Patient acceptance of transvaginal sonographic endometrial thickness assessment compared with hysteroscopy and biopsy for exclusion of endometrial cancer in cases of postmenopausal bleeding.

INTRODUCTION: Available examinations for women with postmenopausal bleeding include transvaginal sonography to measure endometrial thickness (TVS-ET), and invasive endometrial assessment using hysteroscopy/endometrial biopsy. However, selection of the examination method seldom involves consideration of patient preferences. The aim of this study was to examine patient preferences for the method used to investigate postmenopausal bleeding. METHODS: Women were asked to complete an interviewer-administered structured survey before they underwent clinical investigations at a university gynaecology unit from June 2016 to June 2017. Using the standard gamble approach, women were asked to choose between invasive assessment by hysteroscopy/endometrial biopsy (gold standard) or TVS-ET with a risk of missing endometrial cancer. The risk of missing endometrial cancer during TVS-ET was varied until each woman was indifferent to either option. RESULTS: The median detection rate for endometrial cancer required using TVS-ET was 95% (interquartile range=80%-99.9%). In total, 200 women completed the survey, and 77 (38.5%) women required TVS-ET to have a 99.9% detection rate for endometrial cancer. Prior hysteroscopy experience was the only factor that influenced the women's decisions: a significantly higher detection rate was required by this patient group than by patients without previous hysteroscopy experience (P=0.047). CONCLUSION: A substantial proportion of women would accept TVS-ET alone for the investigation of postmenopausal bleeding. In the era of patientcentred care, clinicians should incorporate patient preferences and enable women to make informed choices concerning the management of postmenopausal bleeding.

Autism and toe-walking: are they related? Trends and treatment patterns between 2005 and 2016.

PURPOSE: This study quantified toe-walking trends and treatment decisions in patients with autism spectrum disorder (ASD) in the United States between 2005 and 2016 using a large national private-payer database. METHODS: A retrospective database review was performed on paediatric patients with ASD, and for International Classification of Diseases-9/10 diagnosis codes for toe-walking. Patients were filtered based on treatment type by Current Procedural Terminology (CPT) code. Continued toe-walking rates were assessed for each patient population and treatment group. A Pearson's chi-squared test was used to evaluate differences in group characteristics. RESULTS: Of 2 221 009 paediatric patients in the database, 5739 patients had a diagnosis of ASD, and 8.4% of patients with ASD also had a diagnosis of toe-walking (n = 484). For typically developing children in the database, 0.47% of patients had a diagnosis of persistent toe-walking. In all, 59.3% of ASD patients underwent physical therapy, 7.4% serial casting and 3.3% surgical correction, compared with 38.1%, 3.6% and 1.2% of normally developing children, respectively (chi-square 6.4031; p < 0.040699). Without intervention, 63.6% of patients with ASD continued to toe-walk within ten years of their diagnosis, with 19.3% of patients without ASD (chi-square 82.9762; p < 0.0001). CONCLUSION: This study supports the association between a greater prevalence of toe-walking in children with ASD. We showed that patients with ASD and toe-walking receive surgical correction at nearly triple the rate of children without ASD who toe-walk. The continued rate of toe-walking is comparable between treatment groups as well as between ASD and typically developing children. Typically developing children have higher rates of toe-walking resolution without intervention than children with ASD. LEVEL OF EVIDENCE: Level II.

Peanut allergy and oral immunotherapy.

Peanut allergy is the commonest cause of food-induced anaphylaxis in the world, and it can be fatal. There have been many recent improvements to achieve safe methods of peanut desensitisation, one of which is to use a combination of anti-immunoglobulin E and oral immunotherapy. We have treated 27 patients with anti-immunoglobulin E and oral immunotherapy, and report on the outcomes and incidence of adverse reactions encountered during treatment. The dose of peanut protein tolerated increased from a median baseline of 5 to 2000 mg after desensitisation, which is substantially more than would be encountered through accidental ingestion. The incidence of adverse reactions during the escalation phase of oral immunotherapy was 1.8%, and that during the maintenance phase was 0.6%. Most adverse reactions were mild; three episodes were severe enough to warrant withdrawal from oral immunotherapy, but none required epinephrine injection. Preliminary data suggest that unresponsiveness is lost when daily ingestion of peanuts is stopped after the maintenance period.

Association Between Prepregnancy Cardiovascular Function and Subsequent Preeclampsia or Fetal Growth Restriction.

