bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeted deletion of murineCldn16identifies extra- and intrarenal compensatory mechanisms of Ca2+and Mg2+wasting
Authors: Will Constanze , Breiderhoff Tilman , Thumfart Julia , Stuiver Marchel , Kopplin Kathrin , Sommer Kerstin , Günzel Dorothee , Querfeld Uwe , Meij Iwan C. , Shan Qixian , Bleich Markus , Willnow Thomas E. , Müller Dominik
Published: February 2010

Claudin-16 (CLDN16) is critical for renal paracellular epithelial transport of Ca2+and Mg2+in the thick ascending loop of Henle. To gain novel insights into the role of CLDN16 in renal Ca2+and Mg2+homeostasis and the pathological mechanisms underlying a human disease associated with CLDN16 dysfunction [familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), OMIM 248250], we generated a mouse model of CLDN16 deficiency. Similar to patients, CLDN16-deficient mice displayed hypercalciuria and hypomagnesemia. Contrary to FHHNC patients, nephrocalcinosis was absent in our model, indicating the existence of compensatory pathways in ion handling in this model. In line with the renal loss of Ca2+, compensatory mechanisms like parathyroid hormone and 1,25(OH)2D3were significantly elevated. Also, gene expression profiling revealed transcriptional upregulation of several Ca2+and Mg2+transport systems including Trpv5, Trpm6, and calbindin-D9k. Induced gene expression was also seen for the transcripts of two putative Mg2+transport proteins, Cnnm2 and Atp13a4. Moreover, urinary pH was significantly lower when compared with wild-type mice. Taken together, our findings demonstrate that loss of CLDN16 activity leads to specific alterations in Ca2+and Mg2+homeostasis and that CLDN16-deficient mice represent a useful model to further elucidate pathways involved in renal Ca2+and Mg2+handling.
Vacuolar H+-ATPase apical accumulation in kidney intercalated cells is regulated by PKA and AMP-activated protein kinase
Authors: Gong Fan , Alzamora Rodrigo , Smolak Christy , Li Hui , Naveed Sajid , Neumann Dietbert , Hallows Kenneth R. , Pastor-Soler Núria M.
Published: February 2010

The vacuolar H+-ATPase (V-ATPase) in type A kidney intercalated cells is a major contributor to acid excretion in the collecting duct. The mechanisms of V-ATPase-trafficking regulation in kidney intercalated cells have not been well-characterized. In developmentally related epididymal clear cells, we showed previously that PKA, acting downstream of soluble adenylyl cyclase (sAC), induces V-ATPase apical membrane accumulation. These PKA-mediated effects were inhibited by activators of the metabolic sensor AMP-activated kinase (AMPK) in clear cells. Here, we examined the regulation of V-ATPase subcellular localization in intercalated cells by PKA and AMPK in rat kidney tissue slices ex vivo. Immunofluorescence labeling of kidney slices revealed that the PKA activator N6-monobutyryl cAMP (6-MB-cAMP) induced V-ATPase apical membrane accumulation in collecting duct intercalated cells, whereas the V-ATPase had a more cytosolic distribution when incubated in Ringer buffer alone for 30 min. V-ATPase accumulated at the apical membrane in intercalated cells in kidney slices incubated in Ringer buffer for 75 min, an effect that was prevented by treatment with PKA inhibitor (mPKI). The V-ATPase distribution was cytosolic in intercalated cells treated with the carbonic anhydrase inhibitor acetazolamide or the sAC inhibitor KH7, effects that were overridden by 6-MB-cAMP. Preincubation of kidney slices with an AMPK activator blocked V-ATPase apical membrane accumulation induced by 6-MB-cAMP, suggesting that AMPK antagonizes cAMP/PKA effects on V-ATPase distribution. Taken together, our results suggest that in intercalated cells V-ATPase subcellular localization and therefore its activity may be coupled to acid-base status via PKA, and metabolic status via AMPK.
Preinspiratory and inspiratory hypoglossal motor output during hypoxia-induced plasticity in the rat
Authors: Lee Kun-Ze , Fuller David D.
Published: February 2010

Respiratory-related discharge in the hypoglossal (XII) nerve is composed of preinspiratory (pre-I) and inspiratory (I) activity. Our first purpose was to test the hypothesis that hypoxia-induced plasticity in XII motor output is differentially expressed in pre-I vs. I XII bursting. Short-term potentiation (STP) of XII motor output was induced in urethane-anesthetized, vagotomized, and ventilated rats by exposure to isocapnic hypoxia (PaO2 of ∼35 Torr). Both pre-I and I XII discharge abruptly increased at beginning of hypoxia (i.e., acute hypoxic response), and the relative increase in amplitude was much greater for pre-I (507 ± 46% baseline) vs. I bursting (257 ± 16% baseline; P < 0.01). In addition, STP was expressed in I but not pre-I bursting following hypoxia. Specifically, I activity remained elevated following termination of hypoxia but pre-I bursting abruptly returned to prehypoxia levels. Our second purpose was to test the hypothesis that STP of I XII activity results from recruitment of inactive or “silent” XII motoneurons (MNs) vs. rate coding of active MNs. Single fiber recordings were used to classify XII MNs as I, expiratory-inspiratory, or silent based on baseline discharge patterns. STP of I XII activity following hypoxia was associated with increased discharge frequency in active I and silent MNs but not expiratory-inspiratory MNs. We conclude that the expression of respiratory plasticity is differentially regulated between pre-I and I XII activity. In addition, both recruitment of silent MNs and rate coding of active I MNs contribute to increases in XII motor output following hypoxia.
Thinking About Walking: Effects of Conscious Correction Versus Distraction on Locomotor Adaptation
Authors: Malone Laura A. , Bastian Amy J.
Published: February 2010

