bluuebunny/crossref_metadata_2025 huggingface dataset:
Semaphorin 3C is not required for the establishment and target specificity of the GABAergic septohippocampal pathway in vitro
Authors: Rubio Sara E. , Martínez Albert , Chauvet Sophie , Mann Fanny , Soriano Eduardo , Pascual Marta
Published: November 2011

The septohippocampal (SH) pathway comprises cholinergic and GABAergic fibers. Whereas the former establish synaptic contacts with all types of hippocampal neurons, the latter form complex baskets specifically on interneurons. The GABAergic SH function is associated with the control of hippocampal synchronous networks. Little is known about the mechanisms involved in the formation of the GABAergic SH pathway. Semaphorin (Sema) 3C is expressed in most hippocampal interneurons targeted by these axons. To ascertain whether Sema 3C influences the formation of the SH pathway, we analyzed the development of this connection in Sema 3C‐deficient mice. As these animals die at birth, we developed an in vitro organotypic co‐culture model reproducing the postnatal development of the SH pathway. In these SH co‐cultures, the GABAergic SH pathway developed with target specificity similar to that present in vivo. SH axons formed incipient baskets on several types of hippocampal interneurons at 7 days in vitro, which increased their complexity by 18–25 days in vitro. These SH fibers formed symmetric synaptic contacts on GABAergic interneurons. This synaptic specificity was not influenced by the absence of entorhinal afferents. Finally, the absence of Sema 3C in target neurons or its blockage by neuropilin‐1 and ‐2 ectodomains in slice co‐cultures did not lead to major changes in either the target specificity of the GABAergic SH pathway or its density of innervation. We conclude that the formation and synaptic specificity of the GABAergic SH pathway relies on robust molecular mechanisms, independent of Sema 3C, that are retained in our in vitro co‐culture model.
HIV‐1 gp120 upregulates matrix metalloproteinases and their inhibitors in a rat model of HIV encephalopathy
Authors: Louboutin Jean‐Pierre , Reyes Beverly A. S. , Agrawal Lokesh , Van Bockstaele Elisabeth J. , Strayer David S.
Published: November 2011

Matrix metalloproteinases (MMPs) are implicated in diverse processes, such as neuroinflammation, leakiness of the blood–brain barrier (BBB) and direct cellular damage in neurodegenerative and other CNS diseases. Tissue destruction by MMPs is regulated by their endogenous tissue inhibitors (TIMPs). TIMPs prevent excessive MMP‐related degradation of extracellular matrix components. In a rat model of human immunodeficiency virus (HIV)‐related encephalopathy, we described MMP‐2 and MMP‐9 upregulation by HIV‐1 envelope gp120, probably via gp120‐induced reactive oxygen species. Antioxidant gene delivery blunted gp120‐induced MMP production. We also studied the effect of gp120 on TIMP‐1 and TIMP‐2 production. TIMP‐1 and TIMP‐2 levels increased 6 h after gp120 injection into rat caudate‐putamen (CP). TIMP‐1 and TIMP‐2 colocalized mainly with neurons (92 and 95%, respectively). By 24 h, expression of these protease inhibitors diverged, as TIMP‐1 levels remained high but TIMP‐2 subsided. Gene delivery of the antioxidant enzymes Cu/Zn superoxide dismutase or glutathione peroxidase into the CP before injecting gp120 there reduced levels of gp120‐induced TIMP‐1 and TIMP‐2, recapitulating the effect of antioxidant enzymes on gp120‐induced MMP‐2 and MMP‐9. A significant correlation was observed between MMP/TIMP upregulation and BBB leakiness. Thus, HIV‐1 gp120 upregulated TIMP‐1 and TIMP‐2 in the CP. Prior antioxidant enzyme treatment mitigated production of these TIMPs, probably by reducing MMP expression.
Use of a gentamicin‐impregnated collagen sheet (Collatamp®) following implantation of a sacral nerve stimulator for faecal incontinence
Authors: Simpson J. A. D. , Peacock J. , Maxwell‐Armstrong C.
Published: November 2011

Aim  Gentamicin‐impregnated collagen (Collatamp®) is well described for the prevention of infection in surgery. This technical note describes its intraoperative use as a prophylactic measure to prevent infection following implantation of a sacral nerve stimulator for faecal incontinence.

Method  Following implantation of the Interstim II Neurostimulator (Medtronic Neuromodulation, 710 Medtronic Parkway, Minneapolis, USA) in a subcutaneous pocket overlying the gluteal muscle, a single sheet of 10 cm × 10 cm gentamicin‐impregnated collagen is placed within the wound covering the implant. The subcutaneous tissue and skin are then closed in separate layers.

Results  To date eight patients [median age 46.5 (30–59) years] have received prophylactic cover with gentamicin‐impregnated collagen following permanent sacral nerve stimulator implantation. At a median interval of 89.5 (51–128) days, none of these patients developed a wound infection at the site of the neurostimulator implant.

Conclusion  Gentamicin‐impregnated collagen (Collatamp®) used in the implantation of a sacral nerve stimulator may be a useful addition to the technique.
The relationship between prostate volume and prostate‐specific antigen variability: data from the Baltimore Longitudinal Study of Aging and the Johns Hopkins Active Surveillance Program
Authors: Nichols John H. , Loeb Stacy , Metter E. Jeffrey , Ferrucci Luigi , Carter H. Ballentine
Published: November 2011

Study Type – Prognostic (cohort)

Level of Evidence 2b

What's known on the subject? and What does the study add?

