bluuebunny/crossref_metadata_2025 huggingface dataset:
Perception of Barriers to Self-care Management Among Diabetic Patients
Authors: Gazmararian Julie A. , Ziemer David C. , Barnes Catherine
Published: June 2009

Purpose

The purpose of this study was to explore individual, educational, and system barriers that limit low-income diabetes patients’ ability to achieve optimal diabetes self-management.

Methods

Economically disadvantaged patients with diabetes who used the Diabetes Clinic of Grady Health System in Atlanta, Georgia, participated in 3 focus group discussions.

Results

The discussions were held with mostly African Americans (n = 35) to explore barriers to achieving optimal diabetes self-management. Most participants were not married, approximately one-third had less than high school level reading skills, and 40% were not currently working. In terms of individual barriers, the emotional toll from the diagnosis of and lifestyle changes to treat diabetes was a recurrent theme, and included stress, frustration, social isolation, interpersonal conflicts, depression, and fear. Denial was often mentioned as the key factor that inhibited adherence to a healthy mode of living. The educational barriers were failure to recognize the risks and consequences of an asymptomatic condition. Many participants did not understand A1C. Finally, several system barriers were identified. The participants identified needed services, including follow-up and refresher courses, support group discussions, nutrition and medication education, availability of different education modalities, and expanded clinic hours.

Conclusions

The focus group discussions identified both barriers to diabetes management and opportunities for improving care for underserved patients with diabetes. The results are useful to improve the delivery of care and to develop quantitative studies to explore particular areas of interest. Based on these results, the current system needs to provide more support and education to patients with diabetes.
The 3-in-1 Procedure for Recurrent Dislocation of the Patella in Skeletally Immature Children and Adolescents
Authors: Oliva Francesco , Ronga Mario , Longo Umile Giuseppe , Testa Vittorino , Capasso Giovanni , Maffulli Nicola
Published: June 2009

Background

Recurrent patellar dislocations are common injuries in children and adolescents. The subjective and functional results of soft tissue surgical management in a population that was skeletally immature at the time of surgery have not been reported.

Hypothesis

The 3-in-1 procedure is an effective treatment for recurrent patellar dislocation in skeletally immature patients.

Study Design

Case series; Level of evidence, 4.

Methods

Twenty-five skeletally immature patients (age at operation, 13.5 ± 3.8 years) who were practicing sports and suffering from recurrent unilateral patellar dislocation were included in the study and followed until skeletal maturation. Clinical evaluation included the modified Cincinnati rating system and the Kujala score, anthropometry, plain radiography, and isokinetic dynamometry.

Results

The average follow-up was 3.8 years (range, 2.5-6 years). The mean modified Cincinnati score increased from 51.7 ± 12.6 preoperatively to 94.3 ± 10.8 (P < .02), while the mean Kujala scores increased from 52.4 ± 12.7 preoperatively to 93.8 ± 14.2 (P < .02). The Insall-Salvati index remained essentially unchanged, being 1.04 ± 0.2 preoperatively and 1.02 ± 0.3 at latest follow-up. Significant differences were found between the operated and the contralateral limb in the various isokinetic strength variables at all angular velocities measured at the latest follow-up (.05 < P < .0042).

Conclusion

The 3-in-1 procedure is a safe, reliable management option for recurrent patellar dislocation in skeletally immature patients. Side-to-side differences in isokinetic strength and in anthropometric indices persist despite subjective success of the procedure.
Incidence of Glenohumeral Instability in Collegiate Athletics
Authors: Owens Brett D. , Agel Julie , Mountcastle Sally B. , Cameron Kenneth L. , Nelson Bradley J.
Published: June 2009

Background

Glenohumeral instability is a common injury sustained by young athletes. Surprisingly, little is known regarding the incidence of glenohumeral instability in collegiate athletes or the relevant risk factors for injury. A better understanding of the populations most at risk may be used to develop preventive strategies.

Hypothesis

The incidence of glenohumeral instability in collegiate athletics is high, and it is affected by sex, sport, type of event, and mechanism of injury.

Study Design

Descriptive epidemiologic study.

Methods

The National Collegiate Athletic Association injury database was queried for all glenohumeral instability events occurring between the years 1989 and 2004. An analysis of the injuries was performed by sport, activity (competition versus practice), sex, type of event (primary versus recurrent), mechanism of injury, and time loss from athletic performance. Incidence rates and incidence rate ratios were calculated.

Results

A total of 4080 glenohumeral instability events were documented for an incidence rate of 0.12 injuries per 1000 athlete exposures. The sport with the greatest injury rate was men's spring football, with 0.40 injuries per 1000 athlete exposures. Overall, athletes sustained more glenohumeral instability events during games than practices (incidence rate ratio [IRR], 3.50; 95% confidence interval [CI], 3.29-3.73). Male athletes sustained more injuries than did female athletes (IRR, 2.67; 95% CI, 2.43-2.93). Female athletes were more likely to sustain an instability event as the result of contact with an object (IRR, 2.43; 95% CI, 2.08-2.84), whereas male athletes were more likely to sustain an event from player contact (IRR, 2.74; 95% CI, 2.31-3.25). Time lost to sport (>10 days) occurred in 45% of glenohumeral instability events.