Preeclampsia and fetal growth restriction during pregnancy are associated with increased risk of maternal cardiovascular disease later in life. It is unclear whether this association is causal or driven by similar antecedent risk factors. Clarification requires recruitment before conception which is methodologically difficult with high attrition rates and loss of outcome numbers to nonconception/miscarriage. Few prospective studies have, therefore, been adequately powered to address these questions. We recruited 530 healthy women (mean age: 35.0 years) intending to conceive and assessed cardiac output, cardiac index, stroke volume, total peripheral resistance, mean arterial pressure, and heart rate before pregnancy. Participants were followed to completion of subsequent pregnancy with repeat longitudinal assessments. Of 356 spontaneously conceived pregnancies, 15 (4.2%) were affected by preeclampsia and fetal growth restriction. Women who subsequently developed preeclampsia/fetal growth restriction had lower preconception cardiac output (4.9 versus 5.8 L/min; P=0.002) and cardiac index (2.9 versus 3.3 L/min per meter2; P=0.031) while mean arterial pressure (87.1 versus 82.3 mm Hg; P=0.05) and total peripheral resistance (1396.4 versus 1156.1 dynes sec cm-5; P<0.001) were higher. Longitudinal trajectories for cardiac output and total peripheral resistance were similar between affected and healthy pregnancies, but the former group showed a more exaggerated fall in mean arterial pressure in the first trimester, followed by a steeper rise and a steeper fall to postpartum values. Significant relationships were observed between cardiac output, total peripheral resistance, and mean arterial pressure and gestational epoch. We conclude that in healthy women, an altered prepregnancy hemodynamic phenotype is associated with the subsequent development of preeclampsia/fetal growth restriction.

Substrate independent ATPase activity may complicate high throughput screening.

Inorganic phosphate release, [Pi], is often measured in an enzymatic reaction in a high throughput setting. Based on the published mechanism, we designed a protocol for our screening for inhibitors of SAICAR synthetase (PurC), and we found a gradual increase in [Pi] in positive control samples over the course of the day. Further investigation indicated that hydrolysis of ATP catalyzed by PurC, rather than substrate-related phosphate release, was responsible for a partial contribution to the signals in the control samples. Thus substrate-independent ATPase activity may complicate high throughput screening.

Low preoperative selenium is associated with post-operative atrial fibrillation in patients having intermediate-risk coronary artery surgery.

BACKGROUND/OBJECTIVES: Post-operative atrial fibrillation (POAF) is a frequent complication of cardiac surgery. Oxidative stress and reduced antioxidant function have major roles in its development. Selenium is a key to normal antioxidant function, and levels are often low before cardiac surgery. This study investigated whether low preoperative selenium levels were associated with POAF in cardiac surgical patients. SUBJECTS/METHODS: Using the Society of Thoracic Surgeons (STS) Mortality risk score, 50 patients having primary coronary artery bypass grafts (CABG) surgery were divided into two groups: (i) low-risk group (STS ⩽0.5%; n=26) and (ii) intermediate-risk group (STS ⩾2.0%; n=24). Plasma levels of selenium, glutathione peroxidase (GPx) and malondialdehyde (MDA) were measured in all patients at anaesthetic induction, after aortic cross-clamp removal, 3 h post cardiopulmonary bypass and on post-operative days 1 and 5. Multiple logistic regression was used to assess whether selenium levels were associated with POAF development. RESULTS: Seventeen patients developed POAF (14 patients in the intermediate-risk group and 3 patients in the low-risk group). Preoperative selenium was lower in patients who developed POAF compared with those with normal sinus rhythm (0.73±0.16 vs 0.89±0.13 µmol/l, P=0.005), and this was independently associated with POAF (PR 0.32; 95% confidence credible interval (95%cI) 0.06-0.85, P=0.016). Regardless of POAF, preoperative selenium was lower in the intermediate-risk patients than in the low-risk patients (0.77±0.15 vs 0.89±0.14 µmol/l; P=0.004). CONCLUSIONS: Intermediate-risk patients with low preoperative selenium levels may be at a greater risk of developing POAF following CABG. This raises the question of whether selenium supplementation in select cardiac surgical patients may reduce their POAF risk.

Generation of functional human serotonergic neurons from fibroblasts.

