Epigenetic effects of folate and related B vitamins on brain health throughout life: Scientific substantiation and translation of the evidence for health improvement strategies.

Suboptimal status of folate and/or interrelated B vitamins (B12 , B6 and riboflavin) can perturb one-carbon metabolism and adversely affect brain development in early life and brain function in later life. Human studies show that maternal folate status during pregnancy is associated with cognitive development in the child, whilst optimal B vitamin status may help to prevent cognitive dysfunction in later life. The biological mechanisms explaining these relationships are not clear but may involve folate-related DNA methylation of epigenetically controlled genes related to brain development and function. A better understanding of the mechanisms linking these B vitamins and the epigenome with brain health at critical stages of the lifecycle is necessary to support evidence-based health improvement strategies. The EpiBrain project, a transnational collaboration involving partners in the United Kingdom, Canada and Spain, is investigating the nutrition-epigenome-brain relationship, particularly focussing on folate-related epigenetic effects in relation to brain health outcomes. We are conducting new epigenetics analysis on bio-banked samples from existing well-characterised cohorts and randomised trials conducted in pregnancy and later life. Dietary, nutrient biomarker and epigenetic data will be linked with brain outcomes in children and older adults. In addition, we will investigate the nutrition-epigenome-brain relationship in B vitamin intervention trial participants using magnetoencephalography, a state-of-the-art neuroimaging modality to assess neuronal functioning. The project outcomes will provide an improved understanding of the role of folate and related B vitamins in brain health, and the epigenetic mechanisms involved. The results are expected to provide scientific substantiation to support nutritional strategies for better brain health across the lifecycle.

Systemic medical complications following joint replacement: a review of the evidence.

INTRODUCTION: Arthroplasty procedures are commonly performed in the UK. Informed consent is required for each procedure. To obtain informed consent the patient and their surgeon should discuss the risks and benefits of the proposed operation. This discussion should include both regional and systemic complication rates. Regional complications of arthroplasty are generally well documented in the literature. Systemic medical complications are less well described. This lack of accurate data could make it difficult for the treating surgeon to obtain valid consent. The aim of this paper was to review and compare the literature regarding the rate of systemic medical complications after common arthroplasty procedures. METHODS: A literature search was conducted using the PubMed, Cochrane Library and MEDLINE databases. Studies regarding the systemic medical complications and mortality rate of joint replacement were included. FINDINGS: We found that systemic complications were more frequent than regional complications following arthroplasty. The systemic complication rates were: hip, 5.1%; knee, 6.9%; ankle, 3.0%; shoulder, 11.2%; elbow, 8.5%; and wrist, 0%. Mortality rates for arthroplasty procedures were: hip, 0.3%; knee, 0.2%; ankle, 0.3%; shoulder, 0.3%; elbow, 0.2%; and wrist, 0%. CONCLUSIONS: The most common systemic medical complication following arthroplasty was venous thromboembolism. Preoperative comorbidity was the most important risk factor for both postoperative mortality and systemic medical complications following arthroplasty procedures. We recommend that to obtain informed consent the given rates of systemic medical complications of joint replacement should be discussed and documented.

SARS-CoV-2-specific antibodies and neutralization capacity in breast milk following infection vs vaccination.

Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies have been found in breast milk following both natural SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19) vaccination. This was a prospective study to evaluate the temporal changes in amount and neutralization capacity of anti-SARS-CoV-2 antibodies in breast milk stimulated by natural infection and by vaccination. Serial breast milk samples were collected from postnatal women who were recruited through convenience sampling. We found a rapid increase in neutralizing SARS-CoV-2-specific antibodies in breast milk from both study groups. Amongst the infection group, the median immunoglobulin A (IgA) level was 16.99 (range, 0-86.56) ng/mL and median binding capacity was 33.65% (range, 0-67.65%), while in the vaccination group these were 30.80 (range, 0-77.40) ng/mL and 23.80% (range, 0-42.80%), respectively. In both groups, both binding capacity and IgA levels decreased progressively over time after peaking. Neutralizing activity had become undetectable by about 150 days after the first dose of the vaccine, but a vaccine booster dose restored secretion of neutralizing IgA, albeit with different levels of response in different individuals. This highlights the importance of the vaccine booster dose in sustaining neutralizing antibody levels in breast milk, which may potentially provide protection for very young children, who cannot receive the COVID-19 vaccine. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Case report: NTRK1-rearranged cervical sarcoma with fibrosarcoma like morphology presenting in a 13-year-old managed with a neo-adjuvant TRK-inhibitor and surgical excision.

