Validity of estimating muscle and fat volume from a single MRI section in older adults with sarcopenia and sarcopenic obesity.

AIM: To determine if there is a correlation between the cross-sectional areas (CSAs) in a single section and the volumes of muscles and fat in the thigh of sarcopenic and sarcopenic obesity (SO) populations using magnetic resonance imaging (MRI), and to assess the correlation between thigh MRI data and patient health status, i.e., normal, obese, sarcopenia, and SO. MATERIALS AND METHODS: One hundred and ninety community-dwelling older adults were recruited and categorised into four subgroups based on Asian established criteria: normal, obese, sarcopenia, and SO. MRI images were acquired and muscles, subcutaneous fat (SF), and intermuscular fat (IMF) were automatically segmented in the thighs. Volumes of muscles and fat were calculated for the middle third of the thigh, while CSAs were assessed using a single section at 50% femur length. RESULTS: Correlation between CSA and volume were significantly high (p<0.001) for all components of muscle (0.907), SF (0.963), and IMF (0.939). Thigh CSA and volume both correlated significantly with a clinical diagnosis of normal, obesity, sarcopenia, and SO (p<0.03). CONCLUSIONS: A single CSA at 50% of femur length yields good estimation of muscle and fat volume in the thighs of older adults and correlates closely with the clinical criteria for sarcopenia and SO. This has the potential to greatly reduce costs, scan time, and post-processing time in clinical practice for the prediction of these conditions.

Controlling the Spin Texture of Topological Insulators by Rational Design of Organic Molecules.

We present a rational design approach to customize the spin texture of surface states of a topological insulator. This approach relies on the extreme multifunctionality of organic molecules that are used to functionalize the surface of the prototypical topological insulator (TI) Bi2Se3. For the rational design we use theoretical calculations to guide the choice and chemical synthesis of appropriate molecules that customize the spin texture of Bi2Se3. The theoretical predictions are then verified in angular-resolved photoemission experiments. We show that, by tuning the strength of molecule-TI interaction, the surface of the TI can be passivated, the Dirac point can energetically be shifted at will, and Rashba-split quantum-well interface states can be created. These tailored interface properties-passivation, spin-texture tuning, and creation of hybrid interface states-lay a solid foundation for interface-assisted molecular spintronics in spin-textured materials.

Initial Experience With Robotic-Assisted Otologic and Lateral Skull Base Surgery.

Robotic-assisted surgery has gained popularity for otolaryngology procedures. It provides high-definition images and surgical precision to perform diverse procedures. It is an alternative to the operating microscope, endoscope, or exoscope when reaching hidden anatomical structures in the ear. In this proof-of-concept study, we aim to demonstrate the possibility of using a robotic-assisted device to perform ear surgery in conjunction with the microscope or the endoscope. In total, there were 9 ear and lateral skull base procedures performed with the use of robotic-assisted surgery. All surgeons underwent surveys to assess the performance and workload of the device compared to the microscope or endoscope. There were no postoperative complications. Robotic-assisted surgery was optimal for providing high image quality, ergonomics, and maintaining surgical performance. The size of the device and mental demand were higher compared to the microscope or endoscope. Robotic-assisted surgery can be an adjuvant to perform otologic and neurotologic surgery.

Social Frailty and Executive Function: Association with Geriatric Syndromes, Life Space and Quality of Life in Healthy Community-Dwelling Older Adults.

