Epigenetic patterns in Atlantic herring (Clupea harengus): Temperature and photoperiod as environmental stressors during larval development.

Understanding the molecular mechanisms underlying individual responses to environmental changes is crucial for species conservation and management. Pelagic fishes including Atlantic herring (Clupea harengus) are of particular interest because of their key ecological and economic roles and their susceptibility to a changing ocean from global warming. Temperature and photoperiod have been linked with spawning time and location in adult herring, but no study has thus far investigated the role of environmental factors on gene regulation during the vulnerable early developmental stages. Here, we examine DNA methylation patterns of larval herring bred under two temperatures (11°C and 13°C) and photoperiod (6 and 12 h) regimes in a 2 × 2 factorial design. We found consistently high levels of global methylation across all individuals and a decline in global methylation with increased developmental stage that was more pronounced at 13°C (p ≤ 0.007) than at 11°C (p ≥ 0.21). Most of the differentially methylated sites were in exon and promoter regions for genes linked to metabolism and development, some of which were hypermethylated at higher temperature. These results demonstrate the important role of DNA methylation during larval development and suggest that this molecular mechanism might be key in regulating early-stage responses to environmental stressors in Atlantic herring.

Ultrasound assessment of the hamstrings complex of athletes with MRI correlation.

Due to anatomical complexity, ultrasound examination of the hamstring muscles is challenging, resulting in potential diagnostic uncertainty and under-confidence in the technique. This leads to a subsequent tendency to favour magnetic resonance imaging (MRI) evaluation, which can delay diagnosis and potential intervention. This article describes a comprehensive technique of ultrasound evaluation of the hamstrings complex, using key anatomical landmarks. A direct comparison of the sonographic landmarks with corresponding MRI appearances is also provided. If these landmarks can be identified successfully, the complex anatomy can be unlocked, thus improving the time and sensitivity of diagnosis of acute injuries, as well as providing a reliable framework for monitoring injury progress and helping to identify candidates for potential intervention. Many of the anatomical landmarks discussed are common areas of injury in elite athletes, encountered frequently in clinical practice.

MRI assessment of anatomy and pathology of the iliofemoral ligament.

The iliofemoral ligament is strongest ligament of the body. We review the magnetic resonance imaging (MRI) appearances of the iliofemoral ligament, and discuss the disease entities that may affect this region.

Direct MR arthrography of the shoulder: current practice in the UK.

There is wide variation in the technique and type of contrast used for MR arthrography of shoulder. In this article, we discuss the current practice in UK and the reason for the change over the last few years.

Recurrent occipital dermatofibrosarcoma protuberans tackled with wide local excision: A case report and current management.

Dermatofibrosarcoma protuberans (DFSP) is a slowgrowing, locally invasive tumour of the dermis. It commonly presents in the trunks and proximal extremities but is seen to a lesser extent in the head and neck regions. We present a case report of a recurrent DFSP in a 48-year-old Iban woman at the occipital region. The patient underwent wide local excision and removal of outer table of cranium, dressing followed by split thickness skin graft. Histopathological examination confirmed dermatofibrosarcoma protuberans with clear lateral surgical margins and a deep margin of 0.5mm. She is currently undergoing radiotherapy and is planned for 50Grey 25cycles.

Pilot study comparing steroid-impregnated and non-steroid-impregnated absorbable nasal dressing following endoscopic sinus surgery.

INTRODUCTION: Endoscopic sinus surgery (ESS) is the mainstay for treatment of chronic rhinosinusitis versus maximal medical therapy. We propose a more economical option, by using steroid-impregnated Gelfoam instead of Nasopore post ESS, as it is less expensive and has showed effectiveness in preventing post-operative bleeding. MATERIALS AND METHODS: A randomised, double-blinded, placebo-controlled trial was carried out in eight patients with chronic rhinosinusitis or nasal polyposis who were planned for bilateral endoscopic sinus surgery. A Peri-operative Sinus Endoscopy (POSE) Score and Lund-Kennedy Endoscopic Score (LKES) were recorded. The use of hydrocortisone-impregnated Gelfoam dressing versus normal saline-impregnated Gelfoam dressing were compared. Scores were repeated post-operatively at one week, three weeks and three months interval. RESULTS: For LKES, at the end of three months, 50% of the patients had the same score difference, 37.5% had better results on the study side while 12.5% had better results on the control side. Meanwhile, for POSE Score, at the end of three months, 75% of the patients had better score difference on the study side while 12.5% had better results on the control side. CONCLUSION: Gelfoam can be used as nasal packing material to deliver topical steroid after endoscopic sinus surgery. Steroid-impregnated nasal dressing after endoscopic sinus surgery may not provide better long-term outcome.