Control of the human walking pattern normally requires little thought, with conscious control used only in the face of a challenging environment or a perturbation. We have previously shown that people can adapt spatial and temporal aspects of walking to a sustained perturbation generated by a split-belt treadmill. Here we tested whether conscious correction of walking, versus distraction from it, modifies adaptation. Conscious correction of stepping may expedite the adaptive process and help to form a new walking pattern. However, because walking is normally an automatic process, it is possible that conscious effort could interfere with adaptation, whereas distraction might improve it by removing competing voluntary control. Three groups of subjects were studied: a control group was given no specific instructions, a conscious correction group was instructed how to step and given intermittent visual feedback of stepping during adaptation, and a distraction group performed a dual-task during adaptation. After adaptation, retention of aftereffects was assessed in all groups during normal treadmill walking without conscious effort, feedback, or distraction. We found that conscious correction speeds adaptation, whereas distraction slows it. Subjects trained with distraction retained aftereffects longest, suggesting that the training used during adaptation predicts the time course of deadaptation. An unexpected finding was that these manipulations affected the adaptation rate of spatial but not temporal elements of walking. Thus conscious processes can preferentially access the spatial walking pattern. It may be that spatial and temporal controls of locomotion are accessible through distinct neural circuits, with the former being most sensitive to conscious effort or distraction.
Contralateral Delay Activity Provides a Neural Measure of the Number of Representations in Visual Working Memory
Authors: Ikkai Akiko , McCollough Andrew W. , Vogel Edward K.
Published: February 2010

Visual working memory (VWM) helps to temporarily represent information from the visual environment and is severely limited in capacity. Recent work has linked various forms of neural activity to the ongoing representations in VWM. One piece of evidence comes from human event-related potential studies, which find a sustained contralateral negativity during the retention period of VWM tasks. This contralateral delay activity (CDA) has previously been shown to increase in amplitude as the number of memory items increases, up to the individual's working memory capacity limit. However, significant alternative hypotheses remain regarding the true nature of this activity. Here we test whether the CDA is modulated by the perceptual requirements of the memory items as well as whether it is determined by the number of locations that are being attended within the display. Our results provide evidence against these two alternative accounts and instead strongly support the interpretation that this activity reflects the current number of objects that are being represented in VWM.
Influence of Bilateral Vestibular Loss on Spinal Stabilization in Humans
Authors: Goodworth Adam D. , Peterka Robert J.
Published: February 2010

The control of upper body (UB) orientation relative to the pelvis in the frontal plane was characterized in bilateral vestibular loss subjects (BVLs) and compared with healthy control subjects (Cs). UB responses to external perturbations were evoked using continuous pelvis tilts (eyes open and eyes closed) at various amplitudes. Lateral sway of the lower body was prevented on all tests. UB sway was summarized using root-mean-square measures and dynamic behavior was characterized using frequency response functions (FRFs) from 0.023 to 10.3 Hz. Both subject groups had similar FRF variations as a function of stimulus frequency and were relatively unaffected by visual availability, indicating that visual orientation cues contributed very little to UB control. BVLs had larger UB sway at frequencies below ∼1 Hz compared with Cs. A feedback model of UB orientation control was used to identify sensory contributions to spinal stability and differences between subject groups. The model-based interpretation of experimental results indicated that a phasic proprioceptive signal encoding the angular velocity of UB relative to lower body motion was a major contributor to overall system damping. Parametric system identification showed that BVLs used proprioceptive information that oriented the UB toward the pelvis to a greater extent compared with Cs. Both subject groups used sensory information that oriented the UB vertical in space to a greater extent as pelvis tilt amplitudes increased. In BVLs, proprioceptive information signaling the UB orientation relative to the fixed lower body provided the vertical reference, whereas in Cs, vestibular information also contributed to the vertical reference.
ATP-Binding Cassette Systems ofBrucella
Authors: Jenner Dominic C. , Dassa Elie , Whatmore Adrian M. , Atkins Helen S.
Published: February 2010

Brucellosis is a prevalent zoonotic disease and is endemic in the Middle East, South America, and other areas of the world. In this study, complete inventories of putative functional ABC systems of fiveBrucellaspecies have been compiled and compared. ABC systems ofBrucella melitensis16M,Brucella abortus9-941,Brucella canisRM6/66,Brucella suis1330, andBrucella ovis63/290 were identified and aligned. High numbers of ABC systems, particularly nutrient importers, were found in allBrucellaspecies. However, differences in the total numbers of ABC systems were identified (B. melitensis, 79;B. suis, 72;B. abortus64;B. canis, 74;B. ovis, 59) as well as specific differences in the functional ABC systems of theBrucellaspecies. SinceB. ovisis not known to cause human brucellosis, functional ABC systems absent in theB. ovisgenome may represent virulence factors in human brucellosis.
Influence of Melatonin on Cerebrovascular Proinflammatory Mediators Expression and Oxidative Stress Following Subarachnoid Hemorrhage in Rabbits
Authors: Fang Qi , Chen Gang , Zhu Weiwei , Dong Wanli , Wang Zhong
Published: February 2010

