Depression and physical health multimorbidity: primary data and country-wide meta-analysis of population data from 190 593 people across 43 low- and middle-income countries.

BACKGROUND: Despite the known heightened risk and burden of various somatic diseases in people with depression, very little is known about physical health multimorbidity (i.e. two or more physical health co-morbidities) in individuals with depression. This study explored physical health multimorbidity in people with clinical depression, subsyndromal depression and brief depressive episode across 43 low- and middle-income countries (LMICs). METHOD: Cross-sectional, community-based data on 190 593 individuals from 43 LMICs recruited via the World Health Survey were analysed. Multivariable logistic regression analysis was done to assess the association between depression and physical multimorbidity. RESULTS: Overall, two, three and four or more physical health conditions were present in 7.4, 2.4 and 0.9% of non-depressive individuals compared with 17.7, 9.1 and 4.9% among people with any depressive episode, respectively. Compared with those with no depression, subsyndromal depression, brief depressive episode and depressive episode were significantly associated with 2.62, 2.14 and 3.44 times higher odds for multimorbidity, respectively. A significant positive association between multimorbidity and any depression was observed across 42 of the 43 countries, with particularly high odds ratios (ORs) in China (OR 8.84), Laos (OR 5.08), Ethiopia (OR 4.99), the Philippines (OR 4.81) and Malaysia (OR 4.58). The pooled OR for multimorbidity and depression estimated by meta-analysis across 43 countries was 3.26 (95% confident interval 2.98-3.57). CONCLUSIONS: Our large multinational study demonstrates that physical health multimorbidity is increased across the depression spectrum. Public health interventions are required to address this global health problem.

Visualization of Pulpal Structures by SWIR in Endodontic Access Preparation.

Endodontic access preparation is one of the initial steps in root canal treatments and can be hindered by the obliteration of pulp canals and formation of tertiary dentin. Until now, methods for direct intraoperative visualization of the 3-dimensional anatomy of teeth have been missing. Here, we evaluate the use of shortwave infrared radiation (SWIR) for navigation during stepwise access preparation. Nine teeth (3 anteriors, 3 premolars, and 3 molars) were explanted en bloc with intact periodontium including alveolar bone and mucosa from the upper or lower jaw of human body donors. Analysis was performed at baseline as well as at preparation depths of 5 mm, 7 mm, and 9 mm, respectively. For reflection, SWIR was used at a wavelength of 1,550 nm from the occlusal direction, whereas for transillumination, SWIR was passed through each sample at the marginal gingiva from the buccal as well as oral side at a wavelength of 1,300 nm. Pulpal structures could be identified as darker areas approximately 2 mm before reaching the pulp chamber using SWIR transillumination, although they were indistinguishable under normal circumstances. Furcation areas in molars appeared with higher intensity than areas with canals. The location of pulpal structures was confirmed by superimposition of segmented micro-computed tomography (µCT) images. By radiomic analysis, significant differences between pulpal and parapulpal areas could be detected in image features. With hierarchical cluster analysis, both segments could be confirmed and associated with specific clusters. The local thickness of µCTs was calculated and correlated with SWIR transillumination images, by which a linear dependency of thickness and intensity could be demonstrated. Lastly, by in silico simulations of light propagation, dentin tubules were shown to be a crucial factor for understanding the visibility of the pulp. In conclusion, SWIR transillumination may allow direct clinical live navigation during endodontic access preparation.

Clinical-guide risk prediction of hepatocellular carcinoma development in chronic hepatitis C patients after interferon-based therapy.

