bluuebunny/crossref_metadata_2025 huggingface dataset:
Alterations in cerebral potentials evoked by rectal distention and drinking ice water in patients with irritable bowel syndrome
Authors: Zuo Xiu Li , Li Yan Qing , Huang Kun Ming , Kuang Rong Guang , Lv Guo Ping , Lu Xue Feng , Li Jun Man , Desmond Paul V
Published: September 2006

Aim:  Visceral hypersensitivity has been found to be present in irritable bowel syndrome (IBS). The current study sought to study visceral afferent hypersensitivity in IBS patients and obtain further objective evidence of alterations in intestinal afferent pathways in IBS patients by cerebral evoked potentials (CEP).

Method:  We studied 30 female IBS patients and 12 female healthy subjects. Rectal perception thresholds to balloon distention were measured and CEP was recorded in response to rhythmic rectal distention (two distention series, each of 100 repetitions at a frequency of 1 Hz) at the volume of perception thresholds. All subjects were then asked to drink 220 mL 4°C ice water and the above steps were repeated 20 min later.

Results:  Rectal distention led to recognizable and reproducible CEP. Compared to healthy subjects, IBS patients demonstrated significantly shorter N1, P1 and N2 latencies (P < 0.05). After drinking ice water, IBS patients exhibited further shortened N1, P1 and N2 latencies (P < 0.05), but drinking did not alter the latencies of healthy controls and the amplitudes of both IBS patients and healthy controls.

Conclusion:  The shorter latency of cerebral potentials evoked by rectal distention and ice water stimulation in IBS patients provided further objective evidence for defective visceral afferent transmission in IBS patients.
Lamivudine resistance in patients with chronic hepatitis B: Role of clinical and virological factors
Authors: Thompson Alexander J V , Ayres Anna , Yuen Lilly , Bartholomeusz Angeline , Bowden D Scott , Iser David M , Chen Robert Y M , Demediuk Barbara , Shaw Gideon , Bell Sally J , Watson Katrina J R , Locarnini Stephen A , Desmond Paul V
Published: September 2006

Background:  Lamivudine resistance is associated with long‐term monotherapy for chronic hepatitis B and can lead to potentially serious clinical consequences. Scant information exists regarding the influence of hepatitis B virus variants in the development of resistance. The present study was designed to identify factors predictive of lamivudine resistance, with a particular focus on the role of precore and basal core promoter variants in the setting of hepatitis B e antigen‐negative disease.

Methods:  Eighty‐five patients, representing four major genotypes, were followed prospectively on lamivudine therapy. Resistance was defined as an increase in viral load, with polymerase gene sequencing confirming a lamivudine resistance mutation. Median follow up was 19 months (6–54 months). The Cox proportional hazards model was used to determine variables independently predicting for the early onset of lamivudine resistance.

Results:  The rate of lamivudine resistance was 6%, 31% and 51% at 12, 24 and 48 months, respectively. Multivariate analysis identified the precore variant, high baseline alanine aminotransferase (ALT), and persistent viremia (at 6 months) as independent predictors of the early development of lamivudine resistance, with rate ratios of 4.93 (95% confidence interval [CI]: 1.32–18.5), 1.22 (95%CI: 1.08–1.49), and 4.73 (95%CI: 1.49–15.0), respectively (P < 0.05). Female sex predicted early resistance (rate ratio 5.27 [95%CI: 1.23–22.5, P < 0.05]) although numbers were small (n = 12). Genotype did not influence treatment response nor time to onset of resistance.

Conclusion:  Patients with precore variant hepatitis B virus are likely to develop lamivudine resistance early and should be considered for alternate first‐line monotherapy. In the future, combination antiviral therapy may limit the development of resistance.
Critical appraisal of the management of severe malnutrition: 4. Implications for Aboriginal child health in northern Australia
Authors: Brewster David R
Published: September 2006

Abstract:  The main implications of this review for the treatment of malnourished Australian Aboriginal children in northern Australia are that the emphasis needs to change from hospital case management with enteral tube‐feeding to improved community management with a focus on environmental health (e.g. housing, hygiene and overcrowding) and child care issues.
Post‐neonatally acquired cerebral palsy in Victoria, Australia, 1970–1999
Authors: Reid Susan M , Lanigan Anna , Reddihough Dinah S
Published: September 2006

Aim: To use the information from a population‐based cerebral palsy register to describe post‐neonatally acquired cerebral palsy, to determine trends over time and relate any aetiological trends to community preventative measures.

Methods: Data on cases of post‐neonatally acquired cerebral palsy, between the birth years 1970 and 1999, were generated from the Victorian Cerebral Palsy Register. Distributions, rates and trends over time were calculated for the entire cohort and for subgroups according to gender, age at acquisition, aetiology, gestation at delivery, birthweight, maternal age at delivery and parity.

Results: 339 cases were found with post‐neonatally acquired cerebral palsy, accounting for 10.7% of all cerebral palsy and giving an overall rate of 1.98/10 000 live births. There was a statistically significant fall in the overall rate of post‐neonatally acquired cerebral palsy (P = 0.001) over the study period. Significant falls were seen in post‐neonatal cerebral palsy due to infection, traumatic head injury and hypoxia and other acute encephalopathies, but not cerebrovascular accidents.