Kernohan-Woltman notch phenomenon: a review article.

Kernohan-Woltman notch phenomenon (KWNP) is a false localising sign which may still cause diagnostic confusion. It was first described by Kernohan and Woltman in 1929, through post-mortem studies on 297 patients following cases of false localisation. They proposed that raised intracranial pressure causes uncal herniation, which can compress the contralateral cerebral peduncle against the tough tentorium, manifesting as hemiparesis ipsilateral to the primary brain lesion. A number of case reports have been written since the original description of this phenomenon, primarily secondary to intracranial bleeds, and little has been written about long-term outcome of patients who develop KNWP. We performed a literature search of all published cases of KWNP, and reviewed its clinical, pathophysiological, imaging and neurophysiological characteristics. Furthermore, we summarise the long-term outcomes of these patients as described by case reports, with the aim to improve understanding of rehabilitation potential. Thirty-eight cases were found through a PubMed search. We also included a case from our own Trust, making the total number of cases in the analysis 39. Thirty-six cases were secondary to intracranial bleeds (22 of which were traumatic), the remainder were due to an arachnoid cyst, high grade glioma, and reabsorption bone syndrome. Additional clinical manifestations to hemibrachiocrural syndrome included third nerve palsy, mydriasis of the contralateral and ipsilateral pupils, facial nerve palsies, and parkinsonism. Twenty-six (67%) patients had improvement in motor function of varying degrees, with twelve (31%) patients attaining complete motor recovery or independence. More studies on long-term outcome of patients who develop KWNP are needed to understand rehabilitation potential.

Alteration of patellar tendon morphology in patellofemoral instability (trochlear dysplasia).

INTRODUCTION: Trochlear Dysplasia (TD) is a condition that is characterized by the presence of an abnormally shaped trochlear groove, which hinders the patellofemoral joint (PFJ) stability. PFJ stability is determined by static and dynamic structures around the knee joint. We analysed whether the patellar tendon morphology is altered in patients with patellofemoral instability in Trochlear Dysplasia (TD). MATERIAL AND METHODS: Magnetic Resonance Imaging (MRI) studies for 50 consecutive knees with TD and 50 consecutive knees with normal PFJ morphology were obtained for evaluation. For each MRI study, the cross-sectional area (CSA) of the medial and lateral components of the patellar tendon was measured and used to calculate the cross-sectional area ratio (CSAR) by two readers. RESULTS: There was a statistically significant difference in the CSAR of the lateral-to-medial components of the patellar tendon between knees with normal PFJ morphology and knees with TD (one way ANOVA, F (4,95) = 7.743, p < 0.001). Pairwise comparisons amongst the Dejour subtypes of TD, revealed a statistically significance difference (p < 0.05) in the CSAR ratio between patients with normal PFJ morphology, and patients with type A (p = 0.007) and type C, TD. There was moderate correlation between the readers on Intraclass Correlation Coefficient (ICC) analysis (ICC- 0.7). CONCLUSION: Our findings reveals hypertrophy of the medial part of the patellar tendon in patients with PFJ instability and TD. These differences could reflect the dynamic compensatory changes occurring at the PFJ to counteract the laterally directed instability vectors found in this condition.

Construction of a novel expression cassette for increasing transgene expression in vivo in endothelial cells of large blood vessels.

