Magnification in undergraduate endodontic teaching in the UK and Ireland: a survey of teaching leads in Endodontology.

AIM: To investigate the use of magnification in undergraduate endodontic teaching in dental schools within the UK and Ireland and identify factors that may impact on levels of adoption. METHODOLOGY: An electronic questionnaire was distributed to teaching leads in undergraduate endodontics in all UK and Ireland dental schools. RESULTS: Completed questionnaires were received from 15 of 18 course leads. The study revealed magnification is not universally embedded within the undergraduate curricula, and the majority of schools had no expectation for students to use magnification, although it was encouraged. The study provided insight into teaching staff factors, student factors and institutional factors that impact upon the adoption of magnification in undergraduate endodontic teaching. Although course leads utilized magnification in their own practice, this did not translate into institutional expectation for students to use magnification. Barriers to adoption of such an institutional expectation included cost and lack of staff training. CONCLUSIONS: Magnification has become viewed as an essential part of endodontic practice. The dental operating microscope has the most significant impact on endodontic visualization; however, the use of dental loupes in nonsurgical endodontics could be considered the minimum standard. The pedagogical dilemma faced by dental educators training undergraduates to behave in a manner that they themselves would not, cannot be rationalized on the basis of cost and lack of staff training. It is proposed that although significant, these barriers are not insurmountable and the use of dental loupe should become an expectation in undergraduate training in the UK and Ireland.

The undivided patient: a retrospective cohort analysis of specialty referrals made from inpatient general medical units comparing regional to metropolitan practice.

BACKGROUND: In an era of growing subspecialisation there has been significant research into the role, determinants and outcomes of outpatient referrals but very little on inpatient specialty referrals from general medical units. AIMS: This study aims to describe and compare the rate of specialty referrals from inpatient general medical units in a regional general and a metropolitan tertiary hospital, and review associated outcomes. METHODS: Retrospective cohort analysis of general medical admissions over the 10-week period extending from 28 March to 5 June 2011. Two hospitals were included in the study; West Gippsland Hospital (WGH) and Monash Medical Centre (MMC). For all admissions, details of patient demographics, episode of care and number of inpatient referrals made per admission were extracted from the medical records. Rates and outcomes of inpatient referrals were calculated and compared. RESULTS: There were 116 admissions to MMC and 108 (107 available for analysis) to WGH during the study period. There were no significant differences in patient demographics between the two sites. However, there were significantly fewer active conditions (2.87 vs 4.01, P < 0.01), fewer specialty fields represented (2.50 vs 3.51, P < 0.01) and fewer specialty referrals made per admission at WGH compared with MMC (0.69 vs 1.74, P < 0.01). The referral rate per diagnosis and the rate of referrals per specialty field represented were significantly higher at MMC compared with WGH (P < 0.01). CONCLUSION: This preliminary study suggests that patients admitted to rural hospital general medical units have fewer active conditions with fewer specialty referrals made per admission, compared with a comparator metropolitan hospital general medical unit. Further research is required to investigate the reasons for such differences and implications for policy and practice.

Dengue virus serotypes in Jamaica, 2003-2007.

BACKGROUND: Dengue virus (DENV) infection is increasing in prevalence and severity globally. The severity of dengue is influenced by several factors including the immune response, viral and host genetic factors. METHOD: The DENV serotypes were determined in 770 serum samples from dengue immunoglobulin (Ig) M antibody positive (n = 469), dengue IgM negative (n = 185) and dengue antibody negative (n = 116) patients with suspected dengue who presented during (n = 150) or after (n = 620) the acute phase of illness during 2003-2007. Dengue antibodies were detected by enzyme-linked immunosorbent assays and DENV RNA by reverse transcriptase-polymerase chain reaction (RT-PCR) performed on serum and cell culture supernatants of C6/36 mosquito cells inoculated with acute phase serum (n = 150). RESULTS: Based on serological profiles, 41% of acute phase sera and 66% of post acute sera were from patients with current primary or secondary dengue, while 41% and 35% of acute and post-acute phase sera, respectively, were from patients with secondary dengue or past exposure only. Dengue virus RNA was found in 20/770 samples (2.6%). Only 1.5% (9/620) of sera collected after the acute phase of illness tested positive for DENV RNA compared with 2.6% (4/150) of sera collected during the acute phase and 7.3% of cell culture supernatants inoculated with acute phase serum (11/150, p = 0.001). All four serotypes including DENV-1 (3/20, 15%), DENV-2 (7/20, 35%), DENV-3 (3/20, 15%) and DENV-4 (7/20, 35%) were identified over the five-year period. These results also showed that DENV-1, 2 and 4 were present during 2007 and that DENV-2 and DENV- 4 were the likely causative viruses of the 2007-2008 dengue outbreak in Jamaica. The three strains of DENV-3 were isolated from infants less than three years of age with primary infection during 2006. CONCLUSION: This study highlights the increasing threat of dengue and severe dengue disease to the Jamaican population. Preventative measures including laboratory surveillance and vector control should be strictly maintained at the highest level.

