Health Impacts of Volcanic Activity in Oceania.

Volcanoes cause a wide range of hazardous phenomena. Close to volcanic vents, hazards can be highly dangerous and destructive and include pyroclastic flows and surges, ballistic projectiles, lava flows, lahars, thick ashfalls, and gas and aerosol emissions. Direct health impacts include trauma, burns, and exacerbation of respiratory diseases. Far-reaching volcanic hazards include volcanic ashfalls, gas and aerosol dispersion, and lahars. Within Oceania, the island arc countries of Papua New Guinea (PNG), the Solomon Islands, Vanuatu, Tonga, and New Zealand are the most at-risk from volcanic activity. Since 1500ad, approximately 10,000 lives have been lost due to volcanic activity across Oceania, with 39 lives lost since 2000. While volcano monitoring and surveillance save lives, residual risks remain from small, sudden, unheralded eruptions, such as the December 9, 2019 eruption of Whakaari/White Island volcano, New Zealand which has a death toll of 21 at the time of writing. Widespread volcanic ashfalls can affect the habitability of downwind communities by contaminating water supplies, damaging crops and buildings, and degrading indoor and outdoor air quality, as well as disrupting transport and communication networks and access to health services. While the fatality rate due to volcanic eruptions may be low, far greater numbers of people may be affected by volcanic activity with approximately 100,000 people in PNG and Vanuatu displaced since 2000. It is challenging to manage health impacts for displaced people, particularly in low-income countries where events such as eruptions occur against a background of low, variable vaccination rates, high prevalence of infectious diseases, poor sanitation infrastructure, and poor nutritional status. As a case study, the 2017-2018 eruption of Ambae volcano, Vanuatu caused no casualties but triggered two separate mandatory off-island evacuations of the entire population of approximately 11,700 people. On the neighboring island of Santo, a health disaster response was coordinated by local government and provided acute care when evacuees arrived. Involving primary care clinicians in this setting enhanced local capacity for health care provision and allowed for an improved understanding of the impact of displacement on evacuee communities.

Pathways to diagnosis of non-small cell lung cancer: a descriptive cohort study.

Little has been published on the diagnostic and referral pathway for lung cancer in Australia. This study set out to quantify general practitioner (GP) and lung specialist attendance and diagnostic imaging in the lead-up to a diagnosis of non-small cell lung cancer (NSCLC) and identify common pathways to diagnosis in New South Wales (NSW), Australia. We used linked health data for participants of the 45 and Up Study (a NSW population-based cohort study) diagnosed with NSCLC between 2006 and 2012. Our main outcome measures were GP and specialist attendances, X-rays and computed tomography (CT) scans of the chest and lung cancer-related hospital admissions. Among our study cohort (N = 894), 60% (n = 536) had ≥4 GP attendances in the 3 months prior to diagnosis of NSCLC, 56% (n = 505) had GP-ordered imaging (chest X-ray or CT scan), 39% (N = 349) attended a respiratory physician and 11% (N = 102) attended a cardiothoracic surgeon. The two most common pathways to diagnosis, accounting for one in three people, included GP and lung specialist (respiratory physician or cardiothoracic surgeon) involvement. Overall, 25% of people (n = 223) had an emergency hospital admission. For 14% of people (N = 129), an emergency hospital admission was the only event identified on the pathway to diagnosis. We found little effect of remoteness of residence on access to services. This study identified a substantial proportion of people with NSCLC being diagnosed in an emergency setting. Further research is needed to establish whether there were barriers to the timely diagnosis of these cases.

Linguistically diverse general practice teaching.

BACKGROUND: Learning about general practice in a context of linguistic diversity is an understudied area. There may be additional learning needs or unrecognised opportunities in this environment. This study explores the experiences of general practitioners (GPs) and medical students on placement where consultations are conducted in a language other than English (LOTE). METHOD: We conducted 19 semi-structured interviews with medical students and GP supervisors who consult in LOTE. We explored experiences of learning, and teaching strategies implemented by GP supervisors. Thematic analysis was undertaken. RESULTS: Participants reported that LOTE consultations provided unique learning opportunities, including use of interpreters and development of cross-cultural communication skills. Facilitators to learning included the GP engaging the student in the consultation by interpreting, and patients being open to student participation. Some students described language as a barrier to learning, where they had difficulty in following the consultation. Time required for interpreting limited interaction and learning in GP consultations. We identified ways to navigate the language barrier; including the GP acting as interpreter, and students learning key phrases in the consultation language to build rapport. DISCUSSION: Learning in the linguistically diverse General Practice environment can be optimised through an active and collaborative approach between the GP, student, and patients. Our findings highlight specific barriers and facilitators to learning. Our participants identified a variety of techniques, including skills in interpreter use and cross-cultural communication skills which can transcend language barriers, to create valuable opportunities for medical students to learn in this setting. Medical students increasingly experience clinical placements in general practices within diverse communities.

