Nanobody-liposomes as novel cancer vaccine platform to efficiently stimulate T cell immunity.

Cancer vaccines can be utilized in combination with checkpoint inhibitors to optimally stimulate the anti-tumor immune response. Uptake of vaccine antigen by antigen presenting cells (APCs) is a prerequisite for T cell priming, but often relies on non-specific mechanisms. Here, we have developed a novel vaccination strategy consisting of cancer antigen-containing liposomes conjugated with CD169- or DC-SIGN-specific nanobodies (single domain antibodies) to achieve specific uptake by APCs. Our studies demonstrate efficient nanobody liposome uptake by human and murine CD169+ and DC-SIGN+ APCs in vitro and in vivo when compared to control liposomes or liposomes with natural ligands for CD169 and DC-SIGN. Uptake of CD169 nanobody liposomes resulted in increased T cell activation by human APCs and stimulated naive T cell priming in mouse models. In conclusion, while nanobody liposomes have previously been utilized to direct drugs to tumors, here we show that nanobody liposomes can be applied as vaccination strategy that can be extended to other receptors on APCs in order to elicit a potent immune response against tumor antigens.

A rare case of adult intussusception.

SUMMARY: Adult intussusception is rare, and its non-specific symptoms make the diagnosis particularly difficult. Imaging modalities such as X-ray, abdominal ultrasound and multidetector computed tomography (MDCT) may improve preoperative detection. In this report, we present a 53-year-old male with an ileocaecal intussusception. The patient underwent an extended right hemicolectomy and double barrel ileocolostomy. Histopathological review of the specimen identified the lead point as an intramural caecal lymph node which, as far as we are aware, is the first time this type of lead point has been reported.

Positive effects of indoor environmental conditions on students and their performance in higher education classrooms: A between-groups experiment.

This study explores if multiple alterations of the classrooms' indoor environmental conditions, which lead to environmental conditions meeting quality class A of Dutch guidelines, result in a positive effect on students' perceptions and performance. A field study, with a between-group experimental design, was conducted during the academic course in 2020-2021. First, the reverberation time (RT) was lowered in the intervention condition to 0.4 s (control condition 0.6 s). Next, the horizontal illuminance (HI) level was raised in the intervention condition to 750 lx (control condition 500 lx). Finally, the indoor air quality (IAQ) in both conditions was improved by increasing the ventilation rate, resulting in a reduction of carbon dioxide concentrations, as a proxy for IAQ, from ~1100 to <800 ppm. During seven campaigns, students' perceptions of indoor environmental quality, health, emotional status, cognitive performance, and quality of learning were measured at the end of each lecture using questionnaires. Furthermore, students' objective cognitive responses were measured with psychometric tests of neurobehavioural functions. Students' short-term academic performance was evaluated with a content-related test. From 201 students, 527 responses were collected. The results showed that the reduction of the RT positively influenced students' perceived cognitive performance. A reduced RT in combination with raised HI improved students' perceptions of the lighting environment, internal responses, and quality of learning. However, this experimental condition negatively influenced students' ability to solve problems, while students' content-related test scores were not influenced. This shows that although quality class A conditions for RT and HI improved students' perceptions, it did not influence their short-term academic performance. Furthermore, the benefits of reduced RT in combination with raised HI were not observed in improved IAQ conditions. Whether the sequential order of the experimental conditions is relevant in inducing these effects and/or whether improving two parameters is already beneficial, is unknown.

An audit of patients clinically deemed as high risk for malignant breast pathology at the Helen Joseph Hospital Breast Clinic.