Conclusion

Glenohumeral instability is a relatively common injury sustained by collegiate athletes. More injuries occurred during competition and among male athletes.
A Biomechanical Comparison of Transosseous–Suture Anchor and Suture Bridge Rotator Cuff Repairs in Cadavers
Authors: Bisson Leslie J. , Manohar Leslie M.
Published: June 2009

Background

Several biomechanical studies comparing open and arthroscopic rotator cuff repair methods have shown inferior performance of arthroscopic repairs. Suture anchor–augmented transosseous repairs and suture bridge repairs have shown superior biomechanical performance when compared with other methods, but these 2 repair methods have not been directly compared.

Hypothesis

There will be no difference in the biomechanical performance of the transosseous–suture anchor and suture bridge techniques.

Study Design

Controlled laboratory study.

Methods

Eight paired cadaveric shoulder specimens (16 specimens) had creation followed by repair of a complete tear of the supraspinatus, with the first member of each pair undergoing repair by a transosseous–suture anchor technique and the second member undergoing repair by the suture bridge technique. Specimens were then cycled from 10 to 180 N for 200 cycles, followed by testing to failure at 33 mm/s. Elongation was measured during cyclic testing, and failure load and stiffness were obtained during load-to-failure testing. Failure method was recorded.

Results

There was no significant difference between transosseous–suture anchor repairs and suture bridge repairs for elongation (4.0 ± 1.60 mm vs 3.5 ± 1.1 mm, P = .31), failure load (408 ± 93 N vs 419 ± 62 N, P = .70), or stiffness (58 ± 10 N/mm vs 58 ± 14 N/mm, P = .94). The most common mode of failure with each method was suture cutting through tendon.

Conclusion

The suture bridge repair exhibited similar biomechanical performance during cyclic and load-to-failure testing as a transosseous–suture anchor repair, which historically has been performed in open or mini-open fashion.

Clinical Relevance

Arthroscopic rotator cuff repairs can be performed that are as strong as open or mini-open repairs.
Victim Character Evidence in Death Penalty Cases
Authors: Younglove Jane A. , Nelligan Peter J. , Reisner Ronald L.
Published: June 2009

The U.S. Supreme Court’s Payne decision opening the door to victim impact testimony in capital cases generally, and to victim character evidence particularly, has been controversial. The issue is whether a murder victim’s character is relevant to the moral blameworthiness of the defendant. Several mock jury simulation studies have shown that such evidence does influence jury decisions imposing the death penalty. The current study took a different direction and examined the nature and extent of actual victim character testimony in samples of death penalty cases in three states. Data were derived from 14 transcripts of the penalty phase of trials in each of three states: California, New Jersey, and Texas, states with different political and legal climates. Content analysis revealed that there were numerous references to victims’ character in the form of positive personality traits, in addition to descriptions of the impact the crime had on the victims’ families and friends. Qualitative analysis revealed that many witnesses were allowed to use photos, videotapes, and other personal items to portray the victim’s life. What emerges from this inside view of practices in courtrooms is disturbing in that the evidence allowed seems to exceed Payne’s already meager limitations.
Identifying Imprisonment Patterns and Their Relation to Crime Among New York Counties 1990-2000
Authors: Schupp Paul , Rivera Craig
Published: June 2009

The current study is an exploratory application of a technique for modeling developmental trajectories as an illustration of how researchers might use trajectory analysis and county-level data to analyze the effects of imprisonment patterns on crime. Using data from 61 New York counties, the authors model the patterns of imprisonment, defined as the percentage of felons sentenced to state prison in a given year, displayed by the counties from 1990 to 1999, and then demonstrate how knowledge of these patterns can be used to estimate the relationship between imprisonment patterns during the 1990s and crime in 2000. Six distinct patterns of imprisonment are identified, and bivariate and multivariate analyses reveal that high or consistently increasing levels of imprisonment were not associated with lower property or violent crime rates in 2000. Even after controlling for crime in the 1990s and other relevant factors, counties with high or consistently increasing imprisonment had significantly higher violent crime in 2000. Implications for future research are discussed.
Cognitive dysfunction in primary progressive multiple sclerosis: a neuropsychological and MRI study
Authors: Ukkonen M , Vahvelainen T , Hämäläinen P , Dastidar P , Elovaara I
Published: June 2009

Although cognitive dysfunction is known to occur in multiple sclerosis (MS), only few studies have reported cognitive performance in patients with primary progressive MS (PPMS). To find out the pattern of cognitive performance in PPMS, 28 PPMS patients underwent an extensive battery of neuropsychological tests. The results were compared to those of healthy controls ( n = 20) and patients with secondary progressive MS (SPMS, n = 28). Furthermore, the results of neuropsychological tests in PPMS were correlated to magnetic resonance imaging findings. Our study showed that the PPMS patients have deficits in several cognitive domains when compared to age-matched and education-matched controls, but the cognitive impairment in the PPMS and SPMS patients appeared to be similar. Cognitive deficits in PPMS patients correlated with diffuse brain lesion, T1- and T2-lesion load, but no correlations were found with atrophy.
Quantitative assessment of brain iron by R2* relaxometry in patients with clinically isolated syndrome and relapsing–remitting multiple sclerosis
Authors: Khalil M , Enzinger C , Langkammer C , Tscherner M , Wallner-Blazek M , Jehna M , Ropele S , Fuchs S , Fazekas F
Published: June 2009

Background

Increased iron deposition has been implicated in the pathophysiology of multiple sclerosis (MS), based on visual analysis of signal reduction on T2-weighted images. R2* relaxometry allows to assess brain iron accumulation quantitatively.

