Arthralgia in midlife Singaporean women: the Integrated Women's Health Program (IWHP).

OBJECTIVE: Arthralgia is a common menopausal complaint in midlife women, and its causes remain unclear. We examined the prevalence of menopausal arthralgia with various factors including sleep quality, depression/anxiety, muscle strength and physical performance among midlife Singaporean women. METHODS: The Integrated Women's Health Program (IWHP) comprised 1120 healthy, community-dwelling women of Chinese, Malay or Indian ethnicities (aged 45-69 years) attending well-women clinics at the National University Hospital, Singapore. Sociodemographic, menopausal, reproductive and health data were obtained with validated questionnaires. Muscle strength, physical performance and dual-energy X-ray absorptiometry were measured. Women with moderate to very severe symptoms using the Menopause Rating Scale were classified as having arthralgia. Multivariable logistic regression analyses examined risk factors for arthralgia. RESULTS: One-third of the participants reported arthralgia, and 12.7%, 16.2% and 71.2% were in the premenopausal, perimenopausal and postmenopausal period, respectively. Menopausal symptoms, such as vaginal dryness (adjusted odds ratio [aOR]: 2.64, 95% confidence interval [CI]: 1.64, 4.24) and physical/mental exhaustion (aOR: 2.83, 95% CI: 1.79, 4.47), were independent risk factors for arthralgia. Poor muscle strength (aOR: 2.20, 95% CI: 1.29, 3.76), obesity (aOR: 1.94, 95% CI: 1.13, 3.32) and rheumatoid arthritis (aOR: 7.73, 95% CI: 4.47, 13.36) were also independently associated with arthralgia after adjustment for confounders. CONCLUSIONS: Arthralgia in midlife Singaporean women was associated with menopausal symptoms of vaginal dryness and physical and mental exhaustion. Women with poor muscle strength were more likely to experience menopausal arthralgia.

Toxicity and human health assessment of an alcohol-to-jet (ATJ) synthetic kerosene developed under an international agreement with Sweden.

Alcohol-to-jet (ATJ) Synthetic Kerosene with Aromatics (SKA) fuels are produced by dehydration and refining of alcohol feed stocks. ATJ SKA fuel known as SB-8 was developed by Swedish Biofuels as a cooperative agreement between Sweden and AFRL/RQTF. SB-8 including standard additives was tested in a 90-day toxicity study with male and female Fischer 344 rats exposed to 0, 200, 700, or 2000 mg/m3 fuel in an aerosol/vapor mixture for 6 hr/day, 5 days/week. Aerosols represented 0.04 and 0.84% average fuel concentration in 700 or 2000 mg/m3 exposure groups. Examination of vaginal cytology and sperm parameters found no marked changes in reproductive health. Neurobehavioral effects were increased rearing activity (motor activity) and significantly decreased grooming (functional observational battery) in 2000 mg/m3 female rats. Hematological changes were limited to elevated platelet counts in 2000 mg/m3 exposed males. Minimal focal alveolar epithelial hyperplasia with increased number of alveolar macrophages was noted in some 2000 mg/m3 males and one female rat. Additional rats tested for genotoxicity by micronucleus (MN) formation did not detect bone marrow cell toxicity or alterations in number of MN; SB-8 was not clastogenic. Inhalation results were similar to effects reported for JP-8. Both JP-8 and SB fuels were moderately irritating under occlusive wrapped conditions but slightly irritating under semi-occlusion. Exposure to SB-8, alone or as 50:50 blend with petroleum-derived JP-8, is not likely to enhance adverse human health risks in the military workplace.

Clinical Outcomes of Conservative Treatment for Low-Risk Ductal Carcinoma in Situ: A Systematic Review and Pooled Analysis.