Conclusion: A large proportion of post‐neonatally acquired cerebral palsy is preventable. While the reported decline in cases in Victoria is encouraging, it will be important to monitor these trends over time, and continue public health measures to further reduce preventable causes.
Sleep architecture in children with adenoidal hypertrophy
Authors: Zhang Xiao‐Wen , Zhou Feng , Li Yuan , Huang Zhao‐Tong , Wang Zhen‐Lin
Published: September 2006

Aim:  Adenoidal hypertrophy (AH) in children is associated with obstructive manifestations like mouth breathing, snoring. Unfortunately, little is known regarding sleep architecture of AH in children. The purpose of this study was therefore undertaken to investigate the polysomnographic variables in children with AH.

Method:  47 children with AH and 11 controls underwent nocturnal polysomnography. Sleep was scored manually according to the standard set by Rechtschaffen.

Results:  In AH, stage 1 sleep percentage and rapid eye movement (REM) latency were increased significantly, while the sleep percentage of stage 2 and REM was decreased remarkably compared with that of controls. Arousal index in AH was much more higher than that in controls. Arousal index in REM sleep was higher than that in non‐rapid eye movement (NREM) sleep in AH, but the number of arousals in REM sleep was lower than that in NREM sleep. Hypopnea events were the most common type of respiratory events, followed by obstructive events in AH and controls. Apnea/hypopnea index in AH was higher in comparison to controls. No significant difference was found between the children with AH and controls in SaO2 nadir (%) and base mean SaO2 (%). Apnea/hypopnea index was related to hypopnea arousal in REM sleep and hypoxemia arousal in NREM sleep.

Conclusion:  AH is predominantly characterised by a hypopnea with little obstruction in children. Our results clearly and for the first time demonstrated that sleep architecture was abnormal in children with AH. We therefore speculate that hypopnea arousal in REM sleep and hypoxemia arousal in NREM sleep may play an important role in the course of respiratory disturbance.
Effect of multiple birth on infant mortality in Bangladesh
Authors: Hong Rathavuth
Published: September 2006

Aim: Levels of infant and child mortality in many developing countries remain unacceptably high, and they are disproportionably higher among high‐risk groups such as newborn and infant of multiple births, particularly in countries where advanced medical cares are available only at regional referral levels with limited access by the poor rural women and children. This study examined the relationship between high‐risk infant of multiple birth and infant mortality in Bangladesh.

Methods: The analysis uses information on 7001 childbirths in 5 years preceding the 2004 Bangladesh Demographic and Health Survey to examine the relationship between multiple birth and infant mortality using multivariate analysis, controlling for child’s sex, birth order, prenatal care, delivery assistance; mother’s age at child birth, nutritional status, education level; household living conditions and several other risk factors.

Results: Results indicate that children born multiple birth were more than six‐times as likely to die during infancy as those born singletons (hazard ratio = 6.51; 95% confidence interval: 4.10, 10.36). Controlling for all other risk factors does not change the strength and direction of the relationship (hazard ratio = 6.18; 95% confidence interval: 3.65, 10.46). Receiving prenatal care and access to safe drinking water are associated with lower risk.

Conclusion: Multiple births are strongly negatively associated with infant survival in Bangladesh independent of other risk factors. This evidence suggests that improving maternal and child health at the community level, screening for high‐risk pregnancies and making referral services for these conditions more accessible to the rural women and children will be key to improving child survival in Bangladesh.
Different signal transduction cascades are activated simultaneously in the rat insular cortex and hippocampus following novel taste learning
Authors: Yefet Keren , Merhav Maayan , Kuulmann‐Vander Shelly , Elkobi Alina , Belelovsky Katya , Jacobson‐Pick Shlomit , Meiri Noam , Rosenblum Kobi
Published: September 2006

Novel taste learning is a robust one‐trial incidental learning process, dependent on functional activity of the insular (taste) cortex. In contrast to that of the cortex, the role of the hippocampus in taste learning is controversial. We set out to identify the time courses of the activation of mitogen‐associated protein kinase (MAPK), transcription factor cAMP‐response element‐binding protein (CREB) and Akt/PKB (protein kinase B) in the insular cortex and hippocampus of rats subsequent to novel taste learning. Following taste learning, an early response (20 min) occurred at the same time in the insular cortex and the hippocampus. However, whereas MAPK was activated specifically in the insular cortex, CREB and Akt were phosphorylated in the hippocampus but not in the cortex. In addition, the immediate early gene, CCAAT/enhancer binding protein (C/EBPβ) was induced in both the hippocampus and the insular cortex 18 h following taste learning. The results demonstrate, for the first time, correlative activation and gene expression in the hippocampus following novel taste learning. Moreover, the results suggest that different signal transduction cascades necessary for taste learning are activated in concert in different brain structures, to enable taste learning and consolidation.
Rapid pH and PO2 changes in the tissue recording chamber during stoppage of a gas‐equilibrated perfusate: effects on calcium currents in ventral horn neurons
Authors: Carlin K. P. , Brownstone R. M.
Published: September 2006

