A case of intussusception secondary to a metastatic malignant melanoma from the nasal cavity.

About 5% of all intussusception are found in adults, up to 90% of these have an anatomical lesion with ~50% of them are malignant. Malignant melanoma commonly metastasizes to the small bowel; however, melanoma causing intussusception is rare. We describe a 57-year-old lady with a history of surgically treated malignant melanoma in her nasal cavity who came with an ambiguous intestinal obstruction. Computed tomography reported ileal-ileal intussusception, which was surgically removed via emergency open laparotomy and bowel resection. Intraoperatively the intussusception was 110 cm from the ileo-cecal valve with multiple palpable lymph nodes. Histopathology confirmed the origin as malignant melanoma with lymphovascular invasion. Our literature review found the mean prevalence of intussusception secondary to melanoma was 6.924% (SD ± 5.155). Minimally invasive techniques are reported non-inferior to open laparotomy. We argue that the open technique can provide informed decisions for adequate resection of affected bowel and lymphatic drainage.

A novel tool to quantify in vivo lumbar spine kinematics and 3D intervertebral disc strains using clinical MRI.

Medical imaging modalities that calculate tissue morphology alone cannot provide direct information regarding the mechanical behaviour of load-bearing musculoskeletal organs. Accurate in vivo measurement of spine kinematics and intervertebral disc (IVD) strains can provide important information regarding the mechanical behaviour of the spine, help to investigate the effects of injuries on the mechanics of the spine, and assess the effectiveness of treatments. Additionally, strains can serve as a functional biomechanical marker for detecting normal and pathologic tissues. We hypothesised that combining digital volume correlation (DVC) with 3T clinical MRI can provide direct information regarding the mechanics of the spine. Here, we have developed a novel non-invasive tool for in vivo displacement and strain measurement within the human lumbar spine and we used this tool to calculate lumbar kinematics and IVD strains in six healthy subjects during lumbar extension. The proposed tool enabled spine kinematics and IVD strains to be measured with errors that did not exceed 0.17 mm and 0.5%, respectively. The findings of the kinematics study identified that during extension the lumbar spine of healthy subjects experiences total 3D translations ranging from 1 mm to 4.5 mm for different vertebral levels. The findings of strain analysis identified that the average of the maximum tensile, compressive, and shear strains for different lumbar levels during extension ranged from 3.5% to 7.2%. This tool can provide base-line data that can be used to describe the mechanical environment of healthy lumbar spine, which can help clinicians manage preventative treatments, define patient-specific treatments, and to monitor the effectiveness of surgical and non-surgical interventions.

National Joint Registry recorded untoward intraoperative events during primary total hip arthroplasty: an investigation into the data accuracy, causal mechanisms and attributability.

INTRODUCTION: Untoward intraoperative events occurring during total hip arthroplasty are recorded by the National Joint Registry through Minimum Data Set (MDS) forms. This data may be used to assess the safety of implants. The aim of this study is to evaluate the accuracy of the untoward intraoperative events, assess the mechanism and ascertain whether these events were attributable to the implants inserted. METHODS: A retrospective analysis was undertaken of primary total hip arthroplasties performed between 2005 and 2018 in which an untoward intraoperative event was recorded. RESULTS: Of 12,802 primary hip replacements, 64 patients (0.5%) had untoward intraoperative events recorded on the MDS form. In 43 of 64 cases, the intraoperative untoward event recorded on the MDS form matched the operation notes. Among these 43 cases, in 30 (69%) patients the intraoperative event could be attributed to the implant recorded. In the remaining 13 (31%) cases, the events recorded could not be attributed to the implant. In six cases, the untoward events were attributed to implants used to manage the events rather than the implants which caused them. In seven cases, the untoward events were related to surgical technique rather than to the implant or instrumentation. CONCLUSIONS: Our analysis highlights that all untoward intraoperative events recorded on the NJR form are not implant related or attributable to the implant inserted. Provision should be made on the MDS form to clarify whether a particular untoward intraoperative event was related to the implant inserted.

Identification of the First Gene Transfer Agent (GTA) Small Terminase in Rhodobacter capsulatus and Its Role in GTA Production and Packaging of DNA.