AIMS: The current gold standard of treatment for ductal carcinoma in situ (DCIS) is surgical resection with or without adjuvant radiotherapy. However, the increased detection and radical treatment of DCIS did not result in a declined incidence of invasive breast cancers, leading to the debate if DCIS has been overtreated. While ongoing randomised controlled trials on active surveillance of DCIS are still in progress, this systematic review aims to evaluate the best evidence on conservative treatment for DCIS from the literature. MATERIALS AND METHODS: This systematic review was conducted in line with the PRISMA statement. We included all relevant studies published up to June 2022 for analysis. The primary outcomes were overall survival and breast cancer-specific survival (BCSS) of conservative treatment for DCIS. RESULTS: Three studies, with a total of 34 007 women with low-risk DCIS, were included in the analysis. Active and conservative treatments both resulted in excellent 10-year BCSS, with no statistically insignificant difference (98.6% versus 96.0%, 31 478 women). One study comparing 5-year BCSS of active and conservative treatments only in subjects aged over 80 years also reported [AQ1]an insignificant difference (98.2% versus 96.0%, 2529 women). One study measuring 5- and 10-year overall survival between the treatment groups also reported [AQ1]an insignificant difference (5-year: 96.2% versus 92.4%; 10-year: 85.6% versus 86.7%, 31 106 women). CONCLUSION: BCSS between active and conservative treatment for women with low-risk DCIS is both excellent and comparable, suggesting that conservative treatment is a possible alternative without compromising survival.

Electrochemotherapy for the palliative management of non-skin-origin head and neck cancer: case series and UK national survey.

OBJECTIVES: Electrochemotherapy uses electric fields to facilitate the influx of chemotherapy into cancer cells, producing a targeted effect. For head and neck cancer, it is mainly used for palliation of non-skin-origin metastases. It is used infrequently in the UK. This paper presents our experience and a UK survey to identify its frequency of use. METHODS: Between 2016 and 2019, a prospective database was created and reviewed. Only patients with non-skin-origin metastatic head and neck cancer, with no other palliative options, were included. Survival length, complications and symptomatic benefit were assessed. The survey was conducted via e-mail. RESULTS: Five patients were included: three with squamous cell carcinoma, one with esthesioneuroblastoma and one with hepatocellular carcinoma. Survival ranged from 1 month to over 20 months. Minor complications were seen. Only 15 out of 69 UK head and neck multidisciplinary teams offer electrochemotherapy. CONCLUSION: Electrochemotherapy is a well-tolerated adjunct to standard palliation of metastatic head and neck cancer, and is offered by a limited number of UK multidisciplinary teams.

Initial data from an experiment to implement a safe procedure to perform PA erect chest radiographs for COVID-19 patients with a mobile radiographic system in a "clean" zone of the hospital ward.

INTRODUCTION: With the current Covid-19 pandemic, general wards have been converted into cohort wards for Covid-19 patients who are stable and ambulant. A 2-radiographer mobile radiography team is required to perform bedside Chest X-rays (CXR) for these patients. Hospital guidelines require both radiographers to be in full Personal Protective Equipment (PPE) throughout the image acquisition process and the mobile radiographic unit needs to be disinfected twice after each case. This affects the efficiency of the procedure and an increase usage of limited PPE resources. This study aims to explore the feasibility of performing mobile chest radiography with the mobile radiographic unit in a "clean" zone of the hospital ward. METHODS: An anthropomorphic body phantom was used during the test. With the mobile radiographic unit placed in a "clean" zone, the phantom and the mobile radiographic unit was segregated by the room door with a clear glass panel. The test was carried out with the room door open and closed. Integrated radiation level and patient dose were measured. A consultant radiologist was invited to review and score all the images acquired using a Barco Medical Grade workstation. The Absolute Visual Grading Analysis (VGA) scoring system was used to score these images. RESULTS: A VGA score of 4 was given to all the 40 test images, suggesting that there is no significant differences in the image quality of the images acquired using the 2 different methods. Radiation exposure received by the patient at the highest kV setting through the glass is comparable to the regular CXR on patient without glass panel at 90 kV, suggesting that there is no significant increase in patient dose. CONCLUSION: The result suggests that acquiring CXR with the X-ray beam attenuating through a glass panel is a safe and feasible way of performing CXR for COVID-19 patients in the newly converted COVID wards. This will allow the mobile radiographic unit as well as one radiographer to be completely segregated from the patient. IMPLICATIONS FOR PRACTICE: This new method of acquiring CXR in an isolation facility set up requires a 2-Radiographer mobile radiography team, and is applicable only for patients who are generally well and not presented with any mobility issues. It is also important to note that a clear glass panel must be present in the barriers set up for segregation between the "clean" zone and patient zone in order to use this new method of acquiring CXR.

Pulmonary granulomas in a patient with positive ANCA and history of tuberculosis: case report.

