Significant Increase In Uptake Research Articles

18F]FDG and [11C]PK11195 PET imaging in the evaluation of brown adipose tissue - effects of cold and pharmacological stimuli and their association with crotamine intake in a male mouse model

This study aimed to evaluate the role of positron emission tomography (PET) with [11C]PK11195 and [18F]FDG in the characterization of brown adipose tissue (BAT). MethodsMale C57BL/6 mice were studied with the glucose analogue [18F]FDG (n = 21) and the TSPO mitochondrial tracer [11C]PK11195 (n = 28), without stimulus and after cold (6–9 °C) or beta-agonist (CL316243) stimuli. PET studies were performed at baseline and after 21 days of daily treatment with crotamine, which is a peptide described to induce adipocyte tissue browning and to increase BAT metabolism. Tracer uptake (SUVmax) was measured in the interscapular BAT and translocator protein 18 kDa (TSPO) expression was evaluated by immunohistochemistry. ResultsThe cold stimulus increased [18F]FDG uptake compared to no-stimulus (5.21 ± 1.05 vs. 2.03 ± 0.21, p < 0.0001) and to beta-agonist stimulus (2.65 ± 0.39, p = 0.0003). After 21 days of treatment with crotamine, there was no significant difference in the [18F]FDG uptake compared to the baseline in the no-stimulus group and in the cold-stimulus group, with a significant increase in uptake after CL stimulus (baseline: 2.65 ± 0.39; 21 days crotamine: 4.77 ± 0.81, p = 0.0003). Evaluation of [11C]PK11195 at baseline shows that CL stimulus increases the BAT uptake compared to no-stimulus (4.47 ± 0.66 vs. 3.36 ± 0.68, p = 0.014). After 21 days of treatment with crotamine, there was no significant difference in the [11C]PK11195 uptake compared to the baseline in the no-stimulus group (2.94 ± 0.58, p = 0.7864) and also after CL stimulus (3.55 ± 0.79, p = 0.085). TSPO expression correlated with [11C]PK11195 uptake (r = 0.83, p = 0.018) but not with [18F]FDG uptake (r = 0.40, p = 0.516). Conclusions[11C]PK11195 allowed the identification of BAT under thermoneutral conditions or after beta3-adrenergic stimulation in a direct correlation with TSPO expression. The beta-adrenergic stimulus, despite presenting a lower intensity of glycolytic activation compared to cold at baseline, allowed the observation of an increase in BAT uptake of [18F]FDG after 21 days of crotamine administration. Although some limitations were observed for the metabolic changes induced by crotamine, this study reinforced the potential of using [11C]PK11195 and/or [18F]FDG-PET to monitor the activation of BAT.

Urban-rural divide in COVID-19 infection and vaccination rates in healthcare workers in British Columbia, Canada.

Healthcare workers (HCWs) play a critical role in responding to the COVID-19 pandemic. Early in the pandemic, urban centres were hit hardest globally; rural areas gradually became more impacted. We compared COVID-19 infection and vaccine uptake in HCWs living in urban versus rural locations within, and between, two health regions in British Columbia (BC), Canada. We also analysed the impact of a vaccine mandate for HCWs. We tracked laboratory-confirmed SARS-CoV-2 infections, positivity rates and vaccine uptake in all 29,021 HCWs in Interior Health (IH) and all 24,634 HCWs in Vancouver Coastal Health (VCH), by occupation, age and home location, comparing to the general population in that region. We then evaluated the impact of infection rates as well as the mandate on vaccination uptake. While we found an association between vaccine uptake by HCWs and HCW COVID-19 rates in the preceding 2-week period, the higher rates of COVID-19 infection in some occupational groups did not lead to increased vaccination in these groups. By 27 October 2021, the date that unvaccinated HCWs were prohibited from providing healthcare, only 1.6% in VCH compared with 6.5% in IH remained unvaccinated. Rural workers in both areas had significantly higher unvaccinated rates compared with urban dwellers. Over 1800 workers, comprising 6.7% of rural HCWs and 3.6% of urban HCWs, remained unvaccinated and set to be terminated from their employment. While the mandate prompted a significant increase in uptake of second doses, the impact on the unvaccinated was less clear. As rural areas often suffer from under-staffing, loss of HCWs could have serious impacts on healthcare provision as well as on the livelihoods of unvaccinated HCWs. Greater efforts are needed to understand how to better address the drivers of rural-related vaccine hesitancy.

Salivary Gland Uptake on 18F-FP-CIT PET as a New Biomarker in Patients With Parkinsonism.