This case report reviews the case of a 13-year-old patient who presented with a 9 cm NTRK1-rearranged cervical sarcoma with fibrosarcoma like morphology. At presentation the lesion filled her vagina and pelvis and any attempt at surgical removal would have been morbid and led to loss of fertility. These neoplasms are extremely rare with 18 cases of the uterine cervix reported in the literature, none of which have occurred in a paediatric patient, and none of whom have received neo-adjuvant therapy prior to excision. Based upon evidence that has shown good tolerability and responses of paediatric NTRK fusion-positive solid tumours to TRK inhibitors, both in the neo-adjuvant and upfront setting, this patient was managed with neo-adjuvant entrectinib. Following a dramatic reduction in tumour size confirmed by imaging, she underwent conservative fertility sparing surgery with final histopathology showing no residual disease.

Relationship between viral load, infection-to-delivery interval and mother-to-child transfer of anti-SARS-CoV-2 antibodies.

OBJECTIVE: To investigate the association of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and infection-to-delivery interval with maternal and cord serum concentrations of anti-SARS-CoV-2 immunoglobulin G (IgG) antibodies and transplacental transfer ratio in pregnant women with active or recovered SARS-CoV-2 infection. METHODS: This was a prospective case series of consecutive pregnant women with laboratory-confirmed SARS-CoV-2 infection between 27 March 2020 and 24 January 2021. We collected information regarding deep throat saliva or nasopharyngeal swab (NPS) reverse transcription polymerase chain reaction (RT-PCR) test results, serial cycle threshold (Ct) values at and after diagnosis, demographic, clinical and outcome data, and neonatal NPS RT-PCR results. Qualitative and quantitative analysis of IgG and immunoglobulin M (IgM) antibodies against SARS-CoV-2 was performed in maternal and cord blood serum samples obtained at delivery. Correlation of maternal Ct values, infection-to-delivery interval, infection duration and viral load area under the curve (AUC) with gestational age (GA) at diagnosis, maternal and cord serum IgG concentrations and transplacental transfer ratio of IgG were evaluated using Pearson's correlation. RESULTS: Twenty pregnant women who consented to participate and who had delivered their babies by 31 January 2021 were included in the study, comprising 14 who had recovered from coronavirus disease 2019 (COVID-19) and six with active infection at delivery. The median GA at clinical manifestation was 32.7 (range, 11.9-39.4) weeks. The median infection-to-delivery interval and infection duration were 41.5 (range, 2-187) days and 10.0 (range, 1-48) days, respectively. The median GA at delivery was 39.1 (range, 32.4-40.7) weeks and the median seroconversion interval was 14 (range, 1-19) days. Of 13 neonates born to seropositive mothers with recovered infection at delivery, 12 tested positive for anti-SARS-CoV-2 IgG. All neonatal NPS samples were negative for SARS-CoV-2 and all cord sera tested negative for IgM. The median transplacental transfer ratio of IgG was 1.3 (interquartile range, 0.9-1.6). There was a negative correlation between infection-to-delivery interval and anti-SARS-CoV-2 IgG concentrations in maternal (r = -0.6693, P = 0.0087) and cord (r = -0.6554, P = 0.0068) serum and a positive correlation between IgG concentration in maternal serum and viral load AUC (r = 0.5109, P = 0.0310). A negative correlation was observed between transfer ratio and viral load AUC (r = -0.4757, P = 0.0409). CONCLUSIONS: In pregnant women who have recovered from COVID-19, anti-SARS-CoV-2 IgG concentrations at delivery increased with increasing viral load during infection and decreased with increasing infection-to-delivery interval. The median transplacental transfer ratio of IgG was 1.3 and it decreased with increasing viral load during infection. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Patient-reported psychosocial distress in adolescents and young adults with germ cell tumours.