In vitro studies often use bicarbonate‐buffered saline solutions to mimic the normal extracellular environment of tissues. These solutions are typically equilibrated with gaseous O2 and CO2, the latter interacting with bicarbonate ions to maintain a physiological pH. In vitro tissue chambers, like those used for electrophysiology, are usually continually perfused with the gassed buffer, but stopping the perfusion to add expensive chemicals or acquire imaging data is a common practice. The present study demonstrates that this procedure leads to rapid (< 30 s) increases in pH and decreases in PO2 of the detained solution in the tissue chamber. During the first 200 s, pH increased by 0.4 units and resulted in a 25% PO2 reduction of the detained solution. The rates of these changes were dependent on the volume of solution in the chamber. In experiments using acute transverse slices from the lumbar spinal cord of neonatal (postnatal day 0–10) mice, perfusion stoppage of the same duration was accompanied by a 34.7% enhancement of the peak voltage‐gated calcium current recorded from ventral horn neurons. In these cells both low voltage‐activated and high voltage‐activated currents were affected. These currents were unaffected by decreasing PO2 when a CO2‐independent buffer was used, suggesting that changes in pH were responsible for the observed effects. It is concluded that the procedure of stopping a bicarbonate/CO2‐buffered perfusate results in rapid changes in pH and PO2 of the solution detained in the tissue chamber, and that these changes have the potential to covertly influence experimental results.
USPIO – enhanced rectal cancer specimen MRI: how well does it correlate with node identification at histopathology?
Authors: Rasheed S. , Guenther T. , Talbot I. , McDonald P. , Northover J. , Stirling J. , Culver L. , Glynne‐Jones R. , Padhani A. R.
Published: September 2006

Introduction:  Detection of lymph node (LN) metastasis is important for the optimal management of rectal cancer patients. Ultrasmall‐particle superparamagnetic iron oxide (USPIO) contrast enhanced magnetic resonance imaging (MRI) has emerged as an effective method of assessing nodal involvement in various malignancies. We have investigated the correlation between nodes seen on specimen MRI and those found at histopathology and the optimum time interval between contrast injection and surgery in USPIO mesorectal lymphography.

Method:  Thirteen rectal cancer patients underwent MRI before and 24 h after intravenous infusion of USPIO contrast (Sinerem®, Advanced Magnetics Inc, Cambridge, MA, USA). Total Mesorectal Excision (TME) surgery was followed by fixed specimen MRI. Lymph nodes seen on specimen MRI and those found at pathology were compared for studies performed <5 days and ≥5 days prior to surgery.

Results:  Histopathological LNs found correlated well with those seen on specimen MRI (all patients, r = 0.73; P = 0.005, figure). Correlation was better for the <5 day group (r = 0.84; P = 0.01) than for the ≥5 day group (r = 0.54; P = 0.35).

Discussion:  USPIO specimen MRI is useful in mesorectal LN assessment. We demonstrate good correlation between specimen MRI and histopathology and show that fewer errors occur in assessment when the time interval between contrast injection and surgery is <5 days.
Factors influencing lymph node retrieval in colorectal cancer and its effect on survival
Authors: Evans M. D. , Rees A. , Stamatakis J. D. , Karandikar S. S.
Published: September 2006

Introduction:  NICE has set standards for lymph node (LN) harvest in surgery for colorectal cancer (CRC). We report the effect of the operating surgeon and reporting pathologist on lymph node yield and the role of LN yield on survival.

Method:  Data on all patients with CRC treated in a single unit between 1999 and 2004 were collected in the ACPGBI database. Lymph node harvest was identified for each of three surgeons and three pathologists. Actuarial survival of all patients with Dukes’ stage B with greater than or less than 8 reported LNs and Dukes’ stage C were compared using log‐rank test (Kaplan–Meier method).

Results:  A total of 380 cases had a curative resection with a unit median LN retrieval of 13.

There was no difference in survival between Dukes’ stage B <8 LN (mean 42 months, 95% CI 29–55) and Dukes stage C (mean 45 months, 95% CI 29–51), log‐rank P = 0.7618. Survival between Dukes stage B (8 LN and Dukes C was significantly different (mean 58 months, 95% CI 53–64 vs 45 months, 95% CI 29–51), log‐rank P = 0.006.

Colorectal surgeon
Non colorectal
Pathologist

1 n = 183
2 n = 64
3 n = 86
n = 47
1 n = 200
2 n = 106
3 n = 57
Locum n = 17

Median lymph node observed (Range)
12*1–37
14*0–25
14*2–42
14* (1–32)
15** (2–42)
12** (1–32)
11** (0–29)
11** (2–39)

95% CI
12.5–14.5
11.7–14.6
13.3–16.6
12.–16.3
14.1–16.0
12.0–14.4
9.7–12.8
7.7–16.9

*P = 0.498 (Kruskal–Wallis).

**P < 0.0001 (Kruskal–Wallis).

Conclusions:  This study demonstrates that within a single unit the reporting pathologist significantly influences LN yield in CRC treatment and that a minimum of eight lymph nodes needs to be examined to stage CRC as Dukes’ C accurately. In this unit the surgeon was not a significant variable.
Evaluation of a ‘lower GI electronic referral protocol’: analysis of 300 referral episodes
Authors: John S. K. , Jones O. M. , Howell R. , Fozard J. B.
Published: September 2006

Introduction:  Appropriate destination and referral urgency of patients with colorectal symptoms is a prerequisite for efficient diagnosis of colorectal cancers (CRC). We aim to evaluate the efficacy of an electronic referral protocol (ERP) for lower GI symptoms in primary care.

Method:  Three hundred referrals including 100 consecutive CRC (group A), 100 actual fast‐track referrals (group B) and 100 routine referrals (group C) were run through the ERP. The ability of the ERP to filter out CRC from all three groups was assessed.

Results:  Only 25% of group A had actually been referred as ‘fast‐track’. The ERP appropriately identified 73% of these cases as ‘fast‐track’ (P = 0.02). The ERP identified 49% of group B patients as ‘fast‐track’, including eight of the 11 cancers in this group. The ERP downgraded from fast‐track 19 of the 28 patients in group B without pathology. In group C, three of the four patients with CRC were upgraded to ‘fast‐track’ and overall 18 routine referrals were directed ‘fast‐track’.