Genetic exchange mediated by viruses of bacteria (bacteriophages) is the primary driver of rapid bacterial evolution. The priority of viruses is usually to propagate themselves. Most bacteriophages use the small terminase protein to identify their own genome and direct its inclusion into phage capsids. Gene transfer agents (GTAs) are descended from bacteriophages, but they instead package fragments of the entire bacterial genome without preference for their own genes. GTAs do not selectively target specific DNA, and no GTA small terminases are known. Here, we identified the small terminase from the model Rhodobacter capsulatus GTA, which then allowed prediction of analogues in other species. We examined the role of the small terminase in GTA production and propose a structural basis for random DNA packaging.IMPORTANCE Random transfer of any and all genes between bacteria could be influential in the spread of virulence or antimicrobial resistance genes. Discovery of the true prevalence of GTAs in sequenced genomes is hampered by their apparent similarity to bacteriophages. Our data allowed the prediction of small terminases in diverse GTA producer species, and defining the characteristics of a "GTA-type" terminase could be an important step toward novel GTA identification. Importantly, the GTA small terminase shares many features with its phage counterpart. We propose that the GTA terminase complex could become a streamlined model system to answer fundamental questions about double-stranded DNA (dsDNA) packaging by viruses that have not been forthcoming to date.

A third of patients treated at a tertiary-level surgical service could be treated at a secondary-level facility.

BACKGROUND: South Africa (SA) has an overburdened public healthcare system. Some patients admitted to Charlotte Maxeke Johannesburg Academic Hospital (CMJAH), SA, may not require tertiary care, but the numbers and details are uncertain. Clinical research in SA is limited by scarce skills and limited access to data. OBJECTIVE: To determine the proportion of and length of stay for secondary-, tertiary- and quaternary-level patients discharged from the Department of Surgery at CMJAH over 1 year. METHODS: This is a retrospective analysis of electronic discharge (ED) summaries from the Department of Surgery at CMJAH between 1 April 2015 and 1 April 2016. An SQL query of the database generated a .csv file of all discharges with the following fields: database reference number, length of stay and level of care. The details of each record were verified by MBBCh V students, using a defined level-ofcare template and the full discharge summary. The data were reviewed by a senior clinician. RESULTS: There were 3 007 discharge summaries - 97 were not classifiable, two were test records and one was a duplicate. These 100 records were excluded. There were no primary-level records. Secondary-level patients represented 29% (854) of those discharged and 19% of total bed days. Tertiary- and quaternary-level patients together represented 71% of the total and 81% of bed days. The average length of stay was 4.31 days for secondary, 6.98 days for tertiary and 9.77 days for quaternary level-of-care allocation. CONCLUSION: Almost one-third (29%) of patients discharged from CMJAH's Department of Surgery were deemed suitable for secondarylevel care. These patients had a shorter length of stay and comprised 19% of total bed days. Students and electronic databases represent an important research resource.

Transient Osteoporosis of the Hip: A Case Report.

Transient osteoporosis of the hip (TOH) is a benign, selflimiting condition characterised by acute onset groin pain in adults. Early diagnosis is important to differentiate it from progressive conditions such as osteonecrosis. We report on a middle-aged male who presented with right groin pain without any prior trauma. The diagnosis of transient osteoporosis of hip was confirmed by Magnetic Resonance Imaging (MRI) and he was successfully treated with a course of Alendronate sodium, anti-inflammatory analgesics and a period of non-weight bearing ambulation.

A third of patients treated at a tertiary-level surgical service could be treated at a secondary-level facility

