Photothermal therapy improves the efficacy of a MEK inhibitor in neurofibromatosis type 1-associated malignant peripheral nerve sheath tumors.

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive tumors with low survival rates and the leading cause of death in neurofibromatosis type 1 (NF1) patients under 40 years old. Surgical resection is the standard of care for MPNSTs, but is often incomplete and can generate loss of function, necessitating the development of novel treatment methods for this patient population. Here, we describe a novel combination therapy comprising MEK inhibition and nanoparticle-based photothermal therapy (PTT) for MPNSTs. MEK inhibitors block activity driven by Ras, an oncogene constitutively activated in NF1-associated MPNSTs, while PTT serves as a minimally invasive method to ablate cancer cells. Our rationale for combining these seemingly disparate techniques for MPNSTs is based on several reports demonstrating the efficacy of systemic chemotherapy with local PTT. We combine the MEK inhibitor, PD-0325901 (PD901), with Prussian blue nanoparticles (PBNPs) as PTT agents, to block MEK activity and simultaneously ablate MPNSTs. Our data demonstrate the synergistic effect of combining PD901 with PBNP-based PTT, which converge through the Ras pathway to generate apoptosis, necrosis, and decreased proliferation, thereby mitigating tumor growth and increasing survival of MPNST-bearing animals. Our results suggest the potential of this novel local-systemic combination nanochemotherapy for treating patients with MPNSTs

Lymph node retrieval in pancreaticoduodenectomy specimens: does educating the pathologist matter?

AbstractBackgroundMany previous studies have suggested that the number of lymph nodes retrieved should serve as a benchmark for assessing the adequacy of the resection. The aim was to retrospectively observe the impact of nodal retrieval after educating the pathologist.MethodsPatients undergoing a pancreaticoduodenectomy (PD) between September 2005 and March 2009 were included in the study. The PDs performed between September 2005 and March 2008 were designated as Group A. The pathologists were educated regarding the importance of nodal counts in PD by the surgeon on the 1st April 2008. PDs performed between April 2008 and March 2009 were designated as Group B.ResultsNinety-eight PDs performed by a single surgeon (D.R.J.) for peri-ampullary malignancy were evaluated. The median number of lymph nodes retrieved in Group A was 11(3–32) nodes. The median number of lymph nodes retrieved in Group B was 22 (10–29) nodes (P < 0.001).The lymph node ratio (positive/total nodes), median number of positive nodes retrieved, and the node positivity (node positive compared to node negative) rate did not change.DiscussionA single intervention with the pathologists did impact the number of lymph nodes retrieved from PD specimens. However, the lymph node ratio and lymph node positivity rate remained unchanged. The pathologist is critical to nodal retrieval in PD, but the use of this lymph node number for benchmark of surgical adequacy may be simplistic

Identifying the barriers and enablers for a triage, treatment, and transfer clinical intervention to manage acute stroke patients in the emergency department : A systematic review using the theoretical domains framework (TDF)

Background Clinical guidelines recommend that assessment and management of patients with stroke commences early including in emergency departments (ED). To inform the development of an implementation intervention targeted in ED, we conducted a systematic review of qualitative and quantitative studies to identify relevant barriers and enablers to six key clinical behaviours in acute stroke care: appropriate triage, thrombolysis administration, monitoring and management of temperature, blood glucose levels, and of swallowing difficulties and transfer of stroke patients in ED. Methods Studies of any design, conducted in ED, where barriers or enablers based on primary data were identified for one or more of these six clinical behaviours. Major biomedical databases (CINAHL, OVID SP EMBASE, OVID SP MEDLINE) were searched using comprehensive search strategies. The barriers and enablers were categorised using the theoretical domains framework (TDF). The behaviour change technique (BCT) that best aligned to the strategy each enabler represented was selected for each of the reported enablers using a standard taxonomy. Results Five qualitative studies and four surveys out of the 44 studies identified met the selection criteria. The majority of barriers reported corresponded with the TDF domains of “environmental, context and resources” (such as stressful working conditions or lack of resources) and “knowledge” (such as lack of guideline awareness or familiarity). The majority of enablers corresponded with the domains of “knowledge” (such as education for physicians on the calculated risk of haemorrhage following intravenous thrombolysis [tPA]) and “skills” (such as providing opportunity to treat stroke cases of varying complexity). The total number of BCTs assigned was 18. The BCTs most frequently assigned to the reported enablers were “focus on past success” and “information about health consequences.” Conclusions Barriers and enablers for the delivery of key evidence-based protocols in an emergency setting have been identified and interpreted within a relevant theoretical framework. This new knowledge has since been used to select specific BCTs to implement evidence-based care in an ED setting. It is recommended that findings from similar future reviews adopt a similar theoretical approach. In particular, the use of existing matrices to assist the selection of relevant BCTs