The aim of this study is to analyze whether melatonin administration influenced the nuclear factor-kappa B (NF-κB) activity, proinflammatory cytokines expression, and oxidative response in the basilar artery after SAH. A total of 48 rabbits were randomly divided into four groups: control group, SAH group, SAH + vehicle group, and SAH + melatonin group. All SAH animals were subjected to injection of autologous blood into cisterna magna twice on day 0 and day 2. The melatonin was administered intraperitoneally at a dose of 5 mg/kg/12 h simultaneously with SAH from day 0 to day 5. The basilar arteries were extracted on day 5 after SAH. As a result, we found that vascular inflammation and oxidative stress were induced in all SAH animals. In animals given melatonin, basilar arterial NF-κB and pro-inflammatory cytokines were decreased in comparison to vehicle-treated animals. Measures of oxidative stress also showed significant downregulation after melatonin treatment. Furthermore, administration of melatonin prevented vasospasm on day 5 following SAH. In conclusion, post-SAH melatonin administration may attenuate inflammatory response and oxidative stress in the spasmodic artery, and this may be one mechanism involved in the therapeutic effect of melatonin on the subsequent vasospasm after SAH.
Chaos and Control of Game Model Based on Heterogeneous Expectations in Electric Power Triopoly
Authors: Ji Weizhuo
Published: February 2010

A dynamic repeated game model has been established based on heterogeneous expectations in electric power triopoly. Theoretical analysis and numerical simulation show the complexity of this model; suppose that the producers make decisions with naive expectation and bounded rationality. The straight‐line stabilization chaos control method was successfully applied to the dynamic repeated game model. The results have important practical value for the producers in the electric power oligopoly.
Prosthodontic Rehabilitation Alternative of Patients with Cleft Lip and Palate (CLP): Two Cases Report
Authors: Ayna Emrah , Başaran Emine Göncü , Beydemir Köksal
Published: February 2010

Although patients with cleft lip and palate (CLP) are not seen regularly in general dental practice, this is a frequent congenital anomaly; approximately one in every 800 live births results in a CLP. The cause of CLP is unknown, but possible causes are malnutrition and irradiation during pregnancy, psychological stress, teratogenic agents, infectious agents (viruses), and inheritance. Most clefts are likely caused by multiple genetic and nongenetic factors. Prosthetic reconstruction of the anterior maxilla is important for these patients. This paper describes the prosthetic rehabilitation of two patients with CLP, 19-year-old and 21-year-old women, both with surgically treated CLP. In both, an examination revealed a residual palatal defect of  mm and missing maxillary lateral incisors. The 19-year-old was treated with a fiber-reinforced composite resin-bonded fixed partial denture. The 21-year-old was treated with a removable partial denture with an extracoronal attachment system. The prosthetic rehabilitation of the two patients with CLP was evaluated clinically. In both, well-planned prosthetic, periodontal, and surgical therapy resulted in satisfactory function and esthetics, alleviating their deformities. With education and appropriate recall, the patients should be able to maintain their oral health.
Growth Mechanism of Cubic‐Silicon Carbide Nanowires
Authors: Cheong K. Y. , Lockman Z.
Published: February 2010

Cubic‐SiC nanowires were synthesized using activated carbon powder and Si substrate in vacuum at 1200–1350∘C for 1–4 hours. The nanowires were grown according to the following proposed mechanisms: (1) diffusion of C/CO into Si substrate, (2) weakening of Si bond and atomic kick‐out, (3) formation of Si‐C in vapor phase, (4) formation of saturated SiC layer, (5) formation of pyramid‐like SiC nanostructure, and (6) formation of SiC nanowires.
Origins and Development of Initiation of Free Radical Polymerization Processes
Authors: Braun Dietrich
Published: February 2010

At present worldwide about 45% of the manufactured plastic materials and 40% of synthetic rubber are obtained by free radical polymerization processes. The first free radically synthesized polymers were produced between 1910 and 1930 by initiation with peroxy compounds. In the 1940s the polymerization by redox processes was found independently and simultaneously at IG Farben in Germany and ICI in Great Britain. In the 1950s the systematic investigation of azo compounds as free radical initiators followed. Compounds with labile C–C-bonds were investigated as initiators only in the period from the end of the 1960s until the early 1980s. At about the same time, iniferters with cleavable S–S-bonds were studied in detail. Both these initiator classes can be designated as predecessors for “living” or controlled free radical polymerizations with nitroxyl-mediated polymerizations, reversible addition fragmentation chain transfer processes (RAFT), and atom transfer radical polymerizations (ATRP).
The M‐Wright Function in Time‐Fractional Diffusion Processes: A Tutorial Survey
Authors: Mainardi Francesco , Mura Antonio , Pagnini Gianni
Published: February 2010

In the present review we survey the properties of a transcendental function of the Wright type, nowadays known as M‐Wright function, entering as a probability density in a
relevant class of self‐similar stochastic processes that we generally refer to as time‐fractional
diffusion processes. Indeed, the master equations governing these processes
generalize the standard diffusion equation by means of time‐integral operators interpreted
as derivatives of fractional order. When these generalized diffusion processes are properly
characterized with stationary increments, the M‐Wright function is shown to play the
same key role as the Gaussian density in the standard and fractional Brownian motions.
Furthermore, these processes provide stochastic models suitable for describing phenomena
of anomalous diffusion of both slow and fast types.
Angiogenesis Inhibition in Prostate Cancer: Current Uses and Future Promises
Authors: Aragon-Ching Jeanny B. , Madan Ravi A. , Dahut William L.
Published: February 2010

