Do Somatic Symptoms Predict the Severity of Depression? A Validation Study of the Korean Version of the Depression and Somatic Symptoms Scale

This study aimed at exploring the psychometric characteristics of the Korean Version of the Depression and Somatic Symptoms Scale (DSSS) in a clinical sample, and investigating the impact of somatic symptoms on the severity of depression. Participants were 203 consecutive outpatients with current major depressive disorders (MDD) or lifetime diagnosis of MDD. The DSSS was compared with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the 17-items Hamilton Depression Rating Scale (HAMD). The DSSS showed a two-factor structure that accounted for 56.8% of the variance, as well as excellent internal consistency (Cronbach’s alpha = 0.95), concurrent validity (r = 0.44–0.82), and temporal stability (intraclass correlation coefficient = 0.79). The DSSS had a high ability to identify patients in non-remission (area under receiver operating characteristic [ROC] curve = 0.887). Maximal discrimination between remission and non-full remission was obtained at a cut-off score of 22 (sensitivity = 82.1%, specificity = 81.4%). The number of somatic symptoms (the range of somatic symptoms) and the scores on the somatic subscale (SS, the severity of somatic symptoms) in non-remission patients were greater than those in remission patients. The number of somatic symptoms (slope = 0.148) and the SS score (slope = 0.472) were confirmed as excellent predictors of the depression severity as indicated by the MADRS scores. The findings indicate that the DSSS is a useful tool for simultaneously, rapidly, and accurately measuring depression and somatic symptoms in clinical practice settings and in consultation fields.     

Prediction of the In Vivo Force–Velocity Relationship of Slow Human Skeletal Muscle from Measurements in Myofibers

Direct measurement of the in vivo contractile properties of an individual muscle cannot be made in humans. The objective of this study was to predict the force–velocity (F–V) properties of slow human skeletal muscle for the in vivo temperature of 37 °C from F–V measurements in type I myofibers. Specifically, to quantitatively link myofiber measurements, which must be conducted at relatively low temperatures, to in vivo properties, the temperature-dependence of contractile properties must be modeled. We estimated the kinetic parameters of a crossbridge model within 15–30 °C from F–V measurements recorded in the myofibers of one subject, extrapolated their values at 37 °C, and then predicted the in vivo shortening and lengthening F–V curves. The prediction for maximal shortening velocity was 2.2 ± 0.2 fiber lengths per second and that for saturation force during lengthening was 2.3 ± 0.2 times isometric force. These estimates agree with previously reported in vivo measurements but are substantially different than those used in muscle models for many musculoskeletal simulations. The results from this study indicate that during low levels of muscle activation when slow motor units are primarily recruited, musculoskeletal models should consider having F–V properties that reflect the contractile properties of type I myofibers.     

Cloning and Overexpression of TGF-β1 cDNA in a Mammary Adenocarcinoma: In Vitro and In Vivo Effects

Abstract

It has been suggested that transforming growth factor beta (TGF-β) may be a potential negative autocrine growth regulator of carcinomas including mammary carcinomas. To directly test this hypothesis we have cloned and expressed human TGF-β1 cDNA in a murine mammary adenocarcinoma which is normally growth-inhibited by addition of exogenous TGF-β in vitro. A number of transfectants over-expressing the foreign TGF-β1 mRNA were selected amd compared to transfectants which did not overexpress the exogenous TGF-β1 cDNAS. Cell lines overexpressing the transfected TGF-β1 mRNA were found to produce total levels of TGF-β7 to 10 fold greater than the parental cells or control transfected clones. However, when levels of active fractions of TGF-β were compared in cell lines overexpressing TGF-β1 to those which did not, no differences were found. This suggests that the activation mechanism is not necessarily induced or altered by increasing levels of latent TGF-β production in a given tumor cell line. The basal in vitro doubling time of TGF-β1 overexpressing clones was identical to the control populations. Similarly, in vivo tumor growth rates after S.C. injection were similar to that of the parental line. Thus the precise role of TGF-β in mediating either the in vitro or in vivo growth control of a sensitive mammary adenocarcinoma cell line remains unclear. It may be that cellular over-secretion of latent TGF-β must be coupled with enhanced cellular TGF-β activation prior to any observed effect on growth rate in vitro or in vivo; this latter event may constitute the “rate-limiting” step of TGF-β activity on tumor behavior.     

Comparative Analysis of Infarct Size Limiting Activity of δ-Opioid Receptor Agonists in Reperfused Heart In Vivo

Bulletin of Experimental Biology and Medicine - The study examined the effects of δ-opioid receptor (OR) agonists on infarct size on cardiac ischemia (45 min) and reperfusion (120 min) in vivo...     

