Additional file 1: of Exploring musculoskeletal injuries in the podiatry profession: an international cross sectional study

FLEXAR survey consent and questions. (PDF 434 kb

Additional file 1: of What is the impact of rerouting a cancer diagnosis from emergency presentation to GP referral on resource use and survival? Evidence from a population-based study

Technical Appendix. Description of the Basu-Manning estimator used in the statistical analysis. (DOCX 23 kb

Association between high ambient temperature and acute work-related injury: a case-crossover analysis using workers’ compensation claims data

Objectives: The aim of this study was to investigate the association between high ambient temperature and acute work-related injury, expanding on previous research in this area. Specifically we examined the relationship between both daytime and overnight temperatures and injury risk and disentangled physically demanding occupational exposures from exposure to outdoor working conditions. Methods: A time-stratified case-crossover study design was used to examine the association between ambient temperatures and acute work-related injuries in Melbourne, Australia, 2002–2012, using workers’ compensation claims to identify work-related injuries. The relationship was assessed for both daily maximum and daily minimum temperatures using conditional logistic regression. Results: Significant positive associations between temperature and acute work-related injury were seen for younger workers (<25 years), with the odds of injury increasing by 1% for each 1 °C increase in daily minimum temperature, and by 0.8% for each 1 °C increase in daily maximum temperature. Statistically significant associations were also observed between daily maximum temperature and risk of injury for workers employed in the highest strength occupations and for male workers, and between daily minimum temperature and injury for all cases combined, female workers, workers aged 25–35 and ≥55 years, "light" and "limited" physical demand groups, and "in vehicle or cab" and "regulated indoor climate" workplace exposure groups. Conclusions: Young workers, male workers and workers engaged in heavy physical work are at increased risk of injury on hot days, and a wider range of worker subgroups are vulnerable to injury following a warm night. In light of climate change projections, this information is important for informing injury prevention strategies.</p

The baseline characteristics of the enrolled cohort.

1<p>CD4-counts were collected from the clinical record. We recorded the last CD4-count prior to study enrolment.</p>2<p>Viral load measurements were collected from the clinical record. We recorded the last viral load prior to study enrolment that was done within 6 months of tuberculosis diagnosis and treatment.</p>3<p>One patient was started on LPV/r-based ART and tuberculosis treatment on the same day in the double dose LPV/r group.</p

Lopinavir concentrations of individual patients during the study period.

<p>The circles indicate lopinavir concentrations measured while patients were receiving tuberculosis treatment, while the squares indicate lopinavir concentrations once tuberculosis treatment has been completed.</p

The profile of the study cohort.

<p>The profile of the study cohort.</p

Image_3_Investigation into the restoration of TRPM3 ion channel activity in post-COVID-19 condition: a potential pharmacotherapeutic target.tif

IntroductionRecently, we reported that post COVID-19 condition patients also have Transient Receptor Potential Melastatin 3 (TRPM3) ion channel dysfunction, a potential biomarker reported in natural killer (NK) cells from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients. As there is no universal treatment for post COVID-19 condition, knowledge of ME/CFS may provide advances to investigate therapeutic targets. Naltrexone hydrochloride (NTX) has been demonstrated to be beneficial as a pharmacological intervention for ME/CFS patients and experimental investigations have shown NTX restored TRPM3 function in NK cells. This research aimed to: i) validate impaired TRPM3 ion channel function in post COVID-19 condition patients compared with ME/CFS; and ii) investigate NTX effects on TRPM3 ion channel activity in post COVID-19 condition patients.MethodsWhole-cell patch-clamp was performed to characterize TRPM3 ion channel activity in freshly isolated NK cells of post COVID-19 condition (N = 9; 40.56 ± 11.26 years), ME/CFS (N = 9; 39.33 ± 9.80 years) and healthy controls (HC) (N = 9; 45.22 ± 9.67 years). NTX effects were assessed on post COVID-19 condition (N = 9; 40.56 ± 11.26 years) and HC (N = 7; 45.43 ± 10.50 years) where NK cells were incubated for 24 hours in two protocols: treated with 200 µM NTX, or non-treated; TRPM3 channel function was assessed with patch-clamp protocol. ResultsThis investigation confirmed impaired TRPM3 ion channel function in NK cells from post COVID-19 condition and ME/CFS patients. Importantly, PregS-induced TRPM3 currents were significantly restored in NTX-treated NK cells from post COVID-19 condition compared with HC. Furthermore, the sensitivity of NK cells to ononetin was not significantly different between post COVID-19 condition and HC after treatment with NTX.DiscussionOur findings provide further evidence identifying similarities of TRPM3 ion channel dysfunction between ME/CFS and post COVID-19 condition patients. This study also reports, for the first time, TRPM3 ion channel activity was restored in NK cells isolated from post COVID-19 condition patients after in vitro treatment with NTX. The TRPM3 restoration consequently may re-establish TRPM3-dependent calcium (Ca2+) influx. This investigation proposes NTX as a potential therapeutic intervention and TRPM3 as a treatment biomarker for post COVID-19 condition.</p