18F-FP-CIT positron emission tomography (PET) is known for its high sensitivity and specificity for evaluating striatal dopamine transporter (DAT) binding. Recently, for the early diagnose of Parkinson's disease, many researchers focused on the diagnosis of synucleinopathy in organs involved in non-motor symptoms of Parkinson's disease. We investigated the feasibility of salivary gland uptake on 18F-FP-CIT PET as a new biomarker in patients with parkinsonism. A total of 219 participants with confirmed or presumed parkinsonism, including 54 clinically diagnosed idiopathic Parkinson's disease (IPD), 59 suspected and yet undiagnosed, and 106 with secondary parkinsonism, were enrolled. The standardized uptake value ratio (SUVR) of the salivary glands was measured on both early and delayed 18F-FP-CIT PET scans using the cerebellum as the reference region. Additionally, the delayed-to-early ratio (DE_ratio) of salivary gland was obtained. The results were compared between patients with different PET patterns. The SUVR in early 18F-FP-CIT PET scan was significantly higher in patients with IPD pattern compared that in the non-dopaminergic degradation group (0.5 ± 0.19 vs. 0.6 ± 0.21, P < 0.001). Compared with the non-dopaminergic degradation group, the DE_ratio was significantly lower in patients with IPD (5.05 ± 1.7 vs. 4.0 ± 1.31, P < 0.001) or atypical parkinsonism patterns (5.05 ± 1.7 vs. 3.76 ± 0.96, P < 0.05). The DE_ratio was moderately and positively correlated with striatal DAT availability in both the whole striatum (r = 0.37, P < 0.001) and posterior putamen (r = 0.36, P < 0.001). Parkinsonism patients with an IPD pattern exhibited a significant increase in uptake on early 18F-FP-CIT PET and a decrease in the DE_ratio in the salivary gland. Our findings suggest that salivary gland uptake of dual-phase 18F-FP-CIT PET can provide diagnostic information on DAT availability in patients with Parkinson's disease.

Impact of community and provider-driven social accountability interventions on contraceptive uptake in Ghana and Tanzania

BackgroundSocial accountability, which is defined as a collective process for holding duty bearers and service providers to account for their actions, has shown positive outcomes in addressing the interrelated barriers to quality sexual and reproductive health services. The Community and Provider driven Social Accountability Intervention (CaPSAI) Project contributes to the evidence on the effects of social accountability processes in the context of a family planning and contraceptive programme.MethodsA quasi-experimental study utilizing an interrupted time series design with a control group (ITS-CG) was conducted to determine the actual number of new users of contraception amongst women 15–49 years old in eight intervention and eight control facilities per country in Ghana and Tanzania. A standardized facility audit questionnaire was used to collect facility data and completed every year in both intervention and control groups in each country from 2018–2020.ResultsIn Ghana, the two-segmented Poisson Generalized Estimating Equation (GEE) model demonstrated no statistically significant difference at post-intervention, between the intervention and control facilities, in the level of uptake of contraceptives (excess level) (p-value = 0.07) or in the rate of change (excess rate) in uptake (p-value = 0.07) after adjusting for baseline differences. Similarly, in Tanzania, there was no statistical difference between intervention and control facilities, in the level of uptake of contraceptives (excess level) (p-value = 0.20), with the rate of change in uptake (p-value = 0.05) after adjusting for the baseline differences. There was no statistical difference in the level of or rate of change in uptake in the two groups in a sensitivity analysis excluding new users recruited in outreach activities in Tanzania.ConclusionsThe CAPSAI project intervention did not result in a statistically significant increase in uptake of contraceptives as measured by the number of or increase in new users. In evaluating the impact of the intervention on the intermediate outcomes such as self-efficacy among service users, trust and countervailing power among social groups/networks, and responsiveness of service providers, cases of change and process evaluation should be considered.Trial registrationThe CaPSAI Project has been registered at the Australian New Zealand Clinical Trials Registry (ACTRN12619000378123, 11/03/2019).

Lysophosphatidic acid receptor type-1 mediates brain activation in micro-positron emission tomography analysis in a fibromyalgia-like mouse model.

The intermittent cold stress-induced generalized pain response mimics the pathophysiological and pharmacotherapeutic features reported for fibromyalgia patients, including the presence of chronic generalized pain and female dominance. In addition, the intermittent cold stress-induced generalized pain is abolished in lysophosphatidic acid receptor type-1 knockout mice, as reported in many cases of neuropathic pain models. This study aimed to identify the brain loci involved in the intermittent cold stress generalized pain response and test their dependence on the lysophosphatidic acid receptor type-1. Positron emission tomography analyses using 2-deoxy-2-[18 F]fluoro-d-glucose in the presence of a pain stimulus showed that intermittent cold stress causes a significant increase in uptake in the ipsilateral regions, including the salience networking-related anterior cingulate cortex and insular cortex and the cognition-related hippocampus. A significant decrease was observed in the default mode network-related posterior cingulate cortex. Almost these intermittent cold stress-induced changes were abolished in lysophosphatidic acid receptor type-1 knockout mice. There results suggest that the intermittent cold stress-induced generalized pain response is mediated by the lysophosphatidic acid receptor type-1 in specific brain loci related to salience networking and cognition, which may lead to further developments in the treatment of fibromyalgia.