BACKGROUND: Granulomatous polyangiitis (GPA) is a rare multisystem autoimmune disease of unknown aetiology that is pathologically characterised by necrotising vasculitis, tissue necrosis and granulomatous inflammation, typically in the presence of anti-neutrophil cytoplasmic antibodies (ANCA). However infectious diseases may induce high titre ANCA and mimic vasculitis. Tuberculosis may share many clinical features with GPA including fever, arthralgia, granulomatous inflammation and pulmonary lesions and patients. CASE PRESENTATION: A 39 year old patient was admitted with ocular irritation and redness, arthralgia and multiple new pulmonary lesions. The past medical history was significant for two episodes of tuberculosis previously requiring prolonged treatment. ANCA antibodies were positive and CT showed multiple pulmonary lesions including cavitatory lesions. After extensive investigation, the patient was treated for GPA with high dose immune suppression with good clinical response. CONCLUSIONS: Here we review the diagnostic considerations between differentiating GPA and tuberculosis in patients from endemic regions. It is recommended that biopsies of lung lesions, sputum microscopy and multidisciplinary team input are sought as part of the workup when these two differentials are being considered.

Safety and efficacy of teriparatide treatment for severe osteoporosis in patients with Duchenne muscular dystrophy.

Osteoporosis is a major concern in patients with Duchenne muscular dystrophy. In this novel study of teriparatide treatment in 6 patients with severe osteoporosis, bone health (fractures, vertebral morphometry, and DXA) remained stable, with no adverse events. These findings will help inform future osteoporosis research in this challenging population. INTRODUCTION: Despite standard therapy with vitamin D and bisphosphonates (BP), many patients with Duchenne muscular dystrophy (DMD) continue to sustain fragility fractures due to long-term glucocorticoid treatment and limited mobility. We aimed to evaluate the safety and efficacy of teriparatide for the treatment of severe osteoporosis in adolescent and young adult patients with DMD. METHODS: We prospectively treated 6 patients with DMD who had severe osteoporosis with teriparatide 20 mcg subcutaneously daily for 1-2 years. Inclusion criteria were long-term glucocorticoid therapy, and severe osteoporosis despite treatment with BP, or intolerance to BP. We examined long bone and vertebral fracture outcomes, including vertebral morphometry measures, bone mineral density and content, bone formation markers, safety indices, and adverse events. RESULTS: The mean age at teriparatide start was 17.9 years (range 13.9-22.1 years). All 6 patients were on daily glucocorticoids (mean ± SD; duration 10.9 ± 2.5 years) and 5 were non-ambulatory. Five patients had been treated with BP for 7.9 ± 4.2 years. All had vertebral and a history of long bone fragility fractures at baseline. Vertebral heights and Genant fracture grading remained stable. Long bone fracture rate appeared to decrease (from 0.84/year to 0.09/year); one patient sustained a long bone fracture at 6 months of treatment. Trajectories for change in bone mineral density and content were not different post- vs. pre-teriparatide. Procollagen type 1 amino-terminal propeptide (P1NP) increased, while laboratory safety indices remained stable and non-concerning. No adverse events were observed. CONCLUSION: In six patients with DMD treated with teriparatide for severe osteoporosis, we observed stable bone health and modest increases in P1NP, without safety concerns. Further studies are needed to better understand teriparatide efficacy for treatment of osteoporosis in patients with DMD.

Identification of novel candidate autoantibodies in Alzheimer's disease.

BACKGROUND AND PURPOSE: Accumulated failures in Alzheimer's disease (AD) clinical trials have highlighted an urgent need to identify additional biomarkers involved in AD. Recently, mounting evidence reported that autoantibodies are ubiquitous in human sera. However, it is unknown whether autoantibodies are upregulated in amyloid-tau biomarker-confirmed AD. METHODS: A total of 40 subjects with mild dementia (Clinical Dementia Rating = 1) were stratified into AD (n = 16) and non-AD (n = 24) groups according to their cerebrospinal fluid levels of tau and Aß42 . Their sera were collected and analyzed using a microarray containing > 1600 potential human autoantigens. Autoantibodies that were present exclusively in the AD group were identified and selected using the penetrance-based fold change method with the following criteria: penetrance fold change(AD)  ≥ 2, frequency(AD)  ≥ 15% and frequency(non-AD)  = 0%. RESULTS: All controls and samples passed the quality control criteria and were further used for biomarker analysis. Six autoantibodies with elevated responses to the following autoantigens were found exclusively in the AD group: nucleosome assembly protein 1-like 3 (31.3%, 5/16 subjects) and microtubule-associated protein 4, pantothenic acid kinase 3, phosphoinositide-3-kinase regulatory subunit 1, protein tyrosine phosphatase type IVA member 1 and SRY (sex-determining region Y)-box 15 (all 18.8%, 3/16 subjects). CONCLUSIONS: Although some identified autoantigens are linked to AD and cognitive dysfunction, the increased autoantibody levels have not been reported in AD. Autoantibodies may provide deeper insights into the pathogenesis of AD and serve as diagnostic biomarkers; their corresponding antigens can be further studied to assess their potential as therapeutic targets.