BACKGROUND: Despite emerging evidence about the association between social frailty and cognitive impairment, little is known about the role of executive function in this interplay, and whether the co-existence of social frailty and cognitive impairment predisposes to adverse health outcomes in healthy community-dwelling older adults. OBJECTIVES: We aim to examine independent associations between social frailty with the MMSE and FAB, and to determine if having both social frailty and cognitive impairment is associated with worse health outcomes than either or neither condition. METHODS: We studied 229 cognitively intact and functionally independent community-dwelling older adults (mean age= 67.2±7.43). Outcome measures comprise physical activity; physical performance and frailty; geriatric syndromes; life space and quality of life. We compared Chinese Mini Mental State Examination (CMMSE) and Chinese Frontal Assessment Battery (FAB) scores across the socially non-frail, socially pre-frail and socially frail. Participants were further recategorized into three subgroups (neither, either or both) based on presence of social frailty and cognitive impairment. Cognitive impairment was defined as a score below the educational adjusted cut-offs in either CMMSE or FAB. We performed logistic regression adjusted for significant covariates and mood to examine association with outcomes across the three subgroups. RESULTS: Compared with CMMSE, Chinese FAB scores significantly decreased across the social frailty spectrum (p<0.001), suggesting strong association between executive function with social frailty. We derived three subgroups relative to relationship with socially frailty and executive dysfunction: (i) Neither, N=140(61.1%), (ii) Either, N=79(34.5%), and (iii) Both, N=10(4.4%). Compared with neither or either subgroups, having both social frailty and executive dysfunction was associated with anorexia (OR=4.79, 95% CI= 1.04-22.02), near falls and falls (OR= 5.23, 95% CI= 1.10-24.90), lower life-space mobility (odds ratio, OR=9.80, 95% CI=2.07-46.31) and poorer quality of life (OR= 13.2, 95% CI= 2.38-73.4). CONCLUSION: Our results explicated the association of executive dysfunction with social frailty, and their synergistic relationship independent of mood with geriatric syndromes, decreased life space and poorer quality of life. In light of the current COVID-19 pandemic, the association between social frailty and executive dysfunction merits further study as a possible target for early intervention in relatively healthy older adults.

Disentangling the Relationship between Frailty and Intrinsic Capacity in Healthy Community-Dwelling Older Adults: A Cluster Analysis.

BACKGROUND: Frailty and intrinsic capacity (IC) are distinct but interrelated constructs. Uncertainty remains regarding how they are related and interact to influence health outcomes. We aim to understand the relationship between frailty and IC by identifying subgroups based on frailty criteria and IC domains and studying one-year outcomes. METHODS: We studied 200 independent community-dwelling older adults (mean age 67.9±7.9 years, Modified Barthel Index (MBI) score 99±2.6). Frailty was defined by modified Fried criteria. Scores (range: 0-2) were assigned to individual IC domains (cognition, psychological, locomotion, and vitality) to yield a total IC score of 8. To identify subgroups, two-step cluster analysis was performed with age, frailty and IC domains. Cluster associations with one-year outcomes (frailty, muscle strength (grip strength, repeated chair stand test), physical performance (gait speed, Short Physical Performance Battery), function (MBI) and quality-of-life (EuroQol (EQ)-5D)) were examined using multiple linear regression adjusted for age, gender and education. RESULTS: Three distinct clusters were identified - Cluster 1: High IC/Robust (N=74, 37%); Cluster 2: Intermediate IC/Prefrail (N=73, 36.5%); and Cluster 3: Low IC/Prefrail-Frail (53, 26.5%). Comparing between clusters, IC domains, cognition, depressive symptoms, nutrition, strength and physical performance were least impaired in Cluster 1, intermediate in Cluster 2 and most impaired in Cluster 3. At one year, the proportion transitioning to frailty or remaining frail was highest in Cluster 3 compared to Cluster 2 and Cluster 1 (39% vs 6.9% vs 2.8%, P<0.001). Compared to Cluster 1, Cluster 3 experienced greatest declines in grip strength (ß=-4.1, P<.001), MBI (ß=-1.24, P=0.045) and EQ-5D utility scores (ß=-0.053, P=0.005), with Cluster 2 intermediate between Cluster 1 and Cluster 3. CONCLUSIONS: Amongst independent community-dwelling older adults, IC is complementary to frailty measures through better risk-profiling of one-year outcomes amongst prefrail individuals into intermediate and high-risk groups. The intermediate group merits follow-up to ascertain longer-term prognosis.

Grip Strength Criterion Matters: Impact of Average Versus Maximum Handgrip Strength on Sarcopenia Prevalence and Predictive Validity for Low Physical Performance.