Group antenatal care for improving retention of adolescent and young pregnant women living with HIV in Kenya

BackgroundPregnant and breastfeeding adolescents and young women living with HIV (AYWLH) have lower retention in prevention of mother-to-child transmission (PMTCT) services compared to older women.MethodsWe evaluated a differentiated service model for pregnant and postnatal AYWLH at seven health facilities in western Kenya aimed at improving retention in antiretroviral treatment (ART) services. All pregnant AYWLH < 25 years presenting for antenatal care (ANC) were invited to participate in group ANC visits including self-care and peer-led support sessions conducted by health facility nurses per national guidelines. ART register data were used to assess loss to follow-up (LTFU) among newly-enrolled pregnant adolescent (< 20 years) and young women (20–24 years) living with HIV starting ART in the pre-period (January-December 2016) and post-period (during implementation; December 2017-January 2019). Poisson regression models compared LTFU incidence rate ratios (IRR) in the first six months after PMTCT enrollment and risk ratios compared uptake of six week testing for HIV-exposed infants (HEI) between the pre- and post-periods.ResultsIn the pre-period, 223 (63.2%) of 353 pregnant AYWLH newly enrolled in ANC had ART data, while 320 (71.1%) of 450 in the post-period had ART data (p = 0.02). A higher proportion of women in the post-period (62.8%) had known HIV-positive status at first ANC visit compared to 49.3% in the pre-period (p < 0.001). Among pregnant AYWLH < 20 years, the incidence rate of LTFU in the first six months after enrollment in ANC services declined from 2.36 per 100 person months (95%CI 1.06–5.25) in the pre-period to 1.41 per 100 person months (95%CI 0.53–3.77) in the post-period. In both univariable and multivariable analysis, AYWLH < 20 years in the post-period were almost 40% less likely to be LTFU compared to the pre-period, although this finding did not meet the threshold for statistical significance (adjusted incidence rate ratio 0.62, 95%CI 0.38–1.01, p = 0.057). Testing for HEI was 10% higher overall in the post-period (adjusted risk ratio 1.10, 95%CI 1.01–1.21, p = 0.04).ConclusionsInterventions are urgently needed to improve outcomes among pregnant and postnatal AYWLH. We observed a trend towards increased retention among pregnant adolescents during our intervention and a statistically significant increase in uptake of six week HEI testing.

Uptake of infant and preschool immunisations in Scotland and England during the COVID-19 pandemic: An observational study of routinely collected data.

In 2020, the SARS-CoV-2 (COVID-19) pandemic and lockdown control measures threatened to disrupt routine childhood immunisation programmes with early reports suggesting uptake would fall. In response, public health bodies in Scotland and England collected national data for childhood immunisations on a weekly or monthly basis to allow for rapid analysis of trends. The aim of this study was to use these data to assess the impact of different phases of the pandemic on infant and preschool immunisation uptake rates. We conducted an observational study using routinely collected data for the year prior to the pandemic (2019) and immediately before (22 January to March 2020), during (23 March to 26 July), and after (27 July to 4 October) the first UK "lockdown". Data were obtained for Scotland from the Public Health Scotland "COVID19 wider impacts on the health care system" dashboard and for England from ImmForm. Five vaccinations delivered at different ages were evaluated; 3 doses of "6-in-1" diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type b, and hepatitis B vaccine (DTaP/IPV/Hib/HepB) and 2 doses of measles, mumps, and rubella (MMR) vaccine. This represented 439,754 invitations to be vaccinated in Scotland and 4.1 million for England. Uptake during the 2020 periods was compared to the previous year (2019) using binary logistic regression analysis. For Scotland, uptake within 4 weeks of a child becoming eligible by age was analysed along with geographical region and indices of deprivation. For Scotland and England, we assessed whether immunisations were up-to-date at approximately 6 months (all doses 6-in-1) and 16 to 18 months (first MMR) of age. We found that uptake within 4 weeks of eligibility in Scotland for all the 5 vaccines was higher during lockdown than in 2019. Differences ranged from 1.3% for first dose 6-in-1 vaccine (95.3 versus 94%, odds ratio [OR] compared to 2019 1.28, 95% confidence intervals [CIs] 1.18 to 1.39) to 14.3% for second MMR dose (66.1 versus 51.8%, OR compared to 2019 1.8, 95% CI 1.74 to 1.87). Significant increases in uptake were seen across all deprivation levels. In England, fewer children due to receive their immunisations during the lockdown period were up to date at 6 months (6-in-1) or 18 months (first dose MMR). The fall in percentage uptake ranged from 0.5% for first 6-in-1 (95.8 versus 96.3%, OR compared to 2019 0.89, 95% CI 0.86- to 0.91) to 2.1% for third 6-in-1 (86.6 versus 88.7%, OR compared to 2019 0.82, 95% CI 0.81 to 0.83). The use of routinely collected data used in this study was a limiting factor as detailed information on potential confounding factors were not available and we were unable to eliminate the possibility of seasonal trends in immunisation uptake. In this study, we observed that the national lockdown in Scotland was associated with an increase in timely childhood immunisation uptake; however, in England, uptake fell slightly. Reasons for the improved uptake in Scotland may include active measures taken to promote immunisation at local and national levels during this period and should be explored further. Promoting immunisation uptake and addressing potential vaccine hesitancy is particularly important given the ongoing pandemic and COVID-19 vaccination campaigns.