Molecular epidemiology of dengue in Jamaica dengue virus genotypes in Jamaica, 2007.

The genotypes of dengue viruses (DENV) isolated from patients with dengue in Jamaica during 2007 were determined using DNA sequencing and phylogenetic analysis of the C-prM gene junction. The 17 DENV analysed included strains of DENVserotypes 1 (DENV-1, n = 3), DENV-2 (n = 7) and DENV-4 (n = 7). All strains ofDENV-1 were classified as genotype III, while 1 of 7 strains of DENV-2 belonged to the Asian American/Asian genotype, genotype I/III (Jamaica genotype), 2 were genotype V, the American genotype and 4 strains clustered with reference strains belonging to genotype IV. The 6 DENV-4 strains from Jamaica and the control strain clustered together in a separate clade from Caribbean/American reference strains, which belong to genotype II and Asian strains, classified as genotypes I and III. There has been little evolution in the DENV-1 strains circulating in Jamaica over the years and this might reduce the risk of outbreaks due to this serotype. In contrast, the high genetic diversity in strains of DENV-2 viruses in circulation, the presence of more recently introduced genotypes and a new clade of DENV-4 might contribute to the epidemic potential of these DENV serotypes. These preliminary data clearly indicate the need to maintain laboratory surveillance, and other control measures against hyperendemicity of dengue in Jamaica.

Dengue HLA associations in Jamaicans.

BACKGROUND: Polymorphisms in the human leukocyte antigen (HLA) genes might predispose certain individuals to dengue fever (DF) and the severe forms of the disease: dengue haemorrhagic fever/ dengue shock syndrome (DHF/DSS). SUBJECTS AND METHOD: A DNA-based HLA typing method was used to determine the HLA class I and II alleles in 50 patients with dengue, including 45 cases of DF 5 cases of DHF and 177 healthy individuals in Jamaica. RESULTS: HLA-A*24 and - DRbeta5*01/02 were significantly associated with dengue infection while possession of HLA-A*23, -CW*04, -DQbeta*02, -DQbeta*03 and DQbeta*06 were protective. No other significant associations were found after correction for the number of alleles tested at each HLA-locus. CONCLUSION: This is the first study to report a significant association with HLA-A*24 and DF although this allele is associated with DHF and DSS in Vietnamese patients. The other HLA associations observed in the Jamaican cohort also are different from those reported in other ethnic groups. Further studies which involve larger numbers of patients with DHF and explore functional aspects of HLA allelic associations with dengue in Jamaicans are necessary.

Disease progression among multiple sclerosis patients before and during a disease-modifying drug program: a longitudinal population-based evaluation.

Randomized controlled trials have demonstrated the efficacy of disease-modifying drugs (DMDs) in persons with relapsing-remitting multiple sclerosis (MS) and secondary progressive MS with superimposed relapses. However, these brief studies of selected patients have focused mainly on reducing attacks and must be complemented by evaluations in 'realworld' clinical settings to establish the effectiveness of DMD programs in slowing disease progression and to inform health policy and program decision-making. We assessed the effectiveness of DMDs as administered in a comprehensive publicly funded drug insurance program that provides DMDs to a geographically defined population of MS patients who meet specific eligibility criteria. Data from 1752 MS patients (10,312 assessments) seen between 1980 and 2004 at a regional MS Clinic serving the entire population of Nova Scotia, Canada were analysed. Using survival methods we observed a statistically significant reduction in disease progression to specific Expanded Disability Status Scale endpoints following the introduction of this program. Subgroup analyses of patients eligible for treatment using hierarchical linear regression methods also suggested that disease progression was slowed in patients treated with the first DMD prescribed. These findings provide evidence supporting DMD program effectiveness that can be used to inform the broader implementation of such programs.