PURPOSE: Germ cell tumours are the most common cancer of male adolescents and young adults (AYA, age 18-39). Men in this age group have been healthy much of their lives, and a diagnosis of cancer can cause significant psychosocial distress. We therefore sought to examine the psychosocial needs of patients with germ cell tumour and determine whether needs vary based on age (AYA vs non-AYA). We hypothesized that AYA experience more anxiety and distress in emotional, practical and physical domains. METHODS: We evaluated the responses of all patients referred to British Columbia (BC) Cancer who completed a pre-consultation health assessment form. This is a validated screening questionnaire for distress, subclinical/clinical symptoms of depression and anxiety and includes the Canadian Problem Checklist domains of emotional, informational, practical, spiritual, social/family and physical concerns. RESULTS: Data were collected for 349 patients (2011-2015). Patient population was predominantly AYA (n = 227) with median age 33 (range 18-83). The top 3 AYA concerns were financial, work/school, frustration and anger. AYA patients more commonly scored positive for symptoms of subclinical/clinical anxiety than non-AYA (39.4% vs. 27.9%, p = 0.028). Those AYA patients with subclinical/clinical anxiety symptoms experienced more fears and worries, concerns regarding work/school, lack of understanding of their disease, finances and frustration and anger. CONCLUSIONS: The results of this study indicate that AYA with testicular cancer have unique needs and experience more self-reported anxiety symptoms with emotional, informational and practical concerns. This is valuable information to stakeholders for allocation of resources to address cancer survivorship amongst these patients.

Serum Myostatin and IGF-1 as Gender-Specific Biomarkers of Frailty and Low Muscle Mass in Community-Dwelling Older Adults.

OBJECTIVES: (i) To investigate serum myostatin (absolute and normalized for total body lean mass (TBLM)) and IGF-1 as biomarkers of frailty and low relative appendicular skeletal muscle mass (RASM) in older adults, and; (ii) to examine gender differences in the association of serum myostatin and IGF-1 levels with frailty and low RASM. DESIGN: Cross-sectional study. SETTING: The "Longitudinal Assessment of Biomarkers for characterization of early Sarcopenia and predicting frailty and functional decline in community-dwelling Asian older adults Study" (GERI-LABS) study in Singapore. PARTICIPANTS: 200 subjects aged 50 years and older residing in the community. MEASUREMENTS: Frailty was assessed using the modified Fried criteria. Low RASM was defined using cutoffs for height-adjusted appendicular skeletal muscle mass measured by dual-energy X-ray absorptiometry as recommended by the Asian Working Group for Sarcopenia. Comorbidities, cognitive and functional performance, physical activity and nutritional status were assessed. Blood samples collected included serum myostatin, insulin-like growth factor 1 (IGF-1) and markers of inflammation (total white cell count, CRP, IL-6 and TNFaR1). Subjects were classified into 4 groups: Frail/Prefrail with low RASM (Frail/Low RASM), Frail/Prefrail with normal RASM (Frail/Normal RASM), Robust with low RASM (Robust/Low RASM) and Robust with normal RASM (Robust/Normal RASM). RESULTS: 63 (32%) subjects were classified as Frail/Low RASM, 53 (27%) Frail/Normal RASM, 28 (14%) Robust/Low RASM and 56 (28%) Robust/Normal RASM respectively. Frail/Low RASM subjects were older and had lower BMI compared to Frail/Normal RASM and robust subjects. Mean (SE) normalized myostatin levels were higher in Frail/Low RASM compared to Frail/Normal RASM subjects (1.0 (0.04) versus 0.84 (0.05) ng/ml/kg, P=0.01). Median (IQR) IGF-1 level was lower amongst Frail/Low RASM subjects compared to Frail/Normal RASM subjects (102.3, (77.7, 102.5) vs 119.7 (82.7, 146.0) ng/ml, P=0.046). No differences in myostatin or IGF-1 were observed among robust individuals with or without low muscle mass. In adjusted multinomial logistic regression models with Robust/Normal RASM as the reference group, myostatin (P=0.05) and IGF-1 (P=0.043) were associated with Frail/Low RASM status in the whole cohort. When stratified by gender, myostatin was significantly associated with Frail/Low RASM status in men only (P=0.03). In women, serum IGF-1 was associated with Frail/Low RASM status (P=0.046), but not myostatin (P=0.53). CONCLUSION: Serum myostatin, normalized for TBLM in men and IGF-1 in women are potential biomarkers for frail individuals with low RASM, and may identify a target group for intervention.