Effect of social marketing on the knowledge, attitude, and uptake of pap smear among women residing in an urban slum in Lagos, Nigeria

IntroductionNigeria has a low uptake of cervical cancer screening and is one of the five countries that represent over half of the global burden of deaths from cervical cancer. Social marketing principles can be used to design and implement interventions to increase uptake of cervical cancer screening. This study assessed the effect of a social marketing intervention on the knowledge, attitude, and uptake of pap smear among women residing in an urban slum in Lagos State, Nigeria.Materials and methodsThis was a quasi-experimental study. The intervention arm consisted of 140 women recruited from Ago-Egun Bariga community and the control arm consisted of 175 women recruited from Oto-Ilogbo extension community. Social marketing intervention was instituted in the intervention group. Data analysis was done using IBM SPSS Statistics version 20 and Stata version 16.0. Between groups comparisons and within groups comparisons were done using bivariate analysis with Chisquare, Students t test and Paired t test as appropriate.ResultsIn both the intervention and control groups, the mean knowledge score of cervical cancer was low at baseline (0.0 ± 0.3 and 0.1 ± 0.9 respectively). In the intervention group, there was a significant increase in mean knowledge score to 15.1 ± 3.7, post-intervention (p < 0.001). In both groups, the mean attitude score of cervical cancer was low at baseline (27.1 ± 0.8 in the intervention group and 27.2 ± 1.4 in the control group). In the intervention group, there was a significant increase in mean attitude score to 36.5 ± 4.8, post-intervention (p < 0.001). In both the intervention and control groups, uptake of pap smear was low at baseline (0.0% and 0.6%, respectively). In the intervention group, there was a significant increase in uptake of pap smear to 84.3%, post-intervention (p < 0.001). There was no statistically significant change in knowledge, attitude or uptake of pap smear in the control group, post-intervention.ConclusionThis study demonstrated that social marketing intervention can be successful in improving knowledge, attitude, and also the uptake of pap smear, even in settings where these are abysmally low. It is recommended that social marketing intervention be employed as a strategy for improving cervical cancer screening among women residing in slums.

DEGREE OF UPTAKE OF ADVANCED SURGICAL TECHNIQUES IN CARDIAC SURGERY - THE ROLE OF AN

<h3>BACKGROUND</h3> Cardiac surgeons have traditionally strived to be innovative while ensuring quality of care. Despite this, the uptake of new, advanced surgical techniques in the pursuit of improved outcomes varies significantly between surgeons and cardiac centres. The purpose of this study was to develop a novel "Innovation Index" to determine the degree of uptake of advanced surgical techniques at a surgical centre. <h3>METHODS AND RESULTS</h3> For the purposes of this study, only non-emergent, first-time procedures being performed at the New Brunswick Heart Centre between 2010 and 2017 were considered. Five procedure categories were identified as being representative of the degree of innovation in most cardiac surgery centres, including: (1) bilateral vs. single internal mammary artery (IMA) for isolated coronary artery bypass grafting (CABG) with >=2 grafts; (2) endoscopic vein harvest (EVH) vs. open vein harvest (OVH) for any CABG with a saphenous vein graft; (3) minimally invasive vs. conventional mitral valve repair (MVrep) or replacement (MVR) for isolated mitral valve disease; (4) mitral valve repair vs. mitral valve replacement for patients with isolated mitral insufficiency; and (5) transcatheter aortic valve implantation (TAVI) vs. isolated surgical aortic valve replacement (SAVR) for severe aortic stenosis. The rates of each innovative procedure vs. a more traditional approach were calculated on yearly basis, and means of the annual rates for each of the 5 procedures were then computed to form the "overall" rate of innovation or the "Innovation Index" for that particular year. P-trend values were then determined using two-sided Cochran-Armitage test and Jonckheere-Terpstra test to determine if trends in innovation were exhibited over time. Over the course of the study period, a total of 285 patients received bilateral IMA vs. 3004 single IMA; 1605 EVH vs. 2736 OVH; 64 minimally invasive MVrep/MVR vs. 115 conventional; 224 MVrep vs. 262 MVR for mitral insufficiency; and 334 TAVI vs. 504 isolated SAVR. While significant increases in uptake of EVH (p < 0.0001), minimally invasive surgery (p=0.04) and TAVI (p < 0.0001) were noted, rates of BIMA declined (p < 0.0001) while rates of MVrep remained relatively static (p=0.51) (Figure 1). When combined, the overall trend was one of increased innovation over time (p=0.006). <h3>CONCLUSION</h3> This study represents the first attempt at devising an "Innovation Index" to determine the degree of uptake of advanced surgical techniques at a surgical centre. This novel metric may be used to compare centres in terms of their willingness to innovate and to identify leaders in practice change.