Comparative Analysis of Infarct Size Limiting Activity of κ-Opioid Receptor Agonists in In Vivo Reperfused Heart

Bulletin of Experimental Biology and Medicine - A 45-min coronary artery occlusion followed by a 120-min reperfusion was performed in rats anesthetized with α-chloralose. The selective...     

Presentation of Interleukin-12/-23 Receptor β1 Deficiency with Various Clinical Symptoms of Salmonella Infections

Clinical disease caused by weakly pathogenic mycobacterial species, Mycobacterium bovis Bacille Calmette-Guérin (BCG) and non-tuberculous environmental mycobacteria (EM), which is known as Mendelian susceptibility to mycobacterial disease (MSMD), is a rare entity defined recently. Infections with the more virulent Mycobacterium species, M. tuberculosis, may have largely gone unnoticed in these patients due to early death. Mutations in five proteins (IFNγR1, IFNγR2, IL-12/IL-23Rβ1, IL-12/IL-23p40 and STAT1) have been found in MSMD. These patients are prone to surprisingly few other infectious diseases mainly to salmonellosis. Here we present three IL-12/IL-23Rβ1 deficient patients from three different families and with different genetic mutations, who presented exclusively with Salmonella infections. Bacteremia and lymph node involvement were common clinical expressions. Leukocytoclastic vasculitis developed in one of these patients. Two patients were not inoculated with BCG, the third patient did not develop BCG infection although BCG vaccine had been given twice at ages of 1 and 7 years. All three patients responded well to antibiotic treatment. In conclusion, patients with chronic, recurrent or complicated Salmonella infections should be screened for MSMD, particularly for IL-12/IL-23p40/IL-12R/-23Rβ1 deficiency. Conversely, in patients with genetic IL-12/-23Rβ1 deficiency a full evaluation for Salmonella infection is required. IL-12/IL-23p40/IL-12R/IL-23Rβ1 deficiency seem to be underdiagnosed in patients with salmonellosis, and since such patients need prolonged therapy, diagnosis is important.     

Microglia Activated with the Toll-Like Receptor 9 Ligand CpG Attenuate Oligomeric Amyloid β Neurotoxicity in in Vitro and in Vivo Models of Alzheimer’s Disease

Soluble oligomeric amyloid β (oAβ) 1-42 causes synaptic dysfunction and neuronal injury in Alzheimer’s disease (AD). Although accumulation of microglia around senile plaques is a hallmark of AD pathology, the role of microglia in oAβ1-42 neurotoxicity is not fully understood. Here, we showed that oAβ but not fibrillar Aβ was neurotoxic, and microglia activated with unmethylated DNA CpG motif (CpG), a ligand for Toll-like receptor 9, attenuated oAβ1-42 neurotoxicity in primary neuron-microglia co-cultures. CpG enhanced microglial clearance of oAβ1-42 and induced higher levels of the antioxidant enzyme heme oxygenase-1 in microglia without producing neurotoxic molecules such as nitric oxide and glutamate. Among subclasses of CpGs, class B and class C activated microglia to promote neuroprotection. Moreover, intracerebroventricular administration of CpG ameliorated both the cognitive impairments induced by oAβ1-42 and the impairment of associative learning in Tg2576 mouse model of AD. We propose that CpG may be an effective therapeutic strategy for limiting oAβ1-42 neurotoxicity in AD.The senile plaque is a pathological hallmark of Alzheimer’s disease (AD). Fibrillar amyloid β (fAβ), a major component of senile plaques, induces tau hyperphosphorylation and neuronal dystrophy.^1,2 Soluble oligomeric Aβ (oAβ) has been reported to exhibit higher neurotoxicity than fAβ. Naturally secreted oAβ inhibits hippocampal long-term potentiation and disrupts synaptic plasticity in rats in vivo³. In addition, oAβ induces neuronal reactive oxygen species (ROS) through a mechanism requiring N-methyl-d-aspartate receptor activation.⁴ Exposure to oAβ induces rapid and massive neuronal death, while fAβ is required at higher concentrations and for longer incubations to cause neuronal dystrophy.⁵Microglia, macrophage-like cells in the central nervous system, cluster both in and around senile plaques and have been proposed to have pivotal roles in the pathogenesis of AD. Microglia activated with Aβ may be involved in the inflammatory component of AD.⁶ Both fAβ and oAβ stimulate microglial secretion of proinflammatory cytokines, chemokines, complement components, and free radicals.⁷ However, microglia also perform neuroprotective functions such as releasing neurotrophic factors⁸ and phagocytosing and degrading Aβ.^9,10Toll-like receptor (TLR) ligands enhance microglial phagocytosis of Aβ. Peptidoglycan, a TLR2 ligand, and unmethylated DNA CpG motifs (CpG), a TLR9 ligand, increase Aβ phagocytosis through the G protein-coupled formyl peptide receptor-like 2.^11,12 Similarly, the TLR4 ligand lipopolysaccharide increases phagocytosis through the CD14 receptor.¹³ However, microglia activated with TLR ligands also produce neurotoxic molecules such as proinflammatory cytokines, nitric oxide (NO), ROS, and peroxynitrite.¹⁴ In particular, lipopolysaccharide-activated microglia produce a large amount of glutamate, a neurotransmitter but also potent neurotoxin.¹⁵ Thus, factors that increase microglial clearance of oAβ without producing inflammatory mediators are candidates for the treatment of AD.Here, we investigated the role of microglia in neurotoxicity mediated by oAβ1-42. We found that microglia activated with a low dose of CpG attenuated the neurotoxic effects of oAβ1-42 without producing other neurotoxic molecules in vitro. Moreover, intracerebroventricular (ICV) administration of CpG ameliorated the cognitive impairment induced by ICV injection of oAβ1-42 and the impairment of associative learning in Tg2576 mouse model of AD.     