BACKGROUND: The Helen Joseph Hospital Breast Clinic has implemented a clinical triage system for patients presenting with a variety of breast concerns. The goal of this system is to expedite the process from initial presentation to radiological assessment of patients with suspected breast malignancy or breast abscess in a resource limited setting. The objective was to assess the clinical, imaging and histological diagnoses of breast disease in these patients with malignancy and sepsis. METHODS: A retrospective audit of patients clinically deemed high risk for malignant breast pathology referred to the breast imaging unit (BIU) in 2018. Patients were triaged based on strict clinical criteria: presence of a breast mass with or without lymph nodes or a breast abscess. Patients that were subsequently referred for mammography/ultrasound were identified using the patient files in the BIU. Results were recorded on Microsoft Excel and analysed using SAS version 9.2. RESULTS: Three hundred and twenty-five patients were included in this study. Eighty-seven (26.8%) were diagnosed with breast cancer and 236 (72.6%) with benign disease. The most common presenting complaint was a palpable mass (n = 227; 69.9%). Ninety-five per cent of patients characterised as BI-RADS 5 had malignant disease. 55.8% of malignancies diagnosed on ultrasound had locally advanced disease. The most common histological diagnosis of malignancy was invasive ductal carcinoma (n = 67, 77%). The most commonly diagnosed benign disease was breast abscess (n = 42, 17.8%). CONCLUSION: BI-RADS findings correspond to similar studies, however, a large number of benign breast disease was diagnosed. This may indicate heightened clinical awareness of breast cancer diagnosis and early detection. A significant percentage of malignancies presented as locally advanced. Except for a lower number of invasive lobular carcinoma, the histological spectrum of malignant disease is similar to comparative studies.

High capacity Pb(II) adsorption characteristics onto raw- and chemically activated waste activated sludge.

The Pb(II) adsorption characteristics of chemically activated waste activated sewage sludge (WAS) were compared to raw WAS. Adsorption kinetics and equilibrium isotherm parameters were fit using classic adsorption models. HCl and H2SO4 activation terminated any significant sludge-based adsorption. Raw and ZnCl2 activated WAS displayed Langmuir adsorption capacities of 307 mg/g and 274 mg/g, respectively. Surface characterization revealed that chemical activation with ZnCl2 increased the BET surface area for raw WAS from 0.97 m2/g to 1.78 m2/g, but did not significantly change the surface structure. FTIR analyzes and XPS were used to further investigate the nature of lead binding. The relationships between equilibrium ion concentration and Pb(II) adsorption suggest cationic exchange with hydrogen, calcium, and zinc as a significant mechanism of Pb(II) removal alongside electrostatic attraction. The pHPZC was determined as 2.58 and 2.30 for ZnCl2 activated WAS and raw WAS respectively. HNO3 and Ca(NO3)2 demonstrated sufficient elution properties for WAS recovery. For authentic industrial effluent both raw and ZnCl2 activated WAS displayed Pb(II) removal behavior comparable to simulated Pb(II) solutions. In comparison with modified and unmodified sludges from literature, this study demonstrates the auspicious potential of raw WAS as an effective Pb(II) adsorbent independent of pyrolytic or chemical activation.

Effective removal of arsenate from wastewater using aluminium enriched ferric oxide-hydroxide recovered from authentic acid mine drainage.

This study explored an eco-friendly approach for the synthesis of novel aluminium enriched ferric oxide-hydroxide (Fe/AlO(OH)) from authentic acid mine drainage (AMD). The synthesized Fe/AlO(OH) was subsequently tested for arsenate removal capabilities. Fe/AlO(OH) was synthesized from bona fide AMD via selective precipitation, thermal activation, and vibratory ball milling. One-factor-at-a-time (OFAAT) method was used to optimize operational parameters, which include adsorbent dosage, concentration, pH, agitation time, and temperature. Optimized conditions were observed to be 150 ppm of As(V), Solid: Liquid ratio - 1 g: 250 mL, contact time of 60 min, and ambient temperature and pH. Limited temperature and pH effects on adsorption were observed. Equilibrium data fits using Langmuir-, Freundlich-, Two surface Langmuir-, Dubinin-Radushkevich-, and Dubinin-Astokov isotherm models showed highly favorable adsorption conditions, the highest known maximum adsorption capacity for As(V) of 102-129 mg g-1, and coupled physisorption/diffusion limited adsorption. Thermodynamic analysis showed positive Gibbs free energy (ΔG°), negative enthalpy change (ΔH°), and positive entropy change (ΔS°) - likely a result of an inner sphere complexation of the As(V) with the Fe/Al surface. Considering the obtained results, valorization of AMD for the synthesis of Fe/AlO(OH) was viable and effective. This initiative could potentially minimize the footprints of AMD and arsenic pollution.

Prediction admission in the older population in the Emergency Department: the CLEARED tool.