A qualitative study assessing the barriers to implementation of enhanced recovery after surgery.

BACKGROUND: Previous studies have quantitatively assessed Enhanced Recovery After Surgery (ERAS) guideline implementation and compliance, and identified the existence of compliance issues with the programs. This is the first study to qualitatively assess the reasons behind compliance issues in ERAS programs. The aim of this study was to elicit barriers to implementation and functioning of the ERAS program at Royal Prince Alfred Hospital. METHODS: A series of interviews were carried out with key stakeholders in order to explore barriers preventing effective functioning of the program 1 year after implementation. Interview transcripts were analysed. Data analysis involved a grounded theory methodology. RESULTS: Analysis of the data identified four key themed areas of practice that presented barriers: patient-related factors, staff-related factors, practice-related issues, and resources. These overarching themes were generated from subcategories that were linked to generate theory. CONCLUSIONS: For the ERAS program to be implemented successfully with high levels of element compliance, the four key areas need to be addressed. As barriers to ongoing effective care become apparent, these should be managed in order to optimize the synergistic effects of this multimodal program of patient care.

Calcium binding is essential for plastin 3 function in Smn-deficient motoneurons.

The actin-binding and bundling protein, plastin 3 (PLS3), was identified as a protective modifier of spinal muscular atrophy (SMA) in some patient populations and as a disease modifier in animal models of SMA. How it functions in this process, however, is not known. Because PLS3 is an actin-binding/bundling protein, we hypothesized it would likely act via modification of the actin cytoskeleton in axons and neuromuscular junctions to protect motoneurons in SMA. To test this, we examined the ability of other known actin cytoskeleton organizing proteins to modify motor axon outgrowth phenotypes in an smn morphant zebrafish model of SMA. While PLS3 can fully compensate for low levels of smn, cofilin 1, profilin 2 and α-actinin 1 did not affect smn morphant motor axon outgrowth. To determine how PLS3 functions in SMA, we generated deletion constructs of conserved PLS3 structural domains. The EF hands were essential for PLS3 rescue of smn morphant phenotypes, and mutation of the Ca(2+)-binding residues within the EF hands resulted in a complete loss of PLS3 rescue. These results indicate that Ca(2+) regulation is essential for the function of PLS3 in motor axons. Remarkably, PLS3 mutants lacking both actin-binding domains were still able to rescue motor axons in smn morphants, although not as well as full-length PLS3. Therefore, PLS3 function in this process may have an actin-independent component.

Early interneuron dysfunction in ALS: insights from a mutant sod1 zebrafish model.

OBJECTIVE: To determine, when, how, and which neurons initiate the onset of pathophysiology in amyotrophic lateral sclerosis (ALS) using a transgenic mutant sod1 zebrafish model and identify neuroprotective drugs. METHODS: Proteinopathies such as ALS involve mutant proteins that misfold and activate the heat shock stress response (HSR). The HSR is indicative of neuronal stress, and we used a fluorescent hsp70-DsRed reporter in our transgenic zebrafish to track neuronal stress and to measure functional changes in neurons and muscle over the course of the disease. RESULTS: We show that mutant sod1 fish first exhibited the HSR in glycinergic interneurons at 24 hours postfertilization (hpf). By 96 hpf, we observed a significant reduction in spontaneous glycinergic currents induced in spinal motor neurons. The loss of inhibition was followed by increased stress in the motor neurons of symptomatic adults and concurrent morphological changes at the neuromuscular junction (NMJ) indicative of denervation. Riluzole, the only approved ALS drug and apomorphine, an NRF2 activator, reduced the observed early neuronal stress response. INTERPRETATION: The earliest event in the pathophysiology of ALS in the mutant sod1 zebrafish model involves neuronal stress in inhibitory interneurons, resulting from mutant Sod1 expression. This is followed by a reduction in inhibitory input to motor neurons. The loss of inhibitory input may contribute to the later development of neuronal stress in motor neurons and concurrent inability to maintain the NMJ. Riluzole, the approved drug for use in ALS, modulates neuronal stress in interneurons, indicating a novel mechanism of riluzole action.

Enhanced recovery programme in colorectal surgery: does one size fit all?

