Subacute thyroiditis presenting as a painful suspicious thyroid nodule.

Summary: We report a case of subacute thyroiditis in a 40-year-old female who initially presented with painful thyroid nodules without clinical and biochemical evidence of hyperthyroidism. Thyroid ultrasound was done to evaluate the thyroid nodules and fine-needle aspiration (FNA) was performed in view of the suspicious features. As the FNA showed a follicular lesion of undetermined significance or atypia of undetermined significance (FLUS/AUS, Bethesda III), she was advised for surgical excision. She was subsequently diagnosed with subacute thyroiditis based on her clinical symptoms, biochemical evidence of hyperthyroidism, raised erythrocyte sedimentation rate (ESR) as well as low uptake on thyroid scintigraphy. The thyroid lesions disappeared after symptomatic treatment. It is important to recognise that subacute thyroiditis can present with painful thyroid lesions with ultrasound features similar to suspicious thyroid nodules which can resolve with the resolution of the thyroiditis. Learning points: Subacute thyroiditis can present with atypical features such as the absence of pain, normal erythrocyte sedimentation rate or absence of hyperthyroidism. In subacute thyroiditis, ultrasound findings are commonly described as focal or multifocal lesions with poorly defined and heterogeneous and hypoechoic echogenicity which can be misdiagnosed as malignancy. Thyroid lesions can resolve with the resolution of thyroiditis with or without symptomatic treatment.

Dengue virus infection among renal transplant recipients in Singapore: a 15-year single-centre retrospective review.

INTRODUCTION: Dengue is a mosquito-borne viral infection endemic in Singapore. Its impact in renal transplantation is limited to small case series. We aimed to characterise the clinical presentation and outcomes of dengue infection among renal transplant recipients in Singapore. METHODS: We conducted a 15-year retrospective review of dengue in renal transplant patients treated at Singapore General Hospital between January 2005 and October 2019. The diagnosis of dengue was made if there were a compatible clinical syndrome and a positive dengue diagnostic assay (Dengue NS1 antigen, IgM or RT-PCR). RESULTS: 31 patients were diagnosed with dengue, 18 (58.1%) were deceased donor recipients. The median age was 52 (IQR 40-61) years; 16 (51.6%) were females. The median time to diagnosis was 99 (IQR 18-169) months from transplant. The most common clinical symptoms were fever (87.1%), myalgia (41.9%), gastrointestinal symptoms (38.7%) and headache (25.8%). 19 (61.3%) patients had dengue without warning signs, 9 (29.0%) had dengue with warning signs, 3 (9.7%) had severe dengue and 30 (96.8%) were hospitalized. 17 (54.8%) patients had graft dysfunction, 16 (94.1%) of whom had recovery of graft function. 1 (3.2%) patient required dialysis and subsequently died. There were two cases of donor-derived infections (DDIs) with favourable outcomes. CONCLUSION: Our experience with dengue in renal transplant recipients is concordant with published data. Although graft dysfunction is common, it is often transient with favourable outcomes. Outpatient management may be considered for mild infections. Although dengue DDIs are uncommon, more stringent donor screening may be considered in endemic regions.

Subjective experiences of participating in an attachment-based early intervention parenting program.

This qualitative study evaluated an attachment-based group parenting program that utilises mentalisation-based approach. The Building Early Attachment and Resilience (BEAR) program was designed to promote parent-child attachment across the perinatal period and has pre- and post-natal arms. The post-natal component targets mothers and infants at risk for early disturbances of attachment to, and emotional interaction. This evaluation study aimed to explore mothers' subjective experiences of the post-natal BEAR program in encouraging mothers' reflection on their role as a parent. Thirteen mothers were interviewed. Transcripts were analysed using thematic analysis, with five themes emerging. Overall, mothers reported that the intervention promoted reflection about the parenting role, contributed to perceptions of improved mother-infant interactions and increased understanding of their infant's internal experiences. The results suggest the BEAR program is acceptable and facilitates the development of secure parent-infant attachment.

Epidemiology of pregnancy-associated pulmonary embolism in South Asian multi-ethnic country: Mortality trends over the last four decades.

