bluuebunny/crossref_metadata_2025 huggingface dataset:
Well-being in residency training: a survey examining resident physician satisfaction both within and outside of residency training and mental health in Alberta
Authors: Cohen Jordan S , Patten Scott
Published: June 2005

Background

Despite the critical importance of well-being during residency training, only a few Canadian studies have examined stress in residency and none have examined well-being resources. No recent studies have reported any significant concerns with respect to perceived stress levels in residency. We investigated the level of perceived stress, mental health and understanding and need for well-being resources among resident physicians in training programs in Alberta, Canada.

Methods

A mail questionnaire was distributed to the entire resident membership of PARA during 2003 academic year. PARA represents each of the two medical schools in the province of Alberta.

Results

In total 415 (51 %) residents participated in the study. Thirty-four percent of residents who responded to the survey reported their life as being stressful. Females reported stress more frequently than males (40% vs. 27%, p < 0.02). Time pressure was reported as the number one factor contributing to stress (44% of males and 57% of females). A considerable proportion of residents would change their specialty program (14%) and even more would not pursue medicine (22%) if given the opportunity to relive their career. Up to 55% of residents reported experiencing intimidation and harassment. Intimidation and harassment was strongly related to gender (12% of males and 38% of females). Many residents (17%) rated their mental health as fair or poor. This was more than double the amount reported in the Canadian Community Health Survey from the province (8%) or the country (7%).

Residents highly valued their colleagues (67%), program directors (60%) and external psychiatrist/psychologist (49%) as well-being resources. Over one third of residents wished to have a career counselor (39%) and financial counselor (38%).

Conclusion

Many Albertan residents experience significant stressors and emotional and mental health problems. Some of which differ among genders. This study can serve as a basis for future resource application, research and advocacy for overall improvements to well-being during residency training.
Secondary prevention of allergic symptoms in a dairy farmer by use of a milking robot
Authors: Korinth Gintautas , Broding Horst Christoph , Uter Wolfgang , Drexler Hans
Published: June 2005

Background

Animal-derived allergens include lipocalins which play an increasing role in occupational respiratory sensitizations. The prevention of sensitization in stock farming is often difficult due to intense exposure, with traditional milking still requiring close animal contact. Complete avoidance of allergen exposure is only possible if stock farming is abandoned. This is, however, often not feasible in small dairy plants because of the resulting loss of income.

Case presentation

In a 37-year-old female farmer daily asthmatic complaints appeared, associated with cow dust-derived allergen exposure by milking with a conventional device. Respiratory symptoms increased during a period of 12 years. Allergic bronchial asthma was diagnosed, caused by sensitization against cow dust-derived allergens, as demonstrated by positive skin prick test and by detection of IgE antibodies. In a separate specific inhalation challenge test using a 10% extract of cow dust-derived allergens a 330% increase of airway resistance was detected. To enable further dairy farming, a milking robot was installed in 1999, i.e., an automatic milking system. The novel milking technique reduced the daily exposure from over 2 hours to approximately 10 min. The clinical course after the installation of the milking robot was favourable, with less frequent allergic and asthmatic symptoms. Furthermore, asthma medication could be reduced. Improvement was noted also in terms of lung-function and decreased total serum IgE.

Conclusion

The case presented and the evidence from the literature indicates that the strategy of exposure minimization to allergens at workplaces can be an effective alternative to total elimination. In farmers with cow dust allergy a milking robot is an appropriate technical measure to minimize allergen-exposure.
Expression and functional properties of antibodies to tissue inhibitors of metalloproteinases (TIMPs) in rheumatoid arthritis
Authors: Bokarewa Maria , Dahlberg Leif , Tarkowski Andrej
Published: June 2005

Tissue inhibitors of matrix metalloproteinases (TIMPs) regulate the breakdown of extracellular matrix components and play an important role in tissue remodelling and growth, in both physiological and pathological conditions. We studied the autoimmune response to TIMPs in patients with rheumatoid arthritis (RA). Eighty-nine paired blood and synovial fluid samples from patients with RA were assessed for their reactivity with recombinant tissue inhibitors of metalloproteinases (TIMPs) 1 to 4 by an ELISA and were compared with blood from 62 healthy controls and 21 synovial fluid samples from patients with degenerative joint diseases. Presence of antibodies was established as the absorbance of the sample more than 2 standard deviations above the mean of the controls. In addition, immunoglobulin G (IgG) from blood samples of RA patients possessing TIMP antibodies was isolated on protein A–sepharose and tested for the in vitro ability to neutralize TIMP-2-dependent effects on metalloproteinase 9 (MMP9). Anti-TIMP antibodies were found in 56% of RA samples but in only 5% of the controls (P < 0.005). RA patients had high frequencies of antibodies against all TIMPs except TIMP-3. TIMP-2 antibodies were most frequently found (33%), being significantly more prevalent (P = 0.024) in patients with nonerosive than erosive RA. TIMP-1 antibodies were significantly more often found in synovial fluid samples than in the matched blood samples (P < 0.025). Importantly, the IgG fraction containing TIMP antibodies down-regulated the TIMP-2 inhibitory effect, thereby supporting MMP9 activity in vitro. In the present study, we show that RA patients frequently develop autoimmune response to TIMPs that may act as a functionally significant regulator of MMP activity and thereby of joint destruction.
Differential expression of chemokine receptors on peripheral blood B cells from patients with rheumatoid arthritis and systemic lupus erythematosus
Authors: Henneken Maren , Dörner Thomas , Burmester Gerd-Rüdiger , Berek Claudia
Published: June 2005