Previous studies have attempted to characterize the normal biological variability in PSA among men without prostate cancer. These reports suggest that PSA variability is unrelated to age, but there are conflicting data on its association with the baseline PSA level. There are limited published data regarding the effects of prostate volume on PSA variability. A prior study assessing whether prostate volume changes would confound the use of PSA velocity in clinical practice reported that prostate volume changes were not significantly related to PSA changes. This study did not directly address the effect of baseline prostate volume on serial PSA variability.

The objective of the current study was to further examine the relationship between prostate volume and PSA variability. Our hypothesis was that larger baseline prostate volume would be associated with increased PSA variability in men without known prostate cancer and in those with suspected small‐volume disease. The results of the study suggest that baseline PSA, not prostate volume, is the primary driver of PSA variability in these populations.

OBJECTIVE

To clarify the relationship between serial prostate‐specific antigen (PSA) variability and prostate volume in both cancer‐free participants from the Baltimore Longitudinal Study of Aging (BLSA) and patients with low‐risk prostate cancer from the Johns Hopkins Active Surveillance Program (AS).

MATERIALS AND METHODS

In all, 287 men from the BLSA and 131 patients from the AS were included in the analysis, all with at least two PSA measurements and concurrent prostate volume measurements.

PSA variability was calculated in ng/mL per year, and a linear mixed‐effects model was used to determine the relative effects of prostate volume, baseline PSA and age on PSA change over time.

RESULTS

In a model with prostate volume, age and baseline PSA, there was no significant relationship between prostate volume and PSA variability (BLSA, P= 0.57; AS, P= 0.49).

Only baseline PSA showed a significant relationship to PSA yearly variability (PSAYV) (P < 0.001). Specifically, a one unit higher baseline PSA (ng/mL) corresponded on average to 0.09 and 0.06 ng/mL per year higher PSAYV in the BLSA and AS populations, respectively.

CONCLUSIONS

The results of the present study suggest that the primary driver of PSA variability is the baseline PSA level, rather than prostate volume.

Clinicians might consider the baseline PSA level to help predict the expected variability in serial PSA measurements.
Effect of delaying surgery on radical prostatectomy outcomes: a contemporary analysis
Authors: Korets Ruslan , Seager Catherine M. , Pitman Max S. , Hruby Gregory W. , Benson Mitchell C. , McKiernan James M.
Published: November 2011

Study Type – Therapy (case series)

Level of Evidence 4

What's known on the subject? and What does the study add?

For patients electing surgical treatment, the question of the effect of surgical delay on clinical outcomes in prostate cancer is controversial. In this study we examined the effect of delay from diagnosis to surgery on outcomes in men with localized prostate cancer and found no association between time to surgery and risk of biochemical recurrence, even for patients with longer delays and high‐risk disease. Men with localized prostate cancer can be reassured that reasonable delays in treatment will not influence disease outcomes.

OBJECTIVE

To examine the effect of time from last positive biopsy to surgery on clinical outcomes in men with localized prostate cancer undergoing radical prostatectomy (RP).

PATIENTS AND METHODS

We conducted a retrospective review of 2739 men who underwent RP between 1990 and 2009 at our institution.

Clinical and pathological features were compared between men undergoing RP ≤ 60, 61–90 and >90 days from the time of prostate biopsy.

A Cox proportional hazards model was used to analyse the association between clinical features and surgical delay with biochemical progression. Biochemical recurrence (BCR)‐free rates were assessed using the Kaplan–Meier method.

RESULTS

Of the 1568 men meeting the inclusion criteria, 1098 (70%), 303 (19.3%) and 167 (10.7%) had a delay of ≤60, 61–90 and >90 days, respectively, between biopsy and RP. A delay of >60 days was not associated with adverse pathological findings at surgery.

The 5‐year survival rate was similar among the three groups (78–85%, P= 0.11).

In a multivariate Cox model, men with higher PSA levels, clinical stages, Gleason sums, and those of African‐American race were all at higher risk for developing BCR.

A delay to surgery of >60 days was not associated with worse biochemical outcomes in a univariate and multivariate model.

CONCLUSIONS

A delay of >60 days is not associated with adverse pathological outcomes in men with localized prostate cancer, nor does it correlate with worse BCR‐free survival.

Patients can be assured that delaying treatment while considering therapeutic options will not adversely affect their outcomes.
Pathological stage distribution in patients treated with radical prostatectomy reflecting the need for protocol‐based active surveillance: results from a contemporary European patient cohort
Authors: Seiler Daniel , Randazzo Marco , Klotz Laurence , Grobholz Rainer , Baumgartner Martin , Isbarn Hendrik , Recker Franz , Kwiatkowski Maciej
Published: November 2011

Study Type – Therapy (case series)

Level of Evidence 4

What's known on the subject? and What does the study add?

Low‐risk prostate cancer is frequently diagnosed in the context of PSA screening or during a routine check‐up. For those patients, to avoid possible overtreatment AS is an increasingly chosen treatment option. However, the concept of AS could possibly misclassify potentially dangerous PCa as a low‐risk disease resulting in inferior cancer control outcomes.