TimeSets: Temporal Sensemaking in Intelligence Analysis.

TimeSets is a temporal data visualization technique designed to reveal insights into event sets, such as all the events linked to one person or organization. In this article, we describe two TimeSets-based visual analytics tools for intelligence analysis. In the first case, TimeSets is integrated with other visual analytics tools to support open-source intelligence analysis with Twitter data, particularly the challenge of finding the right questions to ask. The second case uses TimeSets in a participatory design process with analysts that aims to meet their requirements of uncertainty analysis involving fake news. Lessons learned are potentially beneficial to other application domains.

A high-spin ground-state donor-acceptor conjugated polymer.

Interest in high-spin organic materials is driven by opportunities to enable far-reaching fundamental science and develop technologies that integrate light element spin, magnetic, and quantum functionalities. Although extensively studied, the intrinsic instability of these materials complicates synthesis and precludes an understanding of how fundamental properties associated with the nature of the chemical bond and electron pairing in organic materials systems manifest in practical applications. Here, we demonstrate a conjugated polymer semiconductor, based on alternating cyclopentadithiophene and thiadiazoloquinoxaline units, that is a ground-state triplet in its neutral form. Electron paramagnetic resonance and magnetic susceptibility measurements are consistent with a high-to-low spin energy gap of 9.30 × 10-3 kcal mol-1. The strongly correlated electronic structure, very narrow bandgap, intramolecular ferromagnetic coupling, high electrical conductivity, solution processability, and robust stability open access to a broad variety of technologically relevant applications once thought of as beyond the current scope of organic semiconductors.

Drain-free parotidectomy: a pilot study using ARTISS fibrin sealant.

PURPOSE: Parotidectomy is the definitive procedure for diagnosis and treatment of most parotid masses but, due to the risk of haematoma and seroma formation, has traditionally included a drain. The drain itself comes with its own risks and, in most hospitals, the need for overnight admission, which has significant cost implications (Mallon et al. Ann R Coll Surg Engl 95(4):258-262; 2013). Fibrin glue, with its haemostatic and adhesive properties, reduces the risk of collection or haematoma and therefore may negate the need for a drain. This is the first study to look at the use of ARTISS as an alternative to drains in parotidectomy. METHODS: We performed a retrospective study of all the patients who underwent a partial parotidectomy over a 4-year period from 2014 until 2018 under the same senior surgeon. Patients were divided into those that had a drain and those that had ARTISS. Their operative record, inpatient notes and clinic letters were reviewed to record information regarding length of stay, histology, complications and recurrence. RESULTS: A total of 34 patients were identified; 17 ARTISS and 17 drain patients. We showed that the mean length of stay improved significantly from 1.6 days with the drain to 0.5 days with ARTISS (Fig. 1) but without a difference in complication rate (Fig. 2), which was 5/17 (29%) in each group. CONCLUSIONS: In conclusion, parotidectomy can be undertaken safely as a day-case procedure with the application of ARTISS. This new approach to parotid surgery not only offers less morbidity for patients but also positive financial revenue for public health institutions.

Fish on steroids: Temperature-dependent effects of 17ß-trenbolone on predator escape, boldness, and exploratory behaviors.

