Polycystic ovary syndrome: associations with cardiovascular disease.

Polycystic ovary syndrome (PCOS), characterized by abnormal menstrual periods, elevated androgen levels and polycystic ovary morphology on ultrasound, is the most common endocrine disorder among females. PCOS is associated with cardiovascular disease (CVD) risk factors including diabetes, obesity, metabolic syndrome, adverse pregnancy outcomes such as pre-eclampsia and psychosocial distress including depression. Previous evidence on the association between PCOS and CVD is inconclusive but the latest 2023 International Evidence-Based PCOS Guideline identifies PCOS as a risk factor for CVD. This review will discuss the relationship between PCOS and CVD along with current direction for CVD screening and prevention among individuals with PCOS.

Service evaluation of radiographer-led vetting and protocoling of Computed Tomography (CT) scan requests in a Singapore public healthcare institution.

INTRODUCTION: A service improvement project involving the vetting and protocoling of Computed Tomography (CT) scan requests by qualified CT radiographers was initiated in 2018. AIM: This study provides a comprehensive evaluation of how a radiographer-led initiative aims to ensure that the CT scan requests received by the Radiology department are clinically appropriate, which in turn will reduce interruptions to the interpretation and reporting of imaging examinations by radiologists, who might otherwise be required to attend to clinically inappropriate and wrongly protocolled CT scan requests. METHOD: Outpatient CT scan requests received from July to October 2021 were vetted and protocolled by a qualified CT-trained radiographer for parameters which included the appropriateness of the clinical indication, adequacy of patient preparation for the scan, as well as the suitability of the requested examination protocol pertaining to the need for contrast media, multiple contrast-enhanced imaging phases, and the appropriateness of the scan range. RESULTS: Poor patient preparation and insufficient or inaccurate clinical indications were the most common findings during the vetting process (71%). Out of the 64 CT scan requests with protocol errors, 77% were attributed to contrast media type errors. The odds of incorrect CT scan requests increased with the requesting clinician's rank, while there was no such significant correlation with the clinical specialty of the requesting clinician or the CT scan type. CONCLUSION: The meticulous vetting of imaging requests helps to ensure that limited imaging hardware resources are allocated to more clinically appropriate cases, correct protocols are applied to requested imaging scans, and that patients undergoing imaging are adequately prepared, thereby enhancing overall patient care. IMPLICATIONS FOR PRACTICE: Vetting of imaging requests by radiographers, who are capable to make appropriate clinical decisions related to their enhanced level of practice ensures patient safety and optimisation of Radiology resources.

Detection of enteroviruses during a 2018 hand, foot and mouth disease outbreak in Malaysia.

Hand, foot, and mouth disease (HFMD) is a common childhood disease caused by enteroviruses. In 2018, a HFMD outbreak in Malaysia affected over 76,000 children. In this study, we used RT-qPCR and CODEHOP PCR to detect the causative agents in 89 clinically diagnosed HFMD patients in Kuala Lumpur and Selangor. Most (62.9%) of the children were below 3 years old. PCR with either assay detected enteroviruses in 84.2% (75/89) and CODEHOP PCR successfully typed 66.7% (50/75) of the enteroviruses. Sequencing of CODEHOP amplicons showed co-circulation of multiple enteroviruses with coxsackievirus A6 (CV-A6) and A16 as the predominant serotypes, but not the neurovirulent enterovirus A71. CV-A6 infection was more common in children less than 12 months old (p=0.01) and was more likely to cause vesicles in the gluteal area (p=0.01) compared to other enteroviruses. Establishing a robust identification method during HFMD outbreaks is important for patient management and public health responses.

Enhancement of aerobic fitness improves social functioning in individuals with schizophrenia.