Water at hydrophobic surfaces: weak hydrogen bonding and strong orientation effects.

Vibrational studies that selectively probe molecular structure at CCl4/H2O and hydrocarbon/H2O interfaces show that the hydrogen bonding between adjacent water molecules at these interfaces is weak, in contrast to generally accepted models of water next to fluid hydrophobic surfaces that suggest strong hydrogen bonding. However, interactions between these water molecules and the organic phase result in substantial orientation of these weakly hydrogen-bonded water molecules in the interfacial region. The results have important implications for understanding water adjacent to hydrophobic surfaces and the penetration of water into hydrophobic phases.

Spectroscopic determination of the water pair potential.

A polarizable water pair potential was determined by fitting a potential form to microwave, terahertz, and mid-infrared (D2O)2 spectra through a rigorous calculation of the water dimer eigenstates. It accurately reproduces most ground state vibration-rotation-tunneling spectra and yields excellent second viral coefficients. The calculated dimer structure and dipole moment are very close to those determined from microwave spectroscopy and high-level ab initio calculations. The dimer binding energy and acceptor switching and donor-acceptor interchange tunneling barriers are in excellent agreement with recent ab initio theory, as are cyclic water trimer and tetramer structures and binding energies.

Quantifying hydrogen bond cooperativity in water: VRT spectroscopy of the water tetramer.

Measurement of the far-infrared vibration-rotation tunneling spectrum of the perdeuterated water tetramer is described. Precisely determined rotational constants and relative intensity measurements indicate a cyclic quasi-planar minimum energy structure, which is in agreement with recent ab initio calculations. The O-O separation deduced from the data indicates a rapid exponential convergence to the ordered bulk value with increasing cluster size. Observed quantum tunneling splittings are interpreted in terms of hydrogen bond rearrangements connecting two degenerate structures.

Vital involvement of a natural killer cell activation receptor in resistance to viral infection.

Natural killer (NK) cells are lymphocytes that can be distinguished from T and B cells through their involvement in innate immunity and their lack of rearranged antigen receptors. Although NK cells and their receptors were initially characterized in terms of tumor killing in vitro, we have determined that the NK cell activation receptor, Ly-49H, is critically involved in resistance to murine cytomegalovirus in vivo. Ly-49H requires an immunoreceptor tyrosine-based activation motif (ITAM)-containing transmembrane molecule for expression and signal transduction. Thus, NK cells use receptors functionally resembling ITAM-coupled T and B cell antigen receptors to provide vital innate host defense.

Phenotypic correction of Fanconi anemia in human hematopoietic cells with a recombinant adeno-associated virus vector.

Fanconi anemia (FA) is a recessive inherited disease characterized by defective DNA repair. FA cells are hypersensitive to DNA cross-linking agents that cause chromosomal instability and cell death. FA is manifested clinically by progressive pancytopenia, variable physical anomalies, and predisposition to malignancy. Four complementation groups have been identified, termed A, B, C, and D. The gene for the FA complementation group C, FACC, has been cloned. Expression of the FACC cDNA corrects the phenotypic defect of FA(C) cells, resulting in normalized cell growth in the presence of DNA cross-linking agents such as mitomycin C (MMC). Gene transfer of the FACC gene should provide a survival advantage to transduced hematopoietic cells, suggesting that FA might be an ideal candidate for gene therapy. We demonstrated efficient transduction, expression, and phenotypic correction in lymphoblastoid cell lines derived from FA (C) patients using a recombinant adeno-associated virus (rAAV) vector containing the FACC gene. Molecular characterization of the transduced FACC gene showed an intact unrearranged proviral genome with expression sufficient to normalize cell growth, cell cycle kinetics and chromosomal breakage in the presence of MMC. These observations were extended by testing rAAV transduction in hematopoietic progenitor cells. Peripheral blood CD34+ cells isolated from a FA (C) patient and transduced with rAAV/FACC virus yielded 5-10-fold more progenitor colonies than mock-infected cells, consistent with genetic "rescue" of corrected cells. This is the first demonstration of rAAV gene correction in primary human hematopoietic progenitor cells and has important implications for gene therapy of hematopoietic disorders, specifically FA.

Persistent transport barrier on the West Florida Shelf.