IMPORTANCE: Muscle strength has been elevated to the forefront of sarcopenia diagnosis, with handgrip strength the preferred measure. Extant handgrip protocols adopt different handgrip strength (HGS) criteria. Paucity of direct comparison studies assessing the impact of HGS criterion on prevalence of sarcopenia and predictive validity on physical performance contributes to the lack of standardisation of HGS criteria in sarcopenia diagnosis. OBJECTIVES: Our study aims to compare the effect of average (HGSave) versus maximum (HGSmax) HGS criterion on: (1) prevalence of low HGS and sarcopenia; and (2) association with physical performance at baseline and at 2 years. METHODS: We recruited 200 community dwelling, cognitively intact, and functionally independent older adults. Muscle strength, physical performance measures, cognitive tests and nutritional assessments were performed. Short Physical Performance Battery (SPPB) was administered at baseline and at 2 years. We compared HGSave and HGSmax to assess the prevalence of low HGS and sarcopenia. Univariate analysis was performed comparing baseline characteristics between low and normal groups for each HGS criterion. Significantly different variables were included in logistic regression analysis to examine association of low HGS and SPPB at baseline. Predictive validity of low HGS for SPPB<10 at 2 years was examined by performing logistic regression analysis for HGSave and HGSmax. RESULTS: The prevalence of low HGS and sarcopenia incorporating HGSave criterion is 40% and 33% respectively, whereas that of HGSmax criterion is 21% and 19.5% respectively. There is moderate agreement between the 2 HGS criteria for sarcopenia diagnosis (kappa=0.604) and poorer agreement for low HGS (kappa=0.570). There was no significant association with baseline SPPB for both HGS criteria. At 2 years, only low HGSmax was significantly associated with low SPPB (adjusted OR 3.91, 95% CI 1.24 - 12.33). CONCLUSION: Our study demonstrates that HGS criteria matters in diagnosis of sarcopenia and we support extant HGS protocols using HGSmax criterion in view of better predictive validity for poor physical performance.

Obesity Definitions in Sarcopenic Obesity: Differences in Prevalence, Agreement and Association with Muscle Function.

BACKGROUND: Sarcopenic obesity (SO) is associated with poorer physical performance in the elderly and will increase in relevance with population ageing and the obesity epidemic. The lack of a consensus definition for SO has resulted in variability in its reported prevalence, poor inter-definitional agreement, and disagreement on its impact on physical performance, impeding further development in the field. While sarcopenia definitions have been compared, the impact of obesity definitions in SO has been less well-studied. OBJECTIVES: To compare 3 widely-adopted definitions of obesity in terms of SO prevalence, inter-definitional agreement, and association with muscle function. DESIGN: Cross-sectional. SETTING: GERILABS study, Singapore Participants: 200 community-dwelling, functionally-independent older adults. MEASUREMENTS: We utilized three commonly-used definitions of obesity: body mass index (BMI), waist circumference (WC) and DXA-derived fat mass percentage (FM%). Sarcopenia was defined using Asian Working Group for Sarcopenia criteria. For muscle function, we assessed handgrip strength, gait speed and Short Physical Performance Battery (SPPB). Subjects were classified into 4 body composition phenotypes (normal, obese, sarcopenic and SO), and outcomes were compared between groups. RESULTS: The prevalence rate for SO was lowest for BMI (0.5%) compared to FM% (10.0%) and WC (10.5%). Inter-definitional agreement was lowest between BMI and WC (κ=0.364), and at best moderate between FM% and WC (κ=0.583). SO performed the worst amongst body composition phenotypes in handgrip strength, gait speed and SPPB (all p<0.01) only when defined using WC. In regression analyses, SO was associated with decreased SPPB scores (ß=-0.261, p=0.001) only for the WC definition. CONCLUSION: There is large variation in the prevalence of SO across different obesity definitions, with low-to-moderate agreement between them. Our results corroborate recent evidence that WC, and thus central obesity, is best associated with poorer muscle function in SO. Thus, WC should be further explored in defining obesity for accurate and early characterization of SO among older adults in Asian populations.

Muscle Strength Definitions Matter: Prevalence of Sarcopenia and Predictive Validity for Adverse Outcomes Using the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) Criteria.