Intergenerational transmission of adverse childhood experiences via maternal depression and anxiety and moderation by child sex.

Adverse childhood experiences (ACEs) of parents are associated with a variety of negative health outcomes in offspring. Little is known about the mechanisms by which ACEs are transmitted to the next generation. Given that maternal depression and anxiety are related to ACEs and negatively affect children's behaviour, these exposures may be pathways between maternal ACEs and child psychopathology. Child sex may modify these associations. Our objectives were to determine: (1) the association between ACEs and children's behaviour, (2) whether maternal symptoms of prenatal and postnatal depression and anxiety mediate the relationship between maternal ACEs and children's behaviour, and (3) whether these relationships are moderated by child sex. Pearson correlations and latent path analyses were undertaken using data from 907 children and their mothers enrolled the Alberta Pregnancy Outcomes and Nutrition study. Overall, maternal ACEs were associated with symptoms of anxiety and depression during the perinatal period, and externalizing problems in children. Furthermore, we observed indirect associations between maternal ACEs and children's internalizing and externalizing problems via maternal anxiety and depression. Sex differences were observed, with boys demonstrating greater vulnerability to the indirect effects of maternal ACEs via both anxiety and depression. Findings suggest that maternal mental health may be a mechanism by which maternal early life adversity is transmitted to children, especially boys. Further research is needed to determine if targeted interventions with women who have both high ACEs and mental health problems can prevent or ameliorate the effects of ACEs on children's behavioural psychopathology.

Two cases of differentiation syndrome with ocular manifestations in patients with acute promyelocytic leukaemia treated with all-trans retinoic acid and arsenic trioxide.

PURPOSE: To describe two cases of differentiation syndrome presenting with ocular manifestations including bilateral chorioretinopathy in patients with acute promyelocytic leukaemia treated with all-trans retinoic acid and arsenic trioxide differentiation therapy. OBSERVATIONS: This observational case series identifies two patients at a single tertiary institution diagnosed with differentiation syndrome with associated ophthalmic involvement. Both patients reported bilateral reduction in visual acuity at days fourteen and ten respectively following initiation of differentiation therapy in addition to developing other systemic manifestations of differentiation syndrome. Both patients received the same chemotherapeutic regimen including both all-trans retinoic acid and arsenic trioxide as well as ten days of routine differentiation syndrome prophylaxis with oral prednisolone. Case 1 presented with bilateral pale yellow sub-retinal lesions concentrated at the posterior poles with ocular coherence tomography (OCT) evidence of bilateral multifocal areas of focal RPE elevation and adhesion to the thickened outer retina with interspersed sub-retinal fluid. Fluorescein angiography revealed areas of early hyperflouresence corresponding to the yellow chorioretinal lesions with late diffuse leakage of fluid into the subretinal space. Case 2 presented with a similar characteristic retinal findings on fundoscopy and optical coherence tomography. Both patients experienced rapid improvement in the visual symptoms and marked resolution of the sub-retinal fluid within seven to fourteen days of onset with excellent long-term visual outcome. Both patients achieved molecular remission after induction and received standard consolidation and maintenance therapy without visual disturbance. CONCLUSION AND IMPORTANCE: Ocular manifestations of differentiation syndrome have been only recently recognised. We present a case series of two patients with differentiation syndrome with ocular involvement. Common to both presentations was the presence of bilateral reduction in visual acuity with multifocal serous retinal detachment secondary to chorioretinopathy. The visual outcome from both presentations was excellent with rapid normalisation of visual acuity and resolution of the sub-retinal fluid with only the first case having their differentiation therapy temporarily withheld during the acute phase of illness.

Association of nutrition and immune-endocrine dysfunction with muscle mass and performance in cognitively impaired older adults.