Individuals with schizophrenia display substantial deficits in social functioning (SF), characterized by chronic, lifelong presentations. Yet, at present there are few effective interventions to enhance SF in this population. Emerging evidence from studies of clinical populations that display similar SF deficits suggests that aerobic exercise (AE) may improve social skills. However, this putative impact has not been investigated in schizophrenia. Employing a single-blind, randomized clinical trial design, 33 individuals with schizophrenia were randomized to receive 12 weeks of Treatment-As-Usual (TAU; n = 17) or TAU + AE (n = 16) utilizing active-play video games (Xbox 360 Kinect) and traditional AE equipment. Participants completed an evaluation of aerobic fitness (VO2max) as well as self-, informant-, and clinician-reported SF measures at baseline and after 12 weeks. Twenty-six participants completed the study (79%; TAU = 13; AE = 13). At follow-up, the AE participants improved their VO2max by 18.0% versus - 0.5% in the controls (group x time interaction, F1,24 = 12.88; p = .002). Hierarchical stepwise regression analyses indicated improvements in VO2max significantly predicted enhancement in SF as indexed by self-, informant-, and clinician-reported measures, predicting 47%, 33%, and 25% of the variance, respectively (controlling for baseline demographics, medications, mood symptoms, and social networks). Compared to the TAU group, AE participants reported significant improvement in SF (23.0% vs. - 4.2%; group × time interaction, F1,24 = 7.48, p = .012). The results indicate that VO2max enhancement leads to improvements in SF in people with schizophrenia. Furthermore, low VO2max represents a modifiable risk factor of SF in people with schizophrenia, for which AE training offers a safe, non-stigmatizing, and nearly side-effect-free intervention.

Detection of enteroviruses during a 2018 hand, foot and mouth disease outbreak in Malaysia

@#Hand, foot, and mouth disease (HFMD) is a common childhood disease caused by enteroviruses. In 2018, a HFMD outbreak in Malaysia affected over 76,000 children. In this study, we used RT-qPCR and CODEHOP PCR to detect the causative agents in 89 clinically diagnosed HFMD patients in Kuala Lumpur and Selangor. Most (62.9%) of the children were below 3 years old. PCR with either assay detected enteroviruses in 84.2% (75/89) and CODEHOP PCR successfully typed 66.7% (50/75) of the enteroviruses. Sequencing of CODEHOP amplicons showed co-circulation of multiple enteroviruses with coxsackievirus A6 (CV-A6) and A16 as the predominant serotypes, but not the neurovirulent enterovirus A71. CV-A6 infection was more common in children less than 12 months old (p=0.01) and was more likely to cause vesicles in the gluteal area (p=0.01) compared to other enteroviruses. Establishing a robust identification method during HFMD outbreaks is important for patient management and public health responses.

Prevalence and documented causes of hyponatraemia among geriatric patients attending a primary care clinic.

INTRODUCTION: Hyponatraemia is the commonest electrolyte abnormality and has major clinical implications. However, few studies of hyponatraemia in the primary care setting has been published to date. OBJECTIVES: To determine the prevalence, potential causes and management of hyponatraemia and to identify factors associated with severity of hyponatraemia among older persons in a primary care setting. METHODS: Electronic records were searched to identify all cases aged ≥60 years with a serum sodium <135mmol/l, attending outpatient clinic in 2014. Patients' medical records with the available blood test results of glucose, potassium, urea and creatinine were reviewed. RESULTS: Of the 21,544 elderly, 5873 patients (27.3%) had electrolyte profile tests. 403 (6.9%) had hyponatraemia in at least one blood test. Medical records were available for 253, mean age 72.9±7.3 years, 178 (70.4%) had mild hyponatraemia, 75 (29.6%) had moderate to severe hyponatraemia. Potential causes were documented in 101 (40%). Patients with moderate to severe hyponatraemia were five times more likely to have a cause of hyponatraemia documented (p<0.01). Medications were the commonest documented cause of hyponatraemia (31.7%). Hydrochlorothiazide use was attributed in 25 (78.1%) of 32 with medication-associated hyponatraemia. Repeat renal profile (89%) was the commonest management of hypotonic hyponatraemia. CONCLUSION: Whilst hyponatraemia was common in the clinic setting, many cases were not acknowledged and had no clear management strategies. In view of mild hyponatraemia has deleterious consequences, future studies should determine whether appropriate management of mild hyponatraemia will lead to clinical improvement.