BACKGROUND: EWGSOP2 criteria for sarcopenia recommends the use of either handgrip strength (GS) or 5-times repeated chair stand test (RCS) as a muscle strength measure. We aim to compare the impact of different muscle strength definitions on sarcopenia prevalence and predictive validity for 2-year outcomes, using the EWGSOP2 clinical algorithm. METHODS: We studied 200 community-dwelling older adults, comparing sarcopenia prevalence using three muscle strength definitions: 1) maximum GS (Asian Working Group cutoffs); 2) RCS-1 (standard cutoff >15s); and 3) RCS-2 (ROC-derived cutoff >12.5s). Two-year outcomes include: 1) Incident frailty (modified Fried criteria); 2) Physical performance [Short Physical Performance Battery (SPPB) score <10]; and 3) Quality of life [EuroQol-5 dimension (EQ-5D) <25th percentile]. We performed logistic regression on 2-year outcomes adjusted for age, gender, cognition and mood. RESULTS: Prevalence of confirmed sarcopenia was 14.5%, 4% and 9% for GS, RCS-1 and RCS-2 respectively. For 2-year outcomes (N=183), RCS-2 predicted incident frailty (OR: 5.7, 95% CI 1.4-22.8, p=0.013), low SPPB (OR: 4.4, 95% CI 1.4-13.1, p=0.009), and trended towards predicting low QOL (OR: 2.1, 95% CI 0.9-4.9, p=0.095). In contrast, GS and RCS-1 did not predict frailty nor low QOL, but predicted low SPPB only (GS: OR 3.8, 95% CI 1.3-10.6, p=0.01; RCS-1: OR: 8.8, 95% CI 2.2-35.0, p=0.002). CONCLUSIONS: Sarcopenia prevalence varies with muscle strength definitions, with GS being significantly higher vis-à-vis RCS definitions. Our results also support the use of population-specific over standard cutoffs for RCS to obtain intermediate estimates of sarcopenia prevalence and the best predictive validity for two-year outcomes.

Evaluation of an Electrochemiluminescent SARS-CoV-2 Antibody Assay.

BACKGROUND: Little is known about the performance of the Roche novel severe acute respiratory syndrome coronavirus 2 antibody (anti-SARS-CoV-2) assay. We provide an extensive evaluation of this fully automated assay on Cobas e801/e602 immunoassay analyzers. METHODS: We assessed the linearity, precision, and throughput of the Roche anti-SARS-CoV-2 assay. Sensitivity was calculated from 349 SARS-CoV-2 polymerase chain reaction (PCR) positive samples; specificity was determined from 715 coronavirus disease 2019 (COVID-19)-naive samples. We examined cross-reactivity against other antibody positive samples [syphilis, rheumatoid factor (RF), antinuclear antibody (ANA), double-stranded DNA (ds-DNA), influenza, dengue, hepatitis B (HBV), hepatitis C (HCV)] and the anti-SARS-CoV-2 kinetics. RESULTS: The assay cut-off index (COI) was linear up to 90.8. The interassay precision was 2.9% for a negative control (COI = 0.1) and 5.1% for a positive control (COI = 3.0). Assay time is 18 min and results are available 1 min later; throughput for 300 samples was 76 min. Only 1 case positive for HBsAg tested falsely positive; specificity was 99.9%. The assay has a sensitivity of 97.1% 14 days after PCR positivity (POS) and 100% at ≥21 days POS; 48.2% of cases had anti-SARS-CoV-2 within 6 days POS. In 11 patients in whom serum was available prior to a positive antibody signal (COI ≥1.0) the interval between the last negative and first positive COI (time to "seroconversion") on average is 3 days (range 1-6 days) and 4 more days (range 1-7) for the anti-SARS-CoV-2 to plateau. CONCLUSION: The Roche anti-SARS-CoV-2 assay shows excellent performance with minimal cross-reactivity from other viral and confounding antibodies. Antibody development and seroconversion appears quite early.

Serum Myostatin and IGF-1 as Gender-Specific Biomarkers of Frailty and Low Muscle Mass in Community-Dwelling Older Adults.