Fabrication and Evaluation of Electrospun, 3D-Bioplotted, and Combination of Electrospun/3D-Bioplotted Scaffolds for Tissue Engineering Applications

Electrospun scaffolds provide a dense framework of nanofibers with pore sizes and fiber diameters that closely resemble the architecture of native extracellular matrix. However, it generates limited three-dimensional structures of relevant physiological thicknesses. 3D printing allows digitally controlled fabrication of three-dimensional single/multimaterial constructs with precisely ordered fiber and pore architecture in a single build. However, this approach generally lacks the ability to achieve submicron resolution features to mimic native tissue. The goal of this study was to fabricate and evaluate 3D printed, electrospun, and combination of 3D printed/electrospun scaffolds to mimic the native architecture of heterogeneous tissue. We assessed their ability to support viability and proliferation of human adipose derived stem cells (hASC). Cells had increased proliferation and high viability over 21 days on all scaffolds. We further tested implantation of stacked-electrospun scaffold versus combined electrospun/3D scaffold on a cadaveric pig knee model and found that stacked-electrospun scaffold easily delaminated during implantation while the combined scaffold was easier to implant. Our approach combining these two commonly used scaffold fabrication technologies allows for the creation of a scaffold with more close resemblance to heterogeneous tissue architecture, holding great potential for tissue engineering and regenerative medicine applications of osteochondral tissue and other heterogeneous tissues

Prospects for multi-omics in the microbial ecology of water engineering

Advances in high-throughput sequencing technologies and bioinformatics approaches over almost the last three decades have substantially increased our ability to explore microorganisms and their functions – including those that have yet to be cultivated in pure isolation. Genome-resolved metagenomic approaches have enabled linking powerful functional predictions to specific taxonomical groups with increasing fidelity. Additionally, related developments in both whole community gene expression surveys and metabolite profiling have permitted for direct surveys of community-scale functions in specific environmental settings. These advances have allowed for a shift in microbiome science away from descriptive studies and towards mechanistic and predictive frameworks for designing and harnessing microbial communities for desired beneficial outcomes. Water engineers, microbiologists, and microbial ecologists studying activated sludge, anaerobic digestion, and drinking water distribution systems have applied various (meta)omics techniques for connecting microbial community dynamics and physiologies to overall process parameters and system performance. However, the rapid pace at which new omics-based approaches are developed can appear daunting to those looking to apply these state-of-the-art practices for the first time. Here, we review how modern genome-resolved metagenomic approaches have been applied to a variety of water engineering applications from lab-scale bioreactors to full-scale systems. We describe integrated omics analysis across engineered water systems and the foundations for pairing these insights with modeling approaches. Lastly, we summarize emerging omics-based technologies that we believe will be powerful tools for water engineering applications. Overall, we provide a framework for microbial ecologists specializing in water engineering to apply cutting-edge omics approaches to their research questions to achieve novel functional insights. Successful adoption of predictive frameworks in engineered water systems could enable more economically and environmentally sustainable bioprocesses as demand for water and energy resources increases.BT/Industriele Microbiologi