BACKGROUND: Interferon (IFN)-based therapies could eradicate hepatitis C (HCV) and reduce the risk of hepatocellular carcinoma (HCC). However, HCC could still happen after sustained virological response (SVR). We aimed to develop a simple scoring system to predict the risk of HCC development among HCV patients after antiviral therapies. METHODS: From 1999 to 2009, 1879 patients with biopsy-proven HCV infection treated with IFN-based therapies were analyzed. RESULTS: Multivariable analysis showed old age (adjusted HR (aHR)=1.73, 95% CI=1.13-2.65 for aged 60-69 and aHR=2.20, 95% CI=1.43-3.37 for aged ≥ 70), Male gender (aHR=1.74, 95% CI=1.26-2.41), platelet count <150 × 10(9)/l (HR=1.91, 95% CI=1.27-2.86), α-fetoprotein ≥ 20 ng ml(-1) (HR=2.23, 95% CI=1.58-3.14), high fibrotic stage (HR=3.32, 95% CI=2.10-5.22), HCV genotype 1b (HR=1.53, 95% CI=1.10-2.14), and non SVR (HR=2.40, 95% CI=1.70-3.38) were independent risk factors for HCC. Regression coefficients were used to build up a risk score and the accuracy was evaluated by using the area under the receiver operating characteristic curve (AUC). Three groups as low-, intermediate-, and high-risk are classified based on the risk scores. One hundred sixty patients (12.78%) in the derivation and 82 patients (13.08%) in the validation cohort developed HCC with AUC of 79.4%, sensitivity of 84.38%, and specificity of 60.66%. In the validation cohort, the 5-year HCC incidence was 1.81%, 12.92%, and 29.95% in low-, intermediate-, and high-risk groups, with hazard ratios 4.49 in intermediate- and 16.14 in high-risk group respectively. The risk reduction of HCC is greatest in patients with SVR, with a 5-year and 10-year risk reduction of 28.91% and 27.99% respectively. CONCLUSION: The risk scoring system is accurate in predicting HCC development for HCV patients after antiviral therapies.

Narrow-band imaging with magnifying endoscopy for the screening of esophageal cancer in patients with primary head and neck cancers.

BACKGROUND AND STUDY AIM: Although narrow-band imaging (NBI) in endoscopy can improve detection of early-stage esophageal malignancies in patients with head and neck cancers, false-positive results may be obtained in areas with nonspecific inflammatory changes. This study evaluated the feasibility of primary screening with NBI and magnification for the presence of esophageal malignancies in these cancer patients. PATIENTS AND METHODS: Sixty-nine patients with documented head and neck cancers were enrolled from April 2008 to January 2009. All patients underwent a meticulous endoscopic examination of the esophagus using a conventional white-light system followed by re-examination using the NBI system and final confirmation with NBI plus magnification. RESULTS: Twenty-one patients (30.4 %) were confirmed to have esophageal neoplasia. Among these 21, 16 (76.2 %) had synchronous lesions, 9 (42.9 %) were asymptomatic, and 10 (47.6 %) had early-stage neoplasia. The incidence of multiple esophageal neoplasia was 57.1 %. NBI was more effective than conventional endoscopy in detecting neoplastic lesions (35 lesions in 21 patients vs. 22 lesions in 18 patients) and was particularly effective in patients with dysplasia (13 lesions in 9 patients vs. 3 lesions in 3 patients). The sensitivity and accuracy of detection were 62.9 % and 64.4 % for conventional endoscopy, 100 % and 86.7 % for NBI alone, and 100 % and 95.6 % for NBI with high magnification, respectively. CONCLUSIONS: Compared with current approaches, NBI followed by high magnification significantly increases the accuracy of detection of esophageal neoplasia in patients with head and neck cancers. The result warrants conducting prospective randomized controlled study to confirm its efficacy.

Mechanism of action of Acanthamoeba profilin: demonstration of actin species specificity and regulation by micromolar concentrations of MgCl2.

Acanthamoeba profilin strongly inhibits in a concentration-dependent fashion the rate and extent of Acanthamoeba actin polymerization in 50 mM KCl. The lag phase is prolonged indicating reduction in the rate of nucleus formation. The elongation rates at both the barbed and pointed ends of growing filaments are inhibited. At steady state, profilin increases the critical concentration for polymerization but has no effect on the reduced viscosity above the critical concentration. Addition of profilin to polymerized actin causes it to depolymerize until a new steady-state, dependent on profilin concentration, is achieved. These effects of profilin can be explained by the formation of a 1:1 complex with actin with a dissociation constant of 1 to 4 microM. MgCl2 strongly inhibits these effects of profilin, most likely by binding to the high-affinity divalent cation site on the actin. Acanthamoeba profilin has similar but weaker effects on muscle actin, requiring 5 to 10 times more profilin than with amoeba actin.

Physical, immunochemical, and functional properties of Acanthamoeba profilin.