Background. South Africa (SA) has an overburdened public healthcare system. Some patients admitted to Charlotte Maxeke Johannesburg Academic Hospital (CMJAH), SA, may not require tertiary care, but the numbers and details are uncertain. Clinical research in SA is limited by scarce skills and limited access to data.Objective. To determine the proportion of and length of stay for secondary-, tertiary- and quaternary-level patients discharged from the Department of Surgery at CMJAH over 1 year.Methods. This is a retrospective analysis of electronic discharge (ED) summaries from the Department of Surgery at CMJAH between 1 April 2015 and 1 April 2016. An SQL query of the database generated a .csv file of all discharges with the following fields: database reference number, length of stay and level of care. The details of each record were verified by MBBCh V students, using a defined level-ofcare template and the full discharge summary. The data were reviewed by a senior clinician.Results. There were 3 007 discharge summaries ­ 97 were not classifiable, two were test records and one was a duplicate. These 100 records were excluded. There were no primary-level records. Secondary-level patients represented 29% (854) of those discharged and 19% of total bed days. Tertiary- and quaternary-level patients together represented 71% of the total and 81% of bed days. The average length of stay was 4.31 days for secondary, 6.98 days for tertiary and 9.77 days for quaternary level-of-care allocation.Conclusion. Almost one-third (29%) of patients discharged from CMJAH's Department of Surgery were deemed suitable for secondarylevel care. These patients had a shorter length of stay and comprised 19% of total bed days. Students and electronic databases represent an important research resource

Proteolytic inactivation of nuclear alarmin high-mobility group box 1 by complement protease C1s during apoptosis.

Effective clearance of apoptotic cells by phagocytes prevents the release of intracellular alarmins and manifestation of autoimmunity. This prompt efferocytosis is complemented by intracellular proteolytic degradation that occurs within the apoptotic cells and in the efferosome of the phagocytes. Although the role of extracellular proteases in apoptotic cells clearance is unknown, the strong association of congenital C1s deficiency with Systemic Lupus Erythematosus highlights the protective nature that this extracellular protease has against autoimmunity. The archetypical role of serine protease C1s as the catalytic arm of C1 complex (C1qC1r2C1s2) involve in the propagation of the classical complement pathway could not provide the biological basis for this association. However, a recent observation of the ability of C1 complex to cleave a spectrum of intracellular cryptic targets exposed during apoptosis provides a valuable insight to the underlying protective mechanism. High-mobility group box 1 (HMGB1), an intracellular alarmin that is capable of inducing the formation of antinuclear autoantibodies and causes lupus-like conditions in mice, is identified as a novel potential target by bioinformatics analysis. This is verified experimentally with C1s, both in its purified and physiological form as C1 complex, cleaving HMGB1 into defined fragments of 19 and 12 kDa. This cleavage diminishes HMGB1 ability to enhance lipopolysaccharide mediated pro-inflammatory cytokines production from monocytes, macrophages and dendritic cells. Further mass spectrometric analysis of the C1 complex treated apoptotic cellular proteins demonstrated additional C1s substrates and revealed the complementary role of C1s in apoptotic cells clearance through the proteolytic cleavage of intracellular alarmins and autoantigens. C1 complex may have evolved as, besides the bacteriolytic arm of antibodies in which it activates the complement cascade, a tissue renewal mechanism that reduces the immunogenicity of apoptotic tissue debris and decreases the likelihood of autoimmunity.

Design and fabrication of 3D-printed anatomically shaped lumbar cage for intervertebral disc (IVD) degeneration treatment.

Spinal fusion is the gold standard surgical procedure for degenerative spinal conditions when conservative therapies have been unsuccessful in rehabilitation of patients. Novel strategies are required to improve biocompatibility and osseointegration of traditionally used materials for lumbar cages. Furthermore, new design and technologies are needed to bridge the gap due to the shortage of optimal implant sizes to fill the intervertebral disc defect. Within this context, additive manufacturing technology presents an excellent opportunity to fabricate ergonomic shape medical implants. The goal of this study is to design and manufacture a 3D-printed lumbar cage for lumbar interbody fusion. Optimisations of the proposed implant design and its printing parameters were achieved via in silico analysis. The final construct was characterised via scanning electron microscopy, contact angle, x-ray micro computed tomography (µCT), atomic force microscopy, and compressive test. Preliminary in vitro cell culture tests such as morphological assessment and metabolic activities were performed to access biocompatibility of 3D-printed constructs. Results of in silico analysis provided a useful platform to test preliminary cage design and to find an optimal value of filling density for 3D printing process. Surface characterisation confirmed a uniform coating of nHAp with nanoscale topography. Mechanical evaluation showed mechanical properties of final cage design similar to that of trabecular bone. Preliminary cell culture results showed promising results in terms of cell growth and activity confirming biocompatibility of constructs. Thus for the first time, design optimisation based on computational and experimental analysis combined with the 3D-printing technique for intervertebral fusion cage has been reported in a single study. 3D-printing is a promising technique for medical applications and this study paves the way for future development of customised implants in spinal surgical applications.