Chemokines and their receptors are essential in the recruitment and positioning of lymphocytes. To address the question of B cell migration into the inflamed synovial tissue of patients with rheumatoid arthritis (RA), peripheral blood naive B cells, memory B cells and plasma cells were analyzed for cell surface expression of the chemokine receptors CXCR3, CXCR4, CXCR5, CCR5, CCR6, CCR7 and CCR9. For comparison, B cells in the peripheral blood of patients with the autoimmune disease systemic lupus erythematosus (SLE) or with the degenerative disease osteoarthritis (OA) were analyzed. Expression levels of chemokine receptors were measured by flow cytometry and were compared between the different patient groups and healthy individuals. The analysis of chemokine receptor expression showed that the majority of peripheral blood B cells is positive for CXCR3, CXCR4, CXCR5, CCR6 and CCR7. Whereas a small fraction of B cells were positive for CCR5, practically no expression of CCR9 was found. In comparison with healthy individuals, in patients with RA a significant fraction of B cells showed a decreased expression of CXCR5 and CCR6 and increased levels of CXCR3. The downregulation of CXCR5 correlated with an upregulation of CXCR3. In patients with SLE, significant changes in CXCR5 expression were seen. The functionality of the chemokine receptors CXCR3 and CXCR4 was demonstrated by transmigration assays with the chemokines CXCL10 and CXCL12, respectively. Our results suggest that chronic inflammation leads to modulation of chemokine receptor expression on peripheral blood B cells. However, differences between patients with RA and patients with SLE point toward a disease-specific regulation of receptor expression. These differences may influence the migrational behavior of B cells.
Creation and disruption of protein features by alternative splicing - a novel mechanism to modulate function
Authors: Hiller Michael , Huse Klaus , Platzer Matthias , Backofen Rolf
Published: June 2005

Background

Alternative splicing often occurs in the coding sequence and alters protein structure and function. It is mainly carried out in two ways: by skipping exons that encode a certain protein feature and by introducing a frameshift that changes the downstream protein sequence. These mechanisms are widespread and well investigated.

Results

Here, we propose an additional mechanism of alternative splicing to modulate protein function. This mechanism creates a protein feature by putting together two non-consecutive exons or destroys a feature by inserting an exon in its body. In contrast to other mechanisms, the individual parts of the feature are present in both splice variants but the feature is only functional in the splice form where both parts are merged. We provide evidence for this mechanism by performing a genome-wide search with four protein features: transmembrane helices, phosphorylation and glycosylation sites, and Pfam domains.

Conclusion

We describe a novel type of event that creates or removes a protein feature by alternative splicing. Current data suggest that these events are rare. Besides the four features investigated here, this mechanism is conceivable for many other protein features, especially for small linear protein motifs. It is important for the characterization of functional differences of two splice forms and should be considered in genome-wide annotation efforts. Furthermore, it offers a novel strategy for ab initio prediction of alternative splice events.
A unique lysophospholipid acyltransferase (LPAT) antagonist, CI-976, affects secretory and endocytic membrane trafficking pathways
Authors: Chambers Kimberly , Judson Bret , Brown William J.
Published: June 2005

Previous studies have shown that inhibition of a Golgi-complex-associated lysophospholipid acyltransferase (LPAT) activity by the drug CI-976 stimulates Golgi tubule formation and subsequent redistribution of resident Golgi proteins to the endoplasmic reticulum (ER). Here, we show that CI-976 stimulates tubule formation from all subcompartments of the Golgi complex, and often these tubules formed independently, i.e. individual tubules usually did not contain markers from different subcompartments. Whereas the cis, medial and trans Golgi membranes redistributed to the ER, the trans Golgi network (TGN) collapsed back to a compact juxtanuclear position similar to that seen with brefeldin A (BFA) treatment. Also similar to BFA, CI-976 induced the formation of endosome tubules, but unlike BFA, these tubules did not fuse with TGN tubules. Finally, CI-976 produced an apparently irreversible block in the endocytic recycling pathway of transferrin (Tf) and Tf receptors (TfRs) but had no direct effect on Tf uptake from the cell surface. Tf and TfRs accumulated in centrally located, Rab11-positive vesicles indicating that CI-976 inhibits export of cargo from the central endocytic recycling compartment. These results, together with previous studies, demonstrate that CI-976 inhibits multiple membrane trafficking steps, including ones found in the endocytic and secretory pathways, and imply a wider role for lysophospholipid acyltransferases in membrane trafficking.
Scintigraphic evaluation of nasal mucociliary activity in unilateral chronic otitis media
Authors: Cingi Cemal , Altin Fazilet , Cakli Hamdi , Entok Ernre , Gurbuz Kezban , Cingi Emre
Published: June 2005

Mucociliary clearance is a key defence mechanism in human upper and lower airways. Although mucociliary activity is present in both ears of the patients, most cases of chronic otitis media are unilateral.

