Sustaining efforts to improve family well-being with parents with mental ill health and substance (mis)use.

Research conducted over the past 30 years has developed an extensive body of knowledge on families where parents experience mental ill health and/or substance (mis)use, and interventions that are effective in improving their outcomes. A more recent focus has also explored the importance and nuance of implementation. This perspective article reflects on the concept and practice of sustainability within this body of work and considers underlying assumptions in the field about the goal and direction of interventions that make clarity about sustainability difficult. We identify challenges for understanding sustainability, relating to how and who defines it, what is measured and the impact of context. We conclude by considering how we might be better able to plan and design for sustainability within this field.

Joint patient and clinician priority setting to identify 10 key research questions regarding the long-term sequelae of COVID-19.

Given the large numbers of people infected and high rates of ongoing morbidity, research is clearly required to address the needs of adult survivors of COVID-19 living with ongoing symptoms (long COVID). To help direct resource and research efforts, we completed a research prioritisation process incorporating views from adults with ongoing symptoms of COVID-19, carers, clinicians and clinical researchers. The final top 10 research questions were agreed at an independently mediated workshop and included: identifying underlying mechanisms of long COVID, establishing diagnostic tools, understanding trajectory of recovery and evaluating the role of interventions both during the acute and persistent phases of the illness.

Timing of exposure is critical in a highly sensitive model of SARS-CoV-2 transmission.

Transmission efficiency is a critical factor determining the size of an outbreak of infectious disease. Indeed, the propensity of SARS-CoV-2 to transmit among humans precipitated and continues to sustain the COVID-19 pandemic. Nevertheless, the number of new cases among contacts is highly variable and underlying reasons for wide-ranging transmission outcomes remain unclear. Here, we evaluated viral spread in golden Syrian hamsters to define the impact of temporal and environmental conditions on the efficiency of SARS-CoV-2 transmission through the air. Our data show that exposure periods as brief as one hour are sufficient to support robust transmission. However, the timing after infection is critical for transmission success, with the highest frequency of transmission to contacts occurring at times of peak viral load in the donor animals. Relative humidity and temperature had no detectable impact on transmission when exposures were carried out with optimal timing and high inoculation dose. However, contrary to expectation, trends observed with sub-optimal exposure timing and lower inoculation dose suggest improved transmission at high relative humidity or high temperature. In sum, among the conditions tested, our data reveal the timing of exposure to be the strongest determinant of SARS-CoV-2 transmission success and implicate viral load as an important driver of transmission.

Dual Targeting of PDGFRα and FGFR1 Displays Synergistic Efficacy in Malignant Rhabdoid Tumors.

Subunits of the SWI/SNF chromatin remodeling complex are mutated in a significant proportion of human cancers. Malignant rhabdoid tumors (MRTs) are lethal pediatric cancers characterized by a deficiency in the SWI/SNF subunit SMARCB1. Here, we employ an integrated molecular profiling and chemical biology approach to demonstrate that the receptor tyrosine kinases (RTKs) PDGFRα and FGFR1 are coactivated in MRT cells and that dual blockade of these receptors has synergistic efficacy. Inhibitor combinations targeting both receptors and the dual inhibitor ponatinib suppress the AKT and ERK1/2 pathways leading to apoptosis. MRT cells that have acquired resistance to the PDGFRα inhibitor pazopanib are susceptible to FGFR inhibitors. We show that PDGFRα levels are regulated by SMARCB1 expression, and assessment of clinical specimens documents the expression of both PDGFRα and FGFR1 in rhabdoid tumor patients. Our findings support a therapeutic approach in cancers with SWI/SNF deficiencies by exploiting RTK coactivation dependencies.

Efficacy and long-term safety of StarClose™ for hemostasis of arterial puncture sites distal to common femoral artery bifurcation after percutaneous coronary interventions.

