Myocardial infarction (MI) is the leading cause of death in the developed world. Biomarkers have an essential role in diagnosis, risk stratification, guiding management and clinical decision making in the setting of patients presenting with signs and symptoms of MI. Cardiac troponin (cTn) rose to prominence during the 1990s and has evolved to be the cornerstone for diagnosis of MI. The current criteria for MI diagnosis include a rise and/or fall in cTn with at least one value above the 99th percentile of the upper reference limit. Along with cTn, the natriuretic peptides B-type natriuretic peptide (BNP) and amino-terminal proBNP (NT-proBNP) have an important role in determining prognosis and guiding management. As assays for cTn have been evolved that are capable of reliably detecting smaller and smaller quantities in the blood, a dilemma has emerged as to how to use this new information. Several studies have attempted to answer this question and have shown that these lower concentrations of cTn have important prognostic significance and, more importantly, that intervention in these patients leads to improved clinical outcomes. New algorithms incorporating BNP, NT-proBNP, and more sensitive cTn assays hold promise for more rapid diagnosis or rule-out of MI, allowing for appropriate management steps to be initiated and more efficient and effective utilization of healthcare resources.
Biological Markers/*blood ; Humans ; Myocardial Infarction/*diagnosis/metabolism ; Natriuretic Peptide, Brain/blood ; Peptide Fragments/blood ; Prognosis ; Troponin/blood

Locally advanced non-small cell lung cancer (NSCLC) continues to be a challenging disease to treat. With high rates of both local and distant failures, there is significant interest in finding more biologically active chemotherapy regimens that can contribute to reduce both failures. The phase III PROCLAIM trial, recently published in the Journal of Clinical Oncology entitled“PROCLAIM: randomized phase III trial of pemetrexed–cisplatin or etoposide–cisplatin plus thoracic radiation therapy followed by consolidation chemotherapy in locally advanced nonsquamous non-small-cell lung cancer”, compared two different chemotherapy regimens given concurrently with radiotherapy in patients with stage III non-squamous lung cancer: pemetrexed plus cisplatin versus cisplatin plus etoposide. Both groups received con-solidation chemotherapy. After enrolling 598 of planned 600 patients, the study was stopped early due to futility as no difference was seen in the primary end-point of overall survival. Since PROCLAIM was designed as a superiority trial, these results suggest that pemetrexed regimens do not offer a clinical advantage over standard cisplatin plus etopo-side. There are some subpopulations who might still benefit from pemetrexed, especially if clinicians are concerned about myelosuppression-related adverse events. Future trials are needed to investigate novel biologic agents and irradiation techniques that can result in more durable local and distant disease control in locally advanced NSCLC.

Background: The incidence of diabetes mellitus is ever increasing. Individuals with diabetes mellitus may have concurrent mental health disorders and are shown to have poorer disease outcomes. The objectives of this study were to determine the prevalence of depression, anxiety and stress (DAS) in diabetes patients aged 20 years or more in the primary care setting. Methods: This was a cross-sectional study involving the use of self-administered questionnaire conducted in eight primary care private and government clinics in Pulau Pinang and Melaka, Malaysia. The validated DASS-21 questionnaire was used as a screening tool for the symptoms of DAS. Prior permission was obtained from the patients and, clearance from ethical committee was obtained before the start of the study. Data analysis was done using SPSS statistical software. Results: A total of 320 patients with diabetes from eight centres were enrolled via convenience sampling. Sample size was calculated using the Kish’s formula. The prevalence of DAS among patients with diabetes from our study was 26.6%, 40% and 19.4%, respectively. Depression was found to be significantly associated with marital status and family history of DAS; anxiety was significantly associated with monthly household income, presence of co-morbidities and family history of DAS; and stress was significantly associated with occupation and family history of DAS. Conclusions: The prevalence of DAS was higher in patients with diabetes compared with the general community. We recommend to routinely screen all patients with diabetes using the DASS-21 questionnaire because it is easy to perform and inexpensive.

AIMTo establish an objective, easy-to-use and comprehensive method to analyze corpus cavernosum electromyographic signals (CC-potentials).

METHODSCC-potentials were recorded during flaccidity in 23 young healthy volunteers, with surface electrodes placed on the penile shaft bilaterally. Based on the correlation function of Matlab software, an application program for the analysis of CC-potentials was developed. Individual CC-potentials and their autocorrelation function were evaluated, yielding parameters amplitude (A), duration (D), and dominant frequency (DF). The cross-correlation function of both longitudinal and bilateral pairs of adjacent electrodes was calculated to assess the similarity and mutual delay of CC-potentials recorded simultaneously from different parts of the CC. The parameters derived were squared maximum cross-correlation coefficient (Rmax) and delay (tau). Based on the absolute value of tau and the corresponding inter-electrode distance, propagation velocity (PV) was calculated.