Angiogenesis has been well recognized as a fundamental part of a multistep process in the evolution of cancer progression, invasion, and metastasis. Strategies for inhibiting angiogenesis have been one of the most robust fields of cancer investigation, focusing on the vascular endothelial growth factor (VEGF) family and its receptors. There are numerous regulatory drug approvals to date for the use of these agents in treating a variety of solid tumors. While therapeutic efficacy has been established, challenges remain with regards to overcoming resistance and assessing response to antiangiogenic therapies. Prostate cancer is the most common noncutaneous malignancy among American men and angiogenesis plays a role in disease progression. The use of antiangiogenesis agents in prostate cancer has been promising and is hereby explored.
Increased Number of CpG Island Hypermethylation in Tumor Suppressor Genes of Non-Neoplastic Gastric Mucosa Correlates with Higher Risk of Gastric Cancer
Authors: Tahara Tomomitsu , Shibata Tomoyuki , Nakamura Masakatsu , Yamashita Hiromi , Yoshioka Daisuke , Okubo Masaaki , Yonemura Joh , Maeda Yoshiteru , Maruyama Naoko , Kamano Toshiaki , Kamiya Yoshio , Fujita Hiroshi , Nakagawa Yoshihito , Nagasaka Mitsuo , Iwata Masami , Hirata Ichiro , Arisawa Tomiyasu
Published: February 2010

Background/Aim: We investigated the relationship of gastric cancer (GC) and CpG island hypermethylation (CIHM) in tumor suppressor genes of non-neoplastic gastric mucosa. Methods: Gastric mucosa samples were obtained from 125 GC and 180 non-GC subjects. CIHM of p14, p16, DAP-kinase and CDH1 genes were determined by methylation-specific polymerase chain reaction. High CIHM was defined as three or all methylated CpG islands. Results: Rates of CIHM of p14, CDH1, DAP-kinase, and high CIHM were significantly higher in all GC samples than non-GC samples (p14: 32.2 vs. 50.4%; OR = 1.70, 95% CI = 1.03–2.80, p = 0.04, CDH1: 36.1 vs. 84.0%; OR = 8.65, 95% CI = 14.74–15.77, p < 0.0001, DAP-kinase: 42.2 vs. 83.2%; OR = 5.98, 95% CI = 3.37–10.62, p < 0.0001, and high CIHM: 44.4 vs. 80.8%; OR = 4.40, 95% CI = 2.51–7.72, p < 0.0001). CIHM in CDH1 and DAP-kinase were associated with a greater risk of GC including all of its different subtypes. An increased number of CIHM was associated with an increased risk of all GC (1 CIHM; OR = 2.33, 95% CI = 0.82–6.64, p = 0.11, 2 CIHM; OR = 4.89, 95% CI = 1.79–13.37, p = 0.002, 3 CIHM; OR = 9.43, 95% CI = 3.20–27.78, p < 0.0001, and all CIHM OR = 24.71, 95% CI = 6.70–91.18, p < 0.0001). Three and all CIHM were closely associated with a higher risk of intestinal-type GC, Helicobacter pylori-positive infection status, male gender, and middle and older GC while 3 CIHM was closely associated with a higher risk of diffuse-type GC, H. pylori-negative infection status and younger GC. Conclusions: CIHM of CDH1 and DAP-kinase in non-neoplastic gastric mucosa corresponded to a risk of GC regardless of histological subtype, H. pylori infection status, gender and generation. An increased number of CIHM correlates with a higher GC risk including its various clinico-pathological subtypes.
The Wechsler Digit Symbol Substitution Test as the Best Indicator of the Risk of Impaired Driving in Alzheimer Disease and Normal Aging
Authors: Lafont Sylviane , Marin-Lamellet Claude , Paire-Ficout Laurence , Thomas-Anterion Catherine , Laurent Bernard , Fabrigoule Colette
Published: February 2010

Aims: Our purpose was to identify cognitive tools associated with unsafe driving among elderly drivers of varying cognitive levels. Methods: Twenty drivers with early-stage dementia of the Alzheimer type and 56 nondemented drivers aged 65–85 were recruited. Various cognitive processes were measured and unsafe driving was evaluated during an in-traffic road test with 3 different indicators and a composite indicator. Results: The Wechsler Digit Symbol Substitution Test score was the best cognitive measure to detect unsafe drivers using the composite driving indicator. Conclusion: The Digit Symbol Substitution Test may be used by physicians for the evaluation and follow-up of older patients, with or without Alzheimer-type dementia, as a screening tool of unsafe driving.
Nephroprotective Effect of Telmisartan in Rats with Ischemia/Reperfusion Renal Injury
Authors: Fouad Amr A. , Qureshi Habib A. , Al-Sultan Ali Ibrahim , Yacoubi Mohamed T. , Al-Melhim Walid N.
Published: February 2010