BACKGROUND: With lean mass declining early in Alzheimer's disease, muscle quality beyond quantity is relevant to physical performance. We sought to identify potentially modifiable factors for the differential loss of muscle mass (pre-sarcopenia) and its performance (sarcopenia) in older adults with mild cognitive impairment (MCI) and mild-to-moderate Alzheimer's disease (AD). METHODS: This is a cross-sectional study of 108 community-dwelling older adults with MCI and mild-to-moderate AD. Participants were categorized as: (i) No sarcopenia (normal muscle mass), (ii) Pre-sarcopenia (low muscle mass without weakness or slowness), (iii) Sarcopenia (low muscle mass AND weak grip strength and/or slow gait speed) using Asian cut-offs. Muscle quality was defined as the ratio of grip and knee extension strength to average arm and leg lean mass respectively. We measured cognitive, functional and physical (Short Physical Performance Battery, SPPB) performance; physical activity level; nutritional status; and blood biomarkers of inflammation and endocrine dysfunction. RESULTS: SPPB (p=0.033) and activity level (p=0.010) were highest in the pre-sarcopenic group. Pre-sarcopenic group had highest arm muscle quality [10.6 (7.7-12.2) vs 13.9 (12.6-15.7) vs 11.3 (9.7-12.8), p<0.001], despite significantly lower appendicular lean mass than non-sarcopenic group. In multi-nomial logistic regression reference to non-sarcopenic group, malnutrition independently increased risk for both pre-sarcopenia (Relative risk=7.53, 95% C.I 1.20-47.51, p=0.032) and sarcopenia (Relative risk=11.91, 95% C.I 2.85-49.77, p=0.001). A combined pro-inflammatory and endocrine deficient state significantly increased the risk of sarcopenia (Relative risk=5.17, 95% C.I 1.31-20.37, p=0.019). CONCLUSION: Malnutrition is a precursor for progressive loss of muscle mass, but a pro-inflammatory and endocrine deficient state may potentially aggravate decline in muscle quality to culminate in frank sarcopenia.

The effect of nerve mobilization exercise in patients with rheumatoid arthritis: a pilot study.

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic inflammation of the joints. The neurogenic inflammatory mechanism plays an important role in the inflammatory process of RA, and pathological changes in neural tissues in RA have also been noted. We aim to investigate treatment of the nervous system to relieve joint pain and inflammation in RA. Nerve mobilization, a nervous system-specific therapeutic exercise, was applied on RA patients to determine the effect of nerve mobilization on joint inflammation. Twelve RA patients were recruited from the community and were randomised into an experimental and a control group. In the experimental group, the subjects were taught a set of nerve mobilization exercises while the subjects in the control group were taught a set of gentle joint mobilization exercises. Both groups were instructed to practice the exercises daily. After a 4-week period, their RA pain scale (RAPS) and pain scores were examined, as well as the C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Subjects in the experimental group showed improvements in RAPS and pain scores after 4 weeks of nerve mobilization exercises, while CRP and ESR values remained unaffected. These preliminary data showed that nerve mobilization exercises might be beneficial in controlling joint pain in RA patients.

Associations of B cell-activating factor (BAFF) and anti-BAFF autoantibodies with disease activity in multi-ethnic Asian systemic lupus erythematosus patients in Singapore.

To measure the levels of B cell-activating factor (BAFF) and endogenous anti-BAFF autoantibodies in a cohort of multi-ethnic Asian systemic lupus erythematosus (SLE) patients in Singapore, to determine their correlation with disease activity. Serum samples from 121 SLE patients and 24 age- and sex-matched healthy controls were assayed for BAFF and anti-BAFF immunoglobulin (Ig)G antibody levels by enzyme-linked immunosorbent assay (ELISA). The lowest reliable detection limit for anti-BAFF-IgG antibody levels was defined as 2 standard deviations (s.d.) from blank. Correlation of serum BAFF and anti-BAFF IgG levels with disease activity [scored by SLE Activity Measure revised (SLAM-R)], and disease manifestations were determined in these 121 patients. SLE patients had elevated BAFF levels compared to controls; mean 820 ± 40 pg/ml and 152 pg ± 45/ml, respectively [mean ± standard error of the mean (s.e.m.), P < 0·01], which were correlated positively with anti-dsDNA antibody levels (r = 0·253, P < 0·03), and SLAM-R scores (r = 0·627, P < 0·01). In addition, SLE patients had significantly higher levels of anti-BAFF IgG, which were correlated negatively with disease activity (r = -0·436, P < 0·01), levels of anti-dsDNA antibody (r = -0·347, P < 0·02) and BAFF (r = -0·459, P < 0·01). The majority of patients in this multi-ethnic Asian SLE cohort had elevated levels of BAFF and anti-BAFF antibodies. Anti-BAFF autoantibody levels correlated negatively with clinical disease activity, anti-dsDNA and BAFF levels, suggesting that they may be disease-modifying. Our results provide further information about the complexity of BAFF pathophysiology in different SLE disease populations and phenotypes, and suggest that studies of the influence of anti-cytokine antibodies in different SLE populations will be required when selecting patients for trials using targeted anti-cytokine therapies.