In the present study, we could demonstrate that the histopathological results of patients treated by RP in course of AS are significantly better if the selection criteria for AS are entirely fulfilled. Our findings underline the importance of a strict and precise admittance procedure for patients with early prostate cancer who are willing to undergo an AS programme.

OBJECTIVE

To compare the histopathological outcomes of patients treated with radical prostatectomy (RP) after an initial active surveillance (AS) for localized, low‐risk prostate cancers (PCa) among men who fulfilled the Epstein criteria at diagnosis with those who did not.

PATIENTS AND METHODS

In all, 283 patients with localized PCa were initially managed at our institution with AS.

In all, ≈50% originated from the European Randomized Study of Screening for Prostate Cancer (ERSPC) participants from Switzerland: 75 (26.5%) patients underwent treatment during follow‐up and 61 were treated with RP (21.6%).

These patients were stratified into those who did (n= 39) vs those who did not (n= 22) entirely fulfil AS inclusion criteria according to Epstein et al. at PCa diagnosis.

RESULTS

Patients who did completely fulfil the AS inclusion criteria had significantly lower prostate‐specific antigen (PSA)‐values (4.9 vs 7.8 ng/mL; P= 0.02), a significantly lower PSA density at diagnosis (0.09 vs 0.2 ng/mL/ccm; P= 0.007) and at RP, a higher proportion of organ‐confined cancers (89.7% vs 59.1%, P= 0.02) and fewer positive surgical margins (25.6% vs 40.9%).

However, the rate of favourable histopathological outcome, defined as organ‐confined disease with negative surgical margins, was statistically significantly higher in the group fulfilling AS criteria (69.2% vs 40.9%; P= 0.03).

CONCLUSIONS

In our AS series, 26.5% of the patients underwent definitive therapy.

Most patients treated with RP had organ‐confined disease in the majority of cases, especially when the Epstein criteria were rigorously fulfilled at PCa diagnosis.

This underlines the importance of a strict and precise per protocol AS for patients with early PCa, otherwise there is a risk of missing more significant disease.
European Commission Adoption of IPSAS to Reform Financial Reporting
Authors: GROSSI G. , SOVERCHIA M.
Published: November 2011

The article offers an overview of the modernization of the European Commission (EC) accounting system. It represents an integral part of an overall rationalization of the EC organizational, administrative and financial dimensions which has been carried out over the last decade. The reformed accounting system is a dual one: it is based both on cash accounting, to manage budget appropriations, and on accrual accounting, to draw up the financial statements.

Seventeen accounting rules, which draw upon International Public Sector Accounting Standards (IPSAS) and are based on accrual accounting, were issued by the EC and are the foundation of this reformed system. Drawing on semi‐structured interviews with Commission officials, this article tracks the key turning points, trajectories and outcomes of events within the implementation stage of this part of the EC accounting reform with a focus on the consolidation of annual accounts. The compilation of the consolidated financial statement (CFS) has become more complex. The original European Union (EU) organizational structure (Parliament, Council, Commission, Court of Justice and Court of Auditors) has broadened with the addition of agencies that were created during the early 1990s. Since 2005, these agencies have been included in the CFS of the EU, compiled according to IPSASs 6, 7 and 8.

This article examines how the EU consolidation process has evolved over time and the drivers behind the reformed accounting systems and in particular the new consolidation approach, which is a result of the combination of the Continental and Anglo‐Saxon governmental accounting approaches.
Enhancing disaster management by mapping disaster proneness and preparedness
Authors: Mishra Vishal , Fuloria Sanjay , Bisht Shailendra Singh
Published: November 2011

The focus of most disaster management programmes is to deploy resources—physical and human—from outside the disaster zone. This activity can produce a delay in disaster mitigation and recovery efforts, and a consequent loss of human lives and economic resources. It may be possible to expedite recovery and prevent loss of life by mapping out disaster proneness and the availability of resources in advance. This study proposes the development of two indices to do so. The Indian census data of 2001 is used to develop a methodology for creating one index on disaster proneness and one on resourcefulness for administrative units (tehsils). Findings reveal that tehsil residents face an elevated risk of disaster and that they are also grossly under‐prepared for such events. The proposed indices can be used to map regional service provision facilities and to assist authorities in evaluating immediate, intermediate, and long‐term disaster recovery needs and resource requirements.
Why do Social Innovations in Rural Development Matter and Should They be Considered More Seriously in Rural Development Research? – Proposal for a Stronger Focus on Social Innovations in Rural Development Research
Authors: Neumeier Stefan
Published: November 2011

The article discusses social innovation from a rural development perspective. The central questions addressed are: What are social innovations and why are they important for rural development? How can we gain more insights into the role and functioning of social innovations in rural development? Drawing on different approaches to conceptualise social innovations pursued in economy, management, sociology, psychology and regional economics, planning and development studies, the article outlines the central aspects on which the concept is built. Based on these insights a proposal for a concise basic definition of social innovations is given and a model of the social innovation process is introduced. Reasoning that a lack of social innovation is often one of the strongest restraints of the vitality and further development of rural communities in developed, democratic, capitalist, industrial countries, the second part orf the article highlights the need to put a stronger focus on social innovations in future rural development research. Building on these insights, the third part addresses open research questions and explains why an actor‐oriented network approach seems to be a promising potential methodological way to approach social innovations in rural development research.
Testing children of mothers with HIV infection: experience in three south‐west London HIV clinics
Authors: Andrews S , Handyside R , Carpenter L , Price A , Majewska W , Prime K
Published: November 2011

Objective

There are several reported cases of vertically infected children presenting with advanced HIV infection in the UK. The children of women with HIV infection are at increased risk of being infected. There are few data available on the number of such children that are yet to be tested for HIV. This study looked at the HIV testing status of children whose mothers attend HIV services at three south‐west London clinics.