We investigated the protective effect of telmisartan, an angiotensin II receptor antagonist, against ischemia/reperfusion renal injury in rats. Bilateral ischemia was induced by clamping both renal vascular pedicles for 45 min followed by reperfusion for 3 h. Untreated rats exposed to ischemia/reperfusion showed significant elevations in blood urea nitrogen and serum creatinine levels, renal tissue levels of malondialdehyde, tumor necrosis factor-α and nitric oxide, and caspase-3 activity. This was associated with significant decreases in renal reduced glutathione level, catalase and superoxide dismutase activities. Also, significant increases in serum and renal tissue levels of homocysteine were detected following ischemia/reperfusion. Pre-ischemic treatment with telmisartan (0.3 mg/kg/day, i.p.) for 7 consecutive days significantly attenuated the increases in blood urea nitrogen, serum creatinine, renal malondialdehyde, tumor necrosis factor-α, nitric oxide, caspase-3 activity, and serum and renal homocysteine levels, and significantly restored the renal antioxidant defenses. In addition, light and electron microscopic examinations revealed that telmisartan pre-treatment markedly ameliorated ischemia/reperfusion-induced renal tissue damage. It was concluded that telmisartan, through its antioxidant, anti-inflammatory and antiapoptotic effects, can be considered a potential candidate to protect against acute ischemia/reperfusion renal injury.
Effects of Fentanyl Pretreatment on Regional Cerebral Blood Flow in Focal Cerebral Ischemia in Rats
Authors: Chi Oak Z. , Hunter Christine , Liu Xia , Chokshi Sagar K. , Weiss Harvey R.
Published: February 2010

Background:There are reports that opioid preconditioning induces opioid-receptor-dependent neuroprotection against cerebral ischemia. This experiment was performed to test whether pretreatment with fentanyl, a synthetic primary µ-opioid receptor agonist, would affect the regional cerebral blood flow (rCBF) in focal cerebral ischemia in rats. Methods: Twenty-four hours before permanent and unilateral middle cerebral artery (MCA) occlusion, rats were pretreated with normal saline, 200 µg/kg of fentanyl i.p. or 500 µg/kg of fentanyl i.p. The rats were anesthetized with isoflurane and were mechanically ventilated to cannulate the vessels and to occlude MCA. One hour after MCA occlusion, the rCBF was measured using 14C-iodoantipyrine. Results: The cortical rCBF decreased 1 h after MCA occlusion in all the experimental groups. In the ischemic cortex, the rCBF of the rats treated with 500 µg/kg of fentanyl was significantly greater (+80%, p < 0.05) than that of the control animals. The rCBF of the ischemic cortex of the rats treated with fentanyl 200 µg/kg seemed higher than in the control animals, but the difference was not statistically significant. The rCBF was similar in the nonischemic brain regions such as the contralateral cortex or pons among the experimental groups. Conclusion: Our data demonstrated that pretreatment with fentanyl improved the rCBF in the focal ischemic area without change in rCBF in the nonischemic cortex. Our data suggest that fentanyl could be effective in improving the rCBF in the focal ischemic area when used as a preconditioning agent and that improvement of rCBF could be one of the contributing factors of neuroprotection by opioid preconditioning.
Time Trend in Diagnosing Dementia in Secondary Care
Authors: Phung Thien Kieu Thi , Waltoft Berit Lindum , Kessing Lars Vedel , Mortensen Preben Bo , Waldemar Gunhild
Published: February 2010

Background: To study the trend of diagnosing dementia in the secondary health care sector over time, we conducted a nationwide longitudinal study of the incidence and prevalence of registered dementia diagnoses in the Danish national hospital registers. Methods: All Danish residents born before 1964 and alive at their 40th birthday were followed from their 40th birthday or January 1, 1970, whichever came later, to the date of the first dementia diagnosis recorded in the hospital registers, the date of emigration, date of death, or December 31, 2004, whichever came first. The age- and period-specific incidence and prevalence of dementia were calculated and compared to estimates from large community-based cohort studies in Europe. Results: The study population consisted of 4,723,838 persons with 81,090,583 person-years of follow-up. 154,152 dementia cases were registered from 1970 to 2004. The incidence and prevalence of registered dementia diagnoses showed an increasing trend over time. In 2003, the age-standardized incidence rate ratio was 0.66 when compared to estimates from large European community-based cohort studies. Conclusions: The study shows a marked improvement in the diagnostic rate of dementia in secondary care over time and indicates that this sector can be an important point of entry for patients with dementia.
Quality of Life of Patients with Alzheimer’s Disease: Differential Perceptions between Spouse and Adult Child Caregivers
Authors: Conde-Sala J.L. , Garre-Olmo J. , Turró-Garriga O. , Vilalta-Franch J. , López-Pousa S.
Published: February 2010

Background/Aims: Little research has been conducted into differences in the perceived quality of life of patients (QoL-p) when comparing spouse and adult child caregivers of people with Alzheimer’s disease (AD). The aim of this study was to identify the differential variables in perceived QoL-p between patients and carers, distinguishing between spouse and adult child caregivers. Method: Cross-sectional analytic study of 251 patients and their carers (spouses: 112; adult children: 139) using the QoL-AD scale and sociodemographic and clinical data. Results: The more positive perception of spouses was associated with higher educational levels of the caregiver and greater functional autonomy in the patient. The more negative perception of adult children was associated with greater caregiver burden and higher levels of depression in the patient. The perception of daughter caregivers showed the strongest association with mental health and burden. Conclusions: Spouse caregivers have a more positive perception of the patient’s quality of life than adult child caregivers.
Incidence of Mild Cognitive Impairment: A Systematic Review
Authors: Luck Tobias , Luppa Melanie , Briel Susanne , Riedel-Heller Steffi G.
Published: February 2010