Comparison of the mechanical properties of different skin sites for auricular and nasal reconstruction.

BACKGROUND: Autologous and synthetic nasal and auricular frameworks require skin coverage. The surgeon's decides on the appropriate skin coverage for reconstruction based on colour matching, subcutaneous tissue thickness, expertise and experience. One of the major complications of placing subcutaneous implants is the risk of extrusion (migration through the skin) and infection. However, knowledge of lessening the differential between the soft tissue and the framework can have important implications for extrusion. This study compared the mechanical properties of the skin commonly used as skin sites for the coverage in auricular and nasal reconstruction. METHODS: Using ten fresh human cadavers, the tensile Young's Modulus of the skin from the forehead, forearm, temporoparietal, post-auricular and submandibular neck was assessed. The relaxation rate and absolute relaxation level was also assessed after 90 min of relaxation. RESULTS: The submandibular skin showed the greatest Young's elastic modulus in tension of all regions (1.28 MPa ±0.06) and forearm showed the lowest (1.03 MPa ±0.06). The forehead demonstrated greater relaxation rates among the different skin regions (7.8 MPa-07 ± 0.1). The forearm showed the lowest rate of relaxation (4.74 MPa-07 ± 0.1). The forearm (0.04 MPa ±0.004) and submandibular neck skin (0.04 MPa ±0.005) showed similar absolute levels of relaxation, which were significantly greater than the other skin regions (p < 0.05). CONCLUSIONS: This study provides an understanding into the biomechanical properties of the skin of different sites allowing surgeons to consider this parameter when trying to identify the optimal skin coverage in nasal and auricular reconstruction.

Sex-specific differences in risk factors for sarcopenia amongst community-dwelling older adults.

With considerable variation including potential sex-specific differential rate of skeletal muscle loss, identifying modifiable factors for sarcopenia will be pivotal to guide targeted interventions. This study seeks to identify clinical and biological correlates of sarcopenia in community-dwelling older adults, with emphasis on the role of anabolic and catabolic stimuli, and special reference to gender specificity. In this cross-sectional study involving 200 community-dwelling and functionally independent older adults aged ≥50 years, sarcopenia was defined using the Asian Working Group for Sarcopenia criteria. Comorbidities, cognitive and functional performance, physical activity and nutritional status were routinely assessed. Biochemical parameters included haematological indices, lipid panel, vitamin D level, anabolic hormones [insulin-like growth factor-1 (IGF-1), free testosterone (males only)] and catabolic markers [inflammatory markers (interleukin-6, C-reactive protein) and myostatin]. Multiple logistic regression was performed to identify independent predictors for sarcopenia. Age was associated with sarcopenia in both genders. Malnutrition conferred significantly higher odds for sarcopenia in women (OR = 5.71, 95% CI 1.13-28.84.44, p = 0.035) while higher but acceptable range serum triglyceride was protective in men (OR = 0.05, 95% CI 0.00-0.52, p = 0.012). Higher serum myostatin independently associated with higher odds for sarcopenia in men (OR = 1.11, 95% CI 1.00-1.24, p = 0.041). Serum IGF-1 was significantly lower amongst female sarcopenic subjects, with demonstrable trend for protective effect against sarcopenia in multiple regression models, such that each 1 ng/ml increase in IGF-1 was associated with 1% decline in odds of sarcopenia in women (p = 0.095). Our findings support differential pathophysiological mechanisms for sarcopenia that, if corroborated, may have clinical utility in guiding sex-specific targeted interventions for community-dwelling older adults.