Characterization of MXene as a Cancer Photothermal Agent Under Physiological Conditions

A growing interest has recently emerged in the use of nanomaterials in medical applications. Nanomaterials, such as MXene, have unique properties due to their 2D ultra-thin structure, which is potentially useful in cancer photothermal therapy. To be most effective, photothermal agents need to be internalized by the cancer cells. In this study, MXene was fabricated using chemical reactions and tested as a photothermal agent on MDA-231 breast cancer cells under static and physiological conditions. Fluid shear stress (∼0.1 Dyn/cm2) was applied using a perfusion system to mimic the physiological tumor microenvironment. The uptake of MXene was analyzed under fluid flow compared to static culture using confocal microscopy, scanning electron microscopy (SEM), energy dispersive spectrometer (EDS), and transmission electron microscopy (TEM). Furthermore, a viability assay was used to assess cell’s survival after exposing the treated cells to photothermal laser at different power densities and durations. We showed that when incubated with cancer cells, 2D MXene nanoparticles were successfully internalized into the cells resulting in increased intracellular temperatures when exposed to NIR laser. Interestingly, dynamic culture alone did not result in a significant increase in uptake suggesting the need for surface modifications for enhanced cellular uptake under shear stress.

Phase I trial of acoustic cluster therapy (ACT) with chemotherapy in patients with liver metastases of gastrointestinal origin (ACTIVATE study).

TPS3145 Background: Response to existing chemotherapeutics (chemo) can be limited by exposure, itself limited by systemic toxicity. Interstitial fluid pressure can impede transport of drugs with, in some cases, &lt;5% of systemic chemo penetrating the target tumour. ACT is an innovative platform technology using sonopermeation to induce ultrasound (US) mediated targeting of therapeutic agent of choice by co-administration of an emulsion of microbubble-microdroplet clusters (PS101) for intravenous injection. Dual-frequency US is applied to tumor tissue to concentrate the drug through expansion and oscillation of the clusters, increasing tumoral penetration. Early pre-clinical models of ACT indicate significant increase in uptake of co-administered product at the US targeted site and have demonstrated enhanced efficacy outcomes with co-administered ACT across a range of cancer models. All studies showed significant benefit in disease response and tumour regression/inhibition versus drug alone. The combination of US, microbubbles and chemo has been shown to be feasible in a clinical setting using commercially available equipment with no additional toxicities. This first in human study will primarily investigate the safety and tolerability of PS101 in combination with chemo together with any differential response in ACT-treated versus control lesions to identify the phase 2 recommended dose. Methods: This is an open label non-randomised study with central blinded assessment of tumor response. The study comprises two parts: Part 1, a dose escalation in a 3+3 design followed by dose expansion in Part 2. Patients with advanced solid tumors with liver metastases for whom FOLFOX/FOLFIRI is considered an appropriate treatment option are eligible for Part 1 (n=6-12); two separate cohorts of patients with liver metastases, one with metastatic colorectal cancer eligible for 1L or 2L standard of care (SOC) FOLFOX/FOLFIRI (n=25) and one with metastatic pancreatic ductal adenocarcinoma (n= 6) eligible for SOC gemcitabine-nab-paclitaxel will be treated in Part 2. The starting dose of PS101 is 20 µL/kg with a maximum feasible dose of 40 µL/kg. In Part 1, after sentinel administration of PS101 for PK profiling and toxicity assessment, patients receive PS101 (given as i.v. bolus x 3) in combination with FOLFOX or FOLFIRI and US (to one target lesion) in four q2w cycles. The DLT evaluation period comprises the PK-assessment period plus two cycles of ACT plus chemo. Patients receive a further two cycles of ACT and chemo prior to evaluation of tumor lesions by CT/MRI at the Week 8 timepoint. Assessment is made of the target lesion and the pre-defined control lesions outside of the US field. Part 1 has enrolled 5 patients without DLT, with part 2 expected to start in mid-2021. Clinical trial information: NCT04021277.

Effect of Different Levels of Phosphorus, Phosphorus Solubilising Bacteria and Farmyard Manure on Nutrient Content and Uptake by Bt-Cotton

Aim: To determine the effect of integrated use of inorganic phosphorus along with phosphorus solubilising bacteria and farmyard manure on nutrient Content and uptake in Bt-Cotton.&#x0D; Study Design: The experiment was laid out in randomized block design with three replications.&#x0D; Place of Study: At College Farm, Agricultural College, Bapatla, Guntur district.&#x0D; Methodology: After the preliminary layout, the Tulasi-BG II hybrid of cotton was used as a test crop, with a spacing of 90 cm x 60 cm in the experimental site. Plant samples were collected at 45, 90 DAS, and harvest. Plant samples were shade dried and kept in hot air oven at 75°C until a constant weight was obtained. Samples were powdered and then analysed using standard chemical procedures.&#x0D; Results: The uptake of macronutrients viz., N, P, and K was markedly influenced by the treatments with maximum values recorded by the treatment that received 60 kg P2O5 ha-1 + FYM + PSB. Their uptake significantly differed with increase in dose of phosphorus applied at all growth stages. Combined use of 60 kg P2O5 ha-1 + FYM + PSB resulted in a significant increase in uptake of all micronutrients (Zn, Cu, Mn, and Fe) at all stages except Cu at 90 DAS.&#x0D; Conclusion: Application of phosphorus combined with FYM and PSB not only reduce inorganic phosphorus fertilization but also enhance the uptake of nutrients and plant nutrient content by providing favourable conditions for plant growth. Application of 30 kg P2O5 ha-1+ PSB + FYM was found to be on a par with addition of only 60 kg ha-1P2O5. Hence the P dose can be reduced to half by integrating with PSB and FYM.