Background/Aims: Subjects with mild cognitive impairment (MCI) constitute a risk population of developing dementia and thus a population of clinical interest. This study reviews recent work on the incidence of MCI in the elderly. Methods: Incidence papers were identified by a systematic literature search. Studies on the incidence of MCI were considered if they identified ‘cognitively mildly impaired’ subjects by application of the MCI criteria, used the ‘person-years-at-risk’ method, and were based on population- or community-based samples. Results: Nine studies were identified. The incidence of amnestic MCI subtypes ranged between 9.9 and 40.6 per 1,000 person-years, and the incidence of non-amnestic MCI subtypes was 28 and 36.3 per 1,000 person-years. Regarding any MCI, incidence rates of 51 and 76.8 per 1,000 person-years were found. A higher risk of incident MCI mainly resulted for higher age, lower education and hypertension. Discussion: The incidence rates of MCI varied widely, and possible risk factors for incident MCI were analysed only to a limited extent. The findings call for an agreement concerning the criteria used for MCI and the operationalisation of these criteria.
Smoking Attenuates Increase in Exhaled Nitric Oxide in Atopic but Not in Nonatopic Young Adults with Asthma
Authors: Rouhos Annamari , Ekroos Heikki , Karjalainen Jouko , Sarna Seppo , Haahtela Tari , Sovijärvi Anssi R.A.
Published: February 2010

Background: Measurement of fractional exhaled nitric oxide (FENO) is useful in assessing eosinophilic airway inflammation. Smoking may modify airway inflammation and reduce FENO levels, compromising the diagnostic value of FENO in smokers. How smoking influences FENO in atopic versus nonatopic asthmatics is unknown. The aim of the present study was to compare FENO in atopic and nonatopic steroid-naive young asthmatic adults and in healthy subjects in terms of smoking. Methods: Forty-six (30 atopic) smoking and 70 (54 atopic) nonsmoking steroid-naive army conscripts (mean age 20 years) with current symptomatic asthma underwent FENO measurement, skin prick tests, spirometry with a bronchodilation test, bronchial histamine challenge, and a standardized exercise test. Ten healthy smokers and 9 healthy nonsmokers underwent FENO measurement, spirometry and bronchial histamine challenge. Results: Smokers with asthma showed significantly higher FENO than did healthy smokers and nonsmokers (p = 0.001, both comparisons). Among atopic asthmatics, FENO was lower in smokers than in nonsmokers (p = 0.002) whereas among nonatopic asthmatics no such difference was detectable (p = 0.89). However, even among nonatopic asthmatic smokers FENO was significantly higher than among healthy controls (p = 0.01). Conclusion: Smoking seems to attenuate the increase in FENO in atopic but not in nonatopic asthmatics. This finding suggests differences in biochemical mechanisms of NO formation in atopic and nonatopic asthma. However, FENO was significantly higher both in atopic and nonatopic asthmatic smokers than in healthy controls. This suggests that FENO can be applied for diagnostic purposes also in young adult smokers.
The T Cell Response to Major Grass Allergens Is Regulated and Includes IL-10 Production in Atopic but Not in Non-Atopic Subjects
Authors: Domdey A. , Liu A. , Millner A. , Lund K. , Jacobi H. , Malling H.J. , Søndergaard I. , Würtzen P.A.
Published: February 2010

Background: The incidence of allergic diseases is increasing in industrialized countries and the immunological mechanisms leading to tolerance or allergy are poorly understood. Cytokines with suppressive abilities and CD4+CD25+ regulatory T cells have been suggested to play a central role in allergen-specific responses. The aim was to determine whether major grass allergens induce production of suppressive cytokines in allergic and healthy subjects and to examine the inhibitory effect of these cytokines on allergic responses. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from healthy and grass-allergic donors and stimulated with the major grass allergens Phl p 1 or Phl p 5. The effects of endogenous IL-10 and/or TGF-β on proliferation and cytokine production were determined by use of blocking antibodies. In addition, the number of CD4+CD25+ T cells and their expression of chemokine receptors were investigated by flow cytometry. Results: Phl p 1 and Phl p 5 induced IL-10 production, which down-regulated proliferation and cytokine production, in PBMC cultures from atopic but not from non-atopic donors. Comparable frequencies of CD4+CD25+ T cells were present in PBMCs in the two groups, but fewer cells from atopic donors were CD4+CD25+CCR4+ and more cells were CD4+CD25+CLA+ compared to healthy donors. Conclusion:Allergen-specific responses of grass allergic patients but not in non-atopic subjects are influenced by regulatory cytokines produced in response to the important allergens. Differences in CD4+CD25+ T cell expression of chemokine receptors in allergic compared to non-atopic donors could suggest that the homing of CD4+CD25+ T cells is important for the regulation of allergen-specific responses.
Novel Adenovirus Vectors ‘Capsid-Displaying’ a Human Complement Inhibitor
Authors: Seregin Sergey S. , Hartman Zachary C. , Appledorn Daniel M. , Godbehere Sarah , Jiang Haixiang , Frank Michael M. , Amalfitano Andrea
Published: February 2010

Adenovirus (Ad) vectors are currently the most commonly utilized gene transfer vectors in humans worldwide. Unfortunately, upon contact with the circulatory system, Ads induce several, innate, complement-dependent toxicities that limit the full potential for Ad-based gene transfer applications. Therefore, we have constructed several novel Ad5-based vectors, ‘capsid-displaying’ as fiber or pIX fusion proteins, a complement-regulatory peptide (COMPinh). These novel Ads dramatically minimize Ad-dependent activation of the human and non-human primate complement systems, as determined by several assays. In summary, our work has shown that a novel COMPinh-displaying Ad5 has the potential for broadening the safe use of Ad vectors in future human applications.
Twelve-Year Follow-Up of American Women’s Awareness of Cardiovascular Disease Risk and Barriers to Heart Health
Authors: Mosca Lori , Mochari-Greenberger Heidi , Dolor Rowena J. , Newby L. Kristin , Robb Karen J.
Published: February 2010

Background—

Awareness of cardiovascular disease (CVD) risk has been linked to taking preventive action in women. The purpose of this study was to assess contemporary awareness of CVD risk and barriers to prevention in a nationally representative sample of women and to evaluate trends since 1997 from similar triennial surveys.