Conclusion:  This preliminary study suggests that a ‘Lower GI electronic referral protocol’ in primary care might be more efficient in achieving the twin aims of channelling more patients with CRC through the fast‐track referral pathway, whilst reducing inappropriate referrals through this route. Further studies are needed to see if this ERP will increase the yield from the ‘fast‐track’ referral pathway.
Preoperative plasma MMP‐2 expression is prognostic in colorectal cancer
Authors: Tutton M. G. , Sharif S. P. , Eccles S. A. , George M. L. , Abulafi A. M.
Published: September 2006

Introduction:  The gelatinases (MMP‐2 and MMP‐9) are important in colorectal cancer invasion and metastasis. Plasma concentrations of the gelatinases correlate with clinical stage in colorectal cancer; however, whether this gives prognostic information is unknown.

Method:  Gelatinase mRNA and protein levels in tumour and plasma were determined respectively by RT‐PCR, ELISA and gelatin zymography in a prospective study of 75 colorectal cancer patients. At follow‐up, 40 patients were alive with a median survival of 75 months (range 72–80).

Results:  Expression of the gelatinases was significantly increased within tumour relative to normal colon and within plasma of cancer patients (P < 0.01; Mann–Whitney U‐test). Within plasma, total MMP‐2 and MMP‐9 expression (MMP plus MMP/TIMP complexes), determined by ELISA, and free MMP‐2(72 kDa) determined by gelatin zymography, increased significantly with Dukes’ stage (P < 0.001; Kruskal–Wallis test). As well as correlating with Dukes’ stage, lymphatic and vascular invasion, Kaplan–Meier survival analysis showed that only elevated plasma MMP‐2 was significantly associated with a worse prognosis: free MMP‐2 (worse prognosis with increasing quartile; P < 0.05) and total MMP‐2 (upper quartile cut‐off limit; P = 0.04).

Discussion:  In addition to being an indicator of colorectal cancer invasion, plasma MMP‐2 levels may provide a simple, non‐invasive preoperative test for prognosis in colorectal cancer.
Rectal sensory dysfunction is prevalent in faecal incontinence
Authors: Gooneratne M. , Lunniss P. J. , Hickey F. , Williams N. S. , Scott S. M.
Published: September 2006

Introduction:  There has been increasing interest in the role of rectal sensitivity in continence, particularly as the advent of sacral nerve stimulation (SNS). Both rectal hypersensitivity (RHyper) and hyposensitivity (RHypo) have been described in patients with faecal incontinence (FI). We aimed to determine the prevalence of rectal sensory dysfunction according to the nature of FI.

Method:  A retrospective study of 627 patients (mean age 55 years, range 20–88; 512 F) presenting with FI to a tertiary referral centre, were divided according to their isolated symptoms of urge incontinence (UI), passive incontinence (PI), post defaecatory leakage (PDL), or combined UI and PI/PDL. Patients underwent anorectal physiological assessment including rectal sensitivity to balloon distension. RHyper was classified when the maximum tolerated volume was below the Institution's normal range, and RHypo was deemed present when any of the three sensory distension thresholds were elevated above normal.

Results:  Numbers (percentages) of patient classified according to symptoms and results of rectal sensory testing

OVERALL
UI
PI
PDL
UI + PI/PDL

Normal
416 (66)
117 (28)
114 (19)
56 (12)
97 (23)

RHyper
138 (22)
55 (40)*
27 (14)
5 (3)
43 (31)*

RHypo
73 (12)
19 (26)
24 (25)*
12 (14)**
13 (18)

*P < 0.05.

**P = 0.003 (RHyper vs RHypo).

Conclusion:  One‐third of all patients with FI have a sensory abnormality, predominantly RHyper. RHyper was most significantly associated with symptoms of UI. The increased prevalence of RHypo in patients with PI and PDL is likely to be related to overflow. SNS, perhaps by modulating rectal afferent pathways, may improve incontinence by normalizing extremes of rectal sensitivity.
Predicting nutritional outcome after extensive small bowel resection
Authors: Hyder S. A. , George B. D.
Published: September 2006

Introduction:  Extensive small bowel resection often results in the need for long‐term nutritional support. This study aimed to assess the factors affecting long term nutritional outcome following extensive small bowel resection.

Method:  Patients who underwent extreme small bowel resection were assessed. Indication for small bowel resection, length of remaining small bowel, presence of ileocaecal valve, colonic resection and long term total parental nutritional (TPN) requirements were recorded.

Results:  There were 24 patients of age range 28–79 (median 49 years). Fourteen were male. Indications for small bowel resection included Inflammatory bowel disease (n = 13) Mesenteric ischemia (n = 8) and miscellaneous (n = 3). Patients were divided into three groups:

Conclusion:  Small bowel resection leaving <100 cm of small bowel is associated with a 70% chance of needing long‐term TPN. Presence of ileocaecal valve and/or some colon reduces the risk of long term TPN.
ON THE POSSIBILITIES OF GROUP INJURY
Authors: WINTER STEPHEN
Published: September 2006

Abstract: Normative discourse on genocide frequently refers to group injuries, but this can be problematic for those for whom normative justification ought, in principle, to be reducible to individual terms. Such ethical individualists may hold that an ultimately individualizable description of injury is always theoretically superior (in lacking either superfluous or ontologically suspect entities). Accepting the strictures of individualistic justification, this paper presumes that attributing injury to group subjects will be unsatisfying if this attribution does not include a normatively significant group character. Taking up these challenges, this essay analyzes the conceptual possibility of normatively significant group injury, describing its necessary and sufficient conditions.
Short-Lasting Headaches in Children
Authors: Vieira JP , Salgueiro AB , Alfaro M
Published: September 2006