BACKGROUND: Length of stay (LOS) in the Emergency Department (ED) is correlated with an extended in-hospital LOS and may even increase 30-day mortality. Older patients represent a growing population in the ED and they are especially at risk of adverse outcomes. Screening tools that adequately predict admission could help reduce waiting times in the ED and reduce time to treatment. We aimed to develop and validate a clinical prediction tool for admission, applicable to the aged patient population in the ED. METHODS: Data from 7,606 ED visits of patients aged 70 years and older between 2012 and 2014 were used to develop the CLEARED tool. Model performance was assessed with discrimination using logistic regression and calibration. The model was internally validated by bootstrap resampling in Erasmus Medical Center and externally validated at two other hospitals, Medisch Spectrum Twente (MST) and Leiden University Medical Centre (LUMC). RESULTS: CLEARED contains 10 predictors: body temperature, heart rate, diastolic blood pressure, systolic blood pressure, oxygen saturation, respiratory rate, referral status, the Manchester Triage System category, and the need for laboratory or radiology testing. The internally validated area under the curve (AUC) was 0.766 (95% CI [0.759;0.781]). External validation in MST showed an AUC of 0.797 and in LUMC, an AUC of 0.725. CONCLUSIONS: The developed CLEARED tool reliably predicts admission in elderly patients visiting the ED. It is a promising prompt, although further research is needed to implement the tool and to investigate the benefits in terms of reduction of crowding and LOS in the ED.

Endometrial development during the transition to menopause: preliminary associations with follicular dynamics.

Objective: This study aimed to test the hypothesis that the development of functional luteal phase dominant follicles (LPDFs) is associated with increased endometrial growth as women transition to menopause.Methods: Endometrial thickness (ET), follicle development, and hormone production were characterized in ovulatory women of mid-reproductive age (MRA; 18-35 years, n = 10) and advanced reproductive age (ARA; 45-55 years, n = 16). Transvaginal ultrasonography was conducted every 1-3 days during one interovulatory interval to quantify ET and the diameters of follicles ≥2 mm. Blood was drawn at each visit to measure progesterone, estradiol, inhibin A, follicle stimulating hormone, and luteinizing hormone.Results: In the MRA group, ET was lower (8.87 vs. 10.1 mm) in women with typical versus no LPDFs, in association with greater luteal phase estradiol (91.1 vs. 48.8 ng/l). In the ARA group, luteal phase endometrial growth was greater (12.0 vs. 10.4 mm) in women with typical versus no LPDFs, in association with lower progesterone (10.7 vs. 13.8 µg/l; LPDF effect p < 0.1) and inhibin A (35.6 vs. 51.17 ng/l; p < 0.10).Conclusions: Preliminary findings suggest that ET may be increased in women who develop LPDFs, in association with reduced luteal phase progesterone and inhibin A, during the transition to menopause. Continued research is required to confirm these findings.

[3D printed medical devices and anatomical models: What kind of distribution and which uses in French hospitals?] / Dispositifs médicaux et modèles anatomiques produits par impression 3D : quelle diffusion et quelles utilisations dans les établissements de santé français ?

3D printing plays an increasingly important role in the medical sector and particularly in surgery. Nowadays, numerous manufacturers benefit from this technology to produce their medical devices and some hospitals have also purchased 3D printers. In this context, the aim of the present study was to study the distribution and the use of 3D printing in French hospitals in order to its main features in surgery. By conducting a national survey, we targeted hospitals equipped with 3D printers and those using external providers to benefit from this technology. Forty-seven hospitals were identified as using 3D printing including eight equipped with in-house 3D printers. This work gives us a first picture of 3D printing for hospital use in France and it raises questions about hospital pharmacists' involvement in 3D printed medical device production.

Investigating screening for diabetes in women with a history of gestational diabetes.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is encountered more frequently in women with a history of gestational diabetes (GD). Screening for T2DM after pregnancy is, therefore, recommended every ≥ 1-3 years in this population. Early detection could allow for timely intervention strategies, especially in women of childbearing age. Data on adherence to diabetes screening recommendations and the prevalence of T2DM in this population are not available in the Dutch population. AIM: To investigate the T2DM screening rate and evaluate the risk of T2DM in the five-year period following GD pregnancy. METHODS: Single-centre survey in 85 women diagnosed with GD in 2010, using electronic medical records. Primary care physicians were asked to complete a survey regarding the screening frequency and the onset of T2DM in the five-year period following the GD pregnancy. RESULTS: On average 33% underwent yearly screening. The screening rate, however, went up to 61.2% after primary care physicians were requested to screen this population in 2015. Of the women who were screened, 10 (19.2%) developed T2DM within five years after GD. CONCLUSION: Current screening recommendations are poorly met, leading to missed, or delayed diagnosis of T2DM in our population. T2DM is a frequently occurring long-term complication in those who were screened in the five-year period after delivery. Optimising awareness amongst health care professionals of GD as a risk factor for T2DM is warranted and strategies to improve surveillance are necessary.