Proof of Concept Study for Increasing Tenascin-C-Targeted Drug Delivery to Tumors Previously Subjected to Therapy: X-Irradiation Increases Tumor Uptake

Simple SummaryWe hypothesized that an agent recognizing a specific factor, which is involved in tissue injury repair, could achieve the goal of delivering an additional antitumor agent to tumors during tissue repair after initial anticancer therapy. To demonstrate our concept, the present study employed tenascin-C (TNC) as a target molecule and radiation as initial therapy. Increased TNC expression was observed in tumors after radiation exposure in a pancreatic cancer mouse model. Of our three anti-TNC antibodies, the antibody 3–6 showed statistically significant higher tumor uptake compared with non-irradiated tumors in the by biodistribution and single-photon emission computed tomography with computed tomography studies. This finding strongly supports our concept. Our proposed therapeutic strategy could result in better outcomes for patients with treatment-refractory cancer.In treatment-refractory cancers, tumor tissues damaged by therapy initiate the repair response; therefore, tumor tissues must be exposed to an additional burden before successful repair. We hypothesized that an agent recognizing a molecule that responds to anticancer treatment-induced tissue injury could deliver an additional antitumor agent including a radionuclide to damaged cancer tissues during repair. We selected the extracellular matrix glycoprotein tenascin-C (TNC) as such a molecule, and three antibodies recognizing human and murine TNC were employed to evaluate X-irradiation-induced changes in TNC uptake by subcutaneous tumors. TNC expression was assessed by immunohistochemical staining of BxPC-3 tumors treated with or without X-irradiation (30 Gy) for 7 days. Antibodies against TNC (3–6, 12–2–7, TDEAR) and a control antibody were radiolabeled with 111In and injected into nude mice having BxPC-3 tumors 7 days after X-irradiation, and temporal uptake was monitored for an additional 4 days by biodistribution and single-photon emission computed tomography with computed tomography (SPECT/CT) studies. Intratumoral distribution was analyzed by autoradiography. The immunohistochemical signal for TNC expression was faint in nontreated tumors but increased and expanded with time until day 7 after X-irradiation. Biodistribution studies revealed increased tumor uptake of all three 111In-labeled antibodies and the control antibody. However, a statistically significant increase in uptake was evident only for 111In-labeled 3–6 (35% injected dose (ID)/g for 30 Gy vs. 15% ID/g for 0 Gy at day 1, p < 0.01), whereas limited changes in 111In-labeled TDEAR2, 12–2–27, and control antibody were observed (several % ID/g for 0 and 30 Gy). Serial SPECT/CT imaging with 111In-labeled 3–6 or control antibody provided consistent results. Autoradiography revealed noticeably stronger signals in irradiated tumors injected with 111In-labeled 3–6 compared with each of the nonirradiated tumors and the control antibody. The signals were observed in TNC-expressing stroma. Markedly increased uptake of 111In-labeled 3–6 in irradiated tumors supports our concept that an agent, such as an antibody, that recognizes a molecule involved in tissue injury repair, such as TNC, could enhance drug delivery to tumor tissues that have undergone therapy. The combination of antibody 3–6 coupled to a tumoricidal drug and conventional therapy has the potential to achieve better outcomes for patients with refractory cancer.

Impact of routine opt-out HIV/HCV screening on testing uptake at a syringe services program: An interrupted time series analysis

BackgroundHepatitis C (HCV) is the most common infectious disease among people who inject drugs (PWID). Engaging PWID in harm reduction services, such as syringe service programs (SSPs), is critical to reduce HCV and HIV transmission. Additionally, testing for HIV and HCV among PWID is important to improve diagnosis and linkage to care. On March 1, 2018, Florida's only legal SSP implemented bundled opt-out HIV/HCV testing at enrollment. We aimed to examine the differences in HIV/HCV testing uptake before and after the implementation of the opt-out testing policy. MethodsMultivariable logistic regression was used to assess predictors of accepting HIV/HCV tests, controlling for opt-in and opt-out policy. Monthly estimates of the percent of participants accepting an HIV test, HCV test, or both were generated. Interrupted Time Series (ITS) analysis evaluated the immediate policy impact on level of uptake and trend in uptake over time for bundled HIV/HCV testing before and after the opt-out testing policy. ResultsThe total study period was 37 months between December 2016–January 2020 with 512 SSP participants 15 months prior and 547 SSP participants 22 months after implementation of bundled HIV/HCV opt-out testing. Significant predictors of accepting both HIV/HCV tests were cocaine injection (aOR = 2.36), self-reported HIV positive status (aOR = 0.39) and self-reported HCV positive status (aOR = 0.27). Based on the ITS results, there was a significant increase in uptake of HIV/HCV testing by 42.4% (95% CI: 26.2%–58.5%, p < 0.001) immediately after the policy change to opt-out testing. ConclusionBundled opt-out HIV/HCV testing substantially increased the percentage of SSP clients who received HIV and HCV rapid tests at enrollment into the program, and the effect remained stable across the 22 months post opt-out testing policy. Future investigation must assess PWID-level perspective of testing preferences and examine whether this testing approach improves HIV/HCV detection among PWID previously unaware of their status.