RESULTSThe values of the parameters were determined automatically. No significant difference related to the locations of the electrodes for parameters A, D, and DF was detected. The cross-correlation showed that both longitudinal and bilateral CC-potential pairs had highly similar waveforms (the absolute values of Rmax were 0.80 +/- 0.05 and 0.87 +/- 0.06, respectively). PV of longitudinal pairs was estimated as 6.15 +/- 3.98 cm/s.

CONCLUSIONThe application program for correlation analysis of CC-potentials is a comprehensive and versatile method to analyze corpus cavernosum electromyographic recordings. Its objectiveness makes multi-center application possible.

Electromyography ; methods ; Erectile Dysfunction ; diagnosis ; physiopathology ; Humans ; Male ; Muscle, Smooth ; physiology ; Penis ; physiology ; Statistics as Topic ; methods ; Sympathetic Nervous System ; physiology

The genetics of schizophrenia spectrum disorders have come a long way since the early demonstration of a substantial genetic component by family, twin and adoption studies. After over a decade of intensive molecular genetic studies, initially by linkage scans and candidate gene association studies, and more recently genome-wide association studies, a picture is now emerging that susceptibility to schizophrenia spectrum disorders is determined by many genetic variants of different types, ranging from single nucleotide polymorphisms to copy number variants, including rare and de novo variants, of pleiotropic effects on multiple diagnoses and traits. Further large-scale genome-wide association studies, and the forthcoming availability of affordable whole-genome sequencing technology, will further characterise the genetic variants involved, which in turn will be translated to improved clinical practice.
Gene Dosage ; Genetic Linkage ; Genome-Wide Association Study ; Humans ; Polymorphism, Single Nucleotide ; Schizophrenia ; genetics

AIMTo produce biologically active recombinant human (rh) ZP proteins in a human cell for use in sperm function tests.

METHODSThe human embryonic kidney cell line 293T was employed to produce rhZP1, rhZP2 and rhZP3 proteins individually and together by co-expression. Presence of these proteins in the culture medium and cell lysate was assessed by Western blotting analysis. The effect of the recombinant proteins on the human AR was assessed.

RESULTSRhZP2 and rhZP3 were secreted into the culture medium, whereas rhZP1 was found only in the cell lysate. Interestingly, when all zona pellucida proteins were co-expressed in the same cells, rhZP1 was also secreted into the culture medium. However, despite the presence of all three ZP proteins in sufficient concentration and evidence of heavy glycosylation on gel electrophoresis, biological activity to induce the AR was not observed.

CONCLUSIONRhZP1, rhZP2 and rhZP3 were successfully expressed in the human embryonic kidney cell line 293T. It appears that an interaction amongst these proteins may be required for release of rhZP1 from the cell. Although this approach is not satisfactory for producing active human ZP proteins, it makes a significant contribution to the understanding of the structural and functional characteristics of the ZP proteins.

Acrosome Reaction ; drug effects ; Blotting, Western ; Cell Line ; Egg Proteins ; analysis ; genetics ; pharmacology ; Embryo, Mammalian ; Female ; Fluorescent Antibody Technique ; Gene Expression ; Glycoside Hydrolases ; metabolism ; Glycosylation ; Humans ; Kidney ; Male ; Membrane Glycoproteins ; analysis ; genetics ; pharmacology ; Receptors, Cell Surface ; analysis ; genetics ; Recombinant Proteins ; analysis ; pharmacology ; Zona Pellucida Glycoproteins

BACKGROUND: Overweight, obesity, and cardiovascular disease risk factors are prevalent among firefighters in some developed countries. It is unclear whether physical activity and cardiopulmonary fitness reduce cardiovascular disease risk and the cardiovascular workload at work in firefighters. The present study investigated the relationship between leisure-time physical activity, cardiopulmonary fitness, cardiovascular disease risk factors, and cardiovascular workload at work in firefighters in Hong Kong. METHODS: Male firefighters (n = 387) were randomly selected from serving firefighters in Hong Kong (n = 5,370) for the assessment of cardiovascular disease risk factors (obesity, hypertension, diabetes mellitus, dyslipidemia, smoking, known cardiovascular diseases). One-third (Target Group) were randomly selected for the assessment of off-duty leisure-time physical activity using the short version of the International Physical Activity Questionnaire. Maximal oxygen uptake was assessed, as well as cardiovascular workload using heart rate monitoring for each firefighter for four "normal" 24-hour working shifts and during real-situation simulated scenarios. RESULTS: Overall, 33.9% of the firefighters had at least two cardiovascular disease risk factors. In the Target Group, firefighters who had higher leisure-time physical activity had a lower resting heart rate and a lower average working heart rate, and spent a smaller proportion of time working at a moderateintensity cardiovascular workload. Firefighters who had moderate aerobic fitness and high leisuretime physical activity had a lower peak working heart rate during the mountain rescue scenario compared with firefighters who had low leisure-time physical activities. CONCLUSION: Leisure-time physical activity conferred significant benefits during job tasks of moderate cardiovascular workload in firefighters in Hong Kong.
Cardiovascular Diseases ; Developed Countries ; Diabetes Mellitus ; Dyslipidemias ; Firefighters* ; Heart Rate ; Hong Kong ; Humans ; Hypertension ; Leisure Activities* ; Male ; Motor Activity* ; Obesity ; Overweight ; Oxygen ; Risk Factors* ; Smoke ; Smoking

