apnoea.

Repetitive inspiratory effort against an obstructed airway and intermittent hypoxia may be deleterious to the inspiratory muscles in patients with obstructive sleep apnoea (OSA). We investigated muscular dysfunction by comparing the strength, endurance and fatigability of inspiratory muscles and knee extensors in patients with newly diagnosed severe OSA compared with matched controls. The measurements included strength and endurance tests of both muscles, and a fatigue trial with simultaneous surface electromyography of the diaphragm and the vastus lateralis during voluntary contractions and in response to magnetic stimulation. To our knowledge, this is the first investigation to assess peripheral muscle performance in severe OSA patients versus controls. Patients in the OSA group exhibited significantly lower strength and endurance in both muscles than the control group. The fatigue index decreased significantly exclusively in the inspiratory muscles of OSA patients. Magnetic stimulation-evoked compound muscle action potential latencies increased and the amplitudes decreased significantly in the diaphragm, but not in the vastus lateralis after a fatigue test in the OSA group. In conclusion, a significantly lower functional performance was shown for both inspiratory muscles and knee extensors in the OSA group. However, higher fatigability was only seen in the inspiratory muscles of patients with severe OSA.

Polymorphisms and mutations of human TMPRSS6 in iron deficiency anemia.

Male subjects with iron deficiency from the general population were examined for polymorphisms or sporadic mutations in TMPRSS6 to identify genetic risk factors for iron deficiency anemia. Three uncommon non-synonymous polymorphisms were identified, G228D, R446W, and V795I (allele frequencies 0.0074, 0.023 and 0.0074 respectively), of which the R446W polymorphism appeared to be overrepresented in the anemic population. In addition, three children with iron refractory iron deficiency anemia, and one sibling with iron responsive iron deficiency anemia were also examined for polymorphisms or sporadic mutations in TMPRSS6. Two children (family 1) were compound heterozygotes for a L674F mutation and a previously described splicing defect predicted to cause skipping of exon 13 (IVS13+1 G>A). One child from the second family was homozygous for a deletion (497T) causing a frameshift (L166X+36) and premature termination. The sibling and mother from the second family were compound heterozygotes for the L166X mutation and the uncommon R446W polymorphism. Although in vitro expression studies demonstrated that the R446W isoform was biologically similar to wildtype Tmprss6, clinical data indicate that the R446W produces a milder disease when carried in trans with severe mutation in Tmprss6. The four children carrying mutations in TMPRSS6 all exhibited inappropriately high urinary hepcidin levels for the degree of iron deficiency.

Early age-of-onset iron overload and homozygosity for the novel hemojuvelin mutation HJV R54X (exon 3; c.160A-->T) in an African American male of West Indies descent.

An African American male of West Indies descent was diagnosed to have elevated transferrin saturation, hyperferritinemia, severe iron deposition in hepatocytes, and hepatic cirrhosis at age 4. He was treated with serial phlebotomy to maintain a normal serum ferritin concentration thereafter. We evaluated him at age 23 and confirmed that he had normal serum ferritin levels, severe iron deposition in hepatocytes, hepatic cirrhosis, and portal hypertension. He did not have endocrinopathy, cardiomyopathy, or arthropathy. He was homozygous for the novel hemojuvelin (HJV) premature stop-codon mutation R54X (exon 3; c.160A-->T). He did not have either HFE C282Y, H63D, or S65C, or deleterious coding region mutations of SLC40A1, TFR2, or HAMP. His erythrocyte measures and hemoglobin electrophoresis were consistent with alpha-thalassemia trait. We conclude that homozygosity for HJV R54X accounts for his severe, early age-of-onset hemochromatosis; his phenotype was probably modified by serial phlebotomy therapy.

In vivo monitoring of multiple trace metals in the brain extracellular fluid of anesthetized rats by microdialysis-membrane desalter-ICPMS.