OBJECTIVE: To determine the cumulative incidence, time of occurrence and risk factors of pregnancy-associated pulmonary embolism (PE) in Singapore, and to review the maternal mortality ratio of PE over the last four decades. STUDY DESIGN AND SETTING: In this retrospective epidemiology review, women with pregnancy-associated PE were identified via International Classification of Diseases codes and included if they had been objectively diagnosed on imaging with PE during pregnancy or within 6 weeks postpartum from 2004 to 2016 at KK Women's and Children's Hospital (KKH) and Singapore General Hospital (SGH) in Singapore. The medical records were reviewed and the time of occurrence of confirmed PE cases and risk factors for PE were noted. RESULTS: There were 18 PE cases out of 174 708 deliveries, of which two were fatal, giving a cumulative incidence of PE at 1.03 per 10 000 deliveries and a mortality rate of 11.1%. The maternal mortality ratio is 1.14 per 100 000 deliveries, the lowest compared to that of the previous three decades (2.5-4.9 per 100 000 deliveries). Majority of PE (66.7%) occurred during the first 2 weeks postpartum. Cumulative incidence of postpartum PE was four times more in caesarean section compared to vaginal delivery at 1.58 per 10 000 deliveries and 0.40 per 10 000 deliveries, respectively. CONCLUSION: Although the cumulative incidence of pregnancy-associated PE in Singapore is low, it is comparable to the United Kingdom (UK) and United States (US). Risk assessment and thromboprophylaxis have decreased PE mortality significantly during this period.

Risk factors for pregnancy-associated venous thromboembolism in Singapore.

OBJECTIVES: Pregnancy-associated venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), is associated with increased risk of maternal mortality and morbidity. This study aimed to assess potential risk factors for pregnancy-associated VTE. METHODS: In this case-control study, women with pregnancy-associated VTE were identified via International Classification of Diseases codes and included if they had been objectively diagnosed with VTE during pregnancy or within six weeks postpartum, from 2004 to 2016, at KK Women's and Children's Hospital or Singapore General Hospital in Singapore. Controls, i.e. pregnant women without VTE, were selected from a prospective longitudinal study. The odds ratio (OR) for VTE was computed for a range of maternal and obstetric factors. RESULTS AND CONCLUSIONS: From 2004 to 2016, 89 cases of pregnancy-associated VTE and 926 controls were identifed and analysed using logistic regression. The most significant risk factors for pregnancy-associated VTE were smoking (OR 5.44, p=0.0002) and preterm delivery (OR 5.06, p=0.023). Malay race, multiparity, non-O blood group and caesarean section, were also identified to be of higher risk. These risk factors should be useful in the development of thromboprophylaxis strategies for pregnancy and the postpartum period, especially in Singapore.

COVID-19 in Older Adults: A Series of 76 Patients Aged 85 Years and Older with COVID-19.

BACKGROUND: Clinical presentation and risk factors of death in COVID-19 in oldest adults have not been well characterized. OBJECTIVES: To describe clinical features and outcome of COVID-19 in patients older than 85 years and study risk factors for mortality. DESIGN: Prospective cohort. PARTICIPANTS AND SETTING: Patients aged 85 years and older, admitted in noncritical care units at the University Hospital Lariboisière Fernand-Widal (Paris, France) for confirmed severe acute respiratory syndrome coronavirus 2 infection were included and followed up for 21 days. MEASUREMENTS: Clinical and laboratory findings were collected. Cox survival analysis was performed to explore factors associated with death. RESULTS: From March 14 to April 11, 2020, 76 patients (median age = 90 (86-92) years; women = 55.3%) were admitted for confirmed COVID-19. Of the patients, 64.5% presented with three or more comorbidities. Most common symptoms were asthenia (76.3%), fever (75.0%) and confusion and delirium (71.1%). An initial fall was reported in 25.0% of cases, and digestive symptoms were reported in 22.4% of cases. COVID-19 was severe in 51.3% of cases, moderate in 32.9%, and mild in 15.8%. Complications included acute respiratory syndrome (28.9%), cardiac decompensation (14.5%), and hypotensive shock (9.0%). Fatality at 21 days was 28.9%, after a median course of disease of 13 (8-17) days. Males were overrepresented in nonsurvivors (68.2%). In survivors, median length of stay was 12 (9-19.5) days. Independent predictive factors of death were C-reactive protein level at admission and lymphocyte count at nadir. CONCLUSION: Specific clinical features, multiorgan injury, and high case fatality rate are observed in older adults with COVID-19. However, rapid diagnosis, appropriate care, and monitoring seem to improve prognosis.

Performance feedback promotes proactive but not reactive adaptation of conflict-control.