In this study, we aim to evaluate the difference between nasal mucociliary activity of the affected and non-affected sides in patients with unilateral chronic otitis media. Both nasal transport times of 36 patients with unilateral chronic otitis media were compared statistically with each other and with the control group by independent samples t-test. The nasal mucociliary transport times of the nasal cavity at the same side as the affected ear and as the non-affected ear are significantly different, in the same patients.

Our study shows that impaired or decreased nasal mucociliary activity may result in dysfunction of the eustachian tube and middle-ear ciliary activity, which plays an important role in the aetiopathogenesis of chronic otitis media.
Co-morbidity of migraine and Ménière’s disease – is allergy the link?
Authors: Sen Purushotham , Georgalas Christos , Papesch Michael
Published: June 2005

This study determined the prevalence of migraine and allergy in patients with Ménière’s disease (MD) compared with age- and sex-matched controls. We tested the hypothesis that if migraine and MD is linked by allergy, then allergy should be more prevalent in patients with MD and migraine compared with MD patients without migraine.

A web-based questionnaire was used to recruit patients with MD (n = 108) while the control group consisted of patients attending the ENT clinic for other problems (n = 100).

The prevalence of migraine and allergy was significantly higher in patients with MD compared with age- and sex-matched controls (p ≥ 0.005). In addition, the prevalence of allergy was significantly higher in patients who had both MD and migraine (30/42) than MD alone (26/66,p = 0.002). However, there was no link with any specific allergy types.

This study suggests that migraine and MD may be linked by an immunological determinant.
Congenital stapes footplate fixation associated with duplication of lobule
Authors: Sethi Ashwani , Sareen Deepika , Meher Ravi , Nath Piyush
Published: June 2005

We report the case of an 18-year-old male patient who presented to us with unilateral conductive hearing loss with duplication of the lobule. An exploratory tympanotomy revealed stapes footplate fixation. A stapedotomy with insertion of a Teflon piston was performed with improvement in his hearing. We believe this is the first reported case of such an abnormality.
Bilateral objective tinnitus secondary to congenital middle-ear myoclonus
Authors: Howsam G D , Sharma A , Lambden S P , Fitzgerald J , Prinsley P R
Published: June 2005

Subjective tinnitus (heard only by the patient) is a common otological complaint. Objective tinnitus (heard by the examiner as well as the patient) is extremely rare. There are only a few cases of objective tinnitus, secondary to middle-ear myoclonus, described in the literature.

We present the case of a child with bilateral, congenital, objective tinnitus, secondary to middle-ear myoclonus, with otherwise normal hearing thresholds (250Hz-8kHz), and with no evidence of intra-cerebral or systemic disorders. No similar case has been reported in the world literature.
Matrix metalloproteinases and their inhibitors in non-neoplastic otorhinolaryngological disease
Authors: De S , Fenton J E , Jones A S
Published: June 2005

Matrix metalloproteinases (MMPs) are a family of zinc and calcium-dependent endopeptidases that play a key role in extracellular matrix (ECM) degradation. MMPs are known to be important in normal remodelling processes. Overexpression and activation of MMPs or an imbalance of active MMPs and tissue inhibitors of metalloproteinases (TIMPs) has been linked with a number of specific disease states associated with the breakdown and remodelling of the extracellular matrix. MMPs and TIMPs play a role in the development and progression of conditions such as acute and chronic otitis media, nasal polyposis and Sjogren’s disease of salivary glands. Their role in allergic rhinitis has not been proven although they do appear to have a role in asthma, a condition closely linked to rhinitis. The use of a broad spectrum MMP inhibitor has been shown to alter the outcome of acute otitis media and otitis media with effusion. Therapeutic strategies with anti-MMP molecules are currently being developed and may play a role in modulating the course of non-neoplastic otorhinolaryngological disease in the future.
Hip morphology influences the pattern of damage to the acetabular cartilage
Authors: Beck M. , Kalhor M. , Leunig M. , Ganz R.
Published: June 2005

Recently, femoroacetabular impingement has been recognised as a cause of early osteoarthritis. There are two mechanisms of impingement: 1) cam impingement caused by a non-spherical head and 2) pincer impingement caused by excessive acetabular cover. We hypothesised that both mechanisms result in different patterns of articular damage. Of 302 analysed hips only 26 had an isolated cam and 16 an isolated pincer impingement. Cam impingement caused damage to the anterosuperior acetabular cartilage with separation between the labrum and cartilage. During flexion, the cartilage was sheared off the bone by the non-spherical femoral head while the labrum remained untouched. In pincer impingement, the cartilage damage was located circumferentially and included only a narrow strip. During movement the labrum is crushed between the acetabular rim and the femoral neck causing degeneration and ossification.