A case of chemical assault in Hong Kong (case report).

INTRODUCTION: This case report aims to raise awareness of the unique protocol developed in the Prince of Wales Hospital (PWH) in Hong Kong, for the acute management of acid assault burns. Chemical assaults are rare in the UK, although, previously there have been several high-profile cases in the past three decades. In Hong Kong, acid assaults are more common, and a unique strategy has been developed to deal with the immediate injury. PRESENTATION OF CASE: This case report describes a 16-year-old girl assaulted with an acid solution by her 17-year-old ex-boyfriend. She sustained an 8% TBSA burn involving her face, upper-limbs and back. Immediate lavage was commenced at the local hospital prior to transfer to the PWH burn centre. She underwent urgent (<48h) EUA in theatres and her burns were tangentially shaved to active bleeding. She then received 48h of saline soaks changed two-hourly prior to definitive treatment. DISCUSSION: The conventional strategy for acid burns had been continuous lavage for two to three days, followed by delayed shaving and grafting. Outcomes were often poor with disproportionate needs for reconstructive procedures compared to thermal burns. Since introducing the new protocol three-years ago, outcomes have improved and can be quantitatively assessed in terms of decreased reconstructive needs. CONCLUSION: The benefits of urgent reduction in chemical load is intuitively obvious, and by shaving tangentially to bleeding, vital tissue is preserved. Trying to prove benefit in terms of an RCT is however ethically challenging.

Reducing unnecessary preoperative testing in elective ENT surgery: clinical and financial implications.

Guidelines on appropriate preoperative testing in elective surgery were published by the National Institute for Health and Care Excellence (NICE) in 2003. However, compliance has been poor, with frequent unnecessary tests being performed. We aimed to assess our trust's guideline compliance and to implement changes to optimise adherence. Preoperative investigations performed for elective ENT surgery during a three-month period were retrospectively audited. Unnecessary investigations were identified and costs calculated. A staff-training program was implemented and targeted written information was provided for clinics. A second audit cycle was conducted subsequently. Overall, 69.2% of blood tests were unnecessary (FBC 44.9%, U&Es 63.5%, clotting 99.2%), which equated to £1955.77 with an annual estimate of £7,823.08. None of the test results affected the management of the patient. Post-intervention, full compliance was achieved. It was concluded that preoperative investigations are overused in elective surgery, with obvious financial implications and causing unnecessary anxiety to patients. Through basic training and guideline dissemination, complete compliance can be achieved.

Structural dynamics of GaN microcrystals in Evolutionary Selection Selective Area Growth probed by X-ray microdiffraction.

A method to grow high quality, single crystalline semiconductor material irrespective of the substrate would allow a cost-effective improvement to functionality and performance of optoelectronic devices. Recently, a novel type of substrate-insensitive growth process called Evolutionary Selection Selective Area Growth (ES-SAG) has been proposed. Here we report the use of X-ray microdiffraction to study the structural properties of GaN microcrystals grown by ES-SAG. Utilizing high resolution in both direct and reciprocal spaces, we have unraveled structural dynamics of GaN microcrystals in growth structures of different dimensions. It has been found that the geometric proportions of the growth constrictions play an important role: 2.6 µm and 4.5 µm wide growth tunnels favor the evolutionary selection mechanism, contrary to the case of 8.6 µm growth tunnels. It was also found that GaN microcrystal ensembles are dominated by slight tensile strain irrespective of growth tunnel shape.

The core control system of intracellular iron homeostasis: a mathematical model.

Iron is a metal essential for cellular metabolism. However, excess iron available for reactions contributes to the formation of dangerous reactive oxygen species, such as the hydroxyl radical, via the Fenton reaction. Therefore, intracellular iron levels are tightly constrained by a control system of proteins. This paper contains a mathematical model, in the form of a system of five ordinary differential equations, of the core of this control system, including the labile iron pool as well as proteins that regulate uptake, storage, and export and are connected through negative feedback loops. The model is validated using data from an overexpression experiment with cultured human breast epithelial cells. The parameters in the mathematical model are not known for this particular cell culture system, so the analysis of the model was done for a generic choice of parameters. Through a mixture of analytical arguments and extensive simulations it is shown that for any choice of parameters the model reaches a unique stable steady state, thereby ruling out oscillatory behavior. It is shown furthermore that the model parameters are identifiable through suitable experiments.