Cognitive control refers to the use of internal goals to guide how we process stimuli, and control can be applied proactively (in anticipation of a stimulus) or reactively (once that stimulus has been presented). The application of control can be guided by memory; for instance, people typically learn to adjust their level of attentional selectivity to changing task statistics, such as different frequencies of hard and easy trials in the Stroop task. This type of control-learning is highly adaptive, but its boundary conditions are currently not well understood. In the present study, we assessed how the presence of performance feedback shapes control-learning in the context of item-specific (reactive control, Experiments 1a and 1b) and list-wide (proactive control, Experiments 2a and 2b) proportion of congruency manipulations in a Stroop protocol. We found that performance feedback did not alter the modulation of the Stroop effect by item-specific cueing, but did enhance the modulation of the Stroop effect by a list-wide context. Performance feedback thus selectively promoted proactive, but not reactive, adaptation of cognitive control. These results have important implications for experimental designs, potential psychiatric treatment, and theoretical accounts of the mechanisms underlying control-learning. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Lifelong learning and productive aging among the baby-boomers in Singapore.

Coined in 1982, the term productive aging is commonly associated with active participation in work, although it has since expanded beyond employment to include other dimensions of work, such as volunteering, caregiving and other activities that "produce(s) good/service for society, whether paid or unpaid" (Caro, Bass and Chen, 1993, p. 6). In this paper focusing on examining lifelong learning as one of the other activities in what comprises productive aging, we seek to explore the connections of lifelong learning to the notions of productive aging from the perspective of baby-boomers in Singapore. Using data from the qualitative study of Lifelong Learning among Older Adults in Singapore, which included 64 interviews with learners and non-learners of the baby-boomer generation (age 50-64), we first explore the grounded meanings of productive aging as articulated through lifelong learning. Next, we examine the benefits of lifelong learning as perceived by the baby-boomers, in particular, focusing on general wellbeing in enhancing productive aging. This is followed with a section examining barriers to lifelong learning to provide insight into deterrence to learning. Through the discussion of older adults' perceptions on lifelong learning and their engagement or lack of engagement especially with formal and non-formal learning, we hope to provoke a further re-thinking of what constitutes being productive in later life. Finally, we argue that beyond just another component to productive aging, lifelong learning should perhaps be further recognized as an enabler contributing to capacity-building of the other components including economic production, family care and volunteer services in enhancing productive aging.

Immunotherapy Targeting HPV16/18 Generates Potent Immune Responses in HPV-Associated Head and Neck Cancer.

PURPOSE: Clinical responses with programmed death (PD-1) receptor-directed antibodies occur in about 20% of patients with advanced head and neck squamous cell cancer (HNSCCa). Viral neoantigens, such as the E6/E7 proteins of HPV16/18, are attractive targets for therapeutic immunization and offer an immune activation strategy that may be complementary to PD-1 inhibition. PATIENTS AND METHODS: We report phase Ib/II safety, tolerability, and immunogenicity results of immunotherapy with MEDI0457 (DNA immunotherapy targeting HPV16/18 E6/E7 with IL12 encoding plasmids) delivered by electroporation with CELLECTRA constant current device. Twenty-two patients with locally advanced, p16+ HNSCCa received MEDI0457. RESULTS: MEDI0457 was associated with mild injection site reactions, but no treatment-related grade 3-5 adverse events (AE) were noted. Eighteen of 21 evaluable patients showed elevated antigen-specific T-cell activity by IFNγ ELISpot, and persistent cellular responses surpassing 100 spot-forming units (SFUs)/106 peripheral blood mononuclear cells (PBMCs) were noted out to 1 year. Induction of HPV-specific CD8+ T cells was observed. MEDI0457 shifted the CD8+/FoxP3+ ratio in 4 of 5 post immunotherapy tumor samples and increased the number of perforin+ immune infiltrates in all 5 patients. One patient developed metastatic disease and was treated with anti-PD-1 therapy with a rapid and durable complete response. Flow-cytometric analyses revealed induction of HPV16-specific PD-1+ CD8+ T cells that were not found prior to MEDI0547 (0% vs. 1.8%). CONCLUSIONS: These data demonstrate that MEDI0457 can generate durable HPV16/18 antigen-specific peripheral and tumor immune responses. This approach may be used as a complementary strategy to PD-1/PD-L1 inhibition in HPV-associated HNSCCa to improve therapeutic outcomes.

Stem cells increase in numbers in perinecrotic areas in human renal cancer.