Objective

To investigate regional brain iron deposition in patients with a clinically isolated syndrome (CIS) or relapsing–remitting MS (RRMS) and its associations with demographical, clinical, and conventional magnetic resonance imaging (MRI) parameters.

Methods

We studied 69 patients (CIS, n = 32; RRMS, n = 37) with 3T MRI and analyzed regional R2* relaxation rates and their correlations with age, disease duration, disability, T2 lesion load, and normalized brain volumes.

Results

Basal ganglia R2* relaxation rates increased in parallel with age ( r = 0.3–0.6; P < 0.01) and were significantly higher in RRMS than in CIS ( P < 0.05). Using multivariate linear regression analysis, the rate of putaminal iron deposition was independently predicted by the patients’ age, disease duration, and gray matter atrophy.

Conclusions

Quantitative assessment by R2* relaxometry suggests increased iron deposition in the basal ganglia of MS patients, which is associated with disease duration and brain atrophy. This technique together with long-term follow-up thus appears suited to clarify whether regional iron accumulation contributes to MS morbidity or merely reflects an epiphenomenon.
Sensitivity of conventional memory tests in multiple sclerosis: comparing the Rao Brief Repeatable Neuropsychological Battery and the Minimal Assessment of Cognitive Function in MS
Authors: Strober L , Englert J , Munschauer F , Weinstock-Guttman B , Rao S , Benedict RHB
Published: June 2009

Background

Cognitive impairment is common in multiple sclerosis (MS) affecting roughly 45–60% of patients. Because memory deficits have significant impact on employment, caregiver burden, and social functioning, neuropsychological (NP) assessment is often recommended. Two widely used and validated NP batteries for MS are the Rao Brief Repeatable Neuropsychological Battery (BRNB) and the Minimal Assessment of Cognitive Function in MS (MACFIMS). Although similar, these batteries differ in the specific auditory/verbal and visual/spatial memory tests employed. The relative sensitivity of these memory tests is unknown.

Methods

The BRNB and MACFIMS have considerable overlap but different memory tests: the former includes the Selective Reminding Test (SRT) and the 10/36 Spatial Recall Test (10/36) and the latter the California Verbal Learning Test, Second Edition (CVLT2) and Brief Visuospatial Memory Test, Revised (BVMTR). In 65 patients with MS and 46 demographically matched controls, we compared the sensitivity of these tests, and secondarily their respective batteries.

Results

The BRNB and MACFIMS were comparable in their overall sensitivity to disease status. Although the BVMTR showed greater discriminative validity than the 10/36, the CVLT2 and SRT were comparable in sensitivity. The SDMT was the most sensitive NP test across both batteries.

Conclusions

We conclude that the BRNB and MACFIMS have comparable sensitivity among patients with MS. The sensitivity of the auditory/verbal memory tests from these batteries is similar, but the BVMTR appears to be more sensitive than the 10/36. Clinical implications are discussed.
Is Balloon Angioplasty of Peri-Anastomotic Stenoses of Failing Peripheral Arterial Bypasses Worthwhile?
Authors: Eisenberg Joshua A. , Calligaro Keith D. , Kolakowski Steven , Doerr Kevin J. , Bennett Sandy , Murtha Kathy , Dougherty Matthew J.
Published: June 2009

Introduction: Surgical revision of failing peripheral arterial bypass grafts has generally been shown to provide superior patency rates compared to balloon angioplasty. We analyzed whether balloon angioplasty, specifically of peri-anastomotic stenoses (PAS), provided acceptable patency rates, because surgery for these lesions is more difficult and is likely associated with higher complication rates compared to surgical revision of stenoses in the body of a graft. Methods: This is a retrospective review of PAS balloon angioplasties performed at a single institution between January 1, 1999, and September 1, 2005. We report ‘‘primary site patency’’ as a stenosis treated by balloon angioplasty, ‘‘revised primary site patency’’ as a stenosis treated by repeat balloon angioplasty, and ‘‘secondary site patency’’ as an angioplastied stenosis treated surgically or when the graft thrombosed and was revised surgically. All procedures were performed in an endovascular operating room based on duplex scan findings suggesting a significant stenosis. Results: 48 PAS in 33 autologous vein and 15 prosthetic grafts were treated by balloon angioplasty in 42 patients. Mean follow-up was 12 months (range, 1-49 months). Interventions were performed on 22 femoropopliteal grafts (11 proximal, 11 distal), 20 femorotibial grafts (5 proximal, 15 distal), 2 axillofemoral grafts (2 proximal anastomoses), 2 popliteal-pedal grafts (1 proximal, 1 distal), and 1 common iliac-femoral graft (proximal). Life-table analysis revealed 2-year primary, assisted primary, and secondary patency rates of 38%, 58%, and 84%, respectively. No major complications occurred with any endovascular intervention. Conclusion: Balloon angioplasty of PAS resulted in acceptable 2-year assisted primary patency rate of almost 60%. Endovascular intervention avoided repeat incisions in scarred groins, higher rates of nerve injury and infection, significant blood loss, and longer length of hospital stays. We recommend that balloon angioplasty of PAS be attempted before resorting to surgical intervention, especially in cases of hostile anastomotic wounds.
Lymphopenia-induced spontaneous T-cell proliferation as a cofactor for autoimmune disease development
Authors: Le Campion Armelle , Gagnerault Marie-Claude , Auffray Cédric , Bécourt Chantal , Poitrasson-Rivière Maud , Lallemand Eliette , Bienvenu Boris , Martin Bruno , Lepault Françoise , Lucas Bruno
Published: June 2009