Both cam and pincer impingement lead to osteoarthritis of the hip. Labral damage indicates ongoing impingement and rarely occurs alone.
Triple osteotomy of the pelvis for acetabular dysplasia
Authors: van Hellemondt G. G. , Sonneveld H. , Schreuder M. H. E. , Kooijman M. A. P. , de Kleuver M.
Published: June 2005

We report the long-term results of 51 pelvic osteotomies in 43 patients with a mean follow-up of 15 years (13 to 20). The mean age of the patients was 28 years (14 to 46). At review three patients were lost to follow-up, and six had received a total hip arthroplasty. Of 48 hips, 42 (88%) were preserved, with good to excellent clinical results in 27 (64%). Pre-operatively, 41 (80%) of the treated hips had shown no sign of osteoarthritis. Thirty-one (65%) hips showed no progression of osteoarthritis after follow-up for 15 years. Significant negative factors for good long-term results were the presence of osteoarthritic changes and a fair or poor clinical score pre-operatively. Pelvic reorientation osteotomy for symptomatic hip dysplasia can give satisfactory and reproducible long-term clinical results.
Medium-term results of the Charnley low-offset femoral stem
Authors: Ebied A. , Hoad-Reddick D. A. , Raut V.
Published: June 2005

A reduced femoral offset in total hip replacement has been thought to be disadvantageous. We reviewed the results of 54 consecutive primary total hip replacements in 49 patients (mean age of 68 years) performed between August 1990 and December 1994, with a mean follow-up of 8.8 years (sd 2.1). The mean pre-operative femoral offset for these hips was 41 mm (sd 7.4). All patients received a low-offset Charnley stem and a polyethylene cup inserted by a single surgeon.

At their latest follow-up, surviving patients had a significant improvement in the performance of their hip. Three had undergone revision, one each for deep infection, recurrent dislocation and late pain with subluxation. No hips had been revised, or were at risk of revision, for aseptic loosening. The mean annual linear rate of wear was 0.2 mm (sd 0.08) for the whole group. There was no correlation between the pre-operative femoral offset and the post-operative rate of wear. Our survivorship estimate was 91% when revision for any reason was taken as an end-point, but 100% if aseptic loosening was considered as the end-point. Our study demonstrates that a low-offset femoral stem can produce good, medium-term results.
Natural history of fixed flexion deformity following total knee replacement
Authors: Aderinto J. , Brenkel I. J. , Chan P.
Published: June 2005

We investigated fixed flexion deformity (FFD) after total knee replacement (TKR). Data relating to 369 cruciate-retaining unilateral TKRs performed at a single institution were collected prospectively. Fixed flexion was measured pre-operatively and at one week, six months, 18 months, three years and five years after surgery.

Using binary logistic regression, pre-operative FFD was a predictor of post-operative FFD > 10° at one week (p = 0.006) and six months (p = 0.003) following surgery. Gender was a predictor at one week (p = 0.0073) with 24% of women showing a FFD > 10° compared with 37% of men.

We have shown that a gradual improvement in knee extension can be expected up to three years after surgery in knees with FFD. By this time residual FFD is mild or absent in the majority of patients, including those who had a severe pre-operative FFD.
Influence of surface geometry and the cam-post mechanism on the kinematics of total knee replacement
Authors: Pandit H. , Ward T. , Hollinghurst D. , Beard D. J. , Gill H. S. , Thomas N. P. , Murray D. W.
Published: June 2005

Abnormal sagittal kinematics after total knee replacement (TKR) can adversely affect functional outcome. Two important determinants of knee kinematics are component geometry and the presence or absence of a posterior-stabilising mechanism (cam-post). We investigated the influence of these variables by comparing the kinematics of a TKR with a polyradial femur with a single radius design, both with and without a cam-post mechanism.

We assessed 55 patients, subdivided into four groups, who had undergone a TKR one year earlier by using an established fluoroscopy protocol in order to examine their kinematics in vivo. The kinematic profile was obtained by measuring the patellar tendon angle through the functional knee flexion range (0° to 90°) and the results compared with 14 normal knees. All designs of TKR had abnormal sagittal kinematics compared with the normal knee. There was a significant (p < 0.05) difference between those of the two TKRs near to full extension. The presence of the cam-post mechanism did not influence the kinematics for either TKR design. These differences suggest that surface geometry is a stronger determinant of kinematics than the presence or absence of a cam-post mechanism for these two designs. This may be because the cam-post mechanism is ineffective.
Immobilisation of forearm fractures in children
Authors: Bochang C. , Jie Y. , Zhigang W. , Weigl D. , Bar-On E. , Katz K.
Published: June 2005

Redisplacement of unstable forearm fractures in plaster is common and may be the result of a number of factors. Little attention has been paid to the influence of immobilisation with the elbow extended versus flexed. We prospectively treated 111 consecutive children from two centres with closed forearm fractures by closed reduction and casting with the elbow either extended (60) in China or flexed (51) in Israel. We compared the outcome of the two groups. There was no statistically significant difference in the distribution of the age of the patients, the site of fracture or the amount of angulation and displacement between the groups. During the first two weeks after reduction, redisplacement occurred in no child immobilised with the elbow extended and nine of 51 children (17.6%) immobilised with the elbow flexed. Immobilisation of unstable forearm fractures with the elbow extended appears to be a safe and effective method of maintaining reduction.
Deep-vein thrombosis in high-energy skeletal trauma despite thromboprophylaxis
Authors: Stannard J. P. , Singhania A. K. , Lopez-Ben R. R. , Anderson E. R. , Farris R. C. , Volgas D. A. , McGwin G. R. , Alonso J. E.
Published: June 2005

We report the incidence and location of deep-vein thrombosis in 312 patients who had sustained high-energy, skeletal trauma. They were investigated using magnetic resonance venography and Duplex ultrasound.