PURPOSE: Developing strategies to overcome resistance to sunitinib is a major challenge in human renal cell carcinoma (RCC). We hypothesized that sunitinib-induced tumor necrosis-associated hypoxia could interact with renal cancer stem cells in patients with metastatic RCC. EXPERIMENTAL DESIGN: We studied tissue samples from 7 patients with primary metastatic RCC, before and after sunitinib treatment, and from six xenograft models derived from human RCC. Two xenograft models were responders to sunitinib, the four others were nonresponders. CD133/CXCR4-coexpressing cells derived from the two responder xenograft models were used for in vitro studies. RESULTS: In the seven primary RCCs, we identified a significantly larger number of CD133/CXCR4-coexpressing cells in perinecrotic versus perivascular areas. Their numbers also significantly increased after treatment, in perinecrotic areas. We reproduced these clinical and pathologic results in all six RCC xenograft models with again a preferential perinecrotic distribution of CD133-expressing cells. Necrosis occurred at day 7 in the two responder models treated with sunitinib, whereas it occurred at day 21 in the untreated controls and in the four nonresponder models. Strikingly, when we studied the six RCC xenograft models at the time necrosis, whether spontaneous or sunitinib-induced, occurred, necrosis area correlated with stem-cell number in all 120 xenografted RCCs. When studied under experimental hypoxia, the number of CD133/CXCR4-coexpressing cells and their tumorigenic potency increased whereas their sensitivity to sunitinib decreased. CONCLUSIONS: In human RCC, sunitinib was able to generate resistance to its own therapeutic effect via induced hypoxia in perinecrotic areas where cancer stem cells were found in increased numbers.

The development of a silica nanoparticle-based label-free DNA biosensor.

A silica nanoparticle-based DNA biosensor capable of detecting Bacillus anthracis bacteria through the use of unlabelled ss-oligonucleotides has been developed. The biosensor makes use of the optical changes that accompany a nanoparticle-immobilized cationic conjugated polymer (polythiophene) interacting with single-stranded vs. hybridized oligonucleotides, where a fluorescence signal appears only when hybridized DNA is present (i.e. only when the ss-oligonucleotide interacting with the polymer has hybridized with its complement). In order to enhance the sensitivity of the biosensor, two different nanoparticle architectures were developed and used to elucidate how the presence of neighboring fluorophores on the nanoparticle surface affects Förster-resonant energy transfer (FRET) between the polythiophene/oligonucleotide complex (FRET donor) and the fluorophores (FRET acceptors). We demonstrate that the silica nanoparticle-based FRET platform lowers the limit of detection at least 10-fold in comparison to the polythiophene itself, and allows the detection of ∼2 × 10(-12) moles of ss-oligonucleotide in a 100 µL sample with a standard fluorimeter (i.e. has a limit of detection of ∼2 nM ssDNA). Such nanoparticle-based biosensor platforms are beneficial because of the robustness and stability inherent to their covalent assembly and they provide a valuable new tool that may allow for the sensitive, label-free detection (the target DNA that produces the fluorescence signal is unlabelled) without the use of polymerase chain reaction.

Characterization and transport properties of Nafion/polyaniline composite membranes.

Nafion membranes were modified by chemical polymerization of aniline using ammonium peroxodisulfate as the oxidant. The Nafion-polyaniline composite membranes were extensively characterized using scanning electron microscopy (SEM), atomic force microscopy (AFM), infrared (FTIR-ATR) and X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and ion-exchange capacity measurements. The transport properties were also evaluated by conductivity and electrodialysis measurements. The data show that when a high oxidant concentration (1 M (NH4)2S2O8) is used, polyaniline is mostly formed at the surface of the Nafion membrane with a higher proportion of oligomers. On the contrary, when 0.1 M oxidant is used, polyaniline is mostly formed inside the ionic domains of Nafion, blocking the pathway to ion transport and thus reducing the transport of Zn2+ as well as the transport of H+. These data were also compared to the data obtained with poly(styrene sulfonate)-PANI composite membranes.

Chemical polymerization of aniline on a poly(styrene sulfonic acid) membrane: Controlling the polymerization site using different oxidants.

Poly(styrene sulfonic acid) membranes (Neosepta CMX, Tokuyama Corp.) have been modified by in situ polymerization of aniline. (NH4)2S2O8, FeCl3, H2O2, and KIO3 were used as oxidizing agents, and two different modification methods (single-step versus two-step) were studied. The composite membranes were characterized by scanning electron microscopy, X-ray photoelectron spectroscopy, elemental analysis, electrodialysis, ion-exchange capacity, and conductivity measurements. Our results demonstrate that it is possible to control the polymerization site of aniline which in turn affects the membrane selectivity properties. Hence, composite membranes having a very thin and homogeneous surface polyaniline layer lead to a very low transport of Zn 2+ without increasing significantly the resistance to H+ conductivity. On the other hand, membranes containing about the same quantity of PANI but inside the membrane do not block the transport of Zn 2+.