INTRODUCTION: Child sexual abuse (CSA) adversely affects a child's growth and well-being. This study aimed to describe the profile of children presenting to a tertiary paediatric emergency department(ED) with CSA. METHODS: Children 0-16 years old presenting to KK Women's and Children's Hospital ED from June 2016 to August 2020 with sexual abuse were retrospectively reviewed. We performed a secondary analysis on girls and stratified them by age <13 and ≥13 years old. RESULTS: There were 790 patients who made 833 visits for CSA. Victims were predominantly girls (747, 94.8%) and perpetrators were predominantly men (763, 96.6%). The abuse first occurred before the age of 13 years in 315 victims (39.9%). For 468 (59.2%), more than one incident occurred before presentation. Compared to girls ≥13 years old, girls <13 years old were more frequently abused by a family member (47.7% versus 8.0%, CONCLUSION The findings highlight common characteristics of CSA cases, and can aid the future identification and protection of vulnerable children. The fact that most children presented after more than one incident suggests the need to more closely monitor and protect potentially at-risk children.
Adolescent ; Child ; Child Abuse ; Child Abuse, Sexual ; Child, Preschool ; Emergency Service, Hospital ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Parents ; Retrospective Studies

There have been many clinical trials conducted to evaluate novel systemic regimens for unresectable pancreatic cancer. However, most of the trial results were negative, and gemcitabine monotherapy has remained the standard systemic treatment for years. A number of molecular targeted agents, including those against epidermal growth factor receptor and vascular endothelial growth factor receptors, have also been tested. In recent years, there have been some breakthroughs in the deadlock: three regimens, namely gemcitabine-erlotinib, FOLFIRINOX, and gemcitabine-nab-paclitaxel, have been shown to prolong the overall survival of patients when compared with gemcitabine monotherapy. In addition, emerging data suggested that the membrane protein human equilibrative nucleotide transporter 1 is a potential biomarker with which to predict the efficacy of gemcitabine. Here we review the literature on the development of systemic agents for pancreatic cancer, discuss the current choices of treatment, and provide future directions on the development of novel agents.
Adenocarcinoma ; drug therapy ; Albumins ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Camptothecin ; analogs & derivatives ; Deoxycytidine ; analogs & derivatives ; Equilibrative Nucleoside Transporter 1 ; Erlotinib Hydrochloride ; Fluorouracil ; Humans ; Leucovorin ; Organoplatinum Compounds ; Paclitaxel ; Pancreatic Neoplasms ; drug therapy ; Quinazolines ; Receptor, Epidermal Growth Factor ; Receptors, Vascular Endothelial Growth Factor

Background: and Purpose Intracranial arterial stenosis (ICAS)-related stroke occurs due to three primary mechanisms with distinct infarct patterns: (1) borderzone infarcts (BZI) due to impaired distal perfusion, (2) territorial infarcts due to distal plaque/thrombus embolization, and (3) plaque progression occluding perforators. The objective of the systematic review is to determine whether BZI secondary to ICAS is associated with a higher risk of recurrent stroke or neurological deterioration. Methods: As part of this registered systematic review (CRD42021265230), a comprehensive search was performed to identify relevant papers and conference abstracts (with ≥20 patients) reporting initial infarct patterns and recurrence rates in patients with symptomatic ICAS. Subgroup analyses were performed for studies including any BZI versus isolated BZI and those excluding posterior circulation stroke. The study outcome included neurological deterioration or recurrent stroke during follow-up. For all outcome events, corresponding risk ratios (RRs) and 95% confidence intervals (95% CI) were calculated. Results: A literature search yielded 4,478 records with 32 selected during the title/abstract triage for full text; 11 met inclusion criteria and 8 studies were included in the analysis (n=1,219 patients; 341 with BZI). The meta-analysis demonstrated that the RR of outcome in the BZI group compared to the no BZI group was 2.10 (95% CI 1.52–2.90). Limiting the analysis to studies including any BZI, the RR was 2.10 (95% CI 1.38–3.18). For isolated BZI, RR was 2.59 (95% CI 1.24–5.41). RR was 2.96 (95% CI 1.71–5.12) for studies only including anterior circulation stroke patients. Conclusion This systematic review and meta-analysis suggests that the presence of BZI secondary to ICAS may be an imaging biomarker that predicts neurological deterioration and/or stroke recurrence.