Outcomes of spontaneous bacterial peritonitis in liver transplant recipients with allograft failure.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) carries appreciable morbidity and mortality in the pre-liver transplant (LT) setting. However, the occurrence of SBP and its consequences in the post-LT setting have not been well characterized. METHODS: This is a retrospective study of SBP occurring in post-LT patients between January 2007 and December 2012. Outcomes were compared to a cohort of post-LT patients with allograft failure and ascites without SBP. RESULTS: The most common indication for liver transplantation in this cohort was hepatitis C. A total of 29 episodes of SBP in 21 patients were identified. Escherichia coli (19%) and Klebsiella pneumoniae (10%) were the most frequent pathogens identified. Six patients died during their first episode of SBP. Ten patients were eventually listed for liver re-transplantation (re-LT) after their first episode of SBP; 5 of these patients were transplanted and the other 5 died. Of the 5 who were transplanted, 2 died shortly after re-transplant, and 3 are still alive. The cause of death in the majority of patients was infection (83.3%). The median time from onset of ascites to death was 214 days (range: 10-1085 days) and from the first episode of SBP to death was 50.5 days (range: 4-549 days). In contrast, the median time from onset of ascites to death in patients with allograft failure and ascites without SBP was 331.5 days (45-2400 days). CONCLUSIONS: Allograft failure with ascites is a poor prognostic factor and these patients should be considered high risk for re-LT. SBP may accelerate the time to mortality.

Alignment sensing and control for squeezed vacuum states of light.

Beam alignment is an important practical aspect of the application of squeezed states of light. Misalignments in the detection of squeezed light result in a reduction of the observable squeezing level. In the case of squeezed vacuum fields that contain only very few photons, special measures must be taken in order to sense and control the alignment of the essentially dark beam. The GEO 600 gravitational wave detector employs a squeezed vacuum source to improve its detection sensitivity beyond the limits set by classical quantum shot noise. Here, we present our design and implementation of an alignment sensing and control scheme that ensures continuous optimal alignment of the squeezed vacuum field at GEO 600 on long time scales in the presence of free-swinging optics. This first demonstration of a squeezed light automatic alignment system will be of particular interest for future long-term applications of squeezed vacuum states of light.

The psychometric properties of the Quantitative-Checklist for Autism in Toddlers (Q-CHAT) as a measure of autistic traits in a community sample of Singaporean infants and toddlers.

BACKGROUND: There is growing research evidence that subclinical autistic traits are elevated in relatives of individuals with autism spectrum disorder (ASD), continuously distributed in the general population and likely to share common etiology with ASD. A number of measures have been developed to assess autistic traits quantitatively in unselected samples. So far, the Quantitative-Checklist for Autism in Toddlers (Q-CHAT) is one of very few measures developed for use with toddlers as young as 18 months, but little is known about its measurement properties and factor structure. METHODS: The present study examined internal consistency, factor structure, test-retest stability, and convergent validity of the Q-CHAT in a sample of toddlers in Singapore whose caregivers completed the Q-CHAT at 18 (n = 368) and 24 months (n = 396). RESULTS: Three factors were derived accounting for 38.1 % of the variance: social/communication traits, non-social/behavioral traits, and a speech/language factor. Internal consistency was suboptimal for the total and speech/language scores, but acceptable for the social/communication and non-social/behavioral factor scores. Scores were generally stable between 18 and 24 months. Convergent validity was found with the Pervasive Developmental Disorders subscale of the Child Behavior Checklist (CBCL) completed by caregivers when their children were 24 months. Q-CHAT total scores in this sample were higher than those reported in other unselected samples from the UK. CONCLUSIONS: The Q-CHAT was found to have a three-factor structure, acceptable internal consistency for its two main factor scores (social/communication and non-social/behavioral), normally distributed scores in an unselected sample, and similar structure and measurement properties as those reported in other published studies. Findings are discussed in relation to existing literature and future directions for the validation of the Q-CHAT.