The success of gene therapy hinges on achievement of adequate transgene expression. To ensure high transgene expression, many gene-therapy vectors include highly active virus-derived transcriptional elements. Other vectors include tissue-specific eukaryotic transcriptional elements, intended to limit transgene expression to specific cell types, avoid toxicity and prevent immune responses. Unfortunately, tissue specificity is often accompanied by lower transgene expression. Here, we use eukaryotic (murine) transcriptional elements and a virus-derived posttranscriptional element to build cassettes designed to express a potentially therapeutic gene (interleukin (IL)-10) in large-vessel endothelial cells (ECs) at levels as high as obtained with the cytomegalovirus (CMV) immediate early promoter, while retaining EC specificity. The cassettes were tested by incorporation into helper-dependent adenoviral vectors, and transduction into bovine aortic EC in vitro and rabbit carotid EC in vivo. The murine endothelin-1 promoter showed EC specificity, but expressed only 3% as much IL-10 mRNA as CMV. Inclusion of precisely four copies of an EC-specific enhancer and a posttranscriptional regulatory element increased IL-10 expression to a level at or above the CMV promoter in vivo, while retaining--and possibly enhancing--EC specificity, as measured in vitro. The cassette reported here will likely be useful for maximizing transgene expression in large-vessel EC, while minimizing systemic effects.

Birmingham Intervention Tent Technique (BITT): A Technical Note.

Objective We describe a novel and safe CT biopsy technique that we have termed the "Birmingham intervention tent technique (BITT)." This technique is ideal for biopsying osseous lesions where a direct approach is not possible due to difficult positioning. Methods The BITT uses a plastic surgical forceps clamp attached at an angle to the biopsy needle, creating a tent shape. The finger rings of the forceps is stabilized on the table. Results In our institution, we have already used the BITT successfully in over 10 cases. Conclusion The BITT is an inexpensive and reproducible technique.

Hamstring origin-anatomy, angle of origin and its possible clinical implications.

INTRODUCTION: The posterior compartment of the thigh is composed of three major muscles collectively known as the hamstring muscles. These consist of the biceps femoris short and long head, semimembranosus and semitendinosus. Excluding the short head of biceps femoris, the hamstrings contribute to the movement of the hip and the knee joints as they span across both joints. Our hypothesis is that the nature of the conjoint tendon -ischial angle predisposes to an increased risk of tearing in this hamstring component. We therefore aim to look at the anatomy of the hamstring origin at the ischial tuberosity and spatial relationship between the long head of biceps, semitendinosus and semimembranosus in the form of vector angles. MATERIAL AND METHODS: 100 consecutive pelvic MRIs in patients under the age of 40 years were reviewed by musculoskeletal radiology fellow and a consultant musculoskeletal radiologist with more than 10 years' experience in musculoskeletal radiology and measured the angle of origin of conjoined tendon and semimembranosus at its ischial origin. P value using a paired t-test was less than 0.0001 confirming that the difference in the vector angle of the different hamstring components was statistically significant. RESULTS: The median angle of origin of conjoined tendon was 12° and for semimembranosus was 6°. Applying the concept of Newton's second law to the angles calculated we demonstrated that an increase of 9% force applied to the conjoint tendon origin when compared to the semimembranosus tendon. CONCLUSION: We hypothesis that the difference in the angle of origin of the components of hamstrings might be one of the reasons for the difference in the incidence and patterns of the injuries of the various muscles of the hamstrings.

Development, evaluation and validation of machine learning algorithms to detect atypical and asymptomatic presentations of Covid-19 in hospital practice.

BACKGROUND: Diagnostic methods for Covid-19 have improved, both in speed and availability. Because of atypical and asymptomatic carriage of the virus and nosocomial spread within institutions, timely diagnosis remains a challenge. Machine learning models trained on blood test results have shown promise in identifying cases of Covid-19. AIMS: To train and validate a machine learning model capable of differentiating Covid-19 positive from negative patients using routine blood tests and assess the model's accuracy against atypical and asymptomatic presentations. DESIGN AND METHODS: We conducted a retrospective analysis of medical admissions to our institution during March and April 2020. Participants were categorized into Covid-19 positive or negative groups based on clinical, radiological features or nasopharyngeal swab. A machine learning model was trained on laboratory parameters and validated for accuracy, sensitivity and specificity and externally validated at an unconnected establishment. RESULTS: An Ensemble Bagged Tree model was trained on data collected from 405 patients (212 Covid-19 positive) producing an accuracy of 81.79% (95% confidence interval (CI) 77.53-85.55%), the sensitivity of 85.85% (CI 80.42-90.24%) and specificity of 76.65% (CI 69.49-82.84%). Accuracy was preserved for atypical and asymptomatic subgroups. Using an external data set for 226 patients (141 Covid-19 positive) accuracy of 76.82% (CI 70.87-82.08%), sensitivity of 78.38% (CI 70.87-84.72%) and specificity of 74.12% (CI 63.48-83.01%) was achieved. CONCLUSION: A machine learning model using routine laboratory parameters can detect atypical and asymptomatic presentations of Covid-19 and might be an adjunct to existing screening measures.

