An Investigation of the Relationship Between the Second-to-Fourth Digit Ratio and Sagittal Synostosis.

BACKGROUND: The most common presentation of nonsyndromic craniosynostosis is that of the sagittal suture. Amongst this subgroup there is a significant male preponderance. Although the etiology is largely unknown, androgen exposure in utero has been suggested as a contributing factor. The second-to-fourth digit ratio (2D:4D) is a sexually dimorphic trait, reflective of the levels of androgen and estrogen exposure in utero, with a lower 2D:4D ratio associated with higher androgen exposure.This study aimed to examine the difference in 2D:4D ratio between participants with sagittal synostosis (SS) and gender- matched controls, hypothesizing that alterations in androgen exposure would be reflected in participants' 2D:4D ratio. METHOD: Participants with nonsyndromic SS and gender-matched controls were prospectively recruited from outpatients clinics. Photographs were taken of the right hand, and 3 independent researchers measured the length of the fingers and 2D:4D ratio, with the mean 2D:4D ratio then calculated. RESULTS: Fifty-six participants were recruited to both groups, with 35 males and 21 females in each. The mean age of the study and control groups were 5.6 and 6.3 years, respectively. There was no difference in the 2D:4D ratio between groups overall ( P = 0.126). However, males with SS had a significantly higher 2D:4D ratio in comparison to male controls (0.969 ± 0.379 versus 0.950 ± 0.354, P = 0.038). CONCLUSIONS: Our results suggest that 1 single hormonal pathway is not responsible for suture fusion. Subsequently we consider that an imbalance between testosterone and estrogen signaling may contribute to the development of sagittal craniosynostosis.

Gene expression profiling in melanoma: A view from the clinic.

The treatment of Melanoma, one of the most aggressive human malignancies, has been revolutionised by the advent of novel targeted and immuno-therapies. However, methods utilised to detect early presentations, and to stratify risk for patients diagnosed with invasive melanoma in the clinical setting are lagging. The primary prognostic indicator is restricted to Breslow Thickness, or depth the tumour invades into the dermis. Gene Expression Profiling (GEP), the analysis of molecular gene signatures of an individual tumour, has been implemented with great success in other malignancies, such as breast and prostate cancer. In the setting of melanoma, commercial GEP panels are becoming available, offering patients a personalised approach, though yet to enter widespread clinical use. This short perspective seeks to describe how GEP is currently employed in practice, and its current clinical impact. We also suggest the potential roles for GEP in meeting the key clinical challenges faced by clinicians in melanoma treatment, such as decisions around adjuvant therapy, sentinel lymph node biopsy (SLNB) and surgical resection , thus highlighting areas for future potential research.

Improving diagnostic accuracy in clinically ambiguous paediatric appendicitis: a retrospective review of ultrasound and pathology findings with focus on the non-visualised appendix.

OBJECTIVE: To compare pre-operative ultrasound to histopathological results and retrospectively assess the diagnostic accuracy of ultrasound in paediatric appendicitis. METHODS: 5 year review of all appendectomies performed in patients <16 years old in a tertiary referral university hospital. 983 patients had an appendicectomy over the time period while 189 patients had a preoperative ultrasound. We retrospectively reviewed all of the preoperative imaging in conjunction with the reports for the 189 patients; our aim was to determine the sensitivity of preoperative ultrasound for the diagnosis of acute appendicitis. RESULTS: Of the 189 patients who had an ultrasound, 102 had histology positive for appendicitis and 87 had normal histology. Sensitivity overall was 72.55% [95% confidence interval (CI) 62.82 to 80.92] and specificity was 77.01% (95% CI 66.75 to 85.36). A suggested ultrasound diagnosis of appendicitis made positive pathology three times more likely and a normal ultrasound made positive pathology three times less likely [positive-predictive value 3.16 (95% CI 2.11 to 4.72) negative predictive value 0.36 (95% CI 0.25 to 0.50)]. 77% (67/87) of the patients whose pathology was ultimately normal had an ultrasound which was either normal or suggested an alternative diagnosis. However, in the 33 (17%) of patients with a non-visualised appendix, no secondary signs of inflammation or alternative diagnosis 16 (48%) had pathologically confirmed appendicitis. CONCLUSION: Ultrasound has the potential to improve diagnostic accuracy in clinically ambiguous appendicitis. ADVANCES IN KNOWLEDGE: This paper furthers the evidence on the efficacy of ultrasound as a diagnostic tool in acute appendicitis in children, especially when the diagnosis is clinically equivocal. It also sheds further light on the "non-visualized appendix" with almost half of these patients having pathologically confirmed appendicitis; meaning advanced imaging with CT or MR may be indicated in this cohort.