Oxygen-deficient metabolism and corneal edema.

Wear of low-oxygen-transmissible soft contact lenses swells the cornea significantly, even during open eye. Although oxygen-deficient corneal edema is well-documented, a self-consistent quantitative prediction based on the underlying metabolic reactions is not available. We present a biochemical description of the human cornea that quantifies hypoxic swelling through the coupled transport of water, salt, and respiratory metabolites. Aerobic and anaerobic consumption of glucose, as well as acidosis and pH buffering, are incorporated in a seven-layer corneal model (anterior chamber, endothelium, stroma, epithelium, postlens tear film, contact lens, and prelens tear film). Corneal swelling is predicted from coupled transport of water, dissolved salts, and especially metabolites, along with membrane-transport resistances at the endothelium and epithelium. At the endothelium, the Na+/K+ - ATPase electrogenic channel actively transports bicarbonate ion from the stroma into the anterior chamber. As captured by the Kedem-Katchalsky membrane-transport formalism, the active bicarbonate-ion flux provides the driving force for corneal fluid pump-out needed to match the leak-in tendency of the stroma. Increased lactate-ion production during hypoxia osmotically lowers the pump-out rate requiring the stroma to swell to higher water content. Concentration profiles are predicted for glucose, water, oxygen, carbon dioxide, and hydronium, lactate, bicarbonate, sodium, and chloride ions, along with electrostatic potential and pressure profiles. Although the active bicarbonate-ion pump at the endothelium drives bicarbonate into the aqueous humor, we find a net flux of bicarbonate ion into the cornea that safeguards against acidosis. For the first time, we predict corneal swelling upon soft-contact-lens wear from fundamental biophysico-chemical principles. We also successfully predict that hypertonic tear alleviates contact-lens-induced edema.

Cardiotoxicity and other adverse events associated with mitoxantrone treatment for MS.

BACKGROUND: Mitoxantrone is used for aggressive multiple sclerosis (MS), but concerns about safety, including cardiotoxicity and other laboratory measures, prevail. OBJECTIVE: To evaluate the incidence and potential predictors of adverse events associated with mitoxantrone at the MS Clinic, University of British Columbia, Canada. METHODS: Retrospective review of patients treated with mitoxantrone by standard protocol; maximum cumulative dose = 120 mg/m(2). Left ventricular ejection fraction (LVEF) was measured with regular multiple-gated acquisition (MUGA) scans; blood cell counts and biochemical liver tests were performed before infusions. Generalized estimating equations were used to examine potential predictors of adverse events (graded according to the Common Toxicity Criteria, version 4) in patients with normal baseline and > or =1 follow-up MUGA or laboratory assessment. RESULTS: All 163 patients (58% women) treated with mitoxantrone from 1999 to 2007 were reviewed. Mean baseline age was 41.9 (SD 10.8) years, cumulative dose was 59.7 (SD 26.0) mg/m(2), and median follow-up duration was 14 months (maximum 6.5 years). By study end, 14% developed de novo cardiotoxicity (grade > or =2) as measured by decreased LVEF, 27% neutropenia (grade > or =1), 15% anemia (grade > or =1), and 15% liver toxicity (grade > or =1). Possible predictors of adverse events included sex, age, disease duration, and cumulative dose; only women exposed to a higher cumulative dose were at a greater risk of anemia (adjusted odds ratio 1.26, 95% confidence interval 1.08-1.48 per 10 mg/m(2)). CONCLUSIONS: Based on cardiac and laboratory assessments, mitoxantrone was reasonably well tolerated. However, cardiotoxicity was evident after doses well below current maximum recommended levels. A dose-response effect was not apparent. Findings emphasize the importance of monitoring; the long-term effects of mitoxantrone in multiple sclerosis require investigation.