Despite thromboprophylaxis, 36 (11.5%) developed venous thromboembolic disease with an incidence of 10% in those with non-pelvic trauma and 12.2% in the group with pelvic trauma. Of patients who developed deep-vein thrombosis, 13 of 27 in the pelvic group (48%) and only one of nine in the non-pelvic group (11%) had a definite pelvic deep-vein thrombosis. When compared with magnetic resonance venography, ultrasound had a false-negative rate of 77% in diagnosing pelvic deep-vein thrombosis. Its value in the pelvis was limited, although it was more accurate than magnetic resonance venography in diagnosing clots in the lower limbs. Additional screening may be needed to detect pelvic deep-vein thrombosis in patients with pelvic or acetabular fractures.
Acetabular fractures
Authors: Laird A. , Keating J. F.
Published: June 2005

We prospectively analysed the epidemiology of acetabular fractures over a period of 16 years in order to identify changes in their incidence or other demographic features. Our study cohort comprised a consecutive series of 351 patients with acetabular fractures admitted to a single institution between January 1988 and December 2003.

There was no significant change in the overall incidence of acetabular fractures, which remained at 3 patients/100 000/year. There was, however, a significant reduction in the number of men sustaining an acetabular fracture over the period (p < 0.02). The number of fractures resulting from falls from a height < 10 feet showed a significant increase (p < 0.002), but there was no change in those caused by motor-vehicle accidents. There was a significant reduction in the median Injury Severity score over the period which was associated with a significant decrease in mortality (p < 0.04) and a reduction in the length of hospital stay. The incidence of osteoarthritis noted during follow-up of operatively-treated fractures declined from 31% to 14%, reflecting improved results with increasing subspecialisation. Our findings suggest that there will be a continuing need for some orthopaedic surgeons to specialise in the management of these fractures. In addition, the reductions in the Injury Severity score and mortality may be associated with improved road and vehicle safety.
A study of telephone screening and direct observation of surgical wound infections after discharge from hospital
Authors: Reilly J. , Noone A. , Clift A. , Cochrane L. , Johnston L. , Rowley D. I. , Phillips G. , Sullivan F.
Published: June 2005

Post-discharge surveillance of surgical site infection is necessary if accurate rates of infection following surgery are to be available. We undertook a prospective study of 376 knee and hip replacements in 366 patients in order to estimate the rate of orthopaedic surgical site infection in the community. The inpatient infection was 3.1% and the post-discharge infection rate was 2.1%. We concluded that the use of telephone interviews of patients to identify the group at highest risk of having a surgical site infection (those who think they have an infection) with rapid follow-up by a professional trained to diagnose infection according to agreed criteria is an effective method of identifying infection after discharge from hospital.
Elective Caesarean section is associated with a reduction in developmental dysplasia of the hip in term breech infants
Authors: Lowry C. A. , Donoghue V. B. , O’Herlihy C. , Murphy J. F.
Published: June 2005

We wished to establish whether delivery by Caesarean section influenced the incidence of developmental dysplasia of the hip in term breech infants compared with those delivered vaginally. We used maternal charts, singleton term breech presentation, mode of delivery and incidence of developmental dysplasia of the hip for births between January 1997 and October 2002.

During the study period 46 089 infants were born. We analysed a total of 941 breech infants of whom 756 were delivered by Caesarean section (515 pre-labour, 241 intrapartum) and 185 vaginally. The incidence of developmental dysplasia of the hip according to the mode of delivery was 19 of 515 (3.69%) following pre-labour Caesarean section, 16 of 241 (6.64%) for intrapartum Caesarean section and 15 of 185 (8.11%) after vaginal delivery. There was a lower incidence of developmental dysplasia of the hip among those infants delivered by elective Caesarean section compared with those delivered vaginally (p < 0.02). These results demonstrate a significantly lower incidence of developmental dysplasia of the hip in term singleton breech births delivered by elective, pre-labour Caesarean section and suggest that labour and delivery influence hip stability in predisposed infants.
Osteotomy for congenital elevation of the scapula (Sprengel’s deformity)
Authors: McMurtry I. , Bennet G. C. , Bradish C.
Published: June 2005

We report 12 consecutive cases of vertical scapular osteotomy to correct Sprengel’s deformity, performed during a 16-year period, with a mean follow-up of 10.4 years. The mean increase in abduction of the shoulder was 53°. The cosmetic appearance improved by a mean of 1.5 levels on the Cavendish scale. Neither function nor cosmesis deteriorated with time. We recommend the procedure for correction of moderate deformities with a functional deficit.
Outcomes of Inappropriate Prescribing of β-Blockers After an Acute Myocardial Infarction in a Medicaid Population
Authors: Fernandes Ancilla W , Madhavan S Suresh , Amonkar Mayur M , Bell Dawn , Islam Syed S , Scott Virginia G
Published: June 2005

BACKGROUND:

Acute myocardial infarction (AMI) is associated with high mortality. β-Blockers are known to reduce mortality and reinfarction rates when used for long-term prevention following an AMI.

OBJECTIVE:

To assess the prescribing patterns of β-blockers in patients after experiencing an AMI in the West Virginia Medicaid program and examine its impact on patient outcomes.

METHODS:

One-year pre- and post-AMI data were extracted for 488 Medicaid patients. Prescribing of β-blockers within 90 days after discharge was evaluated among these patients. Based on American Heart Association/American College of Cardiology guidelines, patients were divided into 2 groups: those prescribed therapy appropriately and those prescribed therapy inappropriately (underuse, misuse). One-year all-cause mortality, cardiac mortality, and cardiac morbidity were compared between the groups using survival analysis.