Extracorporeal cardiopulmonary resuscitation in refractory intra-operative cardiac arrest: an observational study of 12-year outcomes in a single tertiary hospital.

Refractory intra-operative cardiac arrest is a challenging issue for anaesthetists. In this study, we analysed the outcomes of adult patients who received extracorporeal cardiopulmonary resuscitation for refractory intra-operative cardiac arrest between 2005 and 2016, using data from our institutional extracorporeal membrane oxygenation registry. We defined refractory intra-operative cardiac arrest as the failure of a return of spontaneous circulation after 30 min of cardiopulmonary resuscitation. The primary outcome measure was neurologically intact survival with a cerebral performance category score of 1 or 2 at hospital discharge. Between 2005 and 2016, extracorporeal cardiopulmonary resuscitation was used to treat 23 patients who experienced refractory cardiac arrest in the operating room. The survival rates of neurologically-intact subjects were 9/23 (39%) and 6/23 (26%) at 24 h postoperatively and at hospital discharge, respectively. The main cause of refractory-intra-operative cardiac arrest was haemorrhagic shock in 13 out of 23 (57%) patients, and the neurologically-intact survival rate in these patients was 3/13 (23%) at discharge. Our study showed that approximately a quarter of patients with refractory intra-operative cardiac arrest caused by haemorrhage would receive survival benefit from extracorporeal cardiopulmonary resuscitation. Therefore, extracorporeal cardiopulmonary resuscitation may be a possible option in this clinically-challenging situation.

Protecting microRNAs from RNase degradation with steric DNA nanostructures.

Tumor suppressive microRNAs are potent molecules that might cure cancer, one day. Despite the many advanced strategies for delivery of these microRNAs to the cell, there are few therapeutic microRNAs in clinical use. Progress in microRNA bioapplications is hindered by a high vulnerability of exogeneous microRNA molecules to RNase degradation that occurs in extra- and intracellular physiological conditions. In this proof-of-concept study, we use a programmable self-assembled DNA nanostructure bearing a "shuriken" shape to not only deliver but more importantly protect a tumor suppressive microRNA-145 for a sufficiently long time to exert its therapeutic effect in human colorectal cancer cells. Our DNA nanostructure harbored complementary sequences that can hybridize with the microRNA cargo. This brings the microRNA-DNA duplex very close to the core structure such that the microRNA cargo becomes sterically shielded from RNase's degradative activity. Our novel DNA nanostructure based protector concept removes the degradative bottleneck that may plague other nucleic acid delivery strategies and presents a new paradigm towards exploiting these microRNAs for anti-cancer therapy.

Multi-subzone algorithm for absolute phase retrieval in digital fringe projection profilometry.

Codewords are important in encoded absolute phase retrieval techniques such as two-frequency, gray-code, and phase-coding. Each sinusoidal fringe is marked by a unique codeword so that an absolute fringe order can be determined by decoding the codeword. However, due to the limited number of unique codewords, sinusoidal fringe patterns do not contain high-frequency fringes without the use of additional patterns. A multi-subzone coding and decoding algorithm is thus proposed to overcome this limitation. Three multi-subzone coding methods based on two-frequency, gray-code, and phase-coding techniques are presented. The coding creates multiple subzones of unique codewords and the decoding enables it to use non-unique codewords to identify absolute fringe order. Specifically, the range of fringe order is estimated by the use of a wrapped phase map and the absolute fringe order is identified by a codeword. Experimental studies demonstrate the advantages of the proposed algorithm over existing coding methods. The proposed algorithm is suitable to measure objects with large step-height surface discontinuities.

Dual-purpose corneal tissue for anterior lamellar keratoplasty and Descemet's membrane endothelial keratoplasty.