Short-lasting headaches have been studied infrequently in children and it is not known if the main categories of primary headaches of this type in adults are applicable to children. We report our experience with a group of 20 children with a brief headache. Two patients had a secondary headache. One patient had a headache with some clinical characteristics of paroxysmal hemicrania. The remaining 17 had a very brief headache. They were in many aspects comparable to others from previous studies on idiopathic stabbing headache in children: no associated symptoms, no other associated headache, frequent family history of migraine. They differed, however, in the younger age of the patients and the more frequent extratrigeminal location of the pain. Extratrigeminal ice-pick pain may be a variant of idiopathic stabbing headache, more prevalent in young children.
Analysis of Case‐Only Studies Accounting for Genotyping Error
Authors: Cheng K. F.
Published: September 2006

The case‐only design provides one approach to assess possible interactions between genetic and environmental factors. It has been shown that if these factors are conditionally independent, then a case‐only analysis is not only valid but also very efficient. However, a drawback of the case‐only approach is that its conclusions may be biased by genotyping errors. In this paper, our main aim is to propose a method for analysis of case‐only studies when these errors occur. We show that the bias can be adjusted through the use of internal validation data, which are obtained by genotyping some sampled individuals twice. Our analysis is based on a simple and yet highly efficient conditional likelihood approach. Simulation studies considered in this paper confirm that the new method has acceptable performance under genotyping errors.
Community‐Acquired Bacterial Meningitis in Older People
Authors: Weisfelt Martijn , Van De Beek Diederik , Spanjaard Lodewijk , Reitsma Johannes B. , De Gans Jan
Published: September 2006

OBJECTIVES: To describe clinical features of bacterial meningitis in older people.

DESIGN: Cohort study.

SETTING: Hospitals in the Netherlands.

PARTICIPANTS: Patients aged over 16 with community‐acquired bacterial meningitis, confirmed using cerebrospinal fluid culture.

MEASUREMENTS: Data were collected prospectively. The cohort was dichotomized with respect to age (≥60 vs 17–59).

RESULTS: Two hundred fifty‐seven of 696 episodes of community‐acquired bacterial meningitis (37%) occurred in elderly patients and 439 (63%) in younger adults. Older people more often presented with the triad of fever, neck stiffness, and altered mental status than younger adults (58% vs 36%; P<.001). In older people, meningitis was due to Streptococcus pneumoniae in 176 episodes (68%). In younger adults, Neisseria meningitidis was the most common pathogen, responsible for 221 episodes (50%). Elderly patients more often developed complications than younger adults (72% vs 57%; P<.001), which resulted in a higher mortality rate (34% vs 13%; P<.001). Older people tended to die more often from cardiorespiratory failure (25% vs 11%; P=.06), whereas younger adults more often died from brain herniation (23% vs 2%; P=.004).

CONCLUSION: Elderly patients with bacterial meningitis often present with classic symptoms of bacterial meningitis. Bacterial meningitis within this age group is predominantly due to S. pneumoniae and is associated with high morbidity and mortality rates. Whereas older people die frequently of cardiorespiratory failure, younger adults more often die of brain herniation.
Reducing Suicidal Ideation in Depressed Older Primary Care Patients
Authors: Unützer Jürgen , Tang Lingqi , Oishi Sabine , Katon Wayne , Williams John W. , Hunkeler Enid , Hendrie Hugh , Lin Elizabeth H.B. , Levine Stuart , Grypma Lydia , Steffens David C. , Fields Julie , Langston Christopher ,   for the IMPACT Investigators
Published: September 2006

OBJECTIVES: To determine the effect of a primary care–based collaborative care program for depression on suicidal ideation in older adults.

DESIGN: Randomized, controlled trial.

SETTING: Eighteen diverse primary care clinics.

PARTICIPANTS: One thousand eight hundred one adults aged 60 and older with major depression or dysthymia.

INTERVENTION: Participants randomized to collaborative care had access to a depression care manager who supported antidepressant medication management prescribed by their primary care physician and offered a course of Problem Solving Treatment in Primary Care for 12 months. Participants in the control arm received care as usual.

MEASUREMENTS: Participants had independent assessments of depression and suicidal ideation at baseline and 3, 6, 12, 18, and 24 months. Depression was assessed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (SCID). Suicidal ideation was determined using the SCID and the Hopkins Symptoms Checklist.

RESULTS: At baseline, 139 (15.3%) intervention subjects and 119 (13.3%) controls reported thoughts of suicide. Intervention subjects had significantly lower rates of suicidal ideation than controls at 6 months (7.5% vs 12.1%) and 12 months (9.8% vs 15.5%) and even after intervention resources were no longer available at 18 months (8.0% vs 13.3%) and 24 months (10.1% vs 13.9%). There were no completed suicides in either group. Information on suicide attempts or hospitalization for suicidal ideation was not available.