Methods

Case notes of women attending the clinics from 1 January to 30 June 2009 were reviewed. When data were incomplete, women were prospectively interviewed.

Results

Case notes of 605 women were reviewed; 478 women had 1107 children. The majority of women (386; 81%) were of Black African ethnicity. Sixty‐one per cent (675 of 1107) of the children were known to have been tested for HIV. The children resident abroad were more likely to be untested compared with those resident in the UK; 186 of 255 (73%) vs. 246 of 852 (29%). A quarter (106 of 432) of the untested children were ≤18 years old; 49 (46%) of these were resident in the UK. The most common reason given by the mothers for not testing was a perceived ‘unlikely risk’.

Conclusions

A significant number of children at risk of vertically transmitted HIV infection, including 49 children ≤18 years and resident in the UK, were identified through this study. The mothers are being encouraged to have these children tested and a multidisciplinary team involving adult and paediatric HIV healthcare professionals has been set up to negotiate and facilitate testing.
Shifting species interactions in terrestrial dryland ecosystems under altered water availability and climate change
Authors: McCluney Kevin E. , Belnap Jayne , Collins Scott L. , González Angélica L. , Hagen Elizabeth M. , Nathaniel Holland J. , Kotler Burt P. , Maestre Fernando T. , Smith Stanley D. , Wolf Blair O.
Published: November 2011

Species interactions play key roles in linking the responses of populations, communities, and ecosystems to environmental change. For instance, species interactions are an important determinant of the complexity of changes in trophic biomass with variation in resources. Water resources are a major driver of terrestrial ecology and climate change is expected to greatly alter the distribution of this critical resource. While previous studies have documented strong effects of global environmental change on species interactions in general, responses can vary from region to region. Dryland ecosystems occupy more than one‐third of the Earth's land mass, are greatly affected by changes in water availability, and are predicted to be hotspots of climate change. Thus, it is imperative to understand the effects of environmental change on these globally significant ecosystems.

Here, we review studies of the responses of population‐level plant‐plant, plant‐herbivore, and predator‐prey interactions to changes in water availability in dryland environments in order to develop new hypotheses and predictions to guide future research. To help explain patterns of interaction outcomes, we developed a conceptual model that views interaction outcomes as shifting between (1) competition and facilitation (plant‐plant), (2) herbivory, neutralism, or mutualism (plant‐herbivore), or (3) neutralism and predation (predator‐prey), as water availability crosses physiological, behavioural, or population‐density thresholds. We link our conceptual model to hypothetical scenarios of current and future water availability to make testable predictions about the influence of changes in water availability on species interactions. We also examine potential implications of our conceptual model for the relative importance of top‐down effects and the linearity of patterns of change in trophic biomass with changes in water availability. Finally, we highlight key research needs and some possible broader impacts of our findings. Overall, we hope to stimulate and guide future research that links changes in water availability to patterns of species interactions and the dynamics of populations and communities in dryland ecosystems.
Restoration of kefir grains subjected to different treatments
Authors: KOŁAKOWSKI PIOTR , OZIMKIEWICZ MAGDALENA
Published: November 2011

The aim of the study was to find a way to recover the quality of kefir grains that had been subjected to the following treatments: homogenisation, rinsing the grains with water, freeze‐drying and milling, freezing in liquid nitrogen and then frozen storage, and cool storage. The grains were studied in respect of their later replication in milk, their size and their microbiota composition. The daily transfer of treated kefir grains, except freeze‐dried ones, into fresh milk was effective in respect of the recovery of their growth dynamics, size and microbiota balance. The growth dynamics of grains in milk seems to be a very good indicator of their vital and technological functions.
Large‐scale evolutionary trends of Acrochordiceratidae Arthaber, 1911 (Ammonoidea, Middle Triassic) and Cope’s rule
Authors: MONNET CLAUDE , BUCHER HUGO , GUEX JEAN , WASMER MARTIN
Published: November 2011