BACKGROUND: Currently approved vascular closure devices (VCDs) are not recommended for use in arterial puncture sites distal to the common femoral artery (CFA) bifurcation. The StarClose™ vascular system (SC) is a unique VCD that does not contain intravascular components, a feature that may allow safe use in smaller vessels. OBJECTIVE: We sought to determine the efficacy and long-term safety of the SC for hemostasis of arterial punctures distal to the CFA bifurcation. METHODS: Consecutive patients with arterial puncture sites located distal to the CFA bifurcation received SC after percutaneous coronary intervention (PCI). Patients were ambulated 4-6 hours later, and the presence of vascular complications was determined clinically before hospital discharge. Clinical and Doppler ultrasound examinations were performed at 8-9 months to assess long-term safety. RESULTS: A total of 106 patients undergoing PCI were included in the study. Mean age was 66 ± 12 years and 63% were male. The arterial puncture site was located in the superficial femoral artery (SFA) in 76 (72%), the profunda femoris artery (PFA) in 22 (21%) and undetermined in 8 (7%) patients. The mean diameter of the CFA was significantly greater than the SFA or the PFA branch with the SC (6.2 ± 1.5 vs. 4.5 ± 1.0 mm for the CFA and branch with SC, respectively; p < 0.0001). Device success was achieved in 102 (96%) patients. At 24 hours, a hematoma ≥ 5 cm was reported in 13 (12%) patients. No other vascular complications occurred. At a mean follow up of 9 ± 2.5 months, there was no clinical or Doppler evidence of arterial insufficiency or vascular complications. CONCLUSION: The SC can be used for hemostasis after PCI in select cases where the arterial puncture site is located distal to the CFA bifurcation without adverse clinical outcomes.

Helicobacter pylori gastritis, the unifying concept for gastric diseases.

Helicobacter pylori infection causes a broad spectrum of clinical diseases and the clinical manifestations of the infection depend on host, environmental, and bacterial factors. These factors have an impact on the pattern and severity of gastritis and ultimately determine the clinical outcome of H. pylori infection. Better staging of gastritis may help to identify patients at risk of gastric cancer. In this article we will examine the complex interaction between host, environmental, and bacterial factors in the pathogenesis of H. pylori infection.

Impact of radial artery cannulation for coronary angiography and angioplasty on radial artery function.

The radial artery is commonly used as a conduit in coronary artery bypass grafting. No data exist on the effects of radial sheath insertion on radial artery function. Because many patients considered for coronary artery bypass grafting have had previous radial procedures, it is important to understand any effects radial sheath insertion may have on radial artery function. Twenty-two patients who underwent elective coronary angiography or angioplasty with a 6Fr sheath through the right radial artery were studied. Radial artery function was assessed using ultrasound to measure flow-mediated dilation (FMD). Reactive hyperemia was produced by 5-minute cuff inflation on the arm to suprasystolic pressures. Radial artery diameter was measured at rest and 1 minute after cuff deflation. FMD was expressed as percent change in radial diameter compared with at rest. In all cases, the left radial artery was studied as a control. Patients were studied before sheath insertion, immediately after sheath insertion, and 6 weeks after sheath insertion. The FMD of the cannulated arm was 13.2% before sheath insertion versus 3.6% immediately after sheath insertion (p <0.01) and 0.2% (p <0.01) 9 weeks after sheath insertion. In contrast, there were no significant changes in the noncannulated arm at either time point. In conclusion, radial artery sheath insertion for coronary angiography or angioplasty results in immediate and persistent blunting of FMD, suggesting severe vasomotor dysfunction. Radial artery sheath insertion has important effects on radial artery function that must be considered when selecting radial conduits for coronary artery bypass grafting.

Chlamydia pneumoniae and atherosclerosis following carotid endarterectomy.

BACKGROUND: Seroepidemiological studies have shown an association between raised antibody titres against Chlamydia pneumoniae, and carotid atherosclerosis or stroke. However, direct evidence for a causal link between arterial infection with C. pneumoniae and carotid disease remains weak. We hypothesized that long-term follow-up of patients with pathologically-proven arterial C. pneumoniae infection might provide further insight into the role of C. pneumoniae in carotid atherosclerosis. METHODS: We followed a cohort of 70 carotid endarterectomy patients for ipsilateral restenosis, contralateral progression, and all-cause mortality (four year median follow-up period). All patients had presence or absence of C. pneumoniae in their carotid plaques documented by immunohistochemistry after endarterectomy. A survival function was generated and the log-rank test was used to assess the difference in survival between subjects with and without documented chlamydial infection in their plaque. RESULTS: Baseline demographic and cardiovascular risk factors were similar between the two groups, and survival analysis demonstrated no difference (p>0.05) in all-cause mortality, or all-cause mortality combined with restenosis and progression. CONCLUSIONS: Our data finds no causal role for C. pneumoniae in restenosis or progression of carotid disease or mortality in this patient population with advanced carotid atherosclerosis.