CONCLUSION: Primary care–based collaborative care programs for depression represent one strategy to reduce suicidal ideation and potentially the risk of suicide in older primary care patients.
Effects of plant and prey characteristics on the predatory behavior of Delphastus catalinae
Authors: Guershon Moshe , Gerling Dan
Published: September 2006

Nymphal setosity of the whitefly Bemisia tabaci Gennadius (Homoptera: Aleyrodidae) has been reported to be induced by mechanical stimuli such as leaf tomentosity, and related to the predatory performance of the coccinellid Delphastus catalinae (Horn) (Coleoptera: Coccinellidae). In this study, a possible adaptive value of this phenomenon for the whitefly is shown through the combined effects of leaf and prey characteristics on the walking and predatory behaviors of the beetle. Leaf tomentosity significantly affected the walking patterns of the beetle and therefore its searching abilities, thus indirectly increasing the influence of prey distribution upon predator's efficiency. Moreover, while searching on tomentose leaves, the beetles showed preference for the smooth prey phenotype. This behavior was found dependent on the experience of the beetle in previous encounters. These results are pertinent to intraspecific competition between the different nymphal phenotypes and to the predatory efficiency of this beetle, which is utilized in biological control of whiteflies.
Remarkable susceptibility of the diamondback moth (Plutella xylostella) to ingestion of Pir toxins from Photorhabdus luminescens
Authors: Blackburn Michael B. , Farrar Robert R. , Novak Nicole G. , Lawrence Susan D.
Published: September 2006

Genes encoding Pir toxins were cloned and sequenced from Photorhabdus luminescens (Enterobacteriaceae) strain Hm. Cultures of Escherichia coli expressing the Pir A and B proteins were highly toxic when fed to larvae of Plutella xylostella L. (Lepidoptera: Plutellidae), as had been reported previously. Histological examination of P. xylostella larvae fed with recombinant E. coli revealed gross abnormalities of the midgut epithelium, with profound swelling and shedding of the apical membranes. However, the recombinant E. coli had no effect on the growth or mortality of larval Heliothis virescens F. (Lepidoptera: Noctuidae), Manduca sexta L. (Lepidoptera: Sphingidae), Lymantria dispar L. (Lepidoptera: Lymantriidae), or Leptinotarsa decemlineata Say (Coleoptera: Chrysomelidae). Based on these results, P. xylostella is at least 300‐fold more susceptible to Pir toxins than other insect species tested, suggesting that they may not be broadly useful as insecticidal proteins. Because Pir B has sequence similarities with N‐terminal portions of Cry proteins from Bacillus thuringiensis, we also tested the recombinant E. coli against a strain of P. xylostella that is resistant to the Cry 1A toxin, but found no difference in mortality between resistant and susceptible strains.
Contribution of morphology and membrane resistance to integration of fast synaptic signals in two thalamic cell types
Authors: Perreault Marie‐Claude , Raastad Morten
Published: September 2006

Thalamocortical cells (TCs) and interneurons (INs) in the lateral geniculate nucleus process visual information from the retina. The TCs have many short dendrites, whereas the INs have fewer and longer dendrites. Because of these morphological differences, it has been suggested that transmission of synaptic signals from dendritic synapses to soma is more efficient in TCs than in INs. However, a higher membrane resistance (Rm) for the INs could, in theory, compensate for the attenuating effect of their long dendrites and allow distal synaptic inputs to significantly depolarize the soma. Compartmental models were made from biocytin filled TCs (n= 15) and INs (n= 3) and adjusted to fit the current‐ and voltage‐clamp recordings from the individual cells. The confidence limits for the passive electrical parameters were explored by simulating the influence of noise, morphometric errors and non‐uniform and active conductances. One of the useful findings was that Rm was accurately estimated despite realistic levels of active conductance. Simulations to explore the somatic influence of dendritic synapses showed that a small (0.5 nS) excitatory synapse placed at different dendritic positions gave similar somatic potentials in the individual TCs, within the TC population and also between TCs and INs. A linear increase in the conductance of the synapse gave increases in somatic potentials that were more sublinear in INs than TCs. However, when the total synaptic conductance was increased by simultaneously activating many small, spatially distributed synapses, the INs converted the synaptic signals to soma potentials almost as efficiently as the TCs. Thus, INs can transfer fast synaptic signals to soma as efficiently as TCs except when the focal conductance is large.
Real‐time measurement of serotonin release and motility in guinea pig ileum
Authors: Bertrand Paul P.
Published: September 2006

Enterochromaffin (EC) cells are sensors that detect chemical or mechanical stimuli and respond with release of serotonin (5‐HT). 5‐HT activates local motor reflexes, but whether local motor reflexes also evoke 5‐HT release is unknown. The aim of the present study was to establish the relationship between the release of 5‐HT and the enteric neural circuits controlling the movements of the intestine. Recordings were made from full‐thickness preparations of guinea pig ileum using electrochemical techniques with carbon fibre electrodes to measure local concentrations of 5‐HT. The tension in the circular muscle (CM) and longitudinal muscle (LM) was recorded with force transducers. The release of 5‐HT from the EC cells was detected selectively and the timing of the events quantified. Pressure‐evoked peristalsis caused detectable 5‐HT release only when the recording site was invaded by a ring of CM contraction. Spontaneous and stretch‐evoked reflex contraction of the CM and LM occurred simultaneously with 5‐HT release. Paralysis of the smooth muscle significantly reduced the stretch‐evoked release. Muscarinic agonists evoked reflexes that were associated with increases in tension in CM and LM simultaneous with 5‐HT release. Tetrodotoxin abolished the coordination between the CM contraction and 5‐HT release but not the direct activation of the CM and EC cells by the agonists. In conclusion, the correlation between local motor reflexes and 5‐HT release observed in the present study is caused primarily by the contraction of the smooth muscle and subsequent deformation of the mucosa. The EC cell is, thus, a site of convergence for mechanical forces that contribute to the release of 5‐HT during motor reflexes.
Targeted expression of Kir6.2 in mitochondria confers protection against hypoxic stress
Authors: Ljubkovic Marko , Marinovic Jasna , Fuchs Andreas , Bosnjak Zeljko J. , Bienengraeber Martin
Published: September 2006

