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Sinny Delacroix,1,2 Ramesh G Chokka,1,3 Adam J Nelson,1,2 Dennis T Wong,4 Samuel Sidharta,1,2 Stephen M Pederson,5 Adil Rajwani,1,2 Joanne Nimmo,1,2 Karen S Teo,1,2 Stephen G Worthley1,2 1Cardiovascular Research Centre, Royal Adelaide Hospital, 2Department of Medicine, University of Adelaide, Adelaide, SA, 3South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, SA, 4Monash Medical Centre, Clayton, VIC, 5Bioinformatics Hub, School of Biological Sciences, University of Adelaide, Adelaide, SA, Australia Aim: Preclinical studies have demonstrated improvements in renal blood flow after renal sympathetic denervation (RSDN); however, such effects are yet to be confirmed in patients with resistant hypertension. Herein, we assessed the effects of RSDN on renal artery blood flow and diameter at multiple time points post-RSDN. Methods and results: Patients (n=11) with systolic blood pressures ≥160 mmHg despite taking three or more antihypertensive medications at maximum tolerated dose were recruited into this single-center, prospective, non-blinded study. Magnetic resonance imaging indices included renal blood flow and renal artery diameters at baseline, 1 month and 6 months. In addition to significant decreases in blood pressures (p

Abstract Chrysophaeum taylorii is a member of an understudied clade of marine algae that can be responsible for harmful coastal blooms and is known to accumulate bioactive natural products including antibiotics of the chrysophaentin class. Whole genome sequencing of laboratory-cultivated samples revealed an extensive and diverse complement of secondary metabolite biosynthetic genes in C. taylorii, alongside a small microbiome with a more limited biosynthetic potential. 16S microbiome analysis of laboratory cultured alongside wild-collected samples revealed several common taxa; however, analysis of biosynthetic genes suggested an algal origin for the chrysophaentins, possibly via one of several non-canonical polyketide synthase genes encoded within the genome.

Abstract Background Patients with terminal diseases may benefit physically and psychosocially from an outpatient palliative care visit. Palliative care services are limited in Pakistan. An improved understanding of the symptom clusters present in our population is needed. The first outpatient palliative care center in Karachi, Pakistan, was established at our tertiary care institution. The primary aim of this study was to evaluate the impact of a palliative care outpatient consultation on symptom burden in patients with a terminal diagnosis. The secondary aim was to analyze the symptom clusters present in our population. Methods Patients with a terminal diagnosis referred to our outpatient palliative department between August 2020-August 2022 were enrolled. The Edmonton Symptom Assessment Scale (ESAS) questionnaire was administered at the initial visit and the first follow-up visit at one month. Change in symptom burden was assessed using a Wilcoxon signed ranks test. A principal component analysis with varimax rotation was performed on the symptoms reported at the initial visit to evaluate symptom clusters. The palliative performance scale (PPS) was used to measure the performance status of palliative care patients. Results Among the 78 patients included in this study, the average age was 59 ± 16.6 years, 52.6% were males, 99% patients had an oncological diagnosis, and the median duration between two visits was 14 (Q1-Q3: (7.0, 21.0) days. The median PPS level was 60% (Q1-Q3: 50–70). Overall, ESAS scores decreased between the two visits (6.0 (2.8, 11.0), p

This paper examines the dynamic linkages of volatility of energy commodities with bullion and the metal market. The proxies of energy commodities are crude oil and natural gas; bullion markets are Gold, silver and platinum and metal markets are copper and zinc. We collect daily data extending from March 18, 2010, to January 15, 2021, a period for about 12 years and employ Granger causality, Dynamic Conditional Correlation (DCC), Diebold Yilmaz (2012), Baruník & Křehlík (2018), and Network analysis for the purpose of examining spillover effect in the data considered. It is observed that there are short-run dynamic spillovers from energy (crude oil) to metal (copper) while long-run linkage is witnessed among all the constituent series. Further, Baruník & Křehlík (2018) test reveals that the total connectedness of the seven data series under study are found to be higher in frequency 2 (6 days to 15 days) than in the short run and long run. Referring to the network analysis, negative correlations are found between each pair of indices considered, i.e., Gold, silver, platinum, zinc, copper with crude oil while positive correlation is witnessed between Gold and silver. In addition, we determine portfolio hedge ratios and portfolio weights for the investors and portfolio managers. It is found that the Crude /Zinc pair had the most expensive optimal hedge ratio, while Crude/Gold had the least expensive hedging.