Lymphopenia is thought to be a major cause of tolerance breakdown. In a lymphopenic environment, self-recognition events induce some T cells to expand strongly (a mechanism known as spontaneous proliferation). In this study, we show that in C57BL/6 mice, the repertoire resulting from lymphopenia-induced spontaneous CD4+ T-cell proliferation included a proportion of regulatory T cells as large as that observed in a normal mouse, and no autoimmune disorder was observed. By contrast, in nonobese diabetic mice, differences in the ability of conventional and regulatory T cells to expand in response to lymphopenia led to an unbalance between these 2 T-cell compartments at the expense of regulatory T cells, resulting in the onset of autoimmune diseases. Notably, this accounted for the rapid transfer of diabetes with small numbers of BDC2.5 CD4+ T cells. Thus, lymphopenia does not itself induce autoimmunity, but it should be considered as a cofactor for the development of autoimmune disorders.
Granulocyte-macrophage colony-stimulating factor (GM-CSF)–secreting cellular immunotherapy in combination with autologous stem cell transplantation (ASCT) as postremission therapy for acute myeloid leukemia (AML)
Authors: Borrello Ivan M. , Levitsky Hyam I. , Stock Wendy , Sher Dorie , Qin Lu , DeAngelo Daniel J. , Alyea Edwin P. , Stone Richard M. , Damon Lloyd E. , Linker Charles A. , Maslyar Daniel J. , Hege Kristen M.
Published: June 2009

Preclinical models have demonstrated the efficacy of granulocyte-macrophage colony-stimulating factor-secreting cancer immunotherapies (GVAX platform) accompanied by immunotherapy-primed lymphocytes after autologous stem cell transplantation in hematologic malignancies. We conducted a phase 2 study of this combination in adult patients with acute myeloid leukemia. Immunotherapy consisted of autologous leukemia cells admixed with granulocyte-macrophage colony-stimulating factor-secreting K562 cells. “Primed” lymphocytes were collected after a single pretransplantation dose of immunotherapy and reinfused with the stem cell graft. Fifty-four subjects were enrolled; 46 (85%) achieved a complete remission, and 28 (52%) received the pretransplantation immunotherapy. For all patients who achieved complete remission, the 3-year relapse-free survival (RFS) rate was 47.4% and overall survival was 57.4%. For the 28 immunotherapy-treated patients, the RFS and overall survival rates were 61.8% and 73.4%, respectively. Posttreatment induction of delayed-type hypersensitivity reactions to autologous leukemia cells was associated with longer 3-year RFS rate (100% vs 48%). Minimal residual disease was monitored by quantitative analysis of Wilms tumor-1 (WT1), a leukemia-associated gene. A decrease in WT1 transcripts in blood was noted in 69% of patients after the first immunotherapy dose and was also associated with longer 3-year RFS (61% vs 0%). In conclusion, immunotherapy in combination with primed lymphocytes and autologous stem cell transplantation shows encouraging signals of potential activity in acute myeloid leukemia (ClinicalTrials.gov: NCT00116467).
Interleukin-27 inhibition of HIV-1 involves an intermediate induction of type I interferon
Authors: Greenwell-Wild Teresa , Vázquez Nancy , Jin Wenwen , Rangel Zoila , Munson Peter J. , Wahl Sharon M.
Published: June 2009

Infection of CD4+ chemokine coreceptor+ targets by HIV is aided and abetted by the proficiency of HIV in eliminating or neutralizing host cell–derived defensive molecules. Among these innate protective molecules, a family of intracellular apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like (APOBEC) cytidine deaminases, is constitutively expressed but inactivated by HIV viral infectivity factor. The ability of interferon-α (IFN-α) to augment cytidine deaminases offered the possibility that the balance between virus and target cell might be altered in favor of the host. Further characterization of transcriptional profiles induced by IFN-α using microarrays, with the intention to identify and dissociate retroviral countermaneuvers from associated toxicities, revealed multiple molecules with suspected antiviral activity, including IL-27. To establish whether IFN-α toxicity might be sidestepped through the use of downstream IL-27 against HIV, we examined whether IL-27 directly regulated cytidine deaminases. Although IL-27 inducesAPOBECs, it does so in a delayed fashion. Dissecting the underlying regulatory events uncovered an initial IL-27–dependent induction of IFN-α and/or IFN-β, which in turn, induces APOBEC3, inhibited by IFN-α/β receptor blockade. In addition to macrophages, the IL-27–IFN-α connection is operative in CD4+ T cells, consistent with an IFN-α–dependent pathway underlying host cell defense to HIV.
Computational analysis of the interaction between transcription factors and the predicted secreted proteome of the yeast Kluyveromyces lactis
Authors: Brustolini Otávio JB , Fietto Luciano G , Cruz Cosme D , Passos Flávia ML
Published: June 2009

Background

Protein secretion is a cell translocation process of major biological and technological significance. The secretion and downstream processing of proteins by recombinant cells is of great commercial interest. The yeast Kluyveromyces lactis is considered a promising host for heterologous protein production. Because yeasts naturally do not secrete as many proteins as filamentous fungi, they can produce secreted recombinant proteins with few contaminants in the medium. An ideal system to address the secretion of a desired protein could be exploited among the native proteins in certain physiological conditions. By applying algorithms to the completed K. lactis genome sequence, such a system could be selected. To this end, we predicted protein subcellular locations and correlated the resulting extracellular secretome with the transcription factors that modulate the cellular response to a particular environmental stimulus.