Methods and Results—

A standardized survey about awareness of CVD risk was completed in 2009 by 1142 women ≥25 years of age, contacted through random digit dialing oversampled for racial/ethnic minorities, and by 1158 women contacted online. There was a significant increase in the proportion of women aware that CVD is the leading cause of death since 1997 (
P
for trend=<0.0001). Awareness among telephone participants was greater in 2009 compared with 1997 (54% versus 30%,
P
<0.0001) but not different from 2006 (57%). In multivariate analysis, African American and Hispanic women were significantly less aware than white women, although the gap has narrowed since 1997. Only 53% of women said they would call 9-1-1 if they thought they were having symptoms of a heart attack. The majority of women cited therapies to prevent CVD that are not evidence-based. Common barriers to prevention were family/caretaking responsibilities (51%) and confusion in the media (42%). Community-level changes women thought would be helpful were access to healthy foods (91%), public recreation facilities (80%), and nutrition information in restaurants (79%).

Conclusions—

Awareness of CVD as the leading cause of death among women has nearly doubled since 1997 but is stabilizing and continues to lag in racial/ethnic minorities. Numerous misperceptions and barriers to prevention persist and women strongly favored environmental approaches to facilitate preventive action.
Wealth Inequalities and Population Dynamics in Early Modern Northern Italy
Authors: Alfani Guido
Published: February 2010

An analysis of the wealth and population of early modern Ivrea—based on the estimi, or property tax, records; the correzioni degli estimi, a continuous series of tax records rarely found elsewhere and hardly ever used before; the census of 1613, another unique and informative source; and other archival records—finds that the city's concentration and distribution of wealth was resilient even in face of acute demographical shocks (such as the plague of 1630) and that inequalities in property underwent a slow increase even in economically stagnant areas during the seventeenth century. The article places these findings in a European perspective, and it debates Jan van Zanden's hypothesis of a positive relationship between inequality in wealth and demographical/economic growth before the Industrial Revolution.
A Simulation Framework for Sensor-Based Systems in Second Life
Authors: Prendinger Helmut , Brandherm Boris , Ullrich Sebastian
Published: February 2010

This paper describes a simulation framework for sensor-based systems based on Second Life, a popular virtual 3D multi-user online world. With this platform, the components of sensor-based systems can be mapped to, or represented by, virtual devices and objects. The intuitive user interface of Second Life (SL) and its comprehensive visualization capability support evaluation tasks of ubiquitous computing applications. Developers, as avatars, can directly control and manipulate virtual devices. In this way, different settings of sensor-based systems can be tested, and interactively improved. A bidirectional interface between sensor-based systems and Second Life has been implemented to demonstrate Second Life as a testbed for an RFID-based positioning system.
Is the Extra-territorial Application of the Human Rights Act Really Justified?
Authors: Farrant James
Published: February 2010

The question of whether the Human Rights Act can apply outside the UK has exercised English appellate courts in a number of recent cases. The European Court of Human Rights in Strasbourg has also dealt with the question of extra-territoriality in respect of the European Convention on Human Rights, most notably in the case of Bankovic v Belgium. This article considers whether, as a matter of strict construction, there can be extra-territorial application of the Act and/or the Convention. It goes on to consider some particular circumstances where extra-territorial application has been found, and attempts to set down some principles governing when the courts ought to apply the Act or Convention outside the territory of a High Contracting Party. The article concludes that the existing jurisprudence both at Strasbourg and in the UK strikes a sensible balance between the Convention's regional character and the need to ensure States Parties are accountable for their conduct abroad. This article applauds the Strasbourg and UK courts' importation of relevant principles of public international law in determining the scope and applicability of the rights protected by the Convention.
Epidemiological Data and Comorbidities of 428 Patients Hospitalized With Erysipelas
Authors: Pereira de Godoy José Maria , Galacini Massari Patricia , Yoshino Rosinha Mônica , Marinelli Brandão Rafael , Foroni Casas André Luís
Published: February 2010

The aim of this study was to evaluate the epidemiological data and the main comorbidities of patients with erysipelas admitted to a tertiary hospital. All patients admitted due to erysipelas during the period from 1999 to 2008 were included in a prospective and cross-sectional study. The Fisher exact test and logistic regression were used for statistical analysis. A total of 428 individuals were hospitalized with 41 rehospitalizations; 51.17% of the patients were women, the mean age was 58.6 years. The main comorbidities were hypertension (51.6%), diabetes mellitus (41.6%), chronic venous insufficiency (36.2%), other cardiovascular diseases (33.2%) including angina, peripheral arterial insufficiency, acute myocardial infarction, and strokes, obesity (12.1%), chronic renal failure (6.8%), neoplasms (4.9%), cirrhosis (4.9%), chronic lymphedema (4.2%), and leg ulcers (2.6%). Erysipelas is a seasonal disease that affects adults and the elderly people, has a repetitive nature, and is associated with comorbidities.
Motivation and Autonomy in Counseling, Psychotherapy, and Behavior Change: A Look at Theory and Practice 1ψ7
Authors: Ryan Richard M. , Lynch Martin F. , Vansteenkiste Maarten , Deci Edward L.
Published: February 2010