Background: Osteoarthritis currently remains a significant health problem due to its high prevalence and morbidity rate. Radiological examination is still used as a gold standard to determine the severity of knee osteoarthritis by using Kellgren-Lawrence grading. Dextrose prolotherapy has been known to be effective in treating pain in knee osteoarthritis, but none has compared the efficacy between mild and moderate-severe knee osteoarthritis. Objective: This study aims to compare the effectiveness of prolotherapy based on its radiological and symptomatic severity in knee osteoarthritis. Methods: In this pre-post study, the participants who underwent dextrose prolotherapy injection (25% intra-articular and 15% periarticular) for three sessions with four weeks intervals were grouped into mild (grade 1-2) and severe (grade 3-4) groups. Participants’ functional status was measured with Western Ontario and McMaster Universities’ arthritis index scores at baseline and week 12. Results: A total of 21 patients (average age 61.42 ± 8.33, BMI 26.81± 3.72) received three therapy sessions. Both groups had significantly better Western Ontario and McMaster Universities arthritis index scores than baseline (-22.57± 11.9; p = 0.002 and -15.42 ± 15.75; p = 0.003). All parameters were improved significantly (p 0.05; CI 95%: -21.3 – 7.05). Conclusion: Prolotherapy effectively improves functional outcomes in all stages of knee osteoarthritis.

Purpose: This paper aims to investigate the interaction of the relationships between group behaviour, group process and learning outcomes in online executive education. Design/methodology/approach: A systematic review of literature in the relevant conceptual domains is performed. Findings: A framework is proposed from the systematic review and proposes a dynamic classroom environment where instructor capability interacts with group process and behaviour to generate new learning outcomes. The impact of institutional context and technology infrastructure are highlighted as drivers of both the classroom and instructor effectiveness. Research limitations/implications: The systematic review highlights several future research trajectories posing the questions--How disruptive innovation impacts on instructor capability development? How alternative theories explain the routines underpinning instructor capability? What is the role of external partners in the development of learning in context? What is the nature of instructor innovation capability? and How does instructor technology capability impact on learning outcomes? Practical implications: Human resource development practitioners are presented with insights as to their existing and potential future roles in enhancing group behaviour, process and learning outcomes in executive classrooms impacted by technological change. The subsequent potential for practitioner enabled learning innovation is highlighted. Originality/value: This paper contributes to contemporary debates regarding the interaction of emerging technologies and the executive online classroom, specifically focusing on the area of group behaviour process and learning.

A secondary (but not primary) dose of the oncolytic virus, VSV, is captured by monocytes and promotes CD8 + T cell recruitment, thereby revealing a mechanism underlying the clinical benefit of repeat dosing in oncolytic virus therapy.

Clinical manifestations of tuberculosis range from asymptomatic infection to a life-threatening disease such as tuberculous meningitis (TBM). Recent studies showed that the spectrum of disease severity could be related to genetic diversity among clinical strains of Mycobacterium tuberculosis (Mtb). Certain strains are reported to preferentially invade the central nervous system, thus earning the label “hypervirulent strains”.However, specific genetic mutations that accounted for enhanced mycobacterial virulence are still unknown. We previously identified a set of 17 mutations in a hypervirulent Mtb strain that was from TBM patient and exhibited significantly better intracellular survivability. These mutations were also commonly shared by a cluster of globally circulating hyper-virulent strains. Here, we aimed to validate the impact of these hypervirulent-specific mutations on the dysregulation of gene networks associated with virulence in Mtb via multi-omic analysis. We surveyed transcriptomic and proteomic differences between the hyper-virulent and low-virulent strains using RNA-sequencing and label-free quantitative LC-MS/MS approach, respectively. We identified 25 genes consistently differentially expressed between the strains at both transcript and protein level, regardless the strains were growing in a nutrient-rich or a physiologically relevant multi-stress condition (acidic pH, limited nutrients, nitrosative stress, and hypoxia). Based on integrated genomic-transcriptomic and proteomic comparisons, the hypervirulent-specific mutations in FadE5 (g. 295,746 C >T), Rv0178 (p. asp150glu), higB (p. asp30glu), and pip (IS6110-insertion) were linked to deregulated expression of the respective genes and their functionally downstream regulons. The result validated the connections between mutations, gene expression, and mycobacterial pathogenicity, and identified new possible virulence-associated pathways in Mtb.