OBJECTIVE: To assess the intraoperative issues and surgical outcomes of preparing a single-donor corneal tissue for same-day use in both deep anterior lamellar keratoplasty (DALK) and Descemet's membrane endothelial keratoplasty (DMEK). DESIGN: Consecutive retrospective case series. PARTICIPANTS: Ten eyes of 10 patients who underwent DALK (5 patients) or DMEK (5 patients) surgery using dual-purpose corneal tissue. METHODS: Five dual-purpose corneoscleral rims were used to prepare tissue for 5 DMEK and 5 DALK procedures. The submerged cornea using backgrounds away technique was first used to harvest the 5 DMEK grafts, and the remaining tissue was used for the 5 DALK grafts. Tissue preparation and operative use occurred on the same day. Tissue preparation challenges, intraoperative complications, and visual recovery were assessed. RESULTS: There were no difficulties in preparing the 5 dual-purpose tissues, and all 10 lamellar transplants were completed successfully. At the 6-month follow-up, the mean best-corrected distance visual acuity improved from 20/250 to 20/80 in the DALK patients, and from 20/300 to 20/25 in the DMEK patients. Postoperative complications after DALK included retained viscoelastic agent at the interface in 1 patient and a double anterior chamber managed with rebubbling in another. After DMEK, a peripheral partial graft detachment occurred in 1 patient and was managed successfully with rebubbling. All corneas demonstrated clarity on slit-lamp examination. CONCLUSIONS: Single-donor corneal tissue can be effectively used for both DALK and DMEK, and may represent a more efficient use of corneal tissue. Complications with the preparation of dual-purpose tissue were not encountered.

Quantitative vibration analysis using a single fringe pattern in time-average speckle interferometry.

In this paper, a novel technique for quantitative vibration analysis using time-average electronic speckle pattern interferometry is proposed. An amplitude-varied time-average refreshing reference frame method is used to capture a fringe pattern with a better fringe contrast than the conventional reference frame technique. The recorded fringe patterns with improved contrast provide better mode shape visibility and are easier to process. A derivative-based regularized phase tracker model is used to retrieve vibration amplitudes from a single fringe pattern. The method does not require a phase shifter to obtain the mode shape or amplitude. The method provides unwrapped amplitude and amplitude derivatives maps directly, so a separate phase unwrapping process is not required. Experimental work is carried out using a circular aluminum plate test specimen and the results are compared with a finite element method modal analysis. Both experimental and numerical results show that the proposed method is robust and accurate.

Multiple-image encryption by space multiplexing based on compressive sensing and the double-random phase-encoding technique.

In this paper, a new multiple-image encryption and decryption technique that utilizes the compressive sensing (CS) concept along with a double-random phase encryption (DRPE) has been proposed. The space multiplexing method is employed for integrating multiple-image data. The method, which results in a nonlinear encryption system, is able to overcome the vulnerability of classical DRPE. The CS technique and space multiplexing are able to provide additional key space in the proposed method. A numerical experiment of the proposed method is implemented and the results show that the proposed method has good accuracy and is more robust than classical DRPE. The proposed system is also employed against chosen-plaintext attacks and it is found that the inclusion of compressive sensing enhances robustness against the attacks.

Oral health and dental treatment needs of people with motor neurone disease.

BACKGROUND: People with motor neurone disease (MND) may present with physical limitations impacting on oral health and access to oral health care. This study aimed to assess the oral health status and treatment needs of people with MND in Victoria, Australia. METHODS: Patients with advanced MND attending a multidisciplinary MND clinic in Melbourne were recruited. Data collection included self-reporting questionnaires on previous dental experience, current oral hygiene practices and current dietary habits, a medical questionnaire, and a clinical examination charting participants' dentition, restorations, caries and periodontal status, plaque and gingival indices, and assessment of oral health. RESULTS: Thirty-three participants took part in the study with eight self-reporting regular dental visits. No participant exhibited probing depths of more than 3 mm. Ten out of 27 dentate participants required extractions and restorations for retained roots and caries, while three presented with non-carious cavities, lost restorations and fractured cusps. Oral health status was not affected by MND presentation in these participants. CONCLUSIONS: The study found that oral health was not affected by advanced MND. Participants' and clinical teams' motivation towards oral health care may have contributed to oral health. The dental profession should be involved as part of the multidisciplinary effort towards ongoing care.