Acanthamoebe profilin has a native molecular weight of 11,700 as measured by sedimentation equilibrium ultracentrifugation and an extinction coefficient at 280 nm of 1.4 X 10(4) M-1cm-1. Rabbit antibodies against Acanthamoeba profilin react only with the 11,700 Mr polypeptide among all other ameba polypeptides separated by electrophoresis. These antibodies react with a 11,700 Mr polypeptide in Physarum but not with any proteins of Dictyostelium or Naeglaria. Antibody-binding assays indicate that approximately 2% of the ameba protein is profilin and that the concentration of profilin is approximately 100 mumol/liter cells. During ion exchange chromatography of soluble extracts of Acanthamoeba on DEAE-cellulose, the immunoreactive profilin splits into two fractions: an unbound fraction previously identified by Reichstein and Korn (1979, J. Biol. Chem., 254:6174-6179) and a tightly bound fraction. Purified profilin from the two fractions is identical by all criteria tested. The tightly bound fraction is likely to be attached indirectly to the DEAE, perhaps by association with actin. By fluorescent antibody staining, profilin is distributed uniformly throughout the cytoplasmic matrix of Acanthamoeba. In 50 mM KCl, high concentrations of Acanthamoeba profilin inhibit the elongation rate of muscle actin filaments measured directly by electron microscopy, but the effect is minimal in KCl with 2 MgCl2. By using the fluorescence change of pyrene-labeled Acanthamoeba actin to assay for polymerization, we confirmed our earlier observation (Tseng, P. C.-H., and T. D. Pollard, 1982, J. Cell Biol. 94:213-218) that Acanthamoeba profilin inhibits nucleation much more strongly than elongation under physiological conditions.

Prevention of Postdental Procedure Bacteremia: A Network Meta-analysis.

Postdental procedure bacteremia is common and troublesome. The comparative efficacy of multiple prophylactic interventions is unclear. We compared the efficacy of interventions for the prevention of postdental procedure bacteremia. We conducted a review of ClinicalKey, Cochrane CENTRAL, Embase, ProQuest, PubMed, ScienceDirect, Web of Science, and ClinicalTrials.gov from inception to December 4, 2018. Randomized controlled trials that evaluated prophylactic interventions for the prevention of postdental procedure bacteremia were eligible. The primary outcome was the incidence of postdental procedure bacteremia. A total of 24 trials were included with 2,147 participants. Our network meta-analysis demonstrated that intravenous administration of 1,000/200 mg of amoxicillin/clavulanate provided the least incidence of postdental procedure bacteremia among all the prophylactic interventions (odds ratio = 0.03, 95% CI = 0.00 to 0.63) as compared with the placebo/controls. Oral 3 g of amoxicillin had the least incidence of postdental procedure bacteremia among all oral or topical forms of prophylactic interventions (odds ratio = 0.10, 95% CI = 0.02 to 0.44) as compared with the placebo/controls. No serious adverse events, such as anaphylactic shock, mortality, and the development of antibiotic-resistant bacteria, were reported. None of the included subjects were of high risk of infectious endocarditis. Our network meta-analysis demonstrates that intravenous amoxicillin/clavulanate and oral amoxicillin might be the best prophylactic interventions in preventing postdental procedure bacteremia among all the oral/topical forms of interventions for the overall populations.

Retrospective study on the utilization and cost of immunosuppressive agents among kidney transplant recipients in Taiwan: a 5-year review.

This study examined the utilization and cost of immunosuppressive agents among kidney transplant recipients in view of the growth under the Taiwan National Health Insurance payment system. Using inpatient expenditures by admissions and the files of the Registry for contracted medical facilities released from the Taiwan National Health Insurance Research Database, we totalled all renal implantations from 1999--2003, sorting them by drug expenditures reimbursed by contracted hospitals. The systematic sampling files of ambulatory care files were used to compute the Defined Daily Dose (DDD) and track drug utilization. The batch analysis was completed using the SPSS English version 13.0 for Windows. During the 5-year period, a total of 663 kidney transplantation surgeries were identified at 26 hospitals. Up to 90% of transplantation surgeries were performed at medical centers with about 55% in Northern Taiwan. Ninety-nine percent of drug expenditures were claimed by the top 12 hospitals. According to the Anatomical Therapeutic Chemical Classification, the most frequently prescribed immunosuppressive agents were Sandimmum Neoral cyclosporine (43%), mycophenolate (30.8%), and tacrolimus (21.3%) with DDDs of 137.5, 1187, and 5.54 mg, respectively. The ambulatory drug expenditure for patients increased 2-fold within the first 5 years, and 11.8 million in 2003 was estimated to be approximately 20 million Taiwanese dollars in 2010.