OBJECTIVES: (i) To investigate serum myostatin (absolute and normalized for total body lean mass (TBLM)) and IGF-1 as biomarkers of frailty and low relative appendicular skeletal muscle mass (RASM) in older adults, and; (ii) to examine gender differences in the association of serum myostatin and IGF-1 levels with frailty and low RASM. DESIGN: Cross-sectional study. SETTING: The "Longitudinal Assessment of Biomarkers for characterization of early Sarcopenia and predicting frailty and functional decline in community-dwelling Asian older adults Study" (GERI-LABS) study in Singapore. PARTICIPANTS: 200 subjects aged 50 years and older residing in the community. MEASUREMENTS: Frailty was assessed using the modified Fried criteria. Low RASM was defined using cutoffs for height-adjusted appendicular skeletal muscle mass measured by dual-energy X-ray absorptiometry as recommended by the Asian Working Group for Sarcopenia. Comorbidities, cognitive and functional performance, physical activity and nutritional status were assessed. Blood samples collected included serum myostatin, insulin-like growth factor 1 (IGF-1) and markers of inflammation (total white cell count, CRP, IL-6 and TNFaR1). Subjects were classified into 4 groups: Frail/Prefrail with low RASM (Frail/Low RASM), Frail/Prefrail with normal RASM (Frail/Normal RASM), Robust with low RASM (Robust/Low RASM) and Robust with normal RASM (Robust/Normal RASM). RESULTS: 63 (32%) subjects were classified as Frail/Low RASM, 53 (27%) Frail/Normal RASM, 28 (14%) Robust/Low RASM and 56 (28%) Robust/Normal RASM respectively. Frail/Low RASM subjects were older and had lower BMI compared to Frail/Normal RASM and robust subjects. Mean (SE) normalized myostatin levels were higher in Frail/Low RASM compared to Frail/Normal RASM subjects (1.0 (0.04) versus 0.84 (0.05) ng/ml/kg, P=0.01). Median (IQR) IGF-1 level was lower amongst Frail/Low RASM subjects compared to Frail/Normal RASM subjects (102.3, (77.7, 102.5) vs 119.7 (82.7, 146.0) ng/ml, P=0.046). No differences in myostatin or IGF-1 were observed among robust individuals with or without low muscle mass. In adjusted multinomial logistic regression models with Robust/Normal RASM as the reference group, myostatin (P=0.05) and IGF-1 (P=0.043) were associated with Frail/Low RASM status in the whole cohort. When stratified by gender, myostatin was significantly associated with Frail/Low RASM status in men only (P=0.03). In women, serum IGF-1 was associated with Frail/Low RASM status (P=0.046), but not myostatin (P=0.53). CONCLUSION: Serum myostatin, normalized for TBLM in men and IGF-1 in women are potential biomarkers for frail individuals with low RASM, and may identify a target group for intervention.

Altered responsiveness to chemokines due to targeted disruption of SHIP.

SHIP has been implicated in negative signaling in a number of hematopoietic cell types and is postulated to downregulate phosphatidylinositol-3-kinase- (PI-3K-) initiated events in diverse receptor signaling pathways. Because PI-3K is implicated in chemokine signaling, we investigated whether SHIP plays any role in cellular responses to chemokines. We found that a number of immature and mature hematopoietic cells from SHIP-deficient mice manifested enhanced directional migration (chemotaxis) in response to the chemokines stromal cell-derived factor-1 (SDF-1) and B-lymphocyte chemoattractant (BLC). SHIP(-/-) cells were also more active in calcium influx and actin polymerization in response to SDF-1. However, colony formation by SHIP-deficient hematopoietic progenitor cell (HPCs) was not inhibited by 13 myelosuppressive chemokines that normally inhibit proliferation of HPCs. These altered biologic activities of chemokines on SHIP-deficient cells are not caused by simple modulation of chemokine receptor expression in SHIP-deficient mice, implicating SHIP in the modulation of chemokine-induced signaling and downstream effects.

Production, Characterization and Evaluation of Kaempferol Nanosuspension for Improving Oral Bioavailability.

CONTEXT: Kaempferol has a large particle size and poor water solubility, leading to poor oral bioavailability. The present work aimed to develop a kaempferol nanosuspension (KNS) to improve pharmacokinetics and absolute bioavailability. METHODS: A nanosuspension was prepared using high pressure homogenization (HPH) techniques. The physico-chemical properties of the kaempferol nanosuspension (KNS) were characterized using photon correlation spectroscopy (PCS), transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FTIR) and x-ray diffractometry (XRD). A reversephase high performance liquid chromatography (RP-HPLC) method for the analysis of the drug in rat plasma was developed and validated as per ICH guidelines. In vivo pharmacokinetic parameters of oral pure kaempferol solution, oral kaempferol nanosuspension and intravenous pure kaempferol were assessed in rats. RESULTS AND DISCUSSION: The kaempferol nanosuspension had a greatly reduced particle size (426.3 ± 5.8 nm), compared to that of pure kaempferol (1737 ± 129 nm). The nanosuspension was stable under refrigerated conditions. No changes in physico-chemical characteristics were observed. In comparison to pure kaempferol, kaempferol nanosuspension exhibited a significantly (P<0.05) increased in Cmax and AUC(0-∞) following oral administration and a significant improvement in absolute bioavailability (38.17%) compared with 13.03% for pure kaempferol. CONCLUSION: These results demonstrate enhanced oral bioavailability of kaempferol when formulated as a nanosuspension.