Male partner testing and sexual behaviour following provision of multiple HIV self-tests to Kenyan women at higher risk of HIV infection in a cluster randomized trial.

IntroductionWithout significant increases in uptake of HIV testing among men, it will be difficult to reduce HIV incidence to disease elimination levels. Secondary distribution of HIV self‐tests by women to their male partners is a promising approach for increasing male testing that is being implemented in several countries. Here, we examine male partner and couples testing outcomes and sexual decision making associated with this approach in a cluster randomized trial.MethodsWe examined data from women at higher risk of HIV participating in the intervention arm of an ongoing pair‐matched cluster randomized trial in Kenya. HIV‐negative women ≥18 years who self‐reported ≥2 partners in the past month were eligible. Participants received self‐tests at enrolment and three‐monthly intervals. They were encouraged to offer tests to sexual partners with whom they anticipated condomless sex. At six months, we collected data on self‐test distribution, male partner and couples testing, and testing and sexual behaviour in the three most recent transactional sex encounters. We used descriptive analyses and generalized estimating equation models to understand how sexual behaviour was influenced by self‐test distribution.ResultsFrom January 2018 to April 2019, 921/1057 (87%) participants completed six‐month follow‐up. Average age was 28 years, 65% were married, and 72% reported income through sex work. Participants received 7283 self‐tests over six months, a median of eight per participant. Participants offered a median three self‐tests to sexual partners. Of participants with a primary partner, 94% offered them a self‐test. Of these, 97% accepted the test. When accepted, couples testing was reported among 91% of participants. Among 1954 transactional sex encounters, 64% included an offer to self‐test. When offered self‐tests were accepted by 93% of partners, and 84% who accepted conducted couples testing. Compared to partners with an HIV‐negative result, condom use was higher when men had a reactive result (56.3% vs. 89.7%, p < 0.01), were not offered a self‐test (56.3% vs. 62.0%, p = 0.02), or refused to self‐test (56.3% vs. 78.3, p < 0.01).ConclusionsProviding women with multiple self‐tests facilitated male partner and couples testing, and led to safer sexual behaviour. These findings suggest secondary distribution is a promising approach for reaching men and has HIV prevention potential. Clinical Trial Number: NCT03135067.

Evaluation of the thermal regeneration of an amine-grafted mesoporous silica used for CO2/N2 separation

In view of the promising applicability of adsorption to the capture of CO2 from post-combustion gases, the use of mesoporous silica functionalized with 3-aminopropyltriethoxysilane (APTES) was studied as adsorbent in a fixed bed for CO2–N2 separation under thermal swings. Characterization of the adsorbent performed before and after functionalization indicated that amine grafting was successful. Additionally, CO2 adsorption on a magnetic suspension balance showed a significant increase in uptake of the APTES-functionalized sample over the support, mainly at low relative pressures. Relatively high values of adsorption enthalpy suggest the occurrence of chemical adsorption attributed to CO2 bonding with the amines. Breakthrough curves were measured for pure CO2, N2 and the CO2/N2 (15/75% v/v) mixture, which showed good agreement with respect to the uptake of the individual gases, as determined from gravimetric tests. Full CO2 desorption from the bed required a temperature rise, which suggests that these materials may be suitable for TSA cyclic processes. A temperature of 90 °C was enough for a complete regeneration of the adsorbent during the desorption phase under dynamic conditions. The material showed very stable behavior after 20 successive cycles.

Prevention of Dominant IgG Adsorption on Nanocarriers in IgG-Enriched Blood Plasma by Clusterin Precoating.

Nanocarriers for medical applications must work reliably within organisms, independent of the individual differences in the blood proteome. Variation in the blood proteome, such as immunoglobulin levels, is a result of environmental, nutrition, and constitution conditions. This variation, however, should not influence the behavior of nanocarriers in biological media. The composition of the protein corona is investigated to understand the influence varying immunoglobulin levels in the blood plasma have on the interactions with nanocarriers. Specifically, the composition of the nanocarriers' coronas is analyzed after incubation in plasma with normal or elevated immunoglobulin G (IgG) levels, and cellular uptake is monitored in cell lines containing different immunoglobulin receptors. Here, it is reported that upon doubling the IgG concentration in plasma, the IgG fraction in the protein corona increases by a factor of 40 independent of the nanocarrier material. This results in a significant increase in uptake in cells exhibiting IgG binding receptors. Furthermore, precoating nanocarriers with clusterin successfully prevents dominant IgG‐adsorption and additionally reduces cellular internalization, after incubation with IgG‐enriched plasma. Therefore, precoating nanocarriers may be utilized as a powerful method to reduce the influence of individual variations in blood composition on the protein corona.