The brain's serotonergic system centrally regulates several physiological processes and its dysfunction has been implicated in the pathophysiology of several neuropsychiatric disorders. While in the past our understanding of serotonergic neurotransmission has come mainly from mouse models, the development of pluripotent stem cell and induced fibroblast-to-neuron (iN) transdifferentiation technologies has revolutionized our ability to generate human neurons in vitro. Utilizing these techniques and a novel lentiviral reporter for serotonergic neurons, we identified and overexpressed key transcription factors to successfully generate human serotonergic neurons. We found that overexpressing the transcription factors NKX2.2, FEV, GATA2 and LMX1B in combination with ASCL1 and NGN2 directly and efficiently generated serotonergic neurons from human fibroblasts. Induced serotonergic neurons (iSNs) showed increased expression of specific serotonergic genes that are known to be expressed in raphe nuclei. iSNs displayed spontaneous action potentials, released serotonin in vitro and functionally responded to selective serotonin reuptake inhibitors (SSRIs). Here, we demonstrate the efficient generation of functional human serotonergic neurons from human fibroblasts as a novel tool for studying human serotonergic neurotransmission in health and disease.

Cadmium in jamaican bush teas.

Samples of Jamaican plants used as bush teas were collected from households in high soil-cadmium (Cd) areas of central Jamaica and analysed by graphite furnace atomic absorption spectrophotometry for total cadmium and for cadmium extractable with a hot water brew as prepared for human consumption to determine their contribution to dietary cadmium exposure. The concentrations ranged from < 0.03 to 6.85 µg/g for total Cd, between 1 and 15% of which was extracted with a hot water brew. One cup (200 ml) of the teas examined was found to contain < 0.04-1.18 µg of Cd and would contribute 0.1-0.3 µg of Cd to a person's dietary intake. This is significantly below the provisional tolerable weekly intake (PTWI) of 7 µg Cd/kg body weight established by the World Health Organization (WHO). While this suggests that bush tea consumption does not contribute significantly to the PTWI, some of the teas examined exceed the WHO recommendation of less than 0.3 mg/kg Cd for medicinal plants.

A novel mutation in pseudohypoparathyroidism type 1a in a Chinese woman and her son with hypocalcaemia.

Pseudohypoparathyroidism is a rare genetic disorder characterised by end-organ resistance to parathyroid hormone due to a defect of the guanine nucleotide-binding protein alpha that simulates activity of the polypeptide 1 (GNAS) gene. Patients with type 1a pseudohypoparathyroidism display different features of Albright's hereditary osteodystrophy as well as multi-hormone resistance. We describe a Chinese woman and her son, who presented with different symptoms of pseudohypoparathyroidism and clinically manifested different degree of Albright's hereditary osteodystrophy. Genetic study detected a mutation [NM_000516.4(GNAS):c682C>T (p.Arg228Cys)] in the GNAS gene.

Hirayama disease in a 17-year-old Chinese man.

Hirayama disease is an uncommon cervical myelopathy associated with neck flexion. It has been postulated to be related to the anterior shifting of the posterior dura of the lower cervical dural canal during neck flexion, resulting in lower cervical cord atrophy with asymmetric flattening. We report a case of Hirayama disease in a 17-year-old Chinese man and demonstrate the use of dynamic flexion magnetic resonance imaging of the cervical spine in the diagnosis of the disease.

Quantitative studies of caspase-3 catalyzed αII-spectrin breakdown.

Under various physiological and patho-physiological conditions, spectrin breakdown reactions generate several spectrin breakdown products (SBDPs)-in particular SBDPs of 150 kDa (SBDP150) and 120 kDa (SBDP120). Recently, numerous studies have shown that reactions leading to SBDPs are physiologically relevant, well regulated, and complex. Yet molecular studies on the mechanism of the SBDP formation are comparatively scarce. We have designed basic systems to allow us to follow the breakdown of αII-spectrin model proteins by caspase-3 in detail with gel electrophoresis, fluorescence and mass spectrometry methods. Amongst the predicted and reported sites, our results show that caspase-3 cleaves after residues D1185 and D1478, but not after residues D888, D1340 and D1475. We also found that the cleavage at these two sites is independent of each other. It may be possible to inhibit one site without affecting the other site. Cleavage after residue D1185 in intact αII-spectrin leads to SBDP150, and cleavage after D1478 site leads to SBDP120. Our results also show that the cleavage after the D1185 residue is unusually efficient, with a kcat/KM value of 40,000 M(-1) s(-1), and the cleavage after the D1478 site is more similar to most of the other reported caspase-3 substrates, with a kcat/KM value of 3000 M(-1) s(-1). We believe that this study lays out a methodology and foundation to study caspase-3 catalyzed spectrin breakdown to provide quantitative information. Molecular understanding may lead to better understanding of brain injuries and more precise and specific biomarker development.

Efficacy of birth ball exercises on labour pain management.

