Current approach to the treatment of vasovagal syncope in adults.

Vasovagal syncope (VVS) is the most common cause of transient loss of consciousness. Although not associated with mortality, it causes injuries, reduces quality of life, and is associated with anxiety and depression. The European and North American cardiac societies recently published syncope clinical practice guidelines. Most patients with VVS do well after specialist evaluation, reassurance and education. Adequate hydration, increased salt intake when not contraindicated, and careful withdrawal of diuretics and specific hypotension-inducing drugs are a reasonable initial strategy. Physical counterpressure maneuvers might be helpful but can be of limited efficacy in older patients and those with short or no prodromes. Orthostatic training lacks long term efficacy and is troubled by non-compliance. Yoga might be helpful, although the biomedical mechanism is unknown. Almost a third of VVS patients continue to faint despite these conservative measures. Metoprolol was not helpful in a pivotal randomized clinical trial. Fludrocortisone and midodrine significantly reduce syncope recurrences with tolerable side effects, when titrated to target doses. Pacing therapy with specialized sensors appears promising in carefully selected population who have not responded conservative measures. Cardioneuroablation may be helpful but has not been studied in a formal clinical trial.

PET/CT Variants and Pitfalls in Breast Cancers.

There are a number of normal variants and pitfalls which are important to consider when evaluating F-18 Fluorodeoxyglucose (FDG) with Positron Emission Tomography (PET) in breast cancer patients. Although FDG-PET is not indicated for the initial diagnosis of breast cancer, focally increased glucose metabolism within breast tissue represents a high likelihood for a neoplastic process and requires further evaluation. Focally increased glucose metabolism is not unique to breast cancer. Other malignancies such as lymphoma, metastases from solid tumors as well as inflammatory changes also may demonstrate increased glucose metabolism either within the breast or at other sites throughout the body. Importantly, benign breast disease may also exhibit increased glucose metabolism, limiting the specificity of FDG-PET. Breast cancer has a wide range of metabolic activity attributed to tumor heterogeneity and breast cancer subtype. Intracellular signaling pathways regulating tumor glucose utilization contribute to these pitfalls of PET/CT in breast cancer. The evaluation of axillary lymph nodes by FDG-PET is less accurate than sentinel lymph node procedure, however is very accurate in identifying level II and III axillary lymph node metastases or retropectoral metastases. It is important to note that non-malignant inflammation in lymph nodes are often detected by modern PET/CT technology. Therefore, particular consideration should be given to recent vaccinations, particularly to COVID-19, which can commonly result in increased metabolic activity of axillary nodes. Whole body FDG-PET for staging of breast cancer requires specific attention to physiologic variants of FDG distribution and a careful comparison with co-registered anatomical imaging. The most important pitfalls are related to inflammatory changes including sarcoidosis, sarcoid like reactions, and other granulomatous diseases as well as secondary neoplastic processes.

Microscopic changes in the spinal extensor musculature in patients experiencing chronic spinal pain: protocol for a systematic review.

INTRODUCTION: Chronic spinal pain (CSP) is the most common musculoskeletal disorder and is a leading cause of disability as per the Global Burden of Diseases. Previous reviews of microscopic changes in the spinal extensor muscles of people with CSP have focused on the lumbar region only and the results have been inconclusive. Therefore, in this protocol, we aim to assess microscopic changes in the extensor muscles of all spinal regions, investigating regionally specific changes in muscle fibre types of the spinal extensor muscles in patients with non-specific CSP. METHODS/ANALYSIS: This protocol was designed using Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines. Searches will use the following databases: MEDLINE, Embase, PubMed, CINAHL Plus and Web of Science along with relevant grey literature searches. Two reviewers will conduct the searches, perform data extraction, apply inclusion criteria and conduct risk of bias assessment using Newcastle-Ottawa Scale. Data will be synthesised and analysed independently. If there is sufficient homogeneity, then meta-analysis will be conducted by the reviewers jointly. If not, meta-synthesis or narrative reporting will be performed. The quality of the evidence will be assessed using Grading of Recommendations, Assessment, Development and Evaluation (GRADE) guidelines. ETHICS AND DISSEMINATION: The results of this study will be submitted for publication to a peer-reviewed journal and will be presented at conferences. Ethical approval for this systematic review was not required due to no patient data being collated. PROSPERO REGISTRATION NUMBER: CRD42020198087.

Impact of a pharmacist-driven pharmacovigilance system in a secondary hospital in the Gauteng Province of South Africa.