Effects of prostaglandin F2 alpha on intracellular pH, intracellular calcium, cell shortening and L-type calcium currents in rat myocytes.

OBJECTIVE: We have studied the mechanisms underlying the positive inotropic action of prostaglandin F2 alpha (PGF2 alpha) by monitoring intracellular calcium transients, intracellular pH, L-type calcium currents and cell shortening in isolated ventricular myocytes. METHODS: Rat myocytes were loaded with fura-2AM for intracellular calcium measurements, or BCECF-AM for pH measurements. Cell shortening was recorded using an edge detection system, and L-type calcium currents measured using whole cell patch clamping. RESULTS: PGF2 alpha (3 nmol l-1-3 mumol l-1 increased single myocyte shortening and reduced resting cell length in a concentration-dependent manner. While myocyte shortening was increased by PGF2 alpha, this was not associated with any change in the amplitude of intracellular calcium transients, diastolic calcium, or L-type calcium currents. However, the same myocytes were capable of responding to catecholamines with increases in calcium transient amplitude and L-type calcium currents. PGF2 alpha (3 mumol l-1 caused a reversible rise in intracellular pH of 0.08 +/- 0.01 pH units (n = 5, p < 0.05). The Na(+)-H+ exchanger inhibitor, HOE 694 (10 mumol l-1, abolished the PGF2 alpha-induced rise in pH and the increase in cell shortening. PGF2 alpha-induced increases in cell shortening and intracellular pH were also attenuated by the protein kinase C (PKC) inhibitor, chelerythrine (2 mumol l-1. CONCLUSION: The positive inotropic action of PGF2 alpha appears to be mediated via activation of the Na(+)-H+ exchanger with the possible involvement of PKC. This suggests that PGF2 alpha-produces intracellular alkalosis, which then sensitizes cardiac myofilaments to calcium.

Sex-specific differences in risk factors for sarcopenia amongst community-dwelling older adults.

With considerable variation including potential sex-specific differential rate of skeletal muscle loss, identifying modifiable factors for sarcopenia will be pivotal to guide targeted interventions. This study seeks to identify clinical and biological correlates of sarcopenia in community-dwelling older adults, with emphasis on the role of anabolic and catabolic stimuli, and special reference to gender specificity. In this cross-sectional study involving 200 community-dwelling and functionally independent older adults aged ≥50 years, sarcopenia was defined using the Asian Working Group for Sarcopenia criteria. Comorbidities, cognitive and functional performance, physical activity and nutritional status were routinely assessed. Biochemical parameters included haematological indices, lipid panel, vitamin D level, anabolic hormones [insulin-like growth factor-1 (IGF-1), free testosterone (males only)] and catabolic markers [inflammatory markers (interleukin-6, C-reactive protein) and myostatin]. Multiple logistic regression was performed to identify independent predictors for sarcopenia. Age was associated with sarcopenia in both genders. Malnutrition conferred significantly higher odds for sarcopenia in women (OR = 5.71, 95% CI 1.13-28.84.44, p = 0.035) while higher but acceptable range serum triglyceride was protective in men (OR = 0.05, 95% CI 0.00-0.52, p = 0.012). Higher serum myostatin independently associated with higher odds for sarcopenia in men (OR = 1.11, 95% CI 1.00-1.24, p = 0.041). Serum IGF-1 was significantly lower amongst female sarcopenic subjects, with demonstrable trend for protective effect against sarcopenia in multiple regression models, such that each 1 ng/ml increase in IGF-1 was associated with 1% decline in odds of sarcopenia in women (p = 0.095). Our findings support differential pathophysiological mechanisms for sarcopenia that, if corroborated, may have clinical utility in guiding sex-specific targeted interventions for community-dwelling older adults.

SHIPs ahoy.