RESULTS:

Approximately 64% of the patients were appropriately prescribed β-blockers and illustrated significantly (p = 0.035%) lower all-cause mortality rates compared with the inappropriately prescribed group at the one-year follow-up. Cardiac mortality evaluation showed no significant findings. The groups differed significantly in morbidity outcome (time to first cardiac hospitalization), with the inappropriate group exhibiting later hospitalization at the end of the year (p = 0.019%). However, the appropriate group had a higher proportion of hypertensive patients, suggesting more severity compared with the inappropriate group.

CONCLUSIONS:

Inappropriate prescribing of β-blockers following AMI was observed in this Medicaid population. Data suggest that there were overall survival benefits associated with appropriate β-blocker prescribing. However, cardiac morbidity associated with inappropriate prescribing needs to be evaluated after adjusting for disease severity between the 2 groups.
Widespread Correlations Between Dominance and Homozygous Effects of Mutations: Implications for Theories of Dominance
Authors: Phadnis Nitin , Fry James D
Published: June 2005

The dominance of deleterious mutations has important consequences for phenomena such as inbreeding depression, the evolution of diploidy, and levels of natural genetic variation. Kacser and Burns' metabolic theory provides a paradigmatic explanation for why most large-effect mutations are recessive. According to the metabolic theory, the recessivity of large-effect mutations is a consequence of a diminishing-returns relationship between flux through a metabolic pathway and enzymatic activity at any step in the pathway, which in turn is an inevitable consequence of long metabolic pathways. A major line of support for this theory was the demonstration of a negative correlation between homozygous effects and dominance of mutations in Drosophila, consistent with a central prediction of the metabolic theory. Using data on gene deletions in yeast, we show that a negative correlation between homozygous effects and dominance of mutations exists for all major categories of genes analyzed, not just those encoding enzymes. The relationship between dominance and homozygous effects is similar for duplicated and single-copy genes and for genes whose products are members of protein complexes and those that are not. A complete explanation of dominance therefore requires either a generalization of Kacser and Burns' theory to nonenzyme genes or a new theory.
A Genetic Linkage Map for the Tiger Pufferfish,Takifugu rubripes
Authors: Kai Wataru , Kikuchi Kiyoshi , Fujita Masashi , Suetake Hiroaki , Fujiwara Atushi , Yoshiura Yasutoshi , Ototake Mitsuru , Venkatesh Byrappa , Miyaki Kadoo , Suzuki Yuzuru
Published: June 2005

The compact genome of the tiger pufferfish, Takifugu rubripes (fugu), has been sequenced to the “draft” level and annotated to identify all the genes. However, the assembly of the draft genome sequence is highly fragmented due to the lack of a genetic or a physical map. To determine the long-range linkage relationship of the sequences, we have constructed the first genetic linkage map for fugu. The maps for the male and female spanning 697.1 and 1213.5 cM, respectively, were arranged into 22 linkage groups by markers heterozygous in both parents. The resulting map consists of 200 microsatellite loci physically linked to genome sequences spanning ∼39 Mb in total. Comparisons of the genome maps of fugu, other teleosts, and mammals suggest that syntenic relationship is more conserved in the teleost lineage than in the mammalian lineage. Map comparisons also show a pufferfish lineage-specific rearrangement of the genome resulting in colocalization of two Hox gene clusters in one linkage group. This map provides a foundation for development of a complete physical map, a basis for comparison of long-range linkage of genes with other vertebrates, and a resource for mapping loci responsible for phenotypic differences among Takifugu species.
A Role for the Saccharomyces cerevisiae Regulation of Ace2 and Polarized Morphogenesis Signaling Network in Cell Integrity
Authors: Kurischko Cornelia , Weiss Gretchen , Ottey Michelle , Luca Francis C
Published: June 2005

Saccharomyces cerevisiae RAM is a conserved signaling network that regulates maintenance of polarized growth and daughter-cell-specific transcription, the latter of which is critical for septum degradation. Consequently, cells defective in RAM function (designated ramΔ) are round in morphology, form feeble mating projections, and fail to separate following cytokinesis. It was recently demonstrated that RAM genes are essential in strains containing functional SSD1 (SSD1-v), which encodes a protein of unknown function that binds the RAM Cbk1p kinase. Here we investigated the essential function of RAM in SSD1-v strains and identified two functional groups of dosage suppressors for ramΔ lethality. We establish that all ramΔ mutants exhibit cell integrity defects and cell lysis. All dosage suppressors rescue the lysis but not the cell polarity or cell separation defects of ramΔ cells. One class of dosage suppressors is composed of genes encoding cell wall proteins, indicating that alterations in cell wall structure can rescue the cell lysis in ramΔ cells. Another class of ramΔ dosage suppressors is composed of ZRG8 and SRL1, which encode two unrelated proteins of unknown function. We establish that ZRG8 and SRL1 share similar genetic interactions and phenotypes. Significantly, Zrg8p coprecipitates with Ssd1p, localizes similarly to RAM proteins, and is dependent on RAM for localization. Collectively, these data indicate that RAM and Ssd1p function cooperatively to control cell integrity and suggest that Zrg8p and Srl1p function as nonessential inhibitors of Ssd1p.
The Element(s) at the NontranscribedXistLocus of the Active X Chromosome Controls Chromosomal Replication Timing in the Mouse
Authors: Diaz-Perez Silvia , Ouyang Yan , Perez Vanessa , Cisneros Roxanna , Regelson Moira , Marahrens York
Published: June 2005