Interventions to increase referral and uptake to pulmonary rehabilitation in people with COPD: a systematic review.

Pulmonary rehabilitation (PR) reduces the number and duration of hospital admissions and readmissions, and improves health-related quality of life in patients with COPD. Despite clinical guideline recommendations, under-referral and limited uptake to PR contribute to poor treatment access. We reviewed published literature on the effectiveness of interventions to improve referral to and uptake of PR in patients with COPD when compared to standard care, alternative interventions, or no intervention. The review followed recognized methods. Search terms included “pulmonary rehabilitation” AND “referral” OR “uptake” applied to MEDLINE, EMBASE, CINAHL, PsycINFO, ASSIA, BNI, Web of Science, and Cochrane Library up to January 2018. Titles, abstracts, and full papers were reviewed independently and quality appraised. The protocol was registered (PROSPERO # 2016:CRD42016043762). We screened 5,328 references. Fourteen papers met the inclusion criteria. Ten assessed referral and five assessed uptake (46,146 patients, 409 clinicians, 82 hospital departments, 122 general practices). One was a systematic review which assessed uptake. Designs, interventions, and scope of studies were diverse, often part of multifaceted evidence-based management of COPD. Examples included computer-based prompts at practice nurse review, patient information, clinician education, and financial incentives. Four studies reported statistically significant improvements in referral (range 3.5%–36%). Two studies reported statistically significant increases in uptake (range 18%–21.5%). Most studies had methodological and reporting limitations. Meta-analysis was not conducted due to heterogeneity of study designs. This review demonstrates the range of approaches aimed at increasing referral and uptake to PR but identifies limited evidence of effectiveness due to the heterogeneity and limitations of study designs. Research using robust methods with clear descriptions of intervention, setting, and target population is required to optimize access to PR across a range of settings.

The Impact of in Intervention Program on Oral Cancer Awareness and Practice of Preventive Behaviors in High-Risk Indigenous Community in Sarawak, Malaysia

Background: Oral cancer is highly prevalent among indigenous people in Sarawak as this population lacks awareness and is known to practice high-risk habits. Aim: This study aimed to develop and evaluate the impact of an educational intervention to improve oral cancer awareness and practice of preventive behavior among high-risk indigenous communities in Sarawak, Malaysia. Methods: A quasi-experimental study was undertaken involving adults in a Bisaya community (with high risk habits) in Limbang, Sarawak. The intervention group received a structured, Health Beliefs Model (HBM) theory-based oral cancer education module, while the control group was exposed to the conventional oral cancer education method during Ministry of Health's community oral cancer and precancer screening program. Face-to-face interviews using a validated structured questionnaire were conducted to obtain baseline information prior to intervention and after one and three months. Descriptive and multivariate statistics were used for analyzing the data using SPSS software. Results: The overall response rate was 99.5%. The final sample comprised of 204 respondents (89 in the control group and 115 in the intervention group). At baseline, 75.1% of respondents had heard about oral cancer, however their in-depth knowledge on risk factors, signs and symptoms and prevention were lacking. The control group had better awareness than the intervention group. Smoking and alcohol drinking were more prevalent in the intervention group, whereas betel quid chewing and practice of mouth self-examination (MSE) were more evident in the control group. At 1-month and 3-month follow-up, there were significantly higher mean scores in all aspects of oral cancer awareness among respondents in the intervention group and these improved levels of awareness were maintained over a period of 1- and 3-months. There were higher proportion of smokers, alcohol drinkers and betel quid chewers in the intervention group who reported quitting their habits or reducing the number of cigarettes smoked per day, frequency of alcohol drinking and betel quid chewing than the control group. The respondents in the intervention group also had significant increase in uptake of MSE and higher proportions who performed it once a month. Conclusion: The structured HBM-based oral cancer health education intervention was shown to have significant impacts on oral cancer knowledge and awareness, cessation and reduction of risk habits and increased the uptake of MSE among respondents in the intervention group of this indigenous community. Therefore, the introduced structured health education intervention is recommended for other communities in Malaysia that practice the same oral cancer risk habits. Considering this indigenous community is of lower socioeconomic status (SES), the introduced intervention could also be extended to other lower SES groups in Malaysia.

Genetically engineered cell factories produce glycoengineered vaccines that target antigen-presenting cells and reduce antigen-specific T-cell reactivity

Genetically engineered cell factories produce glycoengineered vaccines that target antigen-presenting cells and reduce antigen-specific T-cell reactivity