In 1996 three groups independently cloned a hemopoietic specific, src homology 2-containing inositol 5'-phosphatase which, based on its structure, was called SHIP. More recently, a second more widely expressed SHIP-like protein has been cloned and called SHIP2. Both specifically hydrolyze phosphatidylinositol-3,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate in vitro. Moreover, SHIP has been shown in vivo to be the primary enzyme responsible for breaking down phosphatidylinositol-3,4,5-trisphosphate to phosphatidylinositol-3,4-bisphosphate in normal mast cells and, as a result, limits normal and prevents inappropriate mast cell degranulation. Because of their ability to break down phosphatidylinositol-3,4,5-trisphosphate, the SHIPs have the potential to regulate many, if not all, phosphatidylinositol-3-kinase induced events including, proliferation, differentiation, apoptosis, end cell activation, cell movement and adhesion and will thus likely be the subject of intensive research over the next few years.

A retrospective study of endodontically treated mandibular first molars in a Chinese population.

The purpose of this investigation was to study the prevalence of three roots and four root canals in the mandibular first molars of a Chinese population. A total of 832 cases of mandibular first molars that had received root canal treatment clinically were examined by reviewing the clinical records and radiographs. The results showed that: (a) Mandibular first molars with four root canals occur at a frequency of 31.5%. (b) More than two-thirds (68.3%) of the above cases had the fourth canal arising from the third root, an extradistal root. (c) The bilateral occurrence of this extradistal root in mandibular first molars was 67%. In conclusion, the occurrence of four root canals in mandibular first molars among Chinese people was not unusual.

Reheating of soy oil is detrimental to bone metabolism in oestrogen deficient rats.

INTRODUCTION: The short-term and long- term effects of heated soy oil on bone metabolism in ovariectomised Sprague-Dawley rats were studied. METHODS: Three-month-old female rats, were divided into five groups: normal control (NC); ovariectomised control (OVXC); ovariectomised and fed rat chow with added fresh soybean oil (SOF) or once-heated soy oil (SO1) or five-times-heated soy oil (SO5). Short-term parameters measured after one month were serum interleukin-6 (IL-6) and osteocalcin. Long-term parameters measured after six months were the structural bone histomorphometrical parameters. Vitamin E content in the soy oil subjected to the different heating treatments were also measured. RESULTS: Rats in the SO5 group had higher levels of IL-6 after one month compared to the other four groups. Osteocalcin levels in the SO1 and SO5 groups remained high after treatment, while those in the NC and SOF groups declined. After six months, bone mass declined in the SO5 group. Vitamin E assay in the oils showed that levels of alpha-tocopherol decreased after heating the oil once and five times, while levels of gamma- and delta-tocopherols only declined after heating five times. CONCLUSION: Repeated heating of soy oil destroyed the tocopherols causing raised serum IL-6 and osteocalcin levels, leading to increased bone resorption and osteoporosis in the long term.

Half-day urotherapy improves voiding parameters in children with dysfunctional emptying.

OBJECTIVES: Children with voiding dysfunction benefit from intensive bladder emptying re-education; however, hospitalization for such training is not always financially viable or realistic. The aim of this study was to evaluate whether half-day voiding re-education in pairs improved immediate and mid-term voiding parameters. METHODS: 48 children (mean age, 8.9 years; 54% male) identified in the urotherapy clinic as having either (1) abnormal uroflow curves, (2) a postvoid residual urine (PVRU)>10% of voided volume, or (3) proven dysfunctional voiding, were recruited and age- and gender-matched. Training over a half day included postural instruction, abdominal wall muscle pattern recognition, pelvic floor muscle relaxation training, and supervised voiding. Data from the initial clinic visit was compared to that after training, and at 1 and 3 mo follow-up. Families completed a questionnaire after the session. RESULTS: Urine flow curves were abnormal in 76.2% of initial clinic visit voids, 14% of patients after the half-day training session, and 11.7% of children at the 3-mo follow-up. Initial emptying efficiency (voided volume as a percentage of total bladder volume for that void) and mean PVR significantly improved following half-day training with gains maintained at both follow-up visits. CONCLUSION: Training children in pairs over a half day resulted in significantly improved bladder emptying that was sustained at the 3-mo follow-up.

Mandibular premolar with three root canals--two case reports.

The presence of three root canals in the mandibular premolar may sometimes be recognized when there is persistent postoperative discomfort following root canal therapy. This paper presents two cases of root canal treatment of mandibular premolars with three root canals including one mandibular first premolar and one mandibular second premolar. The possibility that there is more than one root canal in lower premolar teeth must be considered in the radiographic and clinical examination during root canal treatment.