We have developed an on-line analytical system involving microdialysis (MD) sampling, a carbohydrate membrane desalter (CMD), and an inductively coupled plasma mass spectrometer (ICPMS) system for the simultaneous determination of multiple trace metals in the extracellular fluid (ECF) in the brains of anesthetized rats. The microdialysate that perfused from the animal at a flow rate of 0.5 microL/min was on-line transferred to the CMD to remove the high-sodium matrix, followed by ICPMS measurement. The role of the CMD in this on-line system was investigated in detail. With prior addition of EDTA to the microdialysate to form anionic complexes of the metal analytes and the use of NH4Cl as a regenerant to exchange Na(+) with NH4(+) ions, both quantitative recovery of the trace metal analytes and quantitative removal of the sodium matrix could be achieved. Two experimental modes of the monitoring system were constructed. For those metals (e.g., Cu, Zn, and Mn) that existed at (sub)nanogram-per-milliliter concentrations in the microdialysate, the temporal resolution was 10 min when using a 10 microL loop for sample collection, followed by CMD and ICPMS; for those elements (e.g., Ca and Mg) that existed at microgram-per-milliliter levels (or greater), near-real-time analysis was possible because the microdialysate could be led, bypassing the sample loop, directly to the CMD for desalting without any time delay. Further improvement of the temporal resolution for the low-concentration elements was not possible without decreasing the detection limits of mass detection. Among the eight trace metals tested using this on-line system, the method detection limits for Cu, Zn, Mn, Co, Ni, and Pb reached subnanogram-per-milliliter levels; for electrolyte species such as Ca and Mg, the detection limits were in the range of 50-100 ng/mL. Analytical accuracy, expressed as spike recovery, was 100% +/- 15% for all of the elements tested. We demonstrate the applicability of the proposed system through the successful measurement of the basal values of Ca, Mg, Cu, Zn, and Mn in the ECF of a living rat brain and through in vivo monitoring of the concentration profiles of Mn and Pt in the ECF after the injection of drugs (MnCl2 and cisplatin) into the rats. This microdialysis system is the first to offer real-time, in vivo monitoring of trace elements such as Ca and Mg.

Effects of vitamin E supplementation on bone metabolism in nicotine-treated rats.

INTRODUCTION: Nicotine has been shown to exert negative effects on bone. This study determined whether vitamin E supplementation is able to repair the nicotine-induced adverse effects in bone. METHODS: 24 male rats were divided into three groups. The fi rst group was the baseline control and killed untreated at the beginning of the study. Groups 2 and 3 received nicotine at 7 mg per kg for three months but during the second and third months, group 2 was supplemented with alpha-tocopherol (N+ATF) while group 3 was given palm tocotrienol mixture (N+TT). Serum interleukin-1 (IL-1), serum interleukin-6 (IL-6), serum osteocalcin, urine deoxypyridinoline (DPD) and bone calcium content were measured. RESULTS: Palm tocotrienol mixture was able to prevent the increment of IL-1 and IL- 6 due to nicotine treatment. No changes were seen in the osteocalcin levels, but the N+ATF group had lower urine DPD levels after treatment. However, bone-remodelling index revealed no significant changes. No significant differences were seen in the femoral bone calcium content results, although the fourth lumbar bone calcium content was reduced in both groups with 66.5 percent reduction in the N+ATF group and 59.6 percent reduction in the N+TT group. CONCLUSION: Palm tocotrienol mixture was better than alpha-tocopherol in reversing the effects of nicotine on IL-1 and IL-6. Both forms of vitamin E were not able to restore the nicotine-induced bone calcium loss, but the N+ATF group suffered a greater loss. Tocotrienol seemed to be superior to alpha-tocopherol in combating against the adverse effect of nicotine.

Polyamorphism in a metallic glass.

A metal, or an alloy, can often exist in more than one crystal structure. The face-centred-cubic and body-centred-cubic forms of iron (or steel) are a familiar example of such polymorphism. When metallic materials are made in the amorphous form, is a parallel 'polyamorphism' possible? So far, polyamorphic phase transitions in the glassy state have been observed only in glasses involving directional and open (such as tetrahedral) coordination environments. Here, we report an in situ X-ray diffraction observation of a pressure-induced transition between two distinct amorphous polymorphs in a Ce(55)Al(45) metallic glass. The large density difference observed between the two polyamorphs is attributed to their different electronic and atomic structures, in particular the bond shortening revealed by ab initio modelling of the effects of f-electron delocalization. This discovery offers a new perspective of the amorphous state of metals, and has implications for understanding the structure, evolution and properties of metallic glasses and related liquids. Our work also opens a new avenue towards technologically useful amorphous alloys that are compositionally identical but with different thermodynamic, functional and rheological properties due to different bonding and structural characteristics.

Zero thermal expansion in a nanostructured inorganic-organic hybrid crystal.

There are very few materials that exhibit zero thermal expansion (ZTE), and of these even fewer are appropriate for electronic and optoelectronic applications. We find that a multifunctional crystalline hybrid inorganic-organic semiconductor, beta-ZnTe(en)(0.5) (en denotes ethylenediamine), shows uniaxial ZTE in a very broad temperature range of 4-400 K, and concurrently possesses superior electronic and optical properties. The ZTE behavior is a result of compensation of contraction and expansion of different segments along the inorganic-organic stacking axis. This work suggests an alternative route to designing materials in a nanoscopic scale with ZTE or any desired positive or negative thermal expansion (PTE or NTE), which is supported by preliminary data for ZnTe(pda)(0.5) (pda denotes 1,3-propanediamine) with a larger molecule.