[Mindfulness training for psychiatrists in residency: a pilot study]. / Mindfulnesstraining voor aiossen psychiatrie: een pilotstudie.

BACKGROUND: Medical students and psychiatrists in residency run a high risk for burnout. Furthermore, while at medical school, students seem to experience a reduction in empathy; this seems to be linked to a high level of stress. Interventions based on mindfulness training appear to reduce stress and increase empathy in medical students. Trainees in psychiatric residency might also benefit from mindfulness training.
AIM: To assess the effects that a mindfulness course has on perceived stress and empathy in psychiatrists in residency.
METHOD: In this pilot study 13 trainees in psychiatric residency participated in an eight-week course in mindfulness. Before and after the training, 11 of the participants completed questionnaires relating to their empathy, perceived stress and mindfulness.
RESULTS: Participants reported experiencing considerably more empathy after their course than before it. Perceived stress also diminished, but not significantly.
CONCLUSION: The results support our suggestion that mindfulness training can be a valuable part of the curriculum for trainees in psychiatric residency.

[Hospital-based health technology assessment in France: how to proceed to evaluate innovative medical devices?]. / Évaluation des technologies de santé en milieu hospitalier : quelle organisation pour évaluer et acquérir des dispositifs médicaux innovants ?

Innovative medical devices offer solutions to medical problems and greatly improve patients' outcomes. Like National Health Technology Assessment (HTA) agencies, hospitals face numerous requests for innovative and costly medical devices. To help local decision-makers, different approaches of hospital-based HTA (HB-HTA) have been adopted worldwide. The objective of the present paper is to explore HB-HTA models for adopting innovative medical devices in France and elsewhere. Four different models have been conceptualized: "ambassador" model, "mini-HTA" model, "HTA unit" model and "internal committee". Apparently, "HTA unit" and "internal committee" (or a mixture of both models) are the prevailing HB-HTA models in France. Nevertheless, some weaknesses of these models have been pointed out in previous works. Only few examples involving hospital pharmacists have been found abroad, except in France and in Italy. Finally, the harmonization of the assessment of innovative medical devices in France needs a better understanding of HB-HTA practices.

Conserving large carnivores: dollars and fence.

Conservationists often advocate for landscape approaches to wildlife management while others argue for physical separation between protected species and human communities, but direct empirical comparisons of these alternatives are scarce. We relate African lion population densities and population trends to contrasting management practices across 42 sites in 11 countries. Lion populations in fenced reserves are significantly closer to their estimated carrying capacities than unfenced populations. Whereas fenced reserves can maintain lions at 80% of their potential densities on annual management budgets of $500 km(-2) , unfenced populations require budgets in excess of $2000 km(-2) to attain half their potential densities. Lions in fenced reserves are primarily limited by density dependence, but lions in unfenced reserves are highly sensitive to human population densities in surrounding communities, and unfenced populations are frequently subjected to density-independent factors. Nearly half the unfenced lion populations may decline to near extinction over the next 20-40 years.

The development and implementation of pharmaceutical care across borders.

The community pharmacist is an essential professional for a high standard healthcare delivery system. However, many indicators, at the EU level or national level, suggest that the tasks entrusted to him, since the beginning of the 20th century, must ensure a safe and efficient treatment to patient. In several member states, the legislation has recently been changed and community pharmacists in Europe have redefined their role in the healthcare delivery system in order to focus more on patients' care. In France, the new reform concerning hospitals and the report on community pharmacy, written by social inspectors for the government, in some aspects, contains propositions similar to those adopted in Canada.

Assessment of parenting and developmental problems in toddlers: development and feasibility of a structured interview.