Hormonal growth promoters (HGPs), widely used in beef cattle production globally, make their way into the environment as agricultural effluent-with potential impacts on aquatic ecosystems. One HPG of particular concern is 17ß-trenbolone, which is persistent in freshwater habitats and can affect the development, morphology and reproductive behaviors of aquatic organisms. Despite this, few studies have investigated impacts of 17ß-trenbolone on non-reproductive behaviors linked to growth and survival, like boldness and predator avoidance. None consider the interaction between 17ß-trenbolone and other environmental stressors, such as temperature, although environmental challenges confronting animals in the wild seldom, if ever, occur in isolation. Accordingly, this study aimed to test the interactive effects of trenbolone and temperature on organismal behavior. To do this, eastern mosquitofish (Gambusia holbrooki) were subjected to an environmentally-relevant concentration of 17ß-trenbolone (average measured concentration 3.0 ±â€¯0.2 ng/L) or freshwater (i.e. control) for 21 days under one of two temperatures (20 and 30 °C), after which the predator escape, boldness and exploration behavior of fish were tested. Predator escape behavior was assayed by subjecting fish to a simulated predator strike, while boldness and exploration were assessed in a separate maze experiment. We found that trenbolone exposure increased boldness behavior. Interestingly, some behavioral effects of trenbolone depended on temperature, sex, or both. Specifically, significant effects of trenbolone on male predator escape behavior were only noted at 30 °C, with males becoming less reactive to the simulated threat. Further, in the maze experiment, trenbolone-exposed fish explored the maze faster than control fish, but only at 20 °C. We conclude that field detected concentrations of 17ß-trenbolone can impact ecologically important behaviors of fish, and such effects can be temperature dependent. Such findings underscore the importance of considering the potentially interactive effects of other environmental stressors when investigating behavioral effects of environmental contaminants.

Inferior vena cava and intra-cardiac invasion of hepatocellular carcinoma: a rare but catastrophic complication.

Intra-cardiac extension of hepatocellular carcinoma (HCC) is an uncommon but serious condition related to poor prognosis. We report a 57-year-old male diagnosed with HCC with intra-cardiac extension into the right atrium at presentation. There were no symptoms related to cardiac involvement and intra-cardiac extension was incidentally noted on radiological imaging. He was offered palliative treatment and succumbed to his disease within 50 days of first diagnosis.

Injectable chondroplasty: Enzymatic reshaping of cartilage grafts.

OBJECTIVE/HYPOTHESIS: To develop an injection-based enzymatic technique that selectively softens cartilage tissue for reshaping cartilaginous structures in the head and neck. MATERIALS AND METHODS: Two groups were formed using fresh rabbit ears: (1) whole rabbit ear group; (2) composite graft group (2.5mm×3.0cm specimens sectioned from the central region of the pinna). Subperichondrial injections using three enzymes (hyaluronidase, pronase, and collagenase II) in sequence were performed for the experimental specimens from both groups. In the control specimens, phosphate buffered saline was injected in a similar fashion. The whole ear specimens were then photographed while held upright in the anatomical vertical position to evaluate for buckling, which corresponds to the integrity of the cartilage. In addition, backlight photography was performed for all specimens to further evaluate the effect of the enzymes, such that increased light intensity represents increased cartilage digestion. RESULTS: The application of the digestive enzymes resulted in marked reduction of cartilage tissue matrix resiliency, while preserving overlying skin layers. Enzymatically treated whole pinnae buckled at the site where enzymes were delivered. Backlit images revealed increased local light intensity at the regions of digestion. There was no obvious destruction of the overlying skin upon visual inspection. CONCLUSIONS: This study demonstrates the feasibility of injectable chondroplasty as a potential alternative method to conventional surgery for auricular cartilage reshaping. Sequential injection of hyaluronidase, pronase, and collagenase II into the subperichondrial space can be performed to digest and soften cartilage structure with minimal involvement of surrounding tissue. Future studies will need to include chondrocyte viability testing and optimization of delivery techniques.

Clinical outcome of head and neck cancer patients: a comparison between ENT patients referred via the 2 weeks wait pathway and alternative routes in the UK health system.

2 weeks wait (2ww) referral was intended to improve cancer outcomes in the UK. However, a previous study found that 2ww failed to detect early stage head and neck cancer. There is no current study to examine the survival outcome of head and neck cancer patients diagnosed on 2ww and non-2ww pathways. The aim of this study is to compare the outcome of cancer patients diagnosed on these pathways. We performed a retrospective review of head and neck cancer patients diagnosed between 2009 and 2013 in the ENT Department at Mid-Yorkshire NHS Hospitals Trust. Gender, age, disease staging, treatment modalities, route of referrals along with survival data were documented. Survival analysis was performed for 2ww and non-2ww cancer patients. There were 4123 patients referred on 2ww during the study period. 147 patients were diagnosed with cancers on 2ww and 89 patients were diagnosed on non-2ww. There were no statistical differences in clinical staging (p = 0.416) and overall survival (p = 0.376) between 2ww and non-2ww patients. This study failed to demonstrate a better overall survival in head and neck cancer patients diagnosed on 2ww pathway within the ENT cohort. Current referral system needs to be refined to improve the survival outcome in head and neck cancer patients.