Comparison of the psychospiritual needs of Chinese heart transplant recipients at pre- and postoperative stages.

PURPOSE: This project sought to compare Chinese heart transplant (HT) recipients' psychospiritual needs during the preoperative (PS) and the postoperative predischarge stage (PDS). METHODS: Thirty HT recipients from two leading medical centers in Taiwan were recruited for this research. Data collected by face-to-face interview were analyzed by content analysis. RESULTS: The patients' ages ranged from 23 to 45 years (mean [M] +/- standard deviation [SD] = 28.5 +/- 4.1); 90% were married. The subjects' cardiac disease history ranged from 4.2 to 12.3 years (M +/- SD = 8.2 +/- 2.3). The waiting time list for HT ranged from 1.2 to 6.4 years (M +/- SD = 3.1 +/- 2.6). The subjects had the following six psychospiritual concerns: death (PS), unfulfilled family responsibilities (PS and PDS), unaccomplished personal life goals (PS and PDS), poor body image (PDS), loss of significant others' support and love (PDS), and discrimination by others (PDS). The following seven needs of help were reported: comforting the fear of failure in heart transplantation (PS and PDS), meeting unfulfilled family responsibilities (PS and PDS), accomplishing personal life goal (PS and PDS), religious support (PS and PDS), establishing confidence in body image (PDS), establishing positive relationship with significant others (PS and PDS), and preparation for dying with dignity when necessary (PS and PDS). CONCLUSION: The in-depth investigation on Chinese HT recipients' psychospiritual needs was first compared in PDS and PS. More distress and needs were found in PDS than PS. These findings were attributed by the dilemma of pursuing prospective future versus taking the risk of loss of life, valuing families' and health professionals' support system, and expecting grief and dying with dignity. Health professionals are encouraged to understand and provide stage-specific support to help them meet psycho-spiritual needs.

Place Cell-Like Activity in the Primary Sensorimotor and Premotor Cortex During Monkey Whole-Body Navigation.

Primary motor (M1), primary somatosensory (S1) and dorsal premotor (PMd) cortical areas of rhesus monkeys previously have been associated only with sensorimotor control of limb movements. Here we show that a significant number of neurons in these areas also represent body position and orientation in space. Two rhesus monkeys (K and M) used a wheelchair controlled by a brain-machine interface (BMI) to navigate in a room. During this whole-body navigation, the discharge rates of M1, S1, and PMd neurons correlated with the two-dimensional (2D) room position and the direction of the wheelchair and the monkey head. This place cell-like activity was observed in both monkeys, with 44.6% and 33.3% of neurons encoding room position in monkeys K and M, respectively, and the overlapping populations of 41.0% and 16.0% neurons encoding head direction. These observations suggest that primary sensorimotor and premotor cortical areas in primates are likely involved in allocentrically representing body position in space during whole-body navigation, which is an unexpected finding given the classical hierarchical model of cortical processing that attributes functional specialization for spatial processing to the hippocampal formation.

Normative values and factors affecting water-perfused esophageal high-resolution impedance manometry for a Chinese population.