BACKGROUND: Assessment of (early signs of) parenting and developmental problems in young children by preventive child health care (CHC) workers is recommended, but no validated instruments exist. The aim of this project was to develop and test an instrument for early detection and assessment of problems in toddlers, using the perspectives and experience of both the parent and the professional. METHODS: Using an iterative process, we adapted and expanded a structured interview on need for parenting support into the Structured Problem Analysis of Raising Kids (SPARK). The SPARK consists of 16 subject areas, ranging from somatic health to family issues. The SPARK was tested in daily practice for feasibility and discriminative capacity. The sample consisted of all toddlers aged 18 months living in Zeeland, a province of the Netherlands, during the study period (n= 1140). RESULTS: The response rate was 97.8%. Although the median level of support needed according to the SPARK was low, 4.5% of the toddlers and their parents required intensive help or immediate action. The risk assessment showed 2.9% high, 16.5% increased and 80.6% low risk for parenting and developmental problems. The risk assessment of the CHC professional was associated with known risk factors for child maltreatment. CONCLUSIONS: This study shows that a structured interview, named the SPARK, is feasible in daily practice and clarifies risks and care needs for parenting and developmental problems in toddlers.

Germline SMARCB1 mutation and somatic NF2 mutations in familial multiple meningiomas.

BACKGROUND: Multiple meningiomas occur in <10% of meningioma patients. Their development may be caused by the presence of a predisposing germline mutation in the neurofibromatosis type 2 (NF2) gene. The predisposing gene in patients with non-NF2 associated multiple meningiomas remains to be identified. Recently, SMARCB1 was reported to be a potential predisposing gene for multiple meningiomas in a family with schwannomatosis and multiple meningiomas. However, involvement of this gene in the development of the meningiomas was not demonstrated. RESULTS: Five affected members of a large family with multiple meningiomas were investigated for the presence of mutations in SMARCB1 and NF2. A missense mutation was identified in exon 2 of SMARCB1 as the causative germline mutation predisposing to multiple meningiomas; furthermore, it was demonstrated that, in accordance with the two-hit hypothesis for tumourigenesis, the mutant allele was retained and the wild-type allele lost in all four investigated meningiomas. In addition, independent somatically acquired NF2 mutations were identified in two meningiomas of one patient with concomitant losses of the wild-type NF2 allele. CONCLUSION: It is concluded that, analogous to the genetic events in a subset of schwannomatosis associated schwannomas, a four-hit mechanism of tumour suppressor gene inactivation, involving SMARCB1 and NF2, might be operative in familial multiple meningiomas associated meningiomas.

Effects of trophy hunting on lion and leopard populations in Tanzania.

Tanzania holds most of the remaining large populations of African lions (Panthera leo) and has extensive areas of leopard habitat (Panthera pardus), and both species are subjected to sizable harvests by sport hunters. As a first step toward establishing sustainable management strategies, we analyzed harvest trends for lions and leopards across Tanzania's 300,000 km(2) of hunting blocks. We summarize lion population trends in protected areas where lion abundance has been directly measured and data on the frequency of lion attacks on humans in high-conflict agricultural areas. We place these findings in context of the rapidly growing human population in rural Tanzania and the concomitant effects of habitat loss, human-wildlife conflict, and cultural practices. Lion harvests declined by 50% across Tanzania between 1996 and 2008, and hunting areas with the highest initial harvests suffered the steepest declines. Although each part of the country is subject to some form of anthropogenic impact from local people, the intensity of trophy hunting was the only significant factor in a statistical analysis of lion harvest trends. Although leopard harvests were more stable, regions outside the Selous Game Reserve with the highest initial leopard harvests again showed the steepest declines. Our quantitative analyses suggest that annual hunting quotas be limited to 0.5 lions and 1.0 leopard/1000 km(2) of hunting area, except hunting blocks in the Selous Game Reserve, where harvests should be limited to 1.0 lion and 3.0 leopards/1000 km(2) .

[Protocol for complementary and alternative medicine within the Dutch mental health services]. / Protocol voor complementaire en alternatieve geneeswijzen; naar een verantwoorde toepassing binnen de ggz.

Complementary and alternative medicine (CAM) is the subject of heated debate. There are many prejudices for and against CAM. At the centre for Integrative Psychiatry (CIP) of Lentis CAM is offered alongside conventional treatments, but under strict conditions. Because of the controversy surrounding CAM and the potential health risks involved, the CIP in Lentis has formulated a protocol for CAM which is presented in this article.