Relationship between myocardial β-adrenergic receptor characteristics and the incidence of ascites in broiler chickens

The present study was carried out to determine, first, the cardiac β -adrenergic receptor characteristics of normal chickens and chickens with heart failure and, second, the characteristics of myocardial β -adrenergic receptors in non-hypertrophied hearts in broilers exposed to two different altitude and temperature programmes. The density of β -adrenergic receptors was significantly lower in myocardial cells in right ventricular failure birds compared with healthy birds. The binding capacity of β -adrenergic receptors was reduced in the non-hypertrophied ventricles after exposure to high altitude in the younger but not in older chickens. At both altitudes, β -adrenergic receptor binding capacity was not significantly different in low temperature compared with normal temperature birds. These data support the hypothesis of β -adrenergic receptor downregulation as one of the mechanisms of cardiac cell adaptation to hypertrophy or hypoxia. Second, the acclimatization to high altitude in older chickens resulted in a normalization of β -receptor capacity in those broilers that were not affected by right ventricular failure and ascites.     

Psychosocial and Clinical Correlates of Fatigue in Haemodialysis Patients: the Importance of Patients’ Illness Cognitions and Behaviours

Purpose

Fatigue is commonly experienced in end-stage kidney disease (ESKD) and is associated with poor outcomes. Currently, little research has examined the psychosocial correlates of fatigue severity and its impact on renal disease patients. We predicted that psychological factors (distress, cognitions and behaviours) would be associated with fatigue severity and impairment in ESKD patients even when controlling for clinical and disease factors.

Method

One hundred seventy-four haemodialysis patients completed the Chalder Fatigue Questionnaire (fatigue severity) and the Work and Social Adjustment Scale (fatigue-related impairment) in addition to measures evaluating distress, fatigue perceptions, symptom beliefs and behaviours. Demographic and clinical data were also collected.

Results

Fatigue severity was not related to haemoglobin levels, serum albumin or dialysis vintage. In hierarchical regression models, demographic and clinical factors explained 20 % of the variance in fatigue (ethnicity, body mass index, exercise, log C-reactive protein and multimorbidity). Psychological distress (beta?=?0.21, p?<?0.01), negative beliefs about fatigue (beta?=?0.10, p?=?0.01) and unhelpful behaviours (all-or-nothing behaviour [beta?=?0.28, p?<?0.01] and avoidance [beta?=?0.16, p?<?0.01]) explained an additional 36.4 % of the variance. Fatigue-related impairment was associated with psychological distress, perceptions that symptoms indicate damage, avoidance behaviour and the level of fatigue severity.

Conclusion

Patients’ mood, beliefs and behaviours are associated with fatigue in dialysis patients. Psychological interventions to alter these factors may reduce fatigue severity and fatigue-related disability in ESKD patients.