Motivation has received increasing attention across counseling approaches, presumably because clients’ motivation is key for treatment effectiveness. The authors define motivation using a self-determination theory taxonomy that conceptualizes motivation along a relative-autonomy continuum. The authors apply the taxonomy in discussing how various counseling approaches address client motivation and autonomy, both in theory and in practice. The authors also consider the motivational implications of nonspecific factors such as therapeutic alliance. Across approaches, the authors find convergence around the idea that clients’ autonomy should be respected and collaborative engagement fostered. The authors also address ethical considerations regarding respect for autonomy and relations of autonomy to multicultural counseling. The authors conclude that supporting autonomy is differentially grounded in theories and differentially implemented in approaches. Specifically, outcome-oriented treatments tend to consider motivation a prerequisite for treatment and emphasize transparency and up-front consent; process-oriented treatments tend to consider motivation a treatment aspect and give less emphasis to transparency and consent.
A Comparison of Robbers’ Use of Physical Coercion in Commercial and Street Robberies
Authors: McCluskey John D.
Published: February 2010

The face-to-face confrontation involved in the crime of robbery renders vast amounts of financial, physical, and psychological injury in the United States. This study developed hypotheses from existing literature regarding salient situational factors associated with the prevalence of overt physical coercion during commercial and street robberies. The study examined the effect of situational and personal characteristics on robbers’ use of coercion, with data coded from police reports of 1,281 street and commercial robberies in one precinct of Detroit, Michigan, between 2000 and 2003. The research results are relatively consistent with findings from the literature on robbery in the last 40 years: Street robberies involve a greater prevalence of physical force than do commercial robberies; guns reduce the likelihood of physical force; and victim resistance increases physical force. Additionally, characteristics of victims and offenders play a secondary role in predicting whether physical coercion is brought to bear on the victims of robbery.
Clinical Pharmacokinetics of Pregabalin in Healthy Volunteers
Authors: Bockbrader Howard N. , Radulovic Louis L. , Posvar Edward L. , Strand James C. , Alvey Christine W. , Busch Janice A. , Randinitis Edward J. , Corrigan Brian W. , Haig George M. , Boyd Rebecca A. , Wesche David L.
Published: February 2010

Pregabalin has shown clinical efficacy for treatment of neuropathic pain syndromes, partial seizures, and anxiety disorders. Five studies in healthy volunteers are performed to investigate single‐ and multiple‐dose pharmacokinetics of pregabalin. Pregabalin is rapidly absorbed following oral administration, with peak plasma concentrations occurring between 0.7 and 1.3 hours. Pregabalin oral bioavailability is approximately 90% and is independent of dose and frequency of administration. Food reduces the rate of pregabalin absorption, resulting in lower and delayed maximum plasma concentrations, yet the extent of drug absorption is unaffected, suggesting that pregabalin may be administered without regard to meals. Pregabalin elimination half‐life is approximately 6 hours and steady state is achieved within 1 to 2 days of repeated administration. Corrected for oral bioavailability, pregabalin plasma clearance is essentially equivalent to renal clearance, indicating that pregabalin undergoes negligible nonrenal elimination. Pregabalin demonstrates desirable, predictable pharmacokinetic properties that suggest ease of use. Because pregabalin is eliminated renally, renal function affects its pharmacokinetics.
Population Pharmacokinetics and Pharmacogenetics of Mycophenolic Acid Following Administration of Mycophenolate Mofetil in De Novo Pediatric Renal‐Transplant Patients
Authors: Zhao Wei , Fakhoury May , Deschênes Georges , Roussey Gwenaelle , Brochard Karine , Niaudet Patrick , Tsimaratos Michel , André Jean Luc , Cloarec Sylvie , Cochat Pierre , Bensman Albert , Azougagh Saïd , Jacqz‐Aigrain Evelyne
Published: February 2010

The objective was to develop a population pharmacokinetic‐pharmacogenetic model of mycophenolic acid following administration of mycophenolate mofetil (MMF) in de novo pediatric renal‐transplant patients and identify factors that explain variability. The pharmacokinetic samples were collected from 89 de novo pediatric renal‐transplant patients treated with MMF and studied during the first 60 postoperative days. All patients were genotyped for UGT1A8–A9, UGT2B7, and ABCC2. Population pharmacokinetic analysis was performed with the NONMEM and was validated using bootstrap visual predictive check. The pharmacokinetic data were best described by a 2‐compartment model with Erlang distribution to describe the absorption phase. The covariate analysis identified body weight as an individual factor influencing central volume of distribution and concomitant immunosuppressive medication and identified body weight and UGT2B7 802C>T genotype as individual factors influencing apparent oral clearance (CL/F) of MMF. CL/F in cyclosporine‐MMF‐treated patients was 33% higher than in tacrolimus‐MMF‐treated patients. The CL/F was significantly lower in patients with UGT2B7 802 C/C genotype compared with patients with UGT2B7 802 C/T and 802T/T genotypes, and this effect was independent of concomitant immunosuppressive medication or body weight. The population pharmacokinetic‐pharmacogenetic model of mycophenolic acid was validated. Body weight, concomitant medication, and UGT2B7 genotype contribute significantly to the interindividual variability of MMF disposition in pediatric renal‐transplant patients.