Results

To explore the potential Kluyveromyces lactis extracellular secretome, four computational prediction algorithms were applied to 5076 predicted K. lactis proteins from the genome database. SignalP v3 identified 418 proteins with N-terminal signal peptides. From these 418 proteins, the Phobius algorithm predicted that 176 proteins have no transmembrane domains, and the big-PI Predictor identified 150 proteins as having no glycosylphosphatidylinositol (GPI) modification sites. WoLF PSORT predicted that the K. lactis secretome consists of 109 putative proteins, excluding subcellular targeting. The transcription regulators of the putative extracellular proteins were investigated by searching for DNA binding sites in their putative promoters. The conditions to favor expression were obtained by searching Gene Ontology terms and using graph theory.

Conclusion

A public database of K. lactis secreted proteins and their transcription factors are presented. It consists of 109 ORFs and 23 transcription factors. A graph created from this database shows 134 nodes and 884 edges, suggesting a vast number of relationships to be validated experimentally. Most of the transcription factors are related to responses to stress such as drug, acid and heat resistance, as well as nitrogen limitation, and may be useful for inducing maximal expression of potential extracellular proteins.
Rodent-specific alternative exons are more frequent in rapidly evolving genes and in paralogs
Authors: Nurtdinov Ramil N , Mironov Andrey A , Gelfand Mikhail S
Published: June 2009

Background

Alternative splicing is an important mechanism for generating functional and evolutionary diversity of proteins in eukaryotes. Here, we studied the frequency and functionality of recently gained, rodent-specific alternative exons.

Results

We projected the data about alternative splicing of mouse genes to the rat, human, and dog genomes, and identified exons conserved in the rat genome, but missing in more distant genomes. We estimated the frequency of rodent-specific exons while controlling for possible residual conservation of spurious exons. The frequency of rodent-specific exons is higher among predominantly skipped exons and exons disrupting the reading frame. Separation of all genes by the rate of sequence evolution and by gene families has demonstrated that rodent-specific cassette exons are more frequent in rapidly evolving genes and in rodent-specific paralogs.

Conclusion

Thus we demonstrated that recently gained exons tend to occur in fast-evolving genes, and their inclusion rate tends to be lower than that of older exons. This agrees with the theory that gain of alternative exons is one of the major mechanisms of gene evolution.
Selection and evaluation of reference genes for improved interrogation of microbial transcriptomes: case study with the extremophile Acidithiobacillus ferrooxidans
Authors: Nieto Pamela A , Covarrubias Paulo C , Jedlicki Eugenia , Holmes David S , Quatrini Raquel
Published: June 2009

Background

Normalization is a prerequisite for accurate real time PCR (qPCR) expression analysis and for the validation of microarray profiling data in microbial systems. The choice and use of reference genes that are stably expressed across samples, experimental conditions and designs is a key consideration for the accurate interpretation of gene expression data.

Results

Here, we evaluate a carefully selected set of reference genes derived from previous microarray-based transcriptional profiling experiments performed on Acidithiobacillus ferrooxidans and identify a set of genes with minimal variability under five different experimental conditions that are frequently used in Acidithiobacilli research. Suitability of these and other previously reported reference genes to monitor the expression of four selected target genes from A. ferrooxidans grown with different energy sources was investigated. Utilization of reference genes map, rpoC, alaS and era results in improved interpretation of gene expression profiles in A. ferrooxidans.

Conclusion

This investigation provides a validated set of reference genes for studying A. ferrooxidans gene expression under typical biological conditions and an initial point of departure for exploring new experimental setups in this microorganism and eventually in other closely related Acidithiobacilli. The information could also be of value for future transcriptomic experiments in other bacterial systems.
Prevalence of problem alcohol use among patients attending primary care for methadone treatment
Authors: Ryder Niamh , Cullen Walter , Barry Joseph , Bury Gerard , Keenan Eamon , Smyth Bobby P
Published: June 2009

Background

Problem alcohol use is associated with adverse health outcomes among current or former heroin users and primary care is providing methadone treatment for increasing numbers of this population. This study aimed todetermine the prevalence of problem alcohol use among current or former heroin users attending primary care for methadone treatment and to describe the socio-demographic characteristics and health service utilisation characteristics associated with problem alcohol uses.

Methods

We conducted a cross sectional survey of patients sampled from a national database of patients attending general practice for methadone treatment. Participants were recruited by their general practitioner and data was collected using an interviewer-administered questionnaire, which included the Alcohol Use Disorders Identification Test ('AUDIT'), with a score of >7 considered abnormal (ie 'AUDIT positive cases') and socio-demographic, medical and substance use characteristics.

Results

We interviewed 196 patients (71% of those invited, 31% of those sampled, 11% of the national database). The median age was 32 years, 55% were hepatitis C positive, 79% had used illicit drugs in the previous month and 68% were male. Sixty-eight 'AUDIT positive' cases were identified (prevalence of 35%, 95% CI = 28–41%) and these were more likely to have attended a local Emergency Department in the previous year (p < 0.05) and less likely to have attended a hospital clinic in the previous year (p < 0.05). Twenty-seven (14%) scored 20 or higher indicating possible alcohol dependence.