     

In situ expression of β1, β3 and β4 integrin subunits in non-neoplastic endothelium and vascular tumours

Endothelial cells play an important role in adhesive interactions between circulating cells and extracellular matrix proteins. In vitro studies have shown that many of these processes are mediated by a superfamily of heterodimeric transmembrane glycoproteins called integrins. The distribution patterns of 1, 3 and 4 integrin subunits in endothelial cells (EC) in situ were examined immunohistochemically on serial forzen sections of a wide range of non-neoplastic tissues and of vascular tumours, both benign and malignant. Expression of the 1 subunit was a constitutive feature of EC. Among the 1-associated subunits, 5 and 6 were broadly distributed in EC, irrespective of vessel size and microenvironment. The 3 subunit displayed intermediate levels of expression with a slight preference for small vessel EC. Presence of 1 was confined to EC of capillaries and venules/small veins. Expression of 2 in EC was inconsistent. With rare exceptions, the 4 chain was absent in EC. The 3 and v subunits were expressed in most EC, though not always concomitantly. In contrast to the 1 chain, however, these integrin subunits were absent in EC of glomerular capillaries and were expressed variably in sinusoidal EC. The 4 chain was evenly present in the great majority of EC, except for those of large vessels. In vascular tumours, the patterns of 1 and 1 to 6 subunit expression generally corresponded to those found in their non-neoplastic counterparts. Expression of 3, v and 4 chains, however, decreased in neoplasia, especially in angiosarcomas. These data show that EC dispose of broad and at the same time differential repertoires of integrin subunits that presumably reflect vessel-type associated functional differences among these cells. In vascular tumours, the orthologous distribution patterns of 1 and 1 to 6 chains are conserved in most instances while the amounts of 3, v and 4 subunits expressed in EC tend to decrease in the course of malignant transformation.Dedicated to Prof. Dr. med. Dres. h.c. Wilhelm Doerr on the occasion of his 80th birthday     

Expressions of Estrogen Receptorαand β in the Development and Maturation of Rat Heart

1 IntroductionPhysiological effects of estrogen on myocardium are mediated by two intracellular estrogen receptors (ER), alpha (ERα) and beta (ERβ). Their role in cardiovascular physiology is not well understood. For this reason,we investigated the expressions of ERα and ERβ in the development and maturation of rat heart.2 Materials and Methods2.1 Experimental animals The study on changes of ERs was performed in six newborn rats with both sexes and six adult female Wistar rats respedively.2.2 Semiquantitati...     

Relationship of the changes of cervical MRI,TCD and BAEP in patients with “isolated” vertigo

Objective: To study the relationship and changes of cervical MRI, TCD and BAEP in patients with “isolated” vertigo. Methods: The relationship and changes of cervical MRI, TCD and BAEP were investigated respectively in 125 patients with “isolated” vertigo and 100 healthy controls. Results: There were statistically significant differences between two groups for overall abnormalities of TCD (X² = 61.96, P<0.01), BAEP (X² = 97.99, P<0.01), and cervical MRI severity scale (Z = -8.71, P<0.01). In vertigo group, results showed significant correlations between TCD and cervical MRI, TCD and BAEP as well. And analysis on TCD PI and some items of BAEP demonstrated positive linear correlations. There were no statistical differences or correlations in control group. Conclusions: TCD is a sensitive method of “isolated” vertigo screening. A combined test protocol of cervical MRI, TCD and BAEP has superiorities to assess “isolated” vertigo.     

Effects of Isoflavones and Soybeans Fermented with Bacillus subtilis on Lipopolysaccharide-Induced Production of Tumor Necrosis Factor-α and Fibrinolysis In Vivo

The effects of isoflavones and of a derivative of soybeans fermented with Bacillus subtilis, designated Nattoesse?, on the lipopolysaccharide (LPS)-induced production of tumor necrosis factor-α (TNF-α) and fibrinolysis were investigated in vivo. The dietary supplement Nattoesse? contains several isoflavones. Therefore, we examined the effects of individual isoflavones (daidzein, daidzin, genistein, and genistin) on the LPS-induced production of TNF-α. Intraperitoneal injections of daidzein, daidzin, and genistin (but not of genistein before a challenge with LPS) resulted in significant depression of serum levels of TNF-α in mice. Daidzein had the strongest activity in this assay. Oral administration of daidzein to mice also had a significant suppressive effect, as compared with that of the Citrus flavanone naringin. In galactosamine-sensitized mice, by contrast, the suppression of LPS-induced lethal shock by daidzein was very weak. Nattoesse? did not inhibit the production of TNF-α nor did it prevent lethal shock. However, oral administration of Nattoesse? to mice significantly suppressed LPS-induced increases in scores of the fibrin degradation product, and the effect was both dose- and time-dependent. Thus, it appears that Nattoesse? has fibrinolytic activity during LPS-induced circulatory failure.     

Racial/Ethnic and Social Inequities in Sleep Medicine: The Tip of the Iceberg?

Purpose

It is known that racial disparities exist in terms of disease prevalence and access to health care. However, the link between race/ethnicity and sleep quality is often under-recognized.