Abstract: Directed evolution of life through millions of years, such as increasing adult body size, is one of the most intriguing patterns displayed by fossil lineages. Processes and causes of such evolutionary trends are still poorly understood. Ammonoids (externally shelled marine cephalopods) are well known to have experienced repetitive morphological evolutionary trends of their adult size, shell geometry and ornamentation. This study analyses the evolutionary trends of the family Acrochordiceratidae Arthaber, 1911 from the Early to Middle Triassic (251–228 Ma). Exceptionally large and bed‐rock‐controlled collections of this ammonoid family were obtained from strata of Anisian age (Middle Triassic) in north‐west Nevada and north‐east British Columbia. They enable quantitative and statistical analyses of its morphological evolutionary trends. This study demonstrates that the monophyletic clade Acrochordiceratidae underwent the classical evolute to involute evolutionary trend (i.e. increasing coiling of the shell), an increase in its shell adult size (conch diameter) and an increase in the indentation of its shell suture shape. These evolutionary trends are statistically robust and seem more or less gradual. Furthermore, they are nonrandom with the sustained shift in the mean, the minimum and the maximum of studied shell characters. These results can be classically interpreted as being constrained by the persistence and common selection pressure on this mostly anagenetic lineage characterized by relatively moderate evolutionary rates. Increasing involution of ammonites is traditionally interpreted by increasing adaptation mostly in terms of improved hydrodynamics. However, this trend in ammonoid geometry can also be explained as a case of Cope’s rule (increasing adult body size) instead of functional explanation of coiling, because both shell diameter and shell involution are two possible paths for ammonoids to accommodate size increase.
STATUS QUO IN THE WELFARE ANALYSIS OF TAX REFORMS
Authors: BOURGUIGNON FRANÇOIS
Published: November 2011

The welfare analysis of tax reforms most often consists of comparing the post‐reform distribution of individual welfare with the pre‐reform distribution or possibly that obtained from another reform as if they were completely independent. Such an “anonymous” approach does not take into account “changes” in individual situations, generally the main source of contention in any tax reform debate. This paper proposes a welfare criterion that allows comparison of reforms while taking into account individual status quo—i.e. pre‐reform—situations. This is done by extending standard utilitarian social welfare criteria to the case where individual utilities depend on initial income and income change.
A once‐per‐day, drug‐in‐food protocol for prolonged administration of antiepileptic drugs in animal models
Authors: Ali Atif , Dua Yashomati , Constance Jonathan E. , Franklin Michael R. , Dudek F. Edward
Published: November 2011

Purpose:  Convenient and effective methods for administering potential antiepileptic drugs (AEDs) chronically should facilitate many experiments in animal models of chronic epilepsy with spontaneous recurrent seizures. This proof‐of‐principle study aimed to optimize a once‐per‐day, drug‐in‐food protocol by testing the effect of carbamazepine (CBZ) on the frequency of convulsive seizures in rats with kainate‐induced epilepsy.

Methods:  Adult male rats were given repeated low‐dose kainate injections until convulsive status epilepticus persisted for >3 h. After the rats developed spontaneous recurrent seizures, food pellets with CBZ (30, 100, or 300 mg/kg/day) were provided once per day in three 2‐week trials (n = 7–9 rats) involving 5 days of CBZ or control treatment, separated by two recovery days within a trial. The total amount of food provided and consumed per day corresponded to a normal caloric diet (60 g/kg/day).

Key Findings:  When provided once per day, all animals ate the CBZ‐containing food irregularly but continuously throughout the 24‐h day. With this daily feeding protocol, CBZ significantly reduced the frequency of spontaneous convulsive seizures in a dose‐dependent manner. It is important to note that the effect of CBZ was consistent across the 5 days and throughout each day of the trials. With food administered at 9:00 a.m., and blood assayed at 5:00 p.m., higher food levels of CBZ resulted in higher plasma concentrations of CBZ.

Significance:  This AED‐in‐food protocol is simple, efficient, inexpensive, reliable, and noninvasive; it allows easier long‐term drug administration and is less stressful and more humane than other methods of AED administration.
The Johns Hopkins Delirium Consortium: A Model for Collaborating Across Disciplines and Departments for Delirium Prevention and Treatment
Authors: Neufeld Karin J. , Joseph Bienvenu O. , Rosenberg Paul B. , Mears Simon C. , Lee Hochang B. , Kamdar Biren B. , Sieber Frederick E. , Krumm Sharon K. , Walston Jeremy D. , Hager David N. , Touradji Pegah , Needham Dale M.
Published: November 2011

Delirium is an important syndrome affecting inpatients in various hospital settings. This article focuses on multidisciplinary and interdepartmental collaboration to advance efforts in delirium clinical care and research. The Johns Hopkins Delirium Consortium, which includes members from the disciplines of nursing, medicine, rehabilitation therapy, psychology, and pharmacy within the departments and divisions of anesthesiology, geriatrics, oncology, orthopedic surgery, psychiatry, critical care medicine, and physical medicine and rehabilitation at the Johns Hopkins Hospital and Johns Hopkins Bayview Medical Center, is one model of such collaboration. This article describes the process involved in developing functional collaboration around delirium and highlights projects, opportunities, and challenges resulting from them.
Delirium and Sedation Recognition Using Validated Instruments: Reliability of Bedside Intensive Care Unit Nursing Assessments from 2007 to 2010
Authors: Vasilevskis Eduard E. , Morandi Alessandro , Boehm Leanne , Pandharipande Pratik P. , Girard Timothy D. , Jackson James C , Thompson Jennifer L. , Shintani Ayumi , Gordon Sharon M. , Pun Brenda T. , Wesley Ely E.
Published: November 2011

Objectives

To describe the reliability and sustainability of delirium and sedation measurements of bedside intensive care unit (ICU) nurses.

Design

Prospective cohort study.

Setting

A tertiary care academic medical center.