Pre-conception self-harm, maternal mental health and mother-infant bonding problems:a 20-year prospective cohort study

Background: Self-harm in young people is associated with later problems in social and emotional development. However, it is unknown whether self-harm in young women continues to be a marker of vulnerability on becoming a parent. This study prospectively describes the associations between pre-conception self-harm, maternal depressive symptoms and mother&ndash;infant bonding problems.MethodsThe Victorian Intergenerational Health Cohort Study (VIHCS) is a follow-up to the Victorian Adolescent Health Cohort Study (VAHCS) in Australia. Socio-demographic and health variables were assessed at 10 time-points (waves) from ages 14 to 35, including self-reported self-harm at waves 3&ndash;9. VIHCS enrolment began in 2006 (when participants were aged 28&ndash;29 years), by contacting VAHCS women every 6 months to identify pregnancies over a 7-year period. Perinatal depressive symptoms were assessed with the Edinburgh Postnatal Depression Scale during the third trimester, and 2 and 12 months postpartum. Mother&ndash;infant bonding problems were assessed with the Postpartum Bonding Questionnaire at 2 and 12 months postpartum.ResultsFive hundred sixty-four pregnancies from 384 women were included. One in 10 women (9.7%) reported pre-conception self-harm. Women who reported self-harming in young adulthood (ages 20&ndash;29) reported higher levels of perinatal depressive symptoms and mother&ndash;infant bonding problems at all perinatal time points [perinatal depressive symptoms adjusted &beta; = 5.40, 95% confidence interval (CI) 3.42&ndash;7.39; mother&ndash;infant bonding problems adjusted &beta; = 7.51, 95% CI 3.09&ndash;11.92]. There was no evidence that self-harm in adolescence (ages 15&ndash;17) was associated with either perinatal outcome.ConclusionsSelf-harm during young adulthood may be an indicator of future vulnerability to perinatal mental health and mother&ndash;infant bonding problems.</jats:sec

UPBEAT-UK::a programme of research into the relationship between coronary heart disease and depression in primary care patients

Many people with coronary heart disease (CHD) are depressed and research on people who have had a heart attack found that depression increases the chance of further heart attacks. The UPBEAT-UK team conducted research with people on general practitioner CHD registers in 33 south London practices to: examine any link between CHD, depression and worse future heart disease; and develop case\ud management by practice nurses for people with CHD and depression. We followed 803 people with CHD for up to 3 years, assessing them for depression, chest pain and\ud worsening of heart disease, and also measured care costs. We asked patients, GPs and nurses how people with CHD and depression should be treated. From this, we developed care designed for each person called ‘personalised care’ (PC). We tested it in 41 people (while 40 people received their usual care from GPs)\ud with chest pain and depression, to assess how acceptable it is, whether or not it helps and what the costs would be. PC was acceptable to people, and those who received it reported less chest pain 6 and 12 months later. Costs were lower following PC but the difference was not statistically significant. Just under half of those with CHD had chest pain. Depression was frequent, but anxiety was more\ud common and increased the chances of both heart attacks and death. We conclude that further research is needed to understand the links between anxiety, chest pain and heart\ud disease, and to further develop our promising findings that PC can be helpful in reducing chest pain in\ud general practice

Fabrication and Evaluation of Electrospun, 3D-Bioplotted, and Combination of Electrospun/3D-Bioplotted Scaffolds for Tissue Engineering Applications