Image_1_Investigation into the restoration of TRPM3 ion channel activity in post-COVID-19 condition: a potential pharmacotherapeutic target.tif

IntroductionRecently, we reported that post COVID-19 condition patients also have Transient Receptor Potential Melastatin 3 (TRPM3) ion channel dysfunction, a potential biomarker reported in natural killer (NK) cells from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients. As there is no universal treatment for post COVID-19 condition, knowledge of ME/CFS may provide advances to investigate therapeutic targets. Naltrexone hydrochloride (NTX) has been demonstrated to be beneficial as a pharmacological intervention for ME/CFS patients and experimental investigations have shown NTX restored TRPM3 function in NK cells. This research aimed to: i) validate impaired TRPM3 ion channel function in post COVID-19 condition patients compared with ME/CFS; and ii) investigate NTX effects on TRPM3 ion channel activity in post COVID-19 condition patients.MethodsWhole-cell patch-clamp was performed to characterize TRPM3 ion channel activity in freshly isolated NK cells of post COVID-19 condition (N = 9; 40.56 ± 11.26 years), ME/CFS (N = 9; 39.33 ± 9.80 years) and healthy controls (HC) (N = 9; 45.22 ± 9.67 years). NTX effects were assessed on post COVID-19 condition (N = 9; 40.56 ± 11.26 years) and HC (N = 7; 45.43 ± 10.50 years) where NK cells were incubated for 24 hours in two protocols: treated with 200 µM NTX, or non-treated; TRPM3 channel function was assessed with patch-clamp protocol. ResultsThis investigation confirmed impaired TRPM3 ion channel function in NK cells from post COVID-19 condition and ME/CFS patients. Importantly, PregS-induced TRPM3 currents were significantly restored in NTX-treated NK cells from post COVID-19 condition compared with HC. Furthermore, the sensitivity of NK cells to ononetin was not significantly different between post COVID-19 condition and HC after treatment with NTX.DiscussionOur findings provide further evidence identifying similarities of TRPM3 ion channel dysfunction between ME/CFS and post COVID-19 condition patients. This study also reports, for the first time, TRPM3 ion channel activity was restored in NK cells isolated from post COVID-19 condition patients after in vitro treatment with NTX. The TRPM3 restoration consequently may re-establish TRPM3-dependent calcium (Ca2+) influx. This investigation proposes NTX as a potential therapeutic intervention and TRPM3 as a treatment biomarker for post COVID-19 condition.</p

Table_1_Investigation into the restoration of TRPM3 ion channel activity in post-COVID-19 condition: a potential pharmacotherapeutic target.docx

IntroductionRecently, we reported that post COVID-19 condition patients also have Transient Receptor Potential Melastatin 3 (TRPM3) ion channel dysfunction, a potential biomarker reported in natural killer (NK) cells from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients. As there is no universal treatment for post COVID-19 condition, knowledge of ME/CFS may provide advances to investigate therapeutic targets. Naltrexone hydrochloride (NTX) has been demonstrated to be beneficial as a pharmacological intervention for ME/CFS patients and experimental investigations have shown NTX restored TRPM3 function in NK cells. This research aimed to: i) validate impaired TRPM3 ion channel function in post COVID-19 condition patients compared with ME/CFS; and ii) investigate NTX effects on TRPM3 ion channel activity in post COVID-19 condition patients.MethodsWhole-cell patch-clamp was performed to characterize TRPM3 ion channel activity in freshly isolated NK cells of post COVID-19 condition (N = 9; 40.56 ± 11.26 years), ME/CFS (N = 9; 39.33 ± 9.80 years) and healthy controls (HC) (N = 9; 45.22 ± 9.67 years). NTX effects were assessed on post COVID-19 condition (N = 9; 40.56 ± 11.26 years) and HC (N = 7; 45.43 ± 10.50 years) where NK cells were incubated for 24 hours in two protocols: treated with 200 µM NTX, or non-treated; TRPM3 channel function was assessed with patch-clamp protocol. ResultsThis investigation confirmed impaired TRPM3 ion channel function in NK cells from post COVID-19 condition and ME/CFS patients. Importantly, PregS-induced TRPM3 currents were significantly restored in NTX-treated NK cells from post COVID-19 condition compared with HC. Furthermore, the sensitivity of NK cells to ononetin was not significantly different between post COVID-19 condition and HC after treatment with NTX.DiscussionOur findings provide further evidence identifying similarities of TRPM3 ion channel dysfunction between ME/CFS and post COVID-19 condition patients. This study also reports, for the first time, TRPM3 ion channel activity was restored in NK cells isolated from post COVID-19 condition patients after in vitro treatment with NTX. The TRPM3 restoration consequently may re-establish TRPM3-dependent calcium (Ca2+) influx. This investigation proposes NTX as a potential therapeutic intervention and TRPM3 as a treatment biomarker for post COVID-19 condition.</p

Additional file 1: Table S1. of Validation of an NGS mutation detection panel for melanoma

Complete mutation hotspot list included in Custom Ampliseq gene panel for melanoma, including common driver mutations in BRAF, NRAS, KRAS, MEK, GNAQ, and GNA11. (DOCX 125 kb