Participants

Five hundred ten ICU patients from 2007 to 2010; 627 bedside nurses.

Measurements

Bedside nurses and well‐trained reference‐rater research nurses independently measured delirium and sedation levels in routine care. Bedside nurses were instructed to use the Confusion Assessment Method for the Intensive Care Unit (CAM‐ICU) every 12 hours to measure delirium and the Richmond Agitation‐Sedation Scale (RASS) every 4 hours to measure sedation. CAM‐ICU and RASS assessment agreement were computed using weighted kappa statistics across the entire population and subgroups (e.g., ICU type). Sensitivity and specificity of bedside nurse identification of delirium were calculated to understand sources of discordance.

Results

Six thousand one hundred ninety‐eight CAM‐ICU and 6,880 RASS measurement pairs obtained on 3,846 patient‐days. For CAM‐ICU measurements, agreement between bedside and research nurses was substantial (weighted kappa = 0.67, 95% confidence interval (CI) = 0.66–0.70) and stable over 3 years of data collection. RASS measures also demonstrated substantial agreement (weighted kappa = 0.66, 95% CI = 0.64–0.68), which was stable across all years of data collection. The sensitivity of delirium nurse assessments was 0.81 (95% CI = 0.78–0.83), and the specificity was 0.81 (95% CI = 0.78–0.85).

Conclusion

Bedside nurse measurements of delirium and sedation are sustainable and reliable sources of information. These measures can be used for clinical decision‐making, quality improvement, and quality measurement activities.
Antipsychotics in the Treatment of Delirium in Older Hospitalized Adults: A Systematic Review
Authors: Flaherty Joseph H. , Gonzales Jeffrey P. , Dong Birong
Published: November 2011

Objectives

To examine evidence of the efficacy of antipsychotics in the treatment of delirium in older hospitalized adults.

Design

Systematic literature review.

Setting

Hospital.

Participants

Older adults with delirium.

Measurements

The MEDLINE (January 1980–December 2010) and Cochrane Databases were searched using the keywords “delirium” and “antipsychotics.” References of review articles were reviewed to identify additional studies. Study selection criteria included prospective design, more than 10 participants (in treatment arms), mean age 60 and older, standardized criteria for diagnosing delirium, and validated delirium rating scales for reporting outcomes.

Results

Thirteen articles met selection criteria: six single‐agent and seven comparison studies. Of these, eight (62%) had fewer than 25 participants in treatment arms, 10 (77%) recruited participants from psychiatry referrals, and eight (62%) did not clearly describe their screening methods. All single‐agent studies were open‐label studies. Of the comparison studies, five (71%) used randomization, but only one of these (a placebo‐controlled study) used adequate allocation concealment methods, and only one other study (comparing two antipsychotics) described a double‐blind method in detail. In the only placebo‐controlled study (which was stopped early), no statistically significant differences in mean delirium severity scores were found at individual time points (Days 2, 3, 4, 7, 10). The other 12 studies reported improvements in delirium severity or resolution of delirium based on cutoff scores of the scales, but it is not clear from any of these studies what the natural course of delirium would have been without use of antipsychotics.

Conclusion

Because of severe methodological limitations, the studies in this review do not support the use of antipsychotics in the treatment of delirium in older hospitalized adults. Additional well‐designed randomized placebo‐controlled trials are needed.
Association Between Prescribing of Anticholinergic Medications and Incident Delirium: A Cohort Study
Authors: Campbell Noll , Perkins Anthony , Hui Siu , Khan Babar , Boustani Malaz
Published: November 2011

Objectives

To describe the association between anticholinergic medications and incident delirium in hospitalized older adults with cognitive impairment and to test the hypothesis that anticholinergic medications would increase the risk of incident delirium.

Design

Observational cohort study.

Setting

Urban public hospital in Indianapolis, Indiana.

Participants

One hundred forty‐seven participants aged 65 and older with cognitive impairment who screened negative for delirium at the time of admission to a general medical ward.

Measurements

Cognitive function at the time of admission was assessed using the Short Portable Mental Status Questionnaire (SPMSQ). Anticholinergic medication orders between the time of admission and the final delirium assessment were evaluated. Anticholinergic medication orders were identified using the Anticholinergic Cognitive Burden Scale. Delirium was assessed using the Confusion Assessment Method.

Results

Fifty‐seven percent of the cohort received at least one order for possible anticholinergic medications, and 28% received at least one order for definite anticholinergic medications. The incident rate for delirium was 22% of the entire cohort. After adjusting for age, sex, race, baseline SPMSQ score, and Charlson Comorbidity Index, the odds ratio (OR) for developing delirium in those with orders for possible anticholinergic medications was 0.33 (95% confidence interval (CI) = 0.10–1.03). The OR for developing delirium among those with orders for definite anticholinergic medications was 0.43 (95% CI = 0.11–1.63).