Analysis of drifter trajectories in the Gulf of Mexico has revealed the existence of a region on the southern portion of the West Florida Shelf (WFS) that is not visited by drifters that are released outside of the region. This so-called "forbidden zone" (FZ) suggests the existence of a persistent cross-shelf transport barrier on the southern portion of the WFS. In this letter a year-long record of surface currents produced by a Hybrid-Coordinate Ocean Model simulation of the WFS is used to compute Lagrangian coherent structures (LCSs), which reveal the presence of a persistent cross-shelf transport barrier in approximately the same location as the boundary of the FZ. The location of the cross-shelf transport barrier undergoes a seasonal oscillation, being closer to the coast in the summer than in the winter. A month-long record of surface currents inferred from high-frequency (HF) radar measurements in a roughly 60 km × 80 km region on the WFS off Tampa Bay is also used to compute LCSs, and these also reveal the presence of transient transport barriers. While the HF-radar-derived transport barriers cannot be unambiguously linked to the boundary of the FZ, this analysis does demonstrate the feasibility of monitoring transport barriers on the WFS using a HF-radar-based measurement system. The implications of a persistent cross-shelf transport barrier on the WFS for the development of harmful algal blooms on the shoreward side of the barrier are considered.

Ambulatory laparoscopic cholecystectomy outcomes.

BACKGROUND: Outpatient laparoscopic cholecystectomy is an established practice in the United States, but it is not well established in the United Kingdom, and evidence of experience is scarce. The aim of this study was to evaluate the effect of ambulatory laparoscopic cholecystectomy on postoperative morbidity and possible cost savings. We tried to elucidate possible predictors of unplanned admission and readmission rates after discharge. METHODS: This study was conducted in 2 phases. The first phase involved 112 patients and was a retrospective analysis from January 2002 to July 2003 (19 months). The second was a prospective study involving 86 patients from August 2003 to April 2005 (21 months). Consultants, associate specialists, or higher surgical trainees performed the surgeries in a dedicated outpatient procedure unit. The study ended 6 weeks after the operation. RESULTS: Hospital mortality was zero. Overall, 29 (15%) patients required unplanned admissions. Three (1.5%) patients required conversion to open cholecystectomy. Other causes included simple observations (7), wound pain (6), nausea and vomiting (6), suction drain (2), urinary retention (2), operation in the afternoon (2), and shoulder pain (1). Of the patients discharged, 7 (3.5%) required readmission after the initial discharge. Five of the 7 readmissions were wound related and treated conservatively. Two patients underwent laparotomy. CONCLUSION: Ambulatory laparoscopic cholecystectomy appears to be safe, feasible, and cost-effective with a low conversion rate. The unplanned admission rate can be reduced by better training, criteria for discharge, and improvement in anesthesia. This will have implications for surgical training and healthcare resources.

De novo partial duplication of 17p [dup(17)(p12----p11.2)]: clinical report.

Duplication of band p11.2 and a small proximal portion of band p12 of chromosome 17 was noted in an infant with unusual facial appearance and left calcaneovalgus deformity. Developmental delay was documented over time. Only one other similar case has been found in the literature, but deletion of the same region is known in nine recently described cases [Smith et al, 1986]. This suggests that abnormalities of this small region of 17p are relatively common and only recently detectable with modern high-resolution techniques.

Is Angelman syndrome an alternate result of del(15)(q11q13)?

Two unrelated females, age 15 and 5 years respectively, were studied cytogenetically because of severe mental retardation, seizures and ataxia-like incoordination. A similar deletion of the proximal long arm of chromosome 15 was found in both patients. Re-evaluation showed no voracious appetite or obesity; normal size of hands and feet, minimal to no hypotonia by history or examination and facial features not typical of the Prader-Willi syndrome. However, the facial appearance of the girls was similar to each other with mild hypertelorism. The similarity of these girls and dissimilarity to Prader-Willi syndrome suggest a different syndrome, perhaps the result of deletion of a different segment of 15q. The findings of ataxic-like movements, frequent, unprovoked and prolonged bouts of laughter and facial appearance are more compatible with the diagnosis of Angelman syndrome.

Y-derived sequences detected in a 45,X male by in situ hybridization.