Anatomy and pathology of facet joint.

Facet joints are the only synovial joints in the spine and can be involved in a large number of pathological processes including arthropathy, infection, inflammation, trauma and tumour. In this review article, we present a spectrum of pathologies that arise from or involve facet joints that we have encountered in our tertiary orthopaedic and spinal centre. The objective of this review is to create an aide memoire for the general radiologist who may encounter facet joint pathology, which they may not be familiar with.

Dose-Response Relationship Between Diltiazem and Tacrolimus and Its Safety in Renal Transplant Recipients.

BACKGROUND: Inhibition of calcineurin inhibitor (CNI) metabolism with diltiazem reduces the dose of tacrolimus required to achieve its therapeutic blood concentration in kidney transplant recipients (KTRs). This cost-savings maneuver is practiced in several countries, including Malaysia, but the actual impacts of diltiazem on tacrolimus blood concentration, dose-response relationship, cost-savings, and safety aspects are unknown. METHODS: This retrospective study was performed on all KTRs ≥18 years of age at our center from January 1, 2006 to December 31, 2015, who were prescribed diltiazem as tacrolimus-sparing agent. Blood tacrolimus trough level (TacC0) and other relevant clinical data for 70 eligible KTRs were reviewed. RESULTS: The dose of 1 mg tacrolimus resulted in a median TacC0 of 0.83 ± 0.52 ng/mL. With the introduction of a 90-mg/d dose diltiazem, there was a significant TacC0 increase to 1.39 ± 1.31 ng/mL/mg tacrolimus (P < .01). A further 90-mg increase in diltiazem to 180 mg/d resulted in a further increase of TacC0 to 1.66 ± 2.58 ng/mL/mg tacrolimus (P = .01). After this, despite a progressive increment of every 90-mg/d dose diltiazem to 270 mg/d and 360 mg/d, there was no further increment in TacC0 (1.44 ± 1.15 ng/mL/mg tacrolimus and 1.24 ± 0.94 ng/mL/mg tacrolimus, respectively [P < .01]). Addition of 180 mg/d diltiazem reduced the required tacrolimus dose to 4 mg/d, resulting in a cost-savings of USD 2045.92 per year (per patient) at our center. Adverse effects reported within 3 months of diltiazem introduction were bradycardia (1.4%) and postural hypotension (1.4%), which resolved after diltiazem dose reduction. CONCLUSION: Coadministration of tacrolimus and diltiazem in KTRs appeared to be safe and resulted in a TacC0 increment until reaching a 180-mg/d total diltiazem dose, at which point it began to decrease. This approach will result in a marked savings in immunosuppression costs among KTRs in Malaysia.

Composite pleomorphic xanthoastrocytoma and ganglioglioma: report of four cases and review of the literature.

Composite pleomorphic xanthoastrocytoma (PXA)-ganglioglioma (GG) is a rare recently described entity. Only three examples have been documented, one of which showed evidence of malignant transformation. We report an additional four cases and update the literature. With the exception of an 82-year-old man, all patients have been under 30 years of age. The temporal lobe was involved in three cases and cerebellum in another three. Radiologic features were those common to PXA and GG. Histologically, all were "collision tumors" composed of abutting, although spatially distinct, PXA and GG components. In two cases, the second element was only recognized at reexcision or recurrence. Histologic anaplasia, always in the PXA component, was evident as brisk mitotic activity and/or necrosis in five cases. Of the seven patients, one died of disease 17 years after the onset of seizures and after multiple recurrences, the last of which largely resembled glioblastoma. We conclude that the composite PXA-GG is a rare neoplasm that shares many features of its individual components. In addition to its temporal lobe predilection, the cerebellum is frequently affected. As when it occurs in isolation, the PXA component of composite PXA-GG possesses the potential for malignant transformation.