BACKGROUND AND AIMS: Under-reporting of adverse drug reactions (ADRs) by health-care professionals (HCPs) is a worldwide problem. Spontaneous reporting in hospitals is scarce and several obstacles have been identified for this. Improved hospital-based reports could make important contributions to future care. Consequently, the objective of this study was to develop, implement and evaluate a structured pharmacist-driven pharmacovigilance (PV) system for in-patient ADR reporting in a leading public hospital in South Africa for future use in South Africa and wider. METHOD: Descriptive, operational intervention study with a pre-post design. Pharmacist-driven interventions targeted at ADR reporting were implemented. Convenience sampling was used to recruit HCPs [medical practitioners, pharmacists, pharmacist assistants, and nurses] to complete a self-administered questionnaire. The principal outcome measures were the number of the ADRs reported for inpatients, 18 months prior to and 18 months during the intervention period, as well as an evaluation of the intervention program in terms of continuous information and training. RESULTS: There was a significant increase in the number of HCPs reporting an ADR post-intervention (33.8% up from 12.1%; p < 0.0001). Reasons for non-reporting decreased significantly, e.g. 'How, where and when to report' an ADR (p = 0.0027) and 'Concern that the report may be wrong' (p = 0.0041). HCPs' knowledge of the ADR reporting system also improved appreciably. This was apart from pharmacists who were already knowledgeable. CONCLUSION: The results showed the benefits of pharmacist-driven interventions on HCPs' knowledge and awareness of PV and the number of the ADRs reported. Hospital management and policy makers should consider the important role pharmacists can play in improving rational and safe use of medicines among inpatients, based on appropriate training of HCPs and proper systems. As a result, help achieve the standards established by the Department of Health in South Africa.

Knowledge, attitudes and perspective on adverse drug reaction reporting in a public sector hospital in South Africa: baseline analysis.

OBJECTIVE: Adverse drug reactions (ADRs) can cause significant harm in patients; however, ADRs are under-reported in many countries, including South Africa, where evidence of a pharmacovigilance (PV) system to monitor and manage ADRs is a requirement for compliance with norms and standards for quality healthcare delivery. We conducted an analysis amongst health care professionals (HCPs) at Sebokeng Hospital to assess the situation there and make recommendations. METHODS: Data were collected using a structured self-administered questionnaire, targeting all medical practitioners, nurses, pharmacists and pharmacist assistants in the hospital. Current procedures for reporting of ADRs were documented. Records were reviewed to determine the number of ADR reports submitted for the 18-month period prior to the study. Data were analysed with SAS. Ethical clearance was obtained. RESULTS: The questionnaire was completed by 132 HCPs (nurses: 58.3%; medical practitioners: 23.5%; pharmacist assistants: 11.4%; pharmacists: 6.8%). The vast majority indicated ADR reporting is necessary (96.2%) and their professional obligation (89.4%). Only 18.9% were aware of an existing PV system in the hospital, 15.2% had an ADR form available and 18.9% knew to whom the form should be submitted. The vast majority had never reported an ADR, had never received training in PV, but wanted training on ADR reporting. Factors discouraging ADR reporting included not knowing how to report them (53.8%), lack of time (37.1%), additional work load (22.0%), uncertainty about the outcome of reporting (32.6%), and lack of confidence to discuss ADRs with colleagues (22.0%). Only 2.3% knew how many ADRs were reported, that ADRs are discussed by a committee (6.1%) and that internal feedback is received on reported ADRs (6.1%). CONCLUSION: There is an extensive need in Sebokeng Hospital for training on ADR reporting and implementation of systems to facilitate relevant processes; a need which may also exist in other public hospitals in South Africa.

Syncope recurrence and mortality: a systematic review.

AIMS: Data on adverse events and death rates following syncope are heterogeneous among studies, and knowledge of syncope prognosis could help to better define the correct management of patients. METHODS AND RESULTS: We performed a systematic review of literature by searching for prospective observational studies enrolling consecutive patients presenting to the Emergency Department because of syncope. The outcomes considered were syncope recurrence and short- and long-term mortality. Morbidity and a composite of morbidity and mortality were also assessed. Pooled event rates and 95% confidence intervals (CI) were calculated for each outcome using the random effects model. Twenty-five studies (11 158 patients) were included. The incidence of syncope relapse linearly increased from 0.3% at 30 days to 22% at 2 years follow-up. One-year mortality rate varied between 5.7 and 15.5%; the pooled estimate was 8.4% (95% CI: 6.7-10.2%). The incidence of adverse events (morbidity) varied between 6.1 and 25.2% at 10 days and 2 years, respectively. The short-term (10 days) pooled incidence of the composite of morbidity and mortality was 9.1% (95% CI: 6.6-12.5%). We found a high statistical heterogeneity between studies. CONCLUSION: This meta-analysis of prospective observational studies shows that the chance of being asymptomatic linearly progressively decreased over time after the first syncope. Short-term (10-30 days) mortality after syncope was <2% and that the overall 10-day rate of the composite endpoint of death and major events was ∼9%. The knowledge of syncope prognosis could help clinicians to understand syncope patients' prognosis and researchers to design future studies.