Phase control of squeezed vacuum states of light in gravitational wave detectors.

Quantum noise will be the dominant noise source for the advanced laser interferometric gravitational wave detectors currently under construction. Squeezing-enhanced laser interferometers have been recently demonstrated as a viable technique to reduce quantum noise. We propose two new methods of generating an error signal for matching the longitudinal phase of squeezed vacuum states of light to the phase of the laser interferometer output field. Both provide a superior signal to the one used in previous demonstrations of squeezing applied to a gravitational-wave detector. We demonstrate that the new signals are less sensitive to misalignments and higher order modes, and result in an improved stability of the squeezing level. The new signals also offer the potential of reducing the overall rms phase noise and optical losses, each of which would contribute to achieving a higher level of squeezing. The new error signals are a pivotal development towards realizing the goal of 6 dB and more of squeezing in advanced detectors and beyond.

Impairments to the GH-IGF-I axis in hSOD1G93A mice give insight into possible mechanisms of GH dysregulation in patients with amyotrophic lateral sclerosis.

GH deficiency has been found in subjects with amyotrophic lateral sclerosis (ALS). Disrupted endocrine function could contribute to the progressive muscle loss and hypermetabolism seen in ALS. It is not possible to study all the elements of the GH-IGF-I axis in ALS patients. Consequently, it remains unclear whether dysfunctional GH secretion contributes to disease pathogenesis and why GH and IGF-I directed treatment strategies are ineffective in human ALS. The hSOD1(G93A) transgenic mouse model is useful for the detailed investigation of the pathogenesis of ALS. We report that symptomatic male hSOD1(G93A) transgenic mice exhibit a deficiency in GH secretion similar to that seen in human ALS. Further characterization of the GH-IGF-I axis in hSOD1(G93A) mice reveals central and peripheral abnormalities that are not found in wild-type age-matched controls. Specifically, we observe aberrant endogenous pulsatile GH secretion, reduced pituitary GH content, and decreased circulating levels of IGF-I, indicating global GH deficiency in hSOD1(G93A) mice. Furthermore, a reduction in the expression of the IGF-I receptor α-subunit in skeletal muscle and lumbar spinal cords of hSOD1(G93A) mice suggests impaired IGF-I signaling within these tissues. This is the first account of disrupted GH secretion in a transgenic mouse model of ALS. These observations are essential for the development of effective GH and IGF-I targeted therapies in ALS.

GH does not modulate the early fasting-induced release of free fatty acids in mice.

Fasting results in the mobilization of adipose stores and the elevation of levels of free fatty acids (FFA). In humans, this process is driven by a release in GH. Little is known regarding the role of GH in modulating this process during early stages of fasting in the mouse. Confirmation of the role of GH in modulating FFA release in the fasting mouse is of particular importance given the frequent use of mouse models to study metabolic mechanisms. Here, we correlate the initial release of FFA throughout fasting in mice with pulsatile GH secretion. Observations illustrate the rapid release of FFA in response to food withdrawal. This does not correlate with a rise in GH secretion. Rather, we observed a striking loss in pulsatile secretion of GH throughout the first 6 h of fasting, suggesting that GH does not modulate the initial release of FFA in the mouse in response to fasting. This was confirmed in GH receptor knockout mice, in which we observed a robust fasting-induced rise in FFA. We further illustrate the dynamic relationship between the orexigenic and anorexigenic hormones ghrelin and leptin during fasting in the mouse. Our findings show an initial suppression of leptin and the eventual rise in circulating levels of acyl-ghrelin with fasting. However, altered acyl-ghrelin and leptin secretion occurs well after the rise in FFA and the suppression of GH secretion. Consequently, we conclude that although acyl-ghrelin and leptin may modulate the physiological response to drive food intake, these changes do not contribute to the initial loss of pulsatile GH secretion. Rather, it appears that the suppression of GH secretion in fasting may occur in response to an elevation in fasting levels of FFA or physiological stress. Observations highlight a divergent role for GH in modulating FFA release between man and mouse.

Arthroscopic ankle arthrodesis: are results reproducible irrespective of pre-operative deformity?