Conclusion

The results did not support the hypothesis that prescription of anticholinergic medications increases the risk of incident delirium in hospitalized older adults with cognitive impairment. This relationship needs to be established using prospective study designs with medication dispensing data to improve the performance of predictive models of delirium.
Estimation of Effective Concentrations of ATP‐Regenerating Enzymes in Cilia of Paramecium caudatum
Authors: Kutomi Osamu , Takemura Motoyuki , Kamachi Hiroyuki , Noguchi Munenori
Published: November 2011

The phosphoarginine shuttle system effectively regenerates ATP in the cilia of Paramecium caudatum. To estimate the effective concentration of ATP‐regenerating enzymes, we attempted to reconstitute certain ATP‐regenerating systems within the cilia of intact cortical sheets using exogenous enzymes and high‐energy substances. The addition of phosphoenolpyruvate, which is one of the substrates in glycolysis, did not increase the ciliary beat frequency, whereas phosphocreatine together with exogenous creatine kinase, effectively increased the ciliary beat frequency. In the presence of 0.6 mg/ml creatine kinase and 0.4 mM phosphocreatine, the ciliary beat frequency was comparable to that produced by the addition of phosphoarginine. This result indicates that the reconstituted phosphocreatine shuttle system can work as an artificial ATP‐regenerating system for ciliary movements. The effective concentration of creatine kinase in the reconstituted phosphocreatine shuttle system was estimated to be about 7.4 μM based on the molecular mass of creatine kinase (MW 81,000). Therefore, the effective concentration of arginine kinase in the cilia of live Paramecium is approximately 10 μM. This estimated concentration of intraciliary arginine kinase is sufficient to maintain a high ATP concentration throughout the cilia of P. caudatum.
The effect of surrounding conditions on pixel value of cone beam computed tomography
Authors: Araki Kazuyuki , Okano Tomohiro
Published: November 2011

Objective

The purpose of this study was to evaluate the reliability of pixel value in CBCT, especially with regard to the effect of surrounding objects that are presented outside the field of view (FOV).

Materials and methods

This experiment used the GE Hi‐Speed QXi, a multidetector helical computed tomography (MDCT) scanner, and the 3D Accuitomo FPD 8, a cone beam computed tomography (CBCT) scanner. Two types of phantoms were used, both of which contained Lipiodol Ultra Fluid (Lipiodol UF). The type A phantom was a target phantom for pixel value measurement while type B was used for the surrounding environment. For CBCT, the type A phantom was placed in a water bath, and 4 types of surrounding environmental conditions were created: (1) no other phantom present, (2) phantom type B also within the FOV, (3) half of phantom type B within the FOV, (4) phantom type B entirely outside the FOV but within the path of x‐rays aimed at phantom A.

Results

In MDCT, pixel value (CT number) showed an almost linear correlation with the concentration of Lipiodol UF. In CBCT, on the other hand, pixel value was not linearly correlated with Lipiodol UF concentration. The position of the type B phantom affected pixel values in images of the type A phantom.

Conclusions

Pixel value in CBCT may be affected by various conditions such as beam hardening and surrounding materials, and is therefore not reliable. Caution is essential when pixel values in CBCT are used to estimate bone density at potential implant sites.
Multiple myeloma vs. breast cancer patients with bisphosphonates‐related osteonecrosis of the jaws: a comparative analysis of response to treatment and predictors of outcome
Authors: Fortuna Giulio , Ruoppo Elvira , Pollio Annamaria , Aria Massimo , Adamo Daniela , Leuci Stefania , Orabona Giovanni Dell’Aversana , Mignogna Michele D.
Published: November 2011

J Oral Pathol Med (2012) 41: 222–228

Background:  Multiple myeloma (MM) and breast cancer (BC) are the two most common diseases associated with bisphosphonates‐related osteonecrosis of the jaws (BRONJ), for which different therapeutical approaches have been proposed. The aim of this study was to compare the clinical behaviour of BRONJ in patients with MM vs. BC and the time of healing in terms of clinical and symptomatological remission, following a standardized therapeutic protocol.

Methods:  Twenty‐six BRONJ patients (13 men with MM and 13 women with BC) were prospectively enroled and treated with a specific systemic and topical antibiotic therapy. Several predictors of outcome were also evaluated.

Results:  Nine patients (69.2%) with BC and 10 patients (76.9%) with MM progressed towards a complete clinical remission (CR) in a mean healing time of 183.3 days [SD: 113.7; 95% confidence interval (CI): 95.95–207.7] and 372.0 days (SD: 308.0; 95% CI: 151.7–592.3) (P = 0.776), respectively. The clinical improvement was statistically significant (P = 0.0013 and P = 0.0014), as well as the assessment of pain (P = 0.0015 and P = 0.0015), in MM and BC group, respectively. Cox regression analysis revealed that just triggering events (P = 0.036) were found to be significant predictors of outcome of BRONJ healing.

Conclusions:  Both groups of cancer patients experienced clinical and symptomatological remission regardless their malignancy, but BC patients earlier than MM patients.
Differential activation of proapoptotic molecules between mouse and rat models of distal motor trigeminal denervation
Authors: Harada Shiori , Suzuki Satoshi O. , Seki Yoshihiro , Nakamura Seiji , Iwaki Toru
Published: November 2011

J Oral Pathol Med (2012) 41: 354–360

Background:  We previously developed a rat trigeminal motor neuron axotomy model involving masseter and temporal muscle resection to study pathological changes of the central nucleus after peripheral nerve injury caused by oral surgery. Because motor neurons are reported to be more vulnerable to axotomy in mice than rats, we compared the degeneration process of the trigeminal motor nucleus in the rat model with a similar mouse model.