Implantable rhythm devices in the management of vasovagal syncope.

The ECG registration during syncope allows physicians either to confirm or exclude an arrhythmia as the mechanism of syncope. Implantable loop recorders have an over-writeable memory buffer that continuously records and deletes the patient's ECG for up to three years. Many studies have analyzed the utility of implantable loop recorders in recurrent unexplained or high risk syncope. These studies suggest that early use of the ILR provides more and earlier diagnoses and could help in selecting patients with vasovagal syncope and prolonged asystolic pauses who might benefit from pacemaker therapy. However many questions remain, including its performance in the community by physicians with a range of experience in diagnosing syncope. Furthermore there is no evidence that the use of the ILR changes outcome. Numerous attempts have been made to determine whether patients with predominantly cardioinhibitory syncope benefit from permanent pacemakers, especially if symptoms are frequent and debilitating. While the first open label trials of pacemakers in the treatment of vasovagal syncope showed promising results, this effect has not been confirmed by blinded randomized clinical trials. More recent data seem to suggest that patients over 40years with severe asystolic vasovagal syncope might benefit from permanent pacemakers.

Effects of estuarine sediment hypoxia on nitrogen fluxes and ammonia oxidizer gene transcription.

The effects of sediment hypoxia, resulting from increased carbon loads or decreased dissolved oxygen (DO), on nitrogen cycling in estuarine environments is poorly understood. The important role played by bacterial and archaeal ammonia oxidizers in the eventual removal of nitrogen from estuarine environments is likely to be strongly affected by hypoxic events. In this study, an analysis of the effects of different levels of sediment hypoxia (5%, 20% and 75% DO) was performed in a microcosm experiment. Changes in the nutrient fluxes related to nitrification at 5% DO were observed after 4 h. Quantification of the key nitrification gene ammonium monooxygenase (amoA) in both DNA and RNA extracts suggests that bacterial amoA transcription was reduced at both of the lower DO concentrations, while changes in DO had no significant effect on archaeal amoA transcription. There was no change in the diversity of expressed archaeal amoA, but significant change in bacterial amoA transcriptional diversity, indicative of low- and high-DO phylotypes. This study suggests that groups of ammonia oxidizers demonstrate differential responses to changes in sediment DO, which may be a significant factor in niche partitioning of different ammonia oxidizer groups.

Archaeal ammonia oxidizers and nirS-type denitrifiers dominate sediment nitrifying and denitrifying populations in a subtropical macrotidal estuary.

Nitrification and denitrification are key steps in nitrogen (N) cycling. The coupling of these processes, which affects the flow of N in ecosystems, requires close interaction of nitrifying and denitrifying microorganisms, both spatially and temporally. The diversity, temporal and spatial variations in the microbial communities affecting these processes was examined, in relation to N cycling, across 12 sites in the Fitzroy river estuary, which is a turbid subtropical estuary in central Queensland. The estuary is a major source of nutrients discharged to the Great Barrier Reef near-shore zone. Measurement of nitrogen fluxes showed an active denitrifying community during all sampling months. Archaeal ammonia monooxygenase (amoA of AOA, functional marker for nitrification) was significantly more abundant than Betaproteobacterial (beta-AOB) amoA. Nitrite reductase genes, functional markers for denitrification, were dominated by nirS and not nirK types at all sites during the year. AOA communities were dominated by the soil/sediment cluster of Crenarchaeota, with sequences found in estuarine sediment, marine and terrestrial environments, whereas nirS sequences were significantly more diverse (where operational taxonomic units were defined at both the threshold of 5% and 15% sequence similarity) and were closely related to sequences originating from estuarine sediments. Terminal-restriction fragment length polymorphism (T-RFLP) analysis revealed that AOA population compositions varied spatially along the estuary, whereas nirS populations changed temporally. Statistical analysis of individual T-RF dominance suggested that salinity and C:N were associated with the community succession of AOA, whereas the nirS-type denitrifier communities were related to salinity and chlorophyll-alpha in the Fitzroy river estuary.

Isolation and characterisation of a delta5-fatty acid elongase from the marine microalga Pavlova salina.