A Five-Year Review of Tag Rugby Hand Injuries.

Tag rugby is one of the fastest growing sports in Ireland. It is a soft-contact team game that is loosely based on the rugby league format except players try to remove Velcro tags from their opponents' shorts rather than engage in a typical rugby tackle. The purpose of this study was to examine all tag rugby associated hand injuries over a five-year period in three large tertiary referral hospitals in Ireland. Using the patient corresponding system, 228 patients with hand injury related tag rugby injuries were observed from 2010 to 2015. There were 138 males and 90 females in the study and over 40% of patients required surgery. Most of the patients were young professionals with an average age of 30. Twenty-five patients worked in the financial services whilst there were 23 teachers. Fractures accounted for 124 of the 228 injuries and mallet injuries accounted for 53. Eighty percent of all injuries occurred during the tackle. The mean number of days missed from work was 9.1±13.8 days. These injuries resulted in an average of seven hospital appointments per patient. Considering it is a soft-contact sport, it is surprising the number of hand injuries that we have observed. Although safety measures have been introduced to decrease the number of hand injuries in recent years, there is a need for further improvements. Better player education about seeking prompt medical attention once an injury occurs, coupled with longer shorts worn by players may improve measures for the sport.

Porcine reproductive and respiratory syndrome (PRRS) virus-specific interferon-gamma(+) T-cell responses after PRRS virus infection or vaccination with an inactivated PRRS vaccine.

Although field studies have found porcine reproductive and respiratory syndrome (PRRSV) inactivated vaccines to be beneficial in reducing losses linked to PRRSV infection, immune mechanisms induced by these vaccines need better understanding. In the study reported here, we examined the interferon-gamma(+) (IFNgamma(+)) PRRS-specific T cell responses induced after infection and vaccination with an inactivated PRRS vaccine. Autologous monocyte-derived dendritic cells loaded with the PRRSV P120 strain were used to re-stimulate ex vivo T cells that had been primed in vivo by either the virus or the vaccine, or both. Virus-specific IFNgamma(+) T cells were quantified by using a porcine IFNgamma- ELISpot assay. A specific but low live virus-induced response was observed between days 35 and 70 for most of the pigs tested, while a significant inactivated vaccine-induced PRRSV-specific IFNgamma(+) T-cell response was measured soon after vaccination. Moreover, we observed that vaccination of pre-challenged pigs clearly favoured the PRRSV-specific cell-mediated immunity primed by the live virus. To characterize further the nature of the PRRSV-specific T cells, the different T-cell subsets involved in PRRSV immunity were analyzed by flow cytometry. We showed that the inactivated vaccine was able to prime both CD4(+)CD8(int+) and CD8(high) virus-specific T cells and that CD4(+)CD8(int+) were preferentially recalled by the live virus.

Quantitative analysis of the antigen-specific IFNgamma+ T cell-mediated immune response in conventional outbred pigs: kinetics and duration of the DNA-induced IFNgamma+ CD8+ T cell response.