Conclusion

Problem alcohol use has a high prevalence among current or former heroin users attending primary care for methadone treatment and interventions that address this issue should be explored as a priority. Interventions that address problem alcohol use in this population should be considered as a priority, although the complex medical and psychological needs of this population may make this challenging.
Efficacy of sulphadoxine-pyrimethamine with or without artesunate for the treatment of uncomplicated Plasmodium falciparum malaria in southern Mozambique: a randomized controlled trial
Authors: Allen Elizabeth N , Little Francesca , Camba Tunisio , Cassam Yasmin , Raman Jaishree , Boulle Andrew , Barnes Karen I
Published: June 2009

Background

An artemisinin-based combination therapy, artesunate (AS) plus sulphadoxine-pyrimethamine (SP), was compared to SP monotherapy to provide evidence of further treatment options in southern Mozambique.

Methods

Between 2003 and 2005, 411 patients over one year and 10 kg with uncomplicated Plasmodium falciparum malaria were randomly allocated SP (25/1.25 mg per kg day 0) or AS/SP (as above plus 4 mg/kg artesunate days 0, 1 and 2). Allocation was concealed, but treatment was open-label except to microscopists. The primary objective was the relative risk of treatment failure, which was assessed using World Health Organization response definitions modified to a 42-day follow-up.

Results

Of the 411 subjects enrolled, 359 (87.3%) completed the follow up period (SP n = 175, AS/SP n = 184). A survival analysis including 408 subjects showed that the polymerase chain reaction-adjusted cure rates were 90.4% (95% confidence interval [CI] 84.9%–93.9%) and 98.0% (95% CI 94.8%–99.3%) for SP and AS/SP respectively. Multivariable analysis showed that treatment with AS/SP decreased the relative hazard of treatment failure by 80% compared to SP (hazard ratio [HR] 0.2; 95% CI 0.1–0.6) and age over seven years decreased the relative hazard of failure by 70% (HR 0.3; 95% CI 0.1–0.9), when compared to younger age. However, having a quintuple dhfr/dhps mutation increased the relative hazard of failure compared to fewer mutations (HR 3.2; 95% CI 1.3–7.5) and baseline axillary temperature increased the relative hazard of failure by 50% for each °C increase (HR 1.5; 95% CI 1.1–2.2).

Conclusion

While both treatments were efficacious, AS plus SP significantly decreased the relative hazard of treatment failure compared to SP monotherapy Artesunate plus sulphadoxine-pyrimethamine, but not sulphadoxine-pyrimethamine monotherapy, met the current WHO criteria of >95% efficacy for policy implementation.

Trial registration

NCT00203736 and NCT00203814
n-3 polyunsaturated fatty acids in milk is associate to weight gain and growth in premature infants
Authors: Tinoco Sandra M Barboza , Sichieri Rosely , Setta Cecília L , Moura Anibal S , Carmo Maria G Tavares do
Published: June 2009

Background

Linoleic 18:2 (n-6) and α-linolenic 18:3 (n-3) essential fatty acids and long-chain polyunsaturated fatty acids (LC-PUFA) are essential nutrients for growth and neonatal development. Consumption of preformed n-3 LC-PUFA has been shown to increase gestational duration and to decrease the incidence of premature birth in human studies. This study evaluated the association of essential fatty acids and LC-PUFA in breast milk on the growth of premature children (weight, height and head circumference).

Study design

Thirty-seven premature infants with a gestational age of 37 weeks or less were followed until 6 months of gestational age, adjusted for prematurity. The milk from mothers, weight, height and head circumference measures of children were collected during the follow up. The breast milk fatty acids were quantified by gas-liquid chromatography.

Results

Our results showed that total n-3 PUFA was positively associated with weight gain (p= 0.05), height (p= 0.04) and body mass index (BMI) of children (p= 0.05). Our results also indicate that both linoleic acid and total essential fatty acids were positively associated with BMI and head circumference, whereas oleic acid was positively associated only with head circumference.

Conclusion

These results suggest that the n-3 PUFA composition of milk may be associated with weight gain and growth. Considering the advantages of n-3 LC-PUFA consumption on infant growth and visual function and its association with reduced incidence of premature birth, dietitians should advise pregnant women to increase their intake of foods high in n-3 LC-PUFA.
Effect of hydroxyurea on the promoter occupancy profiles of tumor suppressor p53 and p73
Authors: Huang Vera , Lu Xin , Jiang Yong , Wang Jean YJ
Published: June 2009

Background

The p53 tumor suppressor and its related protein, p73, share a homologous DNA binding domain, and mouse genetics studies have suggested that they have overlapping as well as distinct biological functions. Both p53 and p73 are activated by genotoxic stress to regulate an array of cellular responses. Previous studies have suggested that p53 and p73 independently activate the cellular apoptotic program in response to cytotoxic drugs. The goal of this study was to compare the promoter-binding activity of p53 and p73 at steady state and after genotoxic stress induced by hydroxyurea.