The marine microalga Pavlova salina (Haptophyta, Pavlovophyceae) produces lipids containing approximately 50% n-3 long-chain polyunsaturated fatty acids including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). A full-length cDNA sequence, designated PsElo5, was isolated from P. salina. Sequence alignment showed that the gene was homologous to corresponding ELO-type elongases from other microalgae. Heterologous expression of PsElo5 in yeast and in higher plants confirmed that it encodes a specific Delta5-elongase activity as predicted and, furthermore, within the n-3 pathway, the elongation activity was confined exclusively to EPA.

Isolation and characterization of genes from the marine microalga Pavlova salina encoding three front-end desaturases involved in docosahexaenoic acid biosynthesis.

The marine microalga Pavlova salina produces lipids containing approximately 50% omega-3 long chain polyunsaturated fatty acids (LC-PUFA) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Three cDNA sequences, designated PsD4Des, PsD5Des, PsD8Des, were isolated from P. salina and shown to encode three front-end desaturases with Delta4, Delta5 and Delta8 specificity, respectively. Southern analysis indicated that the P. salina genome contained single copies of all three front-end fatty acid desaturase genes. When grown at three different temperatures, analysis of fatty acid profiles indicated P. salina desaturation conversions occurred with greater than 95% efficiency. Real-Time PCR revealed that expression of PsD8Des was higher than for the other two genes under normal growth conditions, while PsD5Des had the lowest expression level. The deduced amino acid sequences from all three genes contained three conserved histidine boxes and a cytochrome b(5) domain. Sequence alignment showed that the three genes were homologous to corresponding desaturases from other microalgae and fungi. The predicted activities of these three front-end desaturases leading to the synthesis of LC-PUFA were also confirmed in yeast and in higher plants.

Metolachlor-mediated selection of a microalgal strain producing novel polyunsaturated fatty acids.

Long-chain (> or = C(20)) polyunsaturated fatty acids, such as docosahexaenoic acid and eicosapentaenoic acid, are nutritionally important and provide protection against cardiovascular disease, stroke, and cancer. Structural variants of these compounds may have the potential to be used as pharmaceuticals. Marine microalgae are the key producers of long-chain polyunsaturated fatty acids in the global food web. Assuming vast biological and biochemical diversity, we devised a screen to identify microalgae that produce novel fatty acids. The herbicide metolachlor, an inhibitor of long-chain fatty acid biosynthesis, was used in microcosms containing field-collected microalgae to identify naturally resistant strains. We show that one diatom, Melosira cf. moniliformis, is naturally resistant to concentrations of metolachlor, which were cytostatic or lethal to all the other microalgae. Gas chromatography and gas chromatography-mass spectrometry revealed three fatty acids that have not previously been described-18:4 (Delta5,8,11,14), 18:4 (Delta5,9,12,15), and 18:5 (Delta5,8,11,14,17). We propose that this type of screen may be generally applicable to the search of novel compounds produced by marine microorganisms.

Production of eicosapentaenoic and docosahexaenoic acid-containing oils in transgenic land plants for human and aquaculture nutrition.

A large body of evidence suggests that there is a significant underconsumption of omega-3, long-chain, polyunsaturated fatty acids (LC-PUFAs) and that this is the cause of multiple chronic diseases and developmental aberrations. The scope for increasing omega-3 LC-PUFA consumption from seafood is limited because global wild fisheries are unable to increase their harvests, and aquaculture fisheries currently rely on wild fisheries as a source of LC-PUFAs. Agricultural production of oils is highly efficient and has the potential to be sustainable. The transfer of genes from marine microalgae and other microorganisms into oilseed crops has shown that the production of terrestrial omega-3 LC-PUFA oils is indeed possible. The specifications of these oils or whole seeds for use in human and Atlantic salmon (Salmo salar) aquaculture nutrition are discussed.

Drosophila starvin encodes a tissue-specific BAG-domain protein required for larval food uptake.

We describe a developmental, genetic, and molecular analysis of the sole Drosophila member of the BAG family of genes, which is implicated in stress response and survival in mammalian cells. We show that the gene, termed starvin (stv), is expressed in a highly tissue-specific manner, accumulating primarily in tendon cells following germ-band retraction and later in somatic muscles and the esophagus during embryonic stage 15. We show that stv expression falls within known tendon and muscle cell transcriptional regulatory cascades, being downstream of stripe, but not of another tendon transcriptional regulator, delilah, and downstream of the muscle regulator, mef-2. We generated a series of stv alleles and, surprisingly, given the muscle and tendon-specific embryonic expression of stv, found that the gross morphology and function of somatic muscles is normal in stv mutants. Nonetheless, stv mutant larvae exhibit a striking and fully penetrant mutant phenotype of failure to grow after hatching and a severely impaired ability to take up food. Our study provides the first report of an essential, developmentally regulated BAG-family gene.