It is now well established that antigen-specific CD8(+) T cells play a major role in vaccine-induced immunity against intracellular pathogens and tumor cells. The detection of these immune cells in outbred animals has been hampered mainly by the need to generate individual autologous antigen-presenting cells (APCs) due to the high degree of polymorphism of the major histocompatibility complex (MHC) Class I loci. We used individually derived immature porcine dendritic cells infected with a pox-based recombinant viral vector to ex vivo stimulate PBMCs from vaccinated conventional pigs. The frequencies of antigen-specific T cells was determined by the number of IFNgamma-secreting cells in a quantitative enzyme-linked immune spot (ELISPOT) assay. Using this approach we were able to rank different pseudorabies virus (PRV) vaccines strategies for their ability to prime viral-specific IFNgamma(+) T cells. Plasmid DNA has recently emerged as a promising tool with multiple applications in the field of infectious diseases, allergy and cancer. We showed for the first time in this study that DNA immunization induced a long-lived antigen-specific IFNgamma(+) T cells response in conventional pigs. Additional studies allowed us to show that these virus-specific IFNgamma(+) responding cells detected in this ELISPOT assay were MHC-restricted and comprised in the CD8alpha(bright) pig T cell subset. These new data confirm the usefulness of DNA vaccines to control diseases requiring cellular immunity in pigs.

Analysis of microtubule arms and bridges in mitotic and interphase amebae of Dictyostelium discoideum.

We have analyzed transparencies of electron micrographs from ultrathin longitudinal sections through mitotic spindles of undifferentiated amebae of Dictyostelium discoideum for the presence of arms on microtubules (MTs) and bridges between them. We used the technique of microdensitometer scanning and computer-based model matching by cross-correlation and autocorrelation. We also determined that spindle MTs are composed of 13 protofilaments. Although regularly arranged lateral appendages are not a universal feature of MTs in these cells, both cross-correlation and autocorrelation analysis revealed that bridges between a kinetochore MT and its neighbor, and between MTs in the zone of overlap of the central spindle were significantly arranged on a 12-dimer superlattice. In addition, the autocorrelation analysis indicated a slight match with the 12-dimer model for neighboring non-kinetochore MTs. Although electron micrographs revealed putative arms on cytoplasmic and astral MTs, as well as bridges between central spindle MTs outside the zone of overlap, their arrangement did not match any of the models tested. Bridges between non-kinetochore MTs in the half-spindles possibly serve to reinforce the spindle scaffold. Bridges between kinetochore MTs and their neighbors may contribute to the mechanical stability of kinetochore fibers or they may be involved in poleward movements of the chromosomes. In the zone of overlap of the central spindle, the occurrence of frequent and regularly spaced bridges is consistent with models predicting that a sliding mechanism operates between MTs of opposite polarity in this region of the spindle to produce its elongation.

Microdensitometer-computer correlation analysis of two distinct, spatially segregated classes of microtubule bridges in Allogromia pseudopodia.

Previous video-light microscopic studies have shown that the microtubule bundles in the pseudopodia of foraminiferan protists display several types of movements in vivo, including active bending, zipping/splaying, and axial translocations. To gain insight into the types and arrangement of microtubule-associated proteins (e.g., mechanoenzymes, crosslinkers) in such a highly dynamic system, we employed microdensitometric-computer correlation methods to analyze, quantitatively, intermicrotubule bridges in thin-section electron micrographs of Allogromia laticollaris and Allogromia sp. (strain NF). Two distinct bridges occupying mutually exclusive zones between adjacent microtubules were identified. Type I bridges displayed a single axial repeat (34 nm for A. laticollaris and 28 nm for Allogromia sp.) and Type II bridges showed a typical 12-dimer helical superlattice pattern. In A. laticollaris, the two types of bridges were morphologically distinct: Type I bridges were aligned perpendicular to the microtubule wall and were 23-nm wide with an electron-lucent core; Type II bridges were irregular filaments projecting from the microtubules at various angles. When compared with the known distribution of microtubule-associated proteins in other systems, our findings indicate that, in vivo, Allogromia pseudopodial microtubules are decorated with MAP2-like bridges interrupted by discrete clusters of a dynein-like component.