BACKGROUND: Combined esophageal high-resolution impedance manometry (HRIM) measures multiple pressures and bolus transit simultaneously, facilitating detailed assessment of esophageal motility. Currently, normative values for water-perfused HRIM systems for Chinese populations are lacking. METHODS: Healthy volunteers were enrolled for comprehensive anthropometric measures, blood biochemistry tests, and an HRIM study using 22 water-perfused pressure sensors and 12 impedance channels. Ten 5-mL liquid swallows of saline at 30-second intervals were conducted. The following parameters were calculated: distal contractile integral (DCI), distal latency (DL), lower esophageal sphincter (LES) basal pressure, 4-second integrated relaxation pressure (IRP-4s), and complete bolus transit percentage. Normal values were established based on the 5th and 95th percentiles. KEY RESULTS: All 66 participants (34 male, 32 female, aged 21-64 years) completed the study and tolerated the HRIM procedure well. The upper normal limit (95th percentile) of IRP-4 second was 20 mmHg. The 5th-95th percentile range for DCI, DL, and complete bolus transit was 99-2186 mmHg●s●cm, 6.2-11.3 second, and 50%-100%, respectively. Age was negatively correlated with DL. Females had significantly higher upper limits for IRP-4s and median DCI than males. Multivariate analyses confirmed that IRP-4s was higher in females, and that higher body mass index and waist circumference were associated with reduced DL and better bolus transit, respectively. CONCLUSIONS AND INFERENCES: We established normative values for the water-perfused HRIM system for a Chinese population. Gender and anthropometric factors may affect various major HRIM parameters and should be taken into account when interpreting HRIM results in clinical practice.

Enhancement of thermal spin transfer torque by double-barrier magnetic tunnel junctions with a nonmagnetic metal spacer.

Enhancement of thermal spin transfer torque in a double-barrier magnetic tunnel junction with a nonmagnetic-metal spacer is proposed in this study. The results indicate that, given the same temperature difference, thermal spin transfer torque and charge current density for the proposed double barrier magnetic tunnel junction configuration can be approximately twice as much as that of the traditional single-barrier magnetic tunnel junctions. This enhancement can be attributed to the resonant tunneling mechanism in the double-barrier structure.

Comparison of renal safety and efficacy of telbivudine, entecavir and tenofovir treatment in chronic hepatitis B patients: real world experience.

This study aims to assess the nephrotoxicity and efficacy of tenofovir disoproxil fumarate (tenofovir), telbivudine and entecavir. A retrospective study of 587 patients with chronic hepatitis B treated with tenofovir (n = 170), telbivudine (n = 184) and entecavir (n = 233) for at least 1 year. Renal function and efficacy were assessed. The estimated glomerular filtration rate (eGFR) decreased significantly in the tenofovir group after a mean of 17 months treatment (from 92.2 to 85.6 mL/min/1.73 m(2), p < 0.001), but increased in the telbivudine group after a mean of 32 months of treatment (from 86.1 to 95 mL/min/1.73 m(2), p < 0.001). There was no significant change in eGFR in the entecavir group after a mean of 44 months. By multivariate analysis, pre-existing renal insufficiency (p = 0.003), tenofovir (p = 0.007) and diuretic treatment (p = 0.001) were independent predictors for renal function deterioration. Cumulative virological breakthrough was 0% in tenofovir after 2 years, 3.4% in entecavir after 7 years and 22.9% in telbivudine after 5 years. Liver cirrhosis (p = 0.008) and virological breakthrough (p = 0.040) were independently associated with increased risk of hepatocellular carcinoma development. Tenofovir may lead to deterioration in renal function as assessed by serial eGFR measurements. Although telbivudine appeared to be associated with an improvement in eGFR, it was associated with high rates of virological breakthrough, which was an independent risk factor for HCC development. With low rates of virological breakthrough and preservation of renal function, entecavir could be the best choice among these three agents.

Detection of a phase transition in red cell membranes using positronium as a probe.

Positron lifetimes in human red cell ghost membranes have been measured as a function of temperature from 3 degrees C to 25 degrees C. A marked sudden change in the ortho-positronium annihilation rate was found at 16-18 degrees C during the heating cycle and at 18-20 degrees C in the cooling cycle. Such sudden change of microenvironment in the membranes sensed by ortho-positronium is attributed to the sudden change of water diffusion rate through the membranes which is a consequence of the sudden change in free volume, or fluidities in the lipid layers.

The inhibition of high-voltage-activated calcium current by activation of MrgC11 involves phospholipase C-dependent mechanisms.