Electrospun scaffolds provide a dense framework of nanofibers with pore sizes and fiber diameters that closely resemble the architecture of native extracellular matrix. However, it generates limited three-dimensional structures of relevant physiological thicknesses. 3D printing allows digitally controlled fabrication of three-dimensional single/multimaterial constructs with precisely ordered fiber and pore architecture in a single build. However, this approach generally lacks the ability to achieve submicron resolution features to mimic native tissue. The goal of this study was to fabricate and evaluate 3D printed, electrospun, and combination of 3D printed/electrospun scaffolds to mimic the native architecture of heterogeneous tissue. We assessed their ability to support viability and proliferation of human adipose derived stem cells (hASC). Cells had increased proliferation and high viability over 21 days on all scaffolds. We further tested implantation of stacked-electrospun scaffold versus combined electrospun/3D scaffold on a cadaveric pig knee model and found that stacked-electrospun scaffold easily delaminated during implantation while the combined scaffold was easier to implant. Our approach combining these two commonly used scaffold fabrication technologies allows for the creation of a scaffold with more close resemblance to heterogeneous tissue architecture, holding great potential for tissue engineering and regenerative medicine applications of osteochondral tissue and other heterogeneous tissues

Preconception personality disorder and antenatal maternal mental health:a population-based cohort study

BACKGROUND: Prior anxiety and depression have been identified as risk factors for maternal perinatal mental health problems, but other preconception mental disorders have not been prospectively examined. This study investigated prospectively whether women with preconception personality disorder have increased rates of antenatal anxiety and/or depressive symptoms. METHODS: 244 women in a population cohort were assessed for personality disorder at age 24 using the Standardised Assessment of Personality. Five to twelve years later, women were screened with the Clinical Interview Schedule, Revised Anxiety Subscale and the Edinburgh Postnatal Depression Scale during the third trimester of 328 pregnancies. RESULTS: Preconception personality disorder was associated with a three-fold increase in the odds of antenatal anxiety symptoms, which remained with adjustment for preconception background factors and preconception common mental disorder (adjusted OR 2.84, 95% CI 1.31-6.15). Preconception personality disorder was associated with doubled odds of antenatal depressive symptoms, however this was attenuated with adjustment for preconception background factors and preconception common mental disorder (adjusted OR 1.98, 95% CI 0.81-4.81). LIMITATIONS: Our findings are restricted to pregnant women aged 29-35 years. Anxiety and depression may have been under-identified because they were assessed at a single antenatal time point. Residual confounding of the associations by preconception common mental disorder at other time points may have occurred. CONCLUSIONS: Women with personality disorder are at heightened risk of anxiety symptoms in pregnancy, over and above risks associated with prior common mental disorder. This raises a possibility that pregnancy brings particular emotional challenges for women with personality disorders

Child and Parent Physical Activity, Sleep, and Screen Time During COVID-19 and Associations With Mental Health:Implications for Future Psycho-Cardiological Disease?

The COVID-19 pandemic has afforded the opportunity for some to improve lifestyle behaviours, while for others it has presented key challenges. Adverse changes in global lifestyle behaviours, including physical activity, sleep, and screen time can affect proximal mental health and in turn distal cardiovascular outcomes. We investigated differences in physical activity, sleep, and screen time in parents and children during early stages of the COVID-19 pandemic in Australia compared to pre-COVID-19 national data; and estimated associations between these movement behaviours with parent and child mental health. Cross-sectional baseline data from the COVID-19 Pandemic Adjustment Study (CPAS; N = 2,365) were compared to nationally representative pre-pandemic data from the Longitudinal Study of Australian Children (LSAC; N = 9,438). Participants were parents of children aged ≤ 18 years, residing in Australia. Parents provided self-report measures of mental health, physical activity and sleep quality, and reported on child mental health, physical activity and screen time. Children in CPAS had significantly more sleep problems and more weekend screen time. Their parents had significantly poorer sleep quality, despite increased weekly physical activity. Children's sleep problems were significantly associated with increased mental health problems, after accounting for socioeconomic status, physical activity, and screen time. Poorer parent sleep quality and lower levels of physical activity were significantly associated with poorer mental health. Monitoring this cohort over time will be important to examine whether changes in movement behaviour are enduring or naturally improve with the easing of restrictions; and whether these changes have lasting effects on either parent or child mental health, and in turn, future risk for CVD