In female mammalian cells, the inactive X chromosome is replicated late in S phase while the active X chromosome is replicated earlier. The replication times of the X chromosomes reflect a general trend in which late replication is associated with gene repression and earlier replication with transcriptional competence. The X-linked Xist gene is expressed exclusively from the inactive X chromosome where it is involved in the initiation and maintenance of X-inactivation. In contrast, no biological activity has been assigned to the Xist locus of the active X chromosome where the Xist gene is transcriptionally silenced. Here, we provide evidence that the element(s) at the nontranscribed Xist locus of the active X chromosome controls chromosomal replication timing in cis.
Phenotypic Selection for Dormancy Introduced a Set of Adaptive Haplotypes From Weedy Into Cultivated Rice
Authors: Gu Xing-You , Kianian Shahryar F , Foley Michael E
Published: June 2005

Association of seed dormancy with shattering, awn, and black hull and red pericarp colors enhances survival of wild and weedy species, but challenges the use of dormancy genes in breeding varieties resistant to preharvest sprouting. A phenotypic selection and recurrent backcrossing technique was used to introduce dormancy genes from a wild-like weedy rice to a breeding line to determine their effects and linkage with the other traits. Five generations of phenotypic selection alone for low germination extremes simultaneously retained dormancy alleles at five independent QTL, including qSD12 (R2 > 50%), as determined by genome-wide scanning for their main and/or epistatic effects in two BC4F2 populations. Four dormancy loci with moderate to small effects colocated with QTL/genes for one to three of the associated traits. Multilocus response to the selection suggests that these dormancy genes are cumulative in effect, as well as networked by epistases, and that the network may have played a “sheltering” role in maintaining intact adaptive haplotypes during the evolution of weeds. Tight linkage may prevent the dormancy genes from being used in breeding programs. The major effect of qSD12 makes it an ideal target for map-based cloning and the best candidate for imparting resistance to preharvest sprouting.
Estimating the Time to the Whole-Genome Duplication and the Duration of Concerted Evolution via Gene Conversion in Yeast
Authors: Sugino Ryuichi P , Innan Hideki
Published: June 2005

A maximum-likelihood (ML) method is developed to estimate the duration of concerted evolution and the time to the whole-genome duplication (WGD) event in baker's yeast (Saccharomyces cerevisiae). The models with concerted evolution fit the data significantly better than the molecular clock model, indicating a crucial role of concerted evolution via gene conversion after gene duplication in yeast. Our ML estimate of the time to the WGD is nearly identical to the time to the speciation event between S. cerevisiae and Kluyveromyces waltii, suggesting that the WGD occurred in very early stages after speciation or the WGD might have been involved in the speciation event.
Brc1-Mediated DNA Repair and Damage Tolerance
Authors: Sheedy Daniel M , Dimitrova Dora , Rankin Jessica K , Bass Kirstin L , Lee Karen M , Tapia-Alveal Claudia , Harvey Susan H , Murray Johanne M , O'Connell Matthew J
Published: June 2005

The structural maintenance of chromosome (SMC) proteins are key elements in controlling chromosome dynamics. In eukaryotic cells, three essential SMC complexes have been defined: cohesin, condensin, and the Smc5/6 complex. The latter is essential for DNA damage responses; in its absence both repair and checkpoint responses fail. In fission yeast, the UV-C and ionizing radiation (IR) sensitivity of a specific hypomorphic allele encoding the Smc6 subunit, rad18-74 (renamed smc6-74), is suppressed by mild overexpression of a six-BRCT-domain protein, Brc1. Deletion of brc1 does not result in a hypersensitivity to UV-C or IR, and thus the function of Brc1 relative to the Smc5/6 complex has remained unclear. Here we show that brc1Δ cells are hypersensitive to a range of radiomimetic drugs that share the feature of creating lesions that are an impediment to the completion of DNA replication. Through a genetic analysis of brc1Δ epistasis and by defining genes required for Brc1 to suppress smc6-74, we find that Brc1 functions to promote recombination through a novel postreplication repair pathway and the structure-specific nucleases Slx1 and Mus81. Activation of this pathway through overproduction of Brc1 bypasses a repair defect in smc6-74, reestablishing resolution of lesions by recombination.
Temporally and Spatially Heterogeneous Distribution of mTHPC in a Murine Tumor Observed by Two‐color Confocal Fluorescence Imaging and Spectroscopy in a Whole‐mount Model
Authors: Mitra Soumya , Maugain Estelle , Bolotine Lina , Guillemin Francois , Foster Thomas H.
Published: June 2005