Results

We employed chromatin immunoprecipitation, the NimbleGen promoter arrays and a model-based algorithm for promoter arrays to identify promoter sequences enriched in anti-p53 or anti-p73 immunoprecipitates, either before or after treatment with hydroxyurea, which increased the expression of both p53 and p73 in the human colon cancer cell line HCT116-3(6). We calculated a model-based algorithm for promoter array score for each promoter and found a significant correlation between the promoter occupancy profiles of p53 and p73. We also found that after hydroxyurea treatment, the p53-bound promoters were still bound by p73, but p73 became associated with additional promoters that that did not bind p53. In particular, we showed that hydroxyurea induces the binding of p73 but not p53 to the promoter of MLH3, which encodes a mismatch repair protein, and causes an up-regulation of the MLH3 mRNA.

Conclusion

These results suggest that hydroxyurea exerts differential effects on the promoter-binding functions of p53 and p73 and illustrate the power of model-based algorithm for promoter array in the analyses of promoter occupancy profiles of highly homologous transcription factors.
Antimicrobial breakpoint estimation accounting for variability in pharmacokinetics
Authors: Bi Goue DenisGohore , LI Jun , Nekka Fahima
Published: June 2009

Background

Pharmacokinetic and pharmacodynamic (PK/PD) indices are increasingly being used in the microbiological field to assess the efficacy of a dosing regimen. In contrast to methods using MIC, PK/PD-based methods reflect in vivo conditions and are more predictive of efficacy. Unfortunately, they entail the use of one PK-derived value such as AUC or Cmax and may thus lead to biased efficiency information when the variability is large. The aim of the present work was to evaluate the efficacy of a treatment by adjusting classical breakpoint estimation methods to the situation of variable PK profiles.

Methods and results

We propose a logical generalisation of the usual AUC methods by introducing the concept of "efficiency" for a PK profile, which involves the efficacy function as a weight. We formulated these methods for both classes of concentration- and time-dependent antibiotics. Using drug models and in silico approaches, we provide a theoretical basis for characterizing the efficiency of a PK profile under in vivo conditions. We also used the particular case of variable drug intake to assess the effect of the variable PK profiles generated and to analyse the implications for breakpoint estimation.

Conclusion

Compared to traditional methods, our weighted AUC approach gives a more powerful PK/PD link and reveals, through examples, interesting issues about the uniqueness of therapeutic outcome indices and antibiotic resistance problems.
Abnormal auditory ERP N100 in children with dyslexia: comparison with their control siblings
Authors: Papageorgiou Charalabos , Giannakakis Giorgos A , Nikita Konstantina S , Anagnostopoulos Dimitris , Papadimitriou George N , Rabavilas Andreas
Published: June 2009

Background

Recent research has implicated deficits of the working memory (WM) and attention in dyslexia. The N100 component of event-related potentials (ERP) is thought to reflect attention and working memory operation. However, previous studies showed controversial results concerning the N100 in dyslexia. Variability in this issue may be the result of inappropriate match up of the control sample, which is usually based exclusively on age and gender.

Methods

In order to address this question the present study aimed at investigating the auditory N100 component elicited during a WM test in 38 dyslexic children in comparison to those of 19 unaffected sibling controls. Both groups met the criteria of the International Classification of Diseases (ICD-10). ERP were evoked by two stimuli, a low (500 Hz) and a high (3000 Hz) frequency tone indicating forward and reverse digit span respectively.

Results

As compared to their sibling controls, dyslexic children exhibited significantly reduced N100 amplitudes induced by both reverse and forward digit span at Fp1, F3, Fp2, Fz, C4, Cz and F4 and at Fp1, F3, C5, C3, Fz, F4, C6, P4 and Fp2 leads respectively. Memory performance of the dyslexics group was not significantly lower than that of the controls. However, enhanced memory performance in the control group is associated with increased N100 amplitude induced by high frequency stimuli at the C5, C3, C6 and P4 leads and increased N100 amplitude induced by low frequency stimuli at the P4 lead.

Conclusion

The present findings are in support of the notion of weakened capture of auditory attention in dyslexia, allowing for a possible impairment in the dynamics that link attention with short memory, suggested by the anchoring-deficit hypothesis.
Clustered microRNAs' coordination in regulating protein-protein interaction network
Authors: Yuan Xiongying , Liu Changning , Yang Pengcheng , He Shunmin , Liao Qi , Kang Shuli , Zhao Yi
Published: June 2009

Background

MicroRNAs (miRNAs), a growing class of small RNAs with crucial regulatory roles at the post-transcriptional level, are usually found to be clustered on chromosomes. However, with the exception of a few individual cases, so far little is known about the functional consequence of this conserved clustering of miRNA loci. In animal genomes such clusters often contain non-homologous miRNA genes. One hypothesis to explain this heterogeneity suggests that clustered miRNAs are functionally related by virtue of co-targeting downstream pathways.

Results

Integrating of miRNA cluster information with protein protein interaction (PPI) network data, our research supports the hypothesis of the functional coordination of clustered miRNAs and links it to the topological features of miRNAs' targets in PPI network. Specifically, our results demonstrate that clustered miRNAs jointly regulate proteins in close proximity of the PPI network. The possibility that two proteins yield to this coordinated regulation is negatively correlated with their distance in PPI network. Guided by the knowledge of this preference, we found several network communities enriched with target genes of miRNA clusters. In addition, our results demonstrate that the variance of this propensity can also partly be explained by protein's connectivity and miRNA's conservation.