Selective K+ transport in the inner mitochondrial membrane has been attributed to at least three different channel types: ATP‐sensitive, Ca2+‐regulated and voltage‐dependent K+ channels. Studies utilizing their selective modulators have suggested that an increased activity of these channels plays an important role in the cellular protection from metabolic stress. However, direct evidence for this effect is largely absent, and recent findings on the lack of specificity for several channel openers and blockers have questioned the actual contribution of the mitochondrial K+ channels in the preservation of cellular viability. In order to directly investigate the role of enhanced mitochondrial K+ uptake in cellular protection, we selectively expressed the inward rectifying K+ channel Kir6.2 in the mitochondria of HEK293 and HL‐1 cells. Targeted Kir6.2 expression was achieved by cloning the Kir6.2 gene in pCMV/mito/GFP vector and the proper trafficking to mitochondria was confirmed by colocalization studies and Western blot. An increased K+ influx to mitochondria overexpressing Kir6.2, as evidenced by using the K+‐sensitive PBFI AM fluorescent dye, substantially improved the cellular viability after hypoxic stress, which was assessed by lactate dehydrogenase (LDH) release. In parallel, monitoring of mitochondrial Ca2+ during stress, via the specific indicator rhod‐2, revealed a significant attenuation of Ca2+ accumulation in mitochondria overexpressing K+ channels. This effect was abolished in mitochondria expressing an inactive mutant of Kir6.2. Mitochondria expressing Kir6.2 K+ channel also exhibited a significant degree of depolarization that became even more pronounced during the stress. In conclusion, this study provides the first non‐pharmacological evidence that an increased K+ influx to mitochondria protects against hypoxic stress by preventing detrimental effects of Ca2+ overload.
Dynamic but not constitutive association of calmodulin with rat TRPV6 channels enables fine tuning of Ca2+‐dependent inactivation
Authors: Derler Isabella , Hofbauer Michael , Kahr Heike , Fritsch Reinhard , Muik Martin , Kepplinger Klaus , Hack Marlene E. , Moritz Sieglinde , Schindl Rainer , Groschner Klaus , Romanin Christoph
Published: September 2006

The Ca2+‐selective TRPV6 as well as the L‐type Ca2+ channel are regulated by the Ca2+‐binding protein calmodulin (CaM). Here, we investigated the interaction of CaM with rat (r)TRPV6 in response to alterations of intracellular Ca2+, employing Ca2+‐imaging and patch‐clamp techniques. Additionally, confocal Förster resonance energy transfer (FRET) microscopy on living cells was utilized as a key method to visualize in vivo protein–protein interactions essential for CaM regulation of rTRPV6 activity. The effects of overexpressed CaM or its Ca2+‐insensitive mutant (CaMMUT) was probed on various rTRPV6 mutants and fragments in an attempt to elucidate the molecular mechanism of Ca2+/CaM‐dependent regulation and to pinpoint the physiologically relevant rTRPV6–CaM interaction site. A significant reduction of rTRPV6 activity, as well as an increase in current inactivation, were observed when CaM was overexpressed in addition to endogenous CaM. The Ca2+‐insensitive CaMMUT, however, failed to affect rTRPV6‐derived currents. Accordingly, live cell confocal FRET microscopy revealed a robust interaction for CaM but not CaMMUT with rTRPV6, suggesting a strict Ca2+ dependence for their association. Indeed, interaction of rTRPV6 or its C terminus with CaM increased with rising intracellular Ca2+ levels, as observed by dynamic FRET measurements. An rTRPV6Δ695–727 mutant with the very C‐terminal end deleted, yielded Ca2+ currents with a markedly reduced inactivation in accordance with a lack of CaM interaction as substantiated by FRET microscopy. These results, in contrast with those for CaM‐dependent L‐type Ca2+ channel inactivation, demonstrate a dynamic association of CaM with the very C‐terminal end of rTRPV6 (aa 695–727), and this enables acceleration of the rate of rTRPV6 current inactivation with increasing intracellular CaM concentrations.
TheCryptococcus neoformansCatalase Gene Family and ItsRole in Antioxidant Defense
Authors: Giles Steven S. , Stajich Jason E. , Nichols Connie , Gerrald Quincy D. , Alspaugh J. Andrew , Dietrich Fred , Perfect John R.
Published: September 2006

In the present study, we sought to elucidate the contribution of theCryptococcus neoformanscatalase gene family to antioxidant defense. We employed bioinformatics techniques to identify four members of theC. neoformanscatalase gene family and created mutants lacking single or multiple catalase genes. Based on a phylogenetic analysis,CAT1andCAT3encode putative spore-specific catalases,CAT2encodes a putative peroxisomal catalase, andCAT4encodes a putative cytosolic catalase. Only Cat1 exhibited detectable biochemical activity in vitro, and Cat1 activity was constitutive in the yeast form of this organism. Although they were predicted to be important in spores, neitherCAT1norCAT3was essential for mating or spore viability. Consistent with previous studies ofSaccharomyces cerevisiae, the single (cat1,cat2,cat3, andcat4) and quadruple (cat1 cat2 cat3cat4) catalase mutant strains exhibited no oxidative-stress phenotypes under conditions in which either exogenous or endogenous levels of reactive oxygen species were elevated. In addition, there were no significant differences in the mean times to mortality between groups of mice infected withC. neoformanscatalase mutant strains (thecat1andcat1 cat2cat3 cat4mutants) and those infected with wild-type strain H99. We conclude from the results of this study thatC. neoformanspossesses a robust antioxidant system, composed of functionally overlapping and compensatory components that provide protection against endogenous and exogenous oxidative stresses.
Symbiotic “Archaezoa” of the Primitive TermiteMastotermes darwiniensisStill Play a Role in Cellulase Production
Authors: Watanabe Hirofumi , Takase Aya , Tokuda Gaku , Yamada Akinori , Lo Nathan
Published: September 2006