Loss of TAK1 increases cell traction force in a ROS-dependent manner to drive epithelial-mesenchymal transition of cancer cells.

Epithelial-mesenchymal transition (EMT) is a crucial step in tumor progression, and the TGFß-SMAD signaling pathway as an inductor of EMT in many tumor types is well recognized. However, the role of non-canonical TGFß-TAK1 signaling in EMT remains unclear. Herein, we show that TAK1 deficiency drives metastatic skin squamous cell carcinoma earlier into EMT that is conditional on the elevated cellular ROS level. The expression of TAK1 is consistently reduced in invasive squamous cell carcinoma biopsies. Tumors derived from TAK1-deficient cells also exhibited pronounced invasive morphology. TAK1-deficient cancer cells adopt a more mesenchymal morphology characterized by higher number of focal adhesions, increase surface expression of integrin α5ß1 and active Rac1. Notably, these mutant cells exert an increased cell traction force, an early cellular response during TGFß1-induced EMT. The mRNA level of ZEB1 and SNAIL, transcription factors associated with mesenchymal phenotype is also upregulated in TAK1-deficient cancer cells compared with control cancer cells. We further show that TAK1 modulates Rac1 and RhoA GTPases activities via a redox-dependent downregulation of RhoA by Rac1, which involves the oxidative modification of low-molecular weight protein tyrosine phosphatase. Importantly, the treatment of TAK1-deficient cancer cells with Y27632, a selective inhibitor of Rho-associated protein kinase and antioxidant N-acetylcysteine augment and hinders EMT, respectively. Our findings suggest that a dysregulated balance in the activation of TGFß-TAK1 and TGFß-SMAD pathways is pivotal for TGFß1-induced EMT. Thus, TAK1 deficiency in metastatic cancer cells increases integrin:Rac-induced ROS, which negatively regulated Rho by LMW-PTP to accelerate EMT.

Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE-cadherin.

The use of nanomaterials has raised safety concerns, as their small size facilitates accumulation in and interaction with biological tissues. Here we show that exposure of endothelial cells to TiO2 nanomaterials causes endothelial cell leakiness. This effect is caused by the physical interaction between TiO2 nanomaterials and endothelial cells' adherens junction protein VE-cadherin. As a result, VE-cadherin is phosphorylated at intracellular residues (Y658 and Y731), and the interaction between VE-cadherin and p120 as well as ß-catenin is lost. The resulting signalling cascade promotes actin remodelling, as well as internalization and degradation of VE-cadherin. We show that injections of TiO2 nanomaterials cause leakiness of subcutaneous blood vessels in mice and, in a melanoma-lung metastasis mouse model, increase the number of pulmonary metastases. Our findings uncover a novel non-receptor-mediated mechanism by which nanomaterials trigger intracellular signalling cascades via specific interaction with VE-cadherin, resulting in nanomaterial-induced endothelial cell leakiness.

Helicobacter pylori eradication in Western Australia using novel quadruple therapy combinations.

BACKGROUND: Helicobacter pylori eradication rates with standard triple therapy are declining worldwide. The optimal management of H. pylori is evolving and new treatment combinations for antibiotic resistant H. pylori strains are required, especially for patients with penicillin allergy. AIM: To review the effectiveness of alternative antibiotic combinations and necessity of pre-antibiotic sensitivity testing. METHODS: A total of 310 consecutive patients who had failed at least one course of standard 7-day triple therapy initially prescribed by their physicians were included in this study between year 2007 and 2011. Antibiotics were prescribed based on pre-antibiotic sensitivity tests and, if any, patient's allergy to penicillin. RESULTS: In 98.7% of the patients' samples, H. pylori was successfully cultured. The proportion resistant to clarithromycin and metronidazole was 94.1% and 67.6% respectively, with 65% resistant to both. For the in-house primary quadruple therapy, with Proton pump inhibitor, Amoxicillin, Rifabutin and Ciprofloxacin (PARC), H. pylori was successfully eradicated in 95.2% of patients. For patients allergic to amoxicillin, an alternative quadruple therapy using Proton pump inhibitor, Bismuth subcitrate, Rifabutin and Ciprofloxacin (PBRC) gave an eradication rate of 94.2%. Patients needing alternative salvage therapy were given novel personalised combinations consisting of bismuth, rifabutin, tetracycline or furazolidone; the eradication rate was 73.8%. CONCLUSIONS: Patients who present with antibiotic resistant H. pylori can be confidently treated with PARC, PBRC or other personalised salvage therapies. These regimens can be used when treatment options are limited by penicillin allergy. Pre-treatment H. pylori antibiotic sensitivity tests contributed to the high eradication rate in this study.