Conclusion

In summary, this work supports the hypothesis of intra-cluster coordination and investigates the extent of this coordination.
Radical radiotherapy with concurrent weekly cisplatin in loco-regionally advanced squamous cell carcinoma of the head and neck: a single-institution experience
Authors: Gupta Tejpal , Agarwal Jai Prakash , Ghosh-Laskar Sarbani , Parikh Purvish M , D'Cruz Anil K , Dinshaw Ketayun A
Published: June 2009

Background

The dominant pattern of failure for squamous cell carcinoma of head and neck remains loco-regional, although distant metastases are now being increasingly documented. Radical radiotherapy with concurrent chemotherapy is contemporary standard of care in the non-surgical management of these loco-regionally advanced cancers, based on large randomized controlled trials utilizing high-dose cisplatin (80–100 mg/m2) cycled every three-weekly during definitive radiotherapy. Although efficacious, this is associated with high acute morbidity necessitating intensive supportive care with attendant resource implications. The aim of this retrospective study was to assess the efficacy and acute toxicity of an alternative schedule i.e. concurrent weekly cisplatin-based radical radiotherapy and it's potential to be an optimal regimen in advanced head and neck cancers.

Methods

Outcome data of patients with Stage III & IV head and neck squamous cell carcinoma, excluding nasopharynx, planned for radical radiotherapy (66–70 Gy) with concurrent weekly cisplatin (30 mg/m2) treated in a single unit between 1996–2004 was extracted.

Results

The dataset consisted of 264 patients with a median age of 54 years. The median radiotherapy dose was 70 Gy (range 7.2–72 Gy) and median number of chemotherapy cycles was 6 (range 1–7). Two-thirds (65%) of patients received ≥85% of planned cisplatin dose. With a mean follow-up of 19 months, the 5-year local control; loco-regional control; and disease free survival was 57%; 46%; and 43% respectively. Acute grade 3 or worse mucositis and dermatitis was seen in 77 (29%) and 92 (35%) patients respectively, essentially in patients receiving doses ≥66 Gy and 6 or more cycles of chemotherapy. Other toxicities (hematologic, nausea and vomiting) were mild and self-limiting. Overall, the acute toxicity of this concurrent weekly chemo-radiation regimen though mildly increased did not mandate intensive supportive care. Stage grouping, primary site, and intensity of treatment were significant predictors of loco-regional control and disease free survival.

Conclusion

Radical radiotherapy with concurrent weekly cisplatin has moderate efficacy and acceptable acute toxicity with potential to be an optimal regimen in loco-regionally advanced squamous cell carcinoma of the head and neck, particularly in limited-resource settings. Stage grouping, primary site, and treatment intensity are important determinants of outcome.
Distribution and seasonality of rhinovirus and other respiratory viruses in a cross-section of asthmatic children in Trinidad, West Indies
Authors: Matthew Jason , Pinto Pereira Lexley M , Pappas Tressa E , Swenson Cheri A , Grindle Kris A , Roberg Kathy A , Lemanske Robert F , Lee Wai-Ming , Gern James E
Published: June 2009

Background

Childhood asthma in the Caribbean is advancing in prevalence and morbidity. Though viral respiratory tract infections are reported triggers for exacerbations, information on these infections with asthma is sparse in Caribbean territories. We examined the distribution of respiratory viruses and their association with seasons in acute and stable asthmatic children in Trinidad.

Methods

In a cross-sectional study of 70 wheezing children attending the emergency department for nebulisation and 80 stable control subjects (2 to 16 yr of age) in the asthma clinic, nasal specimens were collected during the dry (n = 38, January to May) and rainy (n = 112, June to December) seasons. A multitarget, sensitive, specific high-throughput Respiratory MultiCode assay tested for respiratory-virus sequences for eight distinct groups: human rhinovirus, respiratory syncytial virus, parainfluenza virus, influenza virus, metapneumovirus, adenovirus, coronavirus, and enterovirus.

Results

Wheezing children had a higher [χ2 = 5.561, p = 0.018] prevalence of respiratory viruses compared with stabilized asthmatics (34.3% (24) versus (vs.) 17.5% (14)). Acute asthmatics were thrice as likely to be infected with a respiratory virus (OR = 2.5, 95% CI = 1.2 – 5.3). The predominant pathogens detected in acute versus stable asthmatics were the rhinovirus (RV) (n = 18, 25.7% vs. n = 7, 8.8%; p = 0.005), respiratory syncytial virus B (RSV B) (n = 2, 2.9% vs. n = 4, 5.0%), and enterovirus (n = 1, 1.4% vs. n = 2, 2.5%). Strong odds for rhinoviral infection were observed among nebulised children compared with stable asthmatics (p = 0.005, OR = 3.6, 95% CI = 1.4 – 9.3,). RV was prevalent throughout the year (Dry, n = 6, 15.8%; Rainy, n = 19, 17.0%) and without seasonal association [χ2 = 0.028, p = 0.867]. However it was the most frequently detected virus [Dry = 6/10, (60.0%); Rainy = 19/28, (67.9%)] in both seasons.

Conclusion

Emergent wheezing illnesses during childhood can be linked to infection with rhinovirus in Trinidad's tropical environment. Viral-induced exacerbations of asthma are independent of seasons in this tropical climate. Further clinical and virology investigations are recommended on the role of infections with the rhinovirus in Caribbean childhood wheeze.