OBJECTIVES: To evaluate the efficacy of a birth ball exercise programme conducted by physiotherapists on pain relief, psychological care, and facilitation of the labour process at a labour ward in a regional hospital. DESIGN: Case series with before-after comparisons. SETTING: Kwong Wah Hospital, Hong Kong. PARTICIPANTS: Chinese women admitted to the labour ward for spontaneous vaginal delivery between April and August 2012 were recruited. Physiotherapists taught birth ball exercises in groups or individually for 30 minutes. Labour pain intensity, back pain intensity, frequency of labour pain, stress and anxiety levels, and subjective pressure level over the lower abdomen were captured before and after birth ball exercises. Most of the parameters were measured using self-reported visual analogue scales. After the exercise session, physiotherapists measured the women's satisfaction level. Midwives recorded pethidine usage. RESULTS: A total of 203 pregnant women participated in this programme; 181 were in the latent phase group, whereas 22 were categorised into the no-labour-pain group. In both groups, there were statistically and clinically significant differences in back pain level, stress and anxiety levels, as well as pressure level over the lower abdomen before and after the exercise (P<0.05). In the latent phase group, significant decreases in labour pain and frequency of labour pain were demonstrated. Mean satisfaction scores were high, with visual analogue scale scores higher than 8.2 in both groups. Pethidine usage showed a further decreasing trend (6.4%) compared with the past 2 years. CONCLUSION: Birth ball exercise could be an alternative means of relieving back pain and labour pain in the labour ward, and could decrease pethidine consumption in labouring women.

A pilot randomized study to assess immunogenicity, reactogenicity, safety and tolerability of two human papillomavirus vaccines administered intramuscularly and intradermally to females aged 18-26 years.

Intradermal administration of human papillomavirus (HPV) vaccines could be dose-sparing and cost-saving. This pilot randomized study assessed Cervarix(®) and Gardasil(®) administered either intramuscularly or intradermally, in different doses (full-dose or reduced to 20%) by different methods (needle and syringe or PharmaJet needle-free jet injection device). Following an initial reactogenicity study of 10 male subjects, sexually naïve women aged 18-26 years were randomized to the eight study groups to receive vaccine at 0, 2 and 6 months. 42 female subjects were enrolled and complete data were available for 40 subjects. Intradermal administration of either vaccine raised no safety concerns but was more reactogenic than intramuscular administration, although still tolerable. All subjects demonstrated a seroconversion (titre≥1:320) by Day 95. Further evaluation of intradermal HPV vaccination and its potential for cost reduction in resource poor settings is warranted.

Primary hyperaldosteronism among Chinese hypertensive patients: how are we doing in a local district in Hong Kong.

OBJECTIVES: To estimate the point prevalence of primary hyperaldosteronism in a government out-patient setting and to compare associated patient characteristics with those having essential hypertension. DESIGN: Case series with external comparison. SETTING: A single public hospital (Caritas Medical Centre) and all five associated general out-patient clinics in Sham Shui Po district in Hong Kong. PATIENTS: All patients with confirmed primary hyperaldosteronism and randomly selected patients with essential hypertension from a medical specialist clinic and general out-patient clinics, retrieved from a computer database for the period January 2007 to December 2008. MAIN OUTCOME MEASURES: Estimated point prevalence of primary hyperaldosteronism among hypertensive patients treated in the public sector of Sham Shui Po district. Patient age when hypertension was diagnosed, number of antihypertensive drugs used for treatment, and the presence of target organ damage in the patients with primary hyperaldosteronism and those with essential hypertension were compared. RESULTS: Among the 46 012 patients receiving antihypertensive treatment, 49 were confirmed to have primary hyperaldosteronism. The estimated point prevalence of primary hyperaldosteronism among these hypertensive patients was 0.106% only, which was far smaller than figures from other countries. When compared with the 147 patients with essential hypertension by multivariate analysis, those with primary hyperaldosteronism were: (1) associated with longer durations of hypertension (odds ratio=1.14; 95% confidence interval, 1.06-1.24) despite being younger at the time of study, (2) likely to be taking three or more antihypertensive drugs (odds ratio=2.51; 95% confidence interval, 1.59-3.95), and (3) more likely to have left ventricular hypertrophy (odds ratio=5.01; 95% confidence interval, 1.83-13.69). All primary hyperaldosteronism patients studied presented with hypokalaemia. The need for antihypertensive drugs was markedly reduced after adrenalectomy for adrenal adenoma. CONCLUSIONS: Primary hyperaldosteronism, which is potentially a surgically curable cause of hypertension, appeared to be underdiagnosed in our locality. Screening by aldosterone-renin ratio of high-risk individuals may help improve patient outcomes.