A two-month-old boy with normal genitalia and descended testes was referred for a suspected hematological disorder. Cytogenetic analysis showed a 45,X chromosome constitution. In situ hybridization with the Y-derived probe 50f (provided by Professor Marc Fellous) was performed utilizing metaphase chromosomes to determine whether Y material could be detected. A significant amount of label (17 of 150 cells) was found on chromosome 5p suggesting a 5;Y translocation. This translocation was verified by high-resolution G-banded and G-11-stained chromosomes.

Interstitial deletions of the short arm of chromosome 4 in patients with a similar combination of multiple minor anomalies and mental retardation.

Interstitial deletions of chromosome 4 have been described rarely and have had variable presentations. We describe the phenotypic characteristics associated with interstitial deletion of the p14-16 region of chromosome 4 in 7 patients with multiple minor anomalies in common, and with mental retardation. A review of published cases of interstitial deletions of the short arm of chromosome 4 is provided. These deletions present a distinct phenotype which is different from that of Wolf-Hirschhorn syndrome.

Inverted tandem ("mirror") duplications in human chromosomes: -nv dup 8p, 4q, 22q.

We have studied 4 patients with inverted tandem duplications of parts of chromosomes, a hitherto rarely identified form of a structural rearrangement involving a single chromosome in man. In patients 1 and 2, the duplication involved parts of the short arm of chromosome 8 (regions 8p12 leads to 8p23 and 8p21 leads to 8p23, respectively). Both patients manifested certain characteristics of the mosaic trisomy 8 syndrome. Elevated levels of glutathione reductase (GSR) in their erythrocytes supported the interpretation of a partial duplication of chromosome 8 and indicated a regional localization for the GSR gene locus. In Partient 3, the distal half of the long arm of chromosome 4 was duplicated (region 4q23 leads to 4q35). Clinical evidence supported this interpretation, as Patient 3 resembled phenotypically the 13 reported cases with duplication of the distal 4q. The cytogenetic findings in Patient 4 suggested a possibly inverted duplication of 22q. The clinical correlation was less convincing due to the lack of a well-defined phenotype for trisomy 22. These chromosome aberrations had occurred de novo in all 4 cases. Although they involved different chromosomal regions, they might well have arisen by the same mechanism. Possible modes of origin that are discussed in detail include unequal exchange between homologous chromosomes, between chromatids of 1 chromosome or between strands of 1 DNA duplex.

Parental origin of the extra chromosome in the cat eye syndrome: evidence from heteromorphism and in situ hybridization analysis.

Two individuals, a boy and girl, with a clinical diagnosis of cat eye syndrome had an extra bisatellited chromosome. In the girl, the diagnosis was made on the basis of coloboma of the right iris, right preauricular pit, and imperforate anus; in the boy, bilateral colobomata of the iris, down-slanting palpebral fissures, right preauricular skin tag, and right preauricular pit. Multiple staining techniques were used to characterize the extra chromosomes. With G-banding the extra chromosome usually appeared monocentric with two major G-positive bands, but with satellites on both ends; with C-banding, two C-band positive regions were evident, indicating that the chromosomes were likely dicentric. Silver staining demonstrated the presence of NORs near each end; Q-banding showed satellites on each end, differing in brightness and size. The chromosomes of the parents were normal; comparisons of Q-band heteromorphisms of the acrocentric chromosomes of the parents with those of the extra chromosome showed in each case one short arm/satellite region of the extra chromosome identical in appearance to one chromosome 22 of the mother and the other end of the extra bisatellited chromosome identical to the short arm/satellite of the mother's second chromosome 22. This extra chromosome, then, is the result of a maternal meiotic error in each case. In situ hybridization studies using the chromosome 22-derived probe p22/34, which identifies locus D22S9, showed 16% of the cells from the female patient to have silver grains on the proximal long arm of the normal chromosome 22 and 14% on the extra chromosome, while 10% of cells from the male had grains on the normal chromosomes 22 and an equal number on the extra chromosome, confirming the chromosome 22 origin of the extra chromosome in these patients.

Tandem duplication of proximal 22q: a cause of cat-eye syndrome.

A boy with bilateral colobomas, preauricular pits, and developmental delay had a 46,XY,22q+ karyotype. His parents had normal chromosomes. The abnormality of 22q was interpreted as a de novo tandem duplication of 22q11.1----q11.2. Although no anal abnormality was identified, his manifestations are otherwise consistent with those of the cat-eye syndrome. Blood marker results and the levels of galactosidase-2, galactosidase-B and arylsulfatase-A, which are known to be coded on 22q, are normal.