Enhanced recovery after surgery (ERAS) employs a multimodal perioperative care pathway with the aim of attenuating the stress response to surgery and accelerating recovery. It has been difficult to determine the relative importance of some of the individual components of these pathways such as epidural analgesia and laparoscopic colorectal surgery. Some argue that only a rigid adherence to the published ERAS protocol can achieve the proposed benefits of fast-track surgery. In this article, we explore some of the areas where the evidence base may be changing and ask whether a more flexible and individualised approach should be considered.

An unusual case of acalculous cholecystitis heralding presentation of acute mesenteric ischaemia with typical radiological findings.

INTRODUCTION: Acalculous cholecystitis accounts for 10-15% of cases of cholecystitis. It is often associated with critical illness and has a high morbidity and mortality. PRESENTATION OF CASE: We report an unusual case of an elderly lady who presented with acalculous cholecystitis as the herald event for subsequent fatal intestinal ischaemia. She demonstrated classical radiological features of pneumatosis coli and hepatic porto-venous gas (HPVG). DISCUSSION: The pathogenesis of acalculous cholecystitis remains uncertain but theories including biliary stasis, sepsis and ischaemia have been proposed. The gallbladder is particularly vulnerable to ischaemia which may precipitate the inflammatory process. In this case, we propose that acute acalculous cholecystitis was triggered by ischaemia and was a herald sign of the ischaemia that would later affect the entire gastrointestinal tract. We suggest that the gallbladder's tenuous blood supply made it more vulnerable to the ischaemia that the rest of the bowel subsequently suffered from. CONCLUSION: Intramural and hepatic porto-venous gas are classical, though rarely seen, CT findings in acute intestinal ischaemia. In these situations HPVG is often associated with poor outcome. In this case the acute acalculous cholecystitis may have been a herald sign of mesenteric ischaemia.

A genetic model of amyotrophic lateral sclerosis in zebrafish displays phenotypic hallmarks of motoneuron disease.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that, for approximately 80% of patients, is fatal within five years of diagnosis. To better understand ALS, animal models have been essential; however, only rodent models of ALS exhibit the major hallmarks of the disease. Here, we report the generation of transgenic zebrafish overexpressing mutant Sod1. The construct used to generate these lines contained the zebrafish sod1 gene and approximately 16 kb of flanking sequences. We generated lines expressing the G93R mutation, as well as lines expressing wild-type Sod1. Focusing on two G93R lines, we found that they displayed the major phenotypes of ALS. Changes at the neuromuscular junction were observed at larval and adult stages. In adulthood the G93R mutants exhibited decreased endurance in a swim tunnel test. An analysis of muscle revealed normal muscle force, however, at the end stage the fish exhibited motoneuron loss, muscle atrophy, paralysis and premature death. These phenotypes were more severe in lines expressing higher levels of mutant Sod1 and were absent in lines overexpressing wild-type Sod1. Thus, we have generated a vertebrate model of ALS to complement existing mammal models.

AKT activation predicts outcome in breast cancer patients treated with tamoxifen.

Oestrogen receptor (ERalpha) expression is a strong predictor of response to endocrine therapy. The PI3K/AKT/mTOR signal transduction pathway has been implicated in endocrine resistance in vitro. The present study was carried out to test the hypothesis that AKT activation mediates tamoxifen resistance in clinical breast cancer. Immunohistochemistry (IHC) using AKT1-3, pan-AKT, pAKT (Thr-308), pAKT (Ser-473), pER (Ser-167), and pHER2 antibodies was performed on 402 ERalpha-positive breast carcinomas from patients treated with tamoxifen. High pAKT (Ser-473) activity (p = 0.0406) and low AKT2 expression (p = 0.0115) alone, or in combination [high pAKT (Ser-473)/low AKT2; 'high-risk' patient group] (p = 0.0014), predicted decreased overall survival in tamoxifen-treated patients with ERalpha-positive breast cancers. There was no significant association between tumour levels of AKT expression or activity and disease-free survival (DFS); however, the 'high-risk' patient group was significantly more likely to relapse (p = 0.0491). During tamoxifen treatment, neither AKT2 nor pAKT predicted DFS. Finally, activation of AKT, via phosphorylation, was linked to activation of both HER2 and ERalpha in this patient cohort. The data presented here show that the PI3K/AKT/mTOR pathway is associated with relapse and death in ERalpha-positive breast cancer patients treated with tamoxifen, supporting in vitro evidence that AKT mediates tamoxifen resistance. Patients with a 'high-risk' expression profile were at increased risk of death (hazard ratio 3.22, p = 0.002) relative to 'low-risk' patients, highlighting the potential that tumour profiling, with multiple IHC markers predictive of therapeutic response, may improve patient selection for endocrine therapies, eg tamoxifen or aromatase inhibitor-based treatments.