Efficient intratumor delivery of anticancer drugs and photo‐sensitizers is an important factor in the success of chemotherapy and photodynamic therapy, respectively. Unfortunately, their adequate and uniform intratumor distribution is impeded by several physiological barriers and by binding to tissue components. Measurement of gross tumor drug accumulation is a routine method of investigating the uptake and clearance of chemotherapy agents and photosensitizers but tells little about their extravascular spatial distribution. We use whole‐mount two‐color confocal fluorescence imaging and imaging spectroscopy of unprocessed excised murine tumor fragments to investigate the intratumor distribution of the photosensitizer meso‐tetrahydroxyphenyl chlorin (mTHPC) as a function of distance from blood vessels perfused with 0.2 μm diameter fluorescent microspheres. Significant mismatches between drug and perfused vasculature are caused by heterogeneities in tumor blood supply. We describe complex microscopic mTHPC gradients that reverse dramatically relative to the perfused vasculature with time after injection. This imaging technique can be applied to screen the dynamic intratumor distribution of other fluorescent photosensitizers and anticancer drugs.
Development of a Bioenergetics Model for Humpback Chub and Evaluation of Water Temperature Changes in the Grand Canyon, Colorado River
Authors: Petersen James H. , Paukert Craig P.
Published: June 2005

The construction of Glen Canyon Dam above the Grand Canyon (Arizona) has reduced the water temperature in the Colorado River and altered the growth rate and feeding patterns of the federally endangered humpback chub Gila cypha. A bioenergetics model for humpback chub was developed and used to examine how warmer water temperatures in the lower Colorado River (achieved through a temperature control device [TCD] at Glen Canyon Dam) might influence their growth rate and food requirements. Parameter values for humpback chub were developed by Monte Carlo filtering and fitting to laboratory growth. Parameter bounds were established from the literature for Gila species, random parameter sets were selected within these bounds, and the growth of modeled humpback chub was compared with criteria from a laboratory growth experiment at 24°C. This method of parameter estimation could be applied to other imperiled fishes where physiological studies are impractical. Final parameter values were corroborated by comparison with the growth rates of humpback chub from independent field and laboratory studies. Simulations indicated that increasing water temperatures from approximately 9°C to 16°C during summer and fall, the change expected from the TCD, may have a minimal effect on humpback chub growth rate unless food availability also increases with temperature. To evaluate the effects of increased temperatures on humpback chub in the lower Colorado River, it will be essential to monitor their growth rate, the invertebrate community, and the predators of humpback chub, which are also influenced by temperature changes. Bioenergetics models for humpback chub and their predators should be helpful tools for identifying potential scenarios and evaluating the complex interactions resulting from a TCD.
Isotonic Inference
Authors: Hirotsu C.
Published: June 2005

Various approaches to the order restricted inference other than the isotonic regression approach are developed. They include the testing procedures, the multiple comparisons approach, and the method of the confidence intervals. They have many applications in analyzing a dose–response curve, ordered categorical responses, including two‐ and higher‐way contingency tables and so on. The distribution theories of the concerned statistics are naturally complicated for the restricted parameters as compared with the unrestricted case but in some cases very efficient exact algorithms for calculating the distribution functions are obtained.
Data Acquisition Systems (
DAS
) in General
Authors: Wöstenkühler Gerd
Published: June 2005

This article describes a general structure of a data acquisition system (DAS) that is used in computer‐based measurement and control systems. For measurement, the modules for signal conditioning between the analog signals of sensors and the digital signals of a computer data bus are outlined and briefly described. It also outlines the data flow between the digital computer data bus and the actuators, which work with analog signals controlling the process parameters.
Principles of
MEMS
Authors: Bryzek Janusz
Published: June 2005

Micro Electro Mechanical Systems (MEMS) is a technology defining mechanical structures fabricated with IC processing. This article provides an introduction to MEMS technology, characterizes problems with its commercialization, provides examples of MEMS processes and introduces basic sensing principles.
Modeling the nucleation stage during batch emulsion polymerization
Authors: Fortuny Montserrat , Graillat Christian , McKenna Timothy F. , Araújo Pedro H. H. , Pinto José C.
Published: June 2005

A model based on independently validated stabilization and rate data is used to quantify the rate of formation of particles during the dynamic nucleation stage of a batch emulsion polymerization reaction. Population balance equations (PBEs) that combine kinetic data validated in the absence of coagulation and a DLVO stability model with parameters validated in the absence of reaction were used to account for both micellar and homogeneous nucleation, as well as particle stabilization and growth. The model was tested in different polymerization systems at different ionic strengths. It is shown that a large number of moderately short‐lived particles are formed during the early stages of nucleation and that they contribute to an accelerated rate of polymerization for a short period of time before coagulating onto large structures in the reactor. © 2005 American Institute of Chemical Engineers AIChE J, 2005
Illustrating the Power of Singlet Oxygen Chemistry in a Synthetic Context: Biomimetic Syntheses of Litseaverticillols A–G, I and J and the Structural Reassignment of Litseaverticillol E
Authors: Vassilikogiannakis Georgios , Margaros Ioannis , Montagnon Tamsyn , Stratakis Manolis
Published: June 2005

Biomimetic syntheses of the litseaverticillols A–G, I and J are reported herein. The syntheses rely heavily on the application of two different modes of reaction for photochemically generated singlet oxygen, namely, the [4+2] cycloaddition of singlet oxygen (1O2) with furans and the ene reaction of 1O2 with double bonds. The highlight of these syntheses is a one‐pot cascade sequence, involving five synthetic operations initiated by a [4+2] reaction, to form the fully functionalised litseaverticillol core. A series of regioselective ene reactions are then used to appositely functionalise the side chains. The synthesis of litseaverticillol E (both its originally proposed and its actual structures) allows a structural reassignment of this natural product.