BACKGROUND: Arthroscopic ankle arthrodesis is gaining in popularity. It has been shown to have a shorter time to union and less morbidity than traditional open procedures. The arthroscopic technique has been mainly used for ankles with minimal deformity. Our aim was to find out whether we could reproduce the good results of arthroscopic ankle arthrodesis in both minimally and markedly deformed ankles. METHODS: We reviewed 62 patients who underwent an arthroscopic ankle arthrodesis for end stage arthritis. The average follow up was 63 months (range 21-92 months). Patients were evaluated subjectively and objectively using the Mazur grading system. 4 patients died before final review and 3 were lost to follow-up leaving 55 patients for evaluation. The pre-operative tibiotalar angle in the coronal plane was between 26° valgus and 24° varus. We divided our patients into 2 groups based on the tibiotalar angle. Group A (n=31) had a varus or valgus deformity of less than 15 and Group B (n=24) had a deformity equal to or more than 15°. RESULTS: The overall fusion rate was 91%. Fusion occurred in 29 of 31 (94%) ankles in Group A compared to 21 of 24 (88%) in Group B (p=0.64).The overall mean time to union was 10.4 weeks. The time to union in Group A was 8.8 weeks compared to 12.7 weeks for Group B (p=0.001). Using the Mazur ankle grading system, 84% of the cases in Group A had a good to excellent result compared to 79% in Group B (p=0.73). There were 2 superficial infections, 2 cases of deep vein thrombosis and 3 patients required removal of prominent screws. CONCLUSIONS: We have shown that arthroscopic ankle arthrodesis yields reliable and reproducible results in a District General Hospital setting with high union rates, short time to union and low complication rates. It can be satisfactorily employed for ankles with significant deformity, although this resulted in a longer time to union. The end results remain uniformly good to excellent.

Development of a method for the determination of pulsatile growth hormone secretion in mice.

Measures of pulsatile GH secretion require frequent collection and analysis of blood samples at regular intervals. Due to blood volume constraints, repeat measures of circulating levels of GH in mice remain challenging. Consequently, few observations exist in which the pulsatile pattern of GH secretion in mice have been characterized. To address this, we developed a technique for the collection and analysis of circulating levels of GH at regular and frequent intervals in freely moving mice. This was achieved through the development of a sensitive assay for the detection of GH in small (2 µl) quantities of whole blood. The specificity and accuracy of this assay was validated following guidelines established for single-laboratory validation as specified by the International Union of Pure and Applied Chemistry. We incorporated an established method for tail-clip blood sample collection to determine circulating levels of GH secretion in 36 whole blood samples collected consecutively over a period of 6 h. Resulting measures were characterized by peak secretion periods and interpulse stable baseline secretion periods. Periods characterized by elevated whole blood GH levels consisted of multicomponent peaks. Deconvolution analysis of resulting measures confirmed key parameters associated with pulsatile GH secretion. We show a striking decrease in pulsatile GH secretion in mice after 12-18 h of fasting. This model is necessary to characterize the pulsatile profile of GH secretion in mice and will significantly contribute to current attempts to clarify mechanisms that contribute to the regulation of GH secretion.

Allergic rhinitis: evidence-based practice.

Allergic rhinitis is a common condition in Singapore, with a considerable disease burden. This article reviews the latest evidence-based concepts and current understanding of the disease, including its aetiology, pathogenesis, signs and symptoms, investigations as well as management. Particular attention is given to reviewing principles that will aid the management of this disease from a practical point of view, and the latest evidence for the various pharmacological options as well as immunotherapy is discussed. The article should be of interest to otolaryngologists as well as allergists, respiratory physicians and family practitioners.

Ministry of Health clinical practice guidelines: Management of Rhinosinusitis and Allergic Rhinitis.

The Ministry of Health publishes national clinical practice guidelines to provide doctors and patients in Singapore with evidence-based guidance on managing important medical conditions. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the Ministry of Health clinical practice guidelines on Management of Rhinosinusitis and Allergic Rhinitis, for the information of readers of the Singapore Medical Journal. Chapters, page and figure numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website (http://www.moh.gov.sg/mohcorp/publications.aspx?id=24046). The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.