Multichannel Fourier-transform interferometry for fast signals.

Multichannel Fourier transform interferometry to measure the spectrum of arbitrarily short pulses and of fast time-varying signals was achieved using a micro/nanomanufactured multimirror array. We describe the performance of a demonstrator FTIR that works in the mid-infrared (MIR) range of 700-1400 cm(-1) and reaches a spectral resolution of 10 cm(-1) taking into account apodization. Spectral measurements down to pulse lengths of 319 µs were carried out using a mechanical camera shutter. Arbitrarily short pulses are expected feasible provided the source can deliver enough photons to overcome the noise equivalent number of photons.

Clomifene citrate and intrauterine insemination as first-line treatments for unexplained infertility: are they cost-effective?

BACKGROUND: First-line treatments for unexplained infertility traditionally include clomifene citrate (CC) or unstimulated intrauterine insemination (IUI). A recently published randomized controlled trial considered the effectiveness of CC and IUI in patients with unexplained infertility and found that neither treatment offered a superior live birth rate when compared with expectant management (EM). This paper reports the economic evaluation conducted alongside this trial in order to assess whether health care providers are gaining value for money in this clinical area. METHODS: Five hundred and eighty women across five Scottish hospitals were randomized to either EM, CC or IUI for 6 months. The primary outcome measure was live births. Resource-use data were collected during the trial and costs were calculated from a UK National Health Service (NHS) perspective. Incremental cost-effectiveness ratios were calculated, expressed as cost per live birth, in order to compare the cost-effectiveness of CC and IUI with that of EM to treat unexplained infertility. RESULTS: Live birth rates in the three randomized groups were: EM = 32/193 (17%), CC = 26/194 (13%) and IUI = 43/193 (22%). The mean (standard deviation) costs per treatment cycle were £0 for EM, £83 (£17) for CC and £98 (£31) for IUI. The mean treatment costs per patient for EM, CC and IUI were £12 (£117), £350 (£220) and £331 (£222), respectively. The cost per live birth for EM, CC and IUI was £72 (95% confidence interval £0-£206), £2611 (£1870-£4166) and £1487 (£1116-£2155), respectively. The incremental cost-effectiveness ratio for IUI versus EM was £5604 (-£12204 to £2227), with CC dominated by IUI. CONCLUSIONS: Despite being more expensive, existing treatments such as empirical CC and unstimulated IUI do not offer superior live birth rates compared with EM of unexplained infertility. They are unlikely to be a cost-effective use of limited NHS resources. The study's main limitation is that it did not consider the psychological effects on couples. ISRCT Number: 71762042.

Motion detection using extended fractional Fourier transform and digital speckle photography.

Digital speckle photography is a useful tool for measuring the motion of optically rough surfaces from the speckle shift that takes place at the recording plane. A simple correlation based digital speckle photographic system has been proposed that implements two simultaneous optical extended fractional Fourier transforms (EFRTs) of different orders using only a single lens and detector to simultaneously detect both the magnitude and direction of translation and tilt by capturing only two frames: one before and another after the object motion. The dynamic range and sensitivity of the measurement can be varied readily by altering the position of the mirror/s used in the optical setup. Theoretical analysis and experiment results are presented.