High-voltage-activated (HVA) calcium channels play an important role in synaptic transmission. Activation of Mas-related G-protein-coupled receptor subtype C (MrgC; mouse MrgC11, rat homolog rMrgC) inhibits HVA calcium current (ICa) in small-diameter dorsal root ganglion (DRG) neurons, but the intracellular signaling cascade underlying MrgC agonist-induced inhibition of HVA ICa in native DRG neurons remains unclear. To address this question, we conducted patch-clamp recordings in MrgA3-eGFP-wild-type mice, in which most MrgA3-eGFP(+) DRG neurons co-express MrgC11 and can be identified for recording. We found that the inhibition of HVA ICa by JHU58 (0.001-100nM, a dipeptide, MrgC-selective agonist) was significantly reduced by pretreatment with a phospholipase C (PLC) inhibitor (U73122, 1µM), but not by its inactive analog (U73343) or vehicle. Further, in rats that had undergone spinal nerve injury, pretreatment with intrathecal U73122 nearly abolished the inhibition of mechanical hypersensitivity by intrathecal JHU58. The inhibition of HVA ICa in MrgA3-eGFP(+) neurons by JHU58 (100nM) was partially reduced by pretreatment with a Gßγ blocker (gallein, 100µM). However, applying a depolarizing prepulse and blocking the Gαi and Gαs pathways with pertussis toxin (PTX) (0.5µg/mL) and cholera toxin (CTX) (0.5µg/mL), respectively, had no effect. These findings suggest that activation of MrgC11 may inhibit HVA ICa in mouse DRG neurons through a voltage-independent mechanism that involves activation of the PLC, but not Gαi or Gαs, pathway.

The correlation between mid-brain serotonin transporter availability and intelligence quotient in healthy volunteers.

PURPOSE: This study was performed to investigate the association between the mid-brain serotonin transporter (SERT) availability and intelligence quotient (IQ). METHODS: One hundred and thirteen healthy participants, including 52 male and 61 female subjects, were recruited. We used SPECT with [(123)I]ADAM images to determine the SERT availability in the mid-brain, and measured the subjects' IQ using the WAIS-R. RESULTS: We found a significant positive correlation between the mid-brain SERT availability and the IQ of the participants. Even when controlling for age and sex, the significant association still existed. CONCLUSION: This result implied that the higher the SERT binding in the mid-brain, the better the IQ in healthy participants.

The cytokine CSF-1 (M-CSF) expressed by endometrial carcinomas in vivo and in vitro, may also be a circulating tumor marker of neoplastic disease activity in endometrial carcinoma patients.

Endometrial epithelial cell expression of CSF-1 and FMS antigens was studied in vivo and in vitro in 24 human endometrial carcinoma and 11 benign endometrial biopsy specimens. Twenty-one of 24 adenocarcinomas and 4 of 11 benign lesions stained positively (by IHC) with rabbit anti-human CSF-1 antibodies, while all 24 carcinomas and 3 out of 11 benign lesions (all secretory endometrial specimens) showed significant IHC staining (1+ or greater) of epithelial elements and tissue macrophages with a mouse anti-FMS (CSF-1 receptor) monoclonal antibody. CSF-1 levels in plasma from endometrial carcinoma patients (85 samples, 24 patients) were also found to be markedly elevated (some greater than 100 ng/ml) in patients with active or recurrent disease. In vitro, several endometrial carcinoma cell lines were shown to express FMS complementary transcripts and FMS antigen which were very similar if not identical to those expressed in choriocarcinoma cell line positive controls. Autocrine and paracrine effects mediated by tumor or stromally produced CSF-1 and a tumor epithelial cell CSF-1 receptor may therefore contribute to the biological behavior of endometrial neoplasms in vivo and in vitro.

Respiratory distress syndrome of the newborn and complications of pregnancy.

A group of 412 infants with birthweights between 501 and 2,500 gm and gestational ages of 36 weeks or less were studied for the influence of both prolonged ruputre of amniotic membranes and maternal hypertension on the incidence of idiopathic respiratory distress syndrome (IRDS). The occurrence of these complications was associated with a significant decrease in the incidence of IRDS only in infants with birthweights between 1,501 and 2,500 gm (37.4% in the no complications group versus 12.8% in the complications group; P less than .01) or gestational ages of 33 to 36 weeks (35.2% in the no complications group versus 13.1% in the complications group; P less than .01). In infants with birthweights of 1,500 gm or less or gestational ages of 32 weeks or less, the specific antecedent complications of pregnancy did not alter the incidence of IRDS. Rupture of the membranes for more than 72 hours had no greater effect on the incidence of IRDS than those lasting 24 to 72 hours.