Methods:  We removed masseter and temporal muscles of adult mice or rats. Animals were sacrificed at 3, 7, 14, 28, 42, and 56 days post‐operation, and the trigeminal motor nuclei were histologically analyzed.

Results:  Size reduction, but no neuronal loss, was seen in the trigeminal motor nuclei in both mice and rats. Time‐dependent Noxa expression, starting at 1 week post‐operation (wpo), was seen in the mouse model. By 8 wpo, mice expressed a higher level of Noxa than rats. Additionally, we noted persistent expression of cleaved caspase‐3 in mice but not in rats. Conversely, apoptosis‐inducing factor (AIF), which executes DNA fragmentation in the nucleus, was not translocated to the nucleus in either model.

Conclusions:  Our findings indicate differential activation of motor neuron apoptosis pathways after axotomy in mice and rats. Lack of activation of caspase‐independent pathways and distal end denervation in our model might be related to the survival of motor neurons after axonal injury. These findings could be relevant to future neuroprotective strategies for peripheral nerve injury caused by oral surgeries.
Prognostic significance of matrix metalloproteinase‐2, ‐8, ‐9, and ‐13 in oral tongue cancer
Authors: Mäkinen Laura K. , Häyry Valtteri , Atula Timo , Haglund Caj , Keski‐Säntti Harri , Leivo Ilmo , Mäkitie Antti , Passador‐Santos Fabricio , Böckelman Camilla , Salo Tuula , Sorsa Timo , Hagström Jaana
Published: November 2011

J Oral Pathol Med (2012) 41: 394–399

Background:  Oral tongue squamous cell carcinoma (OTSCC) often metastasizes to cervical lymph nodes. Mechanisms of this disease progression are not fully known. We aimed at finding new predictive markers for diagnosis and disease monitoring.

Methods:  Seventy‐three consecutive T1N0M0 and T2N0M0 OTSCC patients treated at Helsinki University Central Hospital, Helsinki, Finland, in 1992–2002 were included. Tissue array blocks were prepared from primary tumors and immunostained. Immunoexpression of matrix metalloproteinase (MMP)‐2, ‐8, ‐9, and ‐13 was compared with patient characteristics and outcome.

Results:  Nuclear expression of MMP‐13, but not cytoplasmic expression of MMP‐2, ‐8, and ‐9, was associated with invasion depth (P = 0.017) and tumor size (P = 0.008). Furthermore, high nuclear MMP‐13 expression was predictive of poor outcome (P = 0.042).

Conclusion:  Our results suggest that especially MMP‐13 may be regarded as a prognostic biomarker in OTSCC.
DNA methylation changes elicited by social stimuli in the brains of worker honey bees
Authors: Lockett G. A. , Kucharski R. , Maleszka R.
Published: November 2011

Social environments are notoriously multifactorial, yet studies in rodents have suggested that single variables such as maternal care can in fact be disentangled and correlated with specific DNA methylation changes. This study assesses whether non‐detrimental social environmental variation in a highly plastic social insect is correlated with epigenomic modifications at the DNA methylation level. Honey bee workers perform tasks such as nursing and foraging in response to the social environment in the hive, in an age‐linked but not age‐dependent manner. In this study, the methylation levels of 83 cytosine–phosphate–guanosine dinucleotides over eight genomic regions were compared between the brains of age‐matched bees performing nursing or foraging tasks. The results reveal more changes correlated with task than with chronological age, and also hive‐associated methylation at some sites. One methylation site from a gene encoding Protein Kinase C binding protein 1 was consistently more methylated in foragers than nurses, which is suggested to lead to production of task‐specific protein isoforms via alternative splicing. This study illustrates the ability of the neural epigenome to dynamically respond to complex social stimuli.
Relative Contributions of Osteogenic Tissues to New Bone Formation in Periosteal Distraction Osteogenesis: Histological and Histomorphometrical Evaluation in a Rat Calvaria
Authors: Saulacic Nikola , Hug Cladius , Bosshardt Dieter D. , Schaller Benoit , Buser Daniel , Haeniwa Hideya , Iizuka Tateyuki
Published: November 2011

Background: The relative contributions of different, potential factors to new bone formation in periosteal distraction osteogenesis are unknown.

Purpose: The aim of the present study was to assess the influence of original bone and periosteum on bone formation during periosteal distraction osteogenesis in a rat calvarial model by means of histology and histomorphometry.

Methods: A total of 48 rats were used for the experiment. The contribution of the periosteum was assessed by either intact or incised periosteum or an occlusive versus a perforated distraction plate. The cortical bone was either left intact or perforated. Animals were divided in eight experimental groups considering the three possible treatment modalities. All animals were subjected to a 7‐day latency period, a 10‐day distraction period and a 7‐day consolidation period. The newly formed bone was analyzed histologically and histomorphometrically.

Results: New, mainly woven bone was found in all groups. Differences in the maximum height of new bone were observed and depended on location. Under the distraction plate, statistically significant differences in maximum bone height were found between the group with perforations in both cortical bone and distraction plate and the group without such perforations.

Conclusions: If the marrow cavities were not opened, the contribution to new bone formation was dominant from the periosteum. If the bone perforations opened the marrow cavities, a significant contribution to new bone formation originated from the native bone.