The relictualMastotermes darwiniensisis one of the world's most destructive termites. Like all phylogenetically basal termites, it possesses protozoa in its hindgut, which are believed to help it digest wood. L. Li, J. Frohlich, P. Pfeiffer, and H. Konig (Eukaryot. Cell2:1091-1098, 2003) recently cloned the genes encoding cellulases from the protozoa ofM. darwiniensis; however, they claimed that these genes are essentially inactive, not contributing significantly to cellulose digestion. Instead, they suggested that the protozoa sequester enzymes produced by the termite in its salivary glands and use these to degrade cellulose in the hindgut. We tested this idea by performing gel filtration of enzymes in extracts of the hindgut, as well as in a combination of the salivary glands, foregut, and midgut. Three major cellulases were found in the hindgut, each of which had a larger molecular size than termite-derived salivary gland enzymes. N-terminal amino acid sequencing of one of the hindgut-derived enzymes showed that it was identical to the putative amino acid sequence of one mRNA sequence isolated by Li et al. (Eukaryot. Cell2:1091-1098, 2003). The overall activity of the hindgut cellulases was found to be of approximately equal magnitude to the termite-derived cellulases detected in the mixture of salivary gland, foregut, and midguts. Based on these results, we conclude that, contrary to Li et al. (Eukaryot. Cell2:1091-1098, 2003), the hindgut protozoan fauna ofM. darwiniensisactively produce cellulases, which play an important role in cellulose digestion of the host termite.
Chromosome-Wide Analysis of Gene Function by RNA Interference in the African Trypanosome
Authors: Subramaniam Chandra , Veazey Paul , Redmond Seth , Hayes-Sinclair Jamie , Chambers Emma , Carrington Mark , Gull Keith , Matthews Keith , Horn David , Field Mark C.
Published: September 2006

Trypanosomatids of the order
Kinetoplastida
are major contributors to global disease and morbidity, and understanding their basic biology coupled with the development of new drug targets represents a critical need. Additionally, trypanosomes are among the more accessible divergent eukaryote experimental systems. The genome of
Trypanosoma brucei
contains 8,131 predicted open reading frames (ORFs), of which over half have no known homologues beyond the
Kinetoplastida
and a substantial number of others are poorly defined by in silico analysis. Thus, a major challenge following completion of the
T. brucei
genome sequence is to obtain functional data for all trypanosome ORFs. As
T. brucei
is more experimentally tractable than the related
Trypanosoma cruzi
and
Leishmania
spp. and shares >75% of their genes, functional analysis of
T. brucei
has the potential to inform a range of parasite biology. Here, we report methods for systematic mRNA ablation by RNA interference (RNAi) and for phenotypic analysis, together with online data dissemination. This represents the first systematic analysis of gene function in a parasitic organism. In total, 210 genes have been targeted in the bloodstream form parasite, representing an essentially complete phenotypic catalogue of chromosome I together with a validation set. Over 30% of the chromosome I genes generated a phenotype when targeted by RNAi; most commonly, this affected cell growth, viability, and/or cell cycle progression. RNAi against approximately 12% of ORFs was lethal, and an additional 11% had growth defects but retained short-term viability in culture. Although we found no evidence for clustering or a bias towards widely evolutionarily conserved genes within the essential ORF cohort, the putative chromosome I centromere is adjacent to a domain containing genes with no associated phenotype. Involvement of such a large proportion of genes in robust growth in vitro indicates that a high proportion of the expressed trypanosome genome is required for efficient propagation; many of these gene products represent potential drug targets.
EXACT GRAYSCALE IMAGE RECONSTRUCTION FROM PROJECTIONS
Authors: KESIDIS ANASTASIOS L. , PAPAMARKOS NIKOS
Published: September 2006

This paper proposes a new method for the exact reconstruction of gray-scale images from projections. The image projections construct an accumulator array, which is used afterwards to reconstruct the original grayscale image by applying the proposed decomposition algorithm. The proposed method determines the number of projections and the number of rays in each projection that are required in order to achieve the reconstruction. These two parameters also define the dimensions of the accumulator array. Using an accumulator array with proper dimensions ensures that there is always a unique characteristic sample for each pixel, which is used during the reconstruction process to extract the pixel's grayscale value. During the reconstruction phase, the sinusoidal contribution of each pixel is removed from the accumulator array. At the end of the decomposition process the accumulator array becomes empty and the original image is exactly reconstructed. The experimental results confirm the robustness and efficiency of the proposed method.
RELATIVE CONSISTENCY OF PROJECTIVE RECONSTRUCTIONS OBTAINED FROM THE SAME IMAGE PAIR
Authors: OTLU BURÇAK , ATALAY M. VOLKAN , HASSANPOUR REZA
Published: September 2006

This study obtains projective reconstructions of an object or a scene from its image pair and measures relative consistency of these projective reconstructions. 3D points are estimated from an image pair using projective and epipolar geometry. Two measures are presented for verification of projective reconstructions with each other. These measures are based on the equality of ratios between the x-, y- and z-coordinates of 3D reconstructed points which are obtained from the same corresponding points. This information is used for measuring the relative consistency of projective reconstructions obtained from the same image pair.