Digital measurement of torsional eye movement due to postural change and its effect on reading performance.

PURPOSE: Posture induced torsional eye movements have rarely been investigated. The current study made use of digital imaging technology to measure the cycloduction resulting from postural change. The effect of cycloduction on reading performance was also investigated. METHODS: Thirty subjects were recruited and pictures of the right eye were captured using a digital camera at three postures, i.e. sitting, 90 degrees tilted to the right and 90 degrees tilted to the left. With the identification of a conjunctival landmark, torsional eye movement was measured. The subjects were then required to read a custom designed near chart while in those three postures, the reading card being rotated 90 degrees clockwise or 90 degrees anti-clockwise, to match with the tilting of the head. The reproducibility of the torsional eye movement and reading performance measure was determined in 12 of those 30 subjects. RESULTS: Incycloduction was induced when tilting to the right and excycloduction when tilting to the left. This method was found to be reproducible with the 95% confidence limits of 0.80 degrees between visits. The mean incycloduction induced was 6.50 degrees (SD 1.51 degrees ) and 6.41 degrees (SD 1.46 degrees ) for excycloduction. No significant difference in amount was demonstrated (paired t-test: t = 0.624, P = 0.538). No significant difference was found in the reading scores at various postures (Repeated measures ANOVA: df = 2, F = 1.881, P = 0.162). CONCLUSIONS: The results presented here demonstrate that we have developed an objective and instantaneous method with good precision, which could be applied in other studies that require the measurement of torsional eye movements. The induced cycloduction did not affect the reading performance.

Fine needle aspiration cytology of benign adrenal cortical nodules. A comparison of cytologic findings with those of primary and metastatic adrenal malignancies.

OBJECTIVE: To determine the specific cytomorphologic criteria for diagnosing benign adrenal cortical nodule (BACN) by fine needle aspiration (FNA). STUDY DESIGN: The smears from 162 adrenal FNA biopsies were reviewed. A diagnosis of BACN was rendered in 50 cases (31%). The cytologic features of BACN were compared to those of primary and metastatic malignant tumors of the adrenal gland, and the size of BACN as measured by computed tomography was recorded. RESULTS: Bubbly, vacuolated, lipid background; large, cohesive tissue fragments with a syncytial nesting arrangement admixed with sinusoidal endothelial cells; and abundant oval, round, bare nuclei are the three cytomorphologic features most often seen in BACN. The combination of these three features was observed in 40 cases (89%) of BACN and was seen in 4 cases of metastatic carcinoma (6%) in which there was also coexisting adrenal cortical hyperplasia. None of the other primary or metastatic malignancies showed this combination of cytomorphologic features. The mean size of BACN was 2.5 cm, with a standard deviation of 1 cm and a range of 1-5 cm. The sizes of the four metastatic carcinomas with coexisting adrenal cortical hyperplasia were 6.5, 6, 5 and 1.5 cm, respectively (mean, 4.8). CONCLUSION: Our data suggest that combined cytologic features of bare nuclei; bubbly, vacuolated background; and large, cohesive tissue fragments with sinusoidal endothelial cells in a small adrenal nodule (< 3.5 cm) are highly specific to FNA diagnosis of BACN.

Confirmation of the hierarchical folding of RNase H: a protein engineering study.

The kinetic intermediate of RNase H is structured in a core region of the protein. To probe the role of this intermediate in the folding of RNase H, the folding kinetics of mutant proteins with altered native state stabilities were investigated. Mutations within the folding core destabilize the kinetic intermediate and slow refolding in a manner consistent with an obligatory intermediate model. Mutations outside of the folding core, however, do not affect the stability of the kinetic intermediate but do perturb the native state and transition state. These results indicate that interactions formed in the intermediate persist in the transition and native states and that RNase H folds through a hierarchical mechanism.