Objective: Current treatments for osteoarthritis do not resolve the underlying cause. Dextrose prolotherapy is an alternative method that has been proposed for treatment of osteoarthritis, due to its ability to aid tissue regeneration, improve clinical manifestations, and repair damaged tissue structures, which are pathological conditions in osteoarthritis. The aim of this systematic review was to evaluate the efficacy of dextrose prolotherapy compared with other interventions in the management of osteoarthritis. Methods: Electronic databases PubMed, Google Scholar, Cochrane, and BioMed Central were searched from inception to October 2021. Search terms included [(prolotherapy) OR (prolotherapies) OR (dextrose prolotherapy)] AND [(osteoarthritis) OR (osteoarthritides) OR (knee osteoarthritis) OR (hip osteoarthritis) OR (hand osteoarthritis) OR (shoulder osteoarthritis)]. Randomized controlled trials that compared the use of dextrose prolotherapy with other interventions (injection, placebo, therapy, or conservative treatment) in the treatment of osteoarthritis were included. Potential articles were screened for eligibility, and data were extracted by all authors. Risk of bias was assessed using the Cochrane Risk of Bias tool. Study population, methods, and results data were extracted and tabulated by 3 authors. Results: 12 studies reported that DPT was as effective or even more effective in improving functional outcomes compared with other interventions whilst others found that HA, PRP, EP, and ACS were more effective. 14 studies assessed the effectiveness of DPT and ten of them reported that DPT was more effective in reducing pain compared with other interventions. Conclusion: Dextrose prolotherapy in osteoarthritis confers potential benefits for pain and functional outcomes, but this systematic review found that the studies to date are at high risk of bias. LAY ABSTRACT Osteoarthritis is a long-term chronic illness defined by the degeneration of cartilage in joints, causing bones to rub together and causing stiffness, discomfort, and decreased movement. Current treatment options for osteoarthritis do not address the fundamental cause. Dextrose prolotherapy is a potential alternative approach for OA, due to its capacity to help tissue regeneration, improve clinical symptoms, and repair damaged tissue structures, which are pathogenic in osteoarthritis. Despite several comparison studies, the superiority of dextrose prolotherapy in osteoarthritis remains equivocal due to contradictory outcomes. Based on this review, dextrose prolotherapy should be considered as a possible treatment for osteoarthritis.

Summary: Background: Cauda equina syndrome (CES) results from nerve root compression in the lumbosacral spine, usually due to a prolapsed intervertebral disc. Evidence for management of CES is limited by its infrequent occurrence and lack of standardised clinical definitions and outcome measures. Methods: This is a prospective multi-centre observational cohort study of adults with CES in the UK. We assessed presentation, investigation, management, and all Core Outcome Set domains up to one year post-operatively using clinician and participant reporting. Univariable and multivariable associations with the Oswestry Disability Index (ODI) and urinary outcomes were investigated. Findings: In 621 participants with CES, catheterisation for urinary retention was required pre-operatively in 31% (191/615). At discharge, only 13% (78/616) required a catheter. Median time to surgery from symptom onset was 3 days (IQR:1–8) with 32% (175/545) undergoing surgery within 48 h. Earlier surgery was associated with catheterisation (OR:2.2, 95%CI:1.5–3.3) but not with admission ODI or radiological compression. In multivariable analyses catheter requirement at discharge was associated with pre-operative catheterisation (OR:10.6, 95%CI:5.8–20.4) and one-year ODI was associated with presentation ODI (r = 0.3, 95%CI:0.2–0.4), but neither outcome was associated with time to surgery or radiological compression. Additional healthcare services were required by 65% (320/490) during one year follow up. Interpretation: Post-operative functional improvement occurred even in those presenting with urinary retention. There was no association between outcomes and time to surgery in this observational study. Significant healthcare needs remained post-operatively. Funding: DCN Endowment Fund funded study administration. Castor EDC provided database use. No other study funding was received.

Objective: The coronavirus disease 2019 (COVID-19) pandemic reached New York City in March 2020, leading to a state of emergency that affected many lives. Patients who contracted the disease presented with different phenotypes. Multiple reports have described the findings of computed tomography scans of these patients, several with pneumothoraces, pneumomediastinum, and subcutaneous emphysema. Our aim was to describe the incidence and management of pneumothorax, pneumomediastinum, and subcutaneous emphysema related to COVID-19 found on radiologic imaging. Methods: A retrospective chart review was conducted of all confirmed COVID-19 patients admitted between early March and mid-May to two hospitals in New York City. Patient demographics, radiological imaging, and clinical courses were documented. Results: Between early March and mid-May, a total of 1866 patients were diagnosed with COVID-19 in the two hospitals included in the study, of which 386 were intubated. The majority of these patients were men (1090, 58.4%). The distribution of comorbidities included the following: hypertension (1006, 53.9%), diabetes (544, 29.6%), and underlying lung disease (376, 20.6%). Among the 386 intubated patients, 65 developed study-specific complications, for an overall incidence of 16.8%; 36 developed a pneumothorax, 2 developed pneumomediastinum, 1 had subcutaneous emphysema, and 26 had a combination of both. The mean time of invasive ventilation was 14 days (0–46, interquartile range = 6–19, median 11). The average of highest positive end expiratory pressure within 72 h of study complication was 11 (5–24) cmH 2 0. The average of the highest peak inspiratory pressure within 72 h of complication was 35.3 (17–52) cmH 2 O. In non-Intubated patients, 9/1480 had spontaneous pneumothorax, for an overall incidence of 0.61 %. Conclusion: Intubated patients with COVID-19 pneumonia are at high risk of pneumothorax, pneumomediastinum, and subcutaneous emphysema. These should be considered in differential diagnosis of shortness of breath or hypoxia in a patient with a new diagnosis of COVID-19 or worsening hemodynamics or respiratory failure in an intensive care unit setting.