The molecular consequences of FOXF1 missense mutations associated with alveolar capillary dysplasia with misalignment of pulmonary veins.

Background: Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a fatal congenital lung disorder strongly associated with genomic alterations in the Forkhead box F1 (FOXF1) gene and its regulatory region. However, little is known about how FOXF1 genomic alterations cause ACD/MPV and what molecular mechanisms are affected by these mutations. Therefore, the effect of ACD/MPV patient-specific mutations in the FOXF1 gene on the molecular function of FOXF1 was studied.

Technological Applications Contributing to Relieve Care Burden or to Sleep of Caregivers and People With Dementia: A Scoping Review From the Perspective of Social Isolation.

The need for care will increase in the coming years. Most people with a disability or old age receive support from an informal caregiver. Caring for a person with dementia can be difficult because of the BPSD (Behavioral and Psychological Symptoms of Dementia).

Critical changes in hypothalamic gene networks in response to pancreatic cancer as found by single-cell RNA sequencing.

Objective: Cancer cachexia is a devastating chronic condition characterized by involuntary weight loss, muscle wasting, abnormal fat metabolism, anorexia, and fatigue. However, the molecular mechanisms underlying this syndrome remain poorly understood. In particular, the hypothalamus may play a central role in cachexia, given that it has direct access to peripheral signals because of its anatomical location and attenuated blood-brain barrier.

The Balance between Energy, Environmental Security, and Technical Performance: The Regulatory Challenge of Nanofluids.

Nowadays, numerous studies on nanomaterials (NMs) and Nanofluids (NFs) are account a plethora of applications. With the scientific society's common goal of fulfilling the target of sustainable development proposed by the UN by 2030, it is necessary to combine efforts based on the scientific and technological knowledge already acquired, to apply these new systems with safety. There are thousands of publications that examine the use of NFs, their benefits and drawbacks, properties, behaviors, etc.

Chronic cerebral lipocalin 2 exposure elicits hippocampal neuronal dysfunction and cognitive impairment.

Lipocalin 2 (LCN2) is a pleiotropic molecule that is induced in the central nervous system (CNS) in several acute and chronic pathologies. The acute induction of LCN2 evolved as a beneficial process, aimed at combating bacterial infection through the sequestration of iron from pathogens, while the role of LCN2 during chronic, non-infectious disease remains unclear, and recent studies suggest that LCN2 is neurotoxic. However, whether LCN2 is sufficient to induce behavioral and cognitive alterations remains unclear.

The histone H3-lysine 4-methyltransferase Mll4 regulates the development of growth hormone-releasing hormone-producing neurons in the mouse hypothalamus.

In humans, inactivating mutations in MLL4, which encodes a histone H3-lysine 4-methyltransferase, lead to Kabuki syndrome (KS). While dwarfism is a cardinal feature of KS, the underlying etiology remains unclear. Here we report that Mll4 regulates the development of growth hormone-releasing hormone (GHRH)-producing neurons in the mouse hypothalamus.

KRAB-Induced Heterochromatin Effectively Silences Gene Expression in Somatic Cells and is Resilient to TGFβ1 Activation.

Epigenetic editing, an emerging technique used for the modulation of gene expression in mammalian cells, is a promising strategy to correct disease-related gene expression. Although epigenetic reprogramming results in sustained transcriptional modulation in several in vivo models, further studies are needed to develop this approach into a straightforward technology for effective and specific interventions. Important goals of current research efforts are understanding the context-dependency of successful epigenetic editing and finding the most effective epigenetic effector(s) for specific tasks.

Circulating myeloid cells invade the central nervous system to mediate cachexia during pancreatic cancer.

Weight loss and anorexia are common symptoms in cancer patients that occur prior to initiation of cancer therapy. Inflammation in the brain is a driver of these symptoms, yet cellular sources of neuroinflammation during malignancy are unknown. In a mouse model of pancreatic ductal adenocarcinoma (PDAC), we observed early and robust myeloid cell infiltration into the brain.

Author Correction: Single cell transcriptome analysis of developing arcuate nucleus neurons uncovers their key developmental regulators.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Microglia in the hypothalamus respond to tumor-derived factors and are protective against cachexia during pancreatic cancer.

Microglia in the mediobasal hypothalamus (MBH) respond to inflammatory stimuli and metabolic perturbations to mediate body composition. This concept is well studied in the context of high fat diet induced obesity (HFDO), yet has not been investigated in the context of cachexia, a devastating metabolic syndrome characterized by anorexia, fatigue, and muscle catabolism. We show that microglia accumulate specifically in the MBH early in pancreatic ductal adenocarcinoma (PDAC)-associated cachexia and assume an activated morphology.

Single cell transcriptome analysis of developing arcuate nucleus neurons uncovers their key developmental regulators.

Despite the crucial physiological processes governed by neurons in the hypothalamic arcuate nucleus (ARC), such as growth, reproduction and energy homeostasis, the developmental pathways and regulators for ARC neurons remain understudied. Our single cell RNA-seq analyses of mouse embryonic ARC revealed many cell type-specific markers for developing ARC neurons. These markers include transcription factors whose expression is enriched in specific neuronal types and often depleted in other closely-related neuronal types, raising the possibility that these transcription factors play important roles in the fate commitment or differentiation of specific ARC neuronal types.

Balloon catheter for induction of labor in women with one previous cesarean and an unfavorable cervix.

Introduction: When women with a previous cesarean section and an unfavorable cervix have an indication for delivery, the choice is to induce labor or to perform a cesarean section. This study aims to assess the effectiveness and safety of a balloon catheter as a method of induction of labor in women with one previous cesarean section and an unfavorable cervix compared with an elective repeat cesarean section.

Material And Methods: We performed a prospective cohort study in 51 hospitals in the Netherlands on term women with one previous cesarean section, a live singleton fetus in cephalic position, an unfavorable cervix and an indication for delivery.

Abnormal Nailfold Capillaroscopy Is Common in Patients with Connective Tissue Disease and Associated with Abnormal Pulmonary Function Tests.

Objective: To assess the presence of a systemic sclerosis (SSc) pattern on nailfold capillary microscopy (NCM) in patients with Raynaud phenomenon (RP) and to explore its association with abnormal pulmonary function tests (PFT).

Methods: NCM patterns were assessed in 759 consecutive patients with RP. Patterns were classified as normal (n = 354), nonspecific (n = 159), or SSc pattern (n = 246).

Perceptions of Patients With Chronic Obstructive Pulmonary Disease and Their Physiotherapists Regarding the Use of an eHealth Intervention.

Background: If eHealth interventions are not used (properly), their potential benefits cannot be fulfilled. User perceptions of eHealth are an important determinant of its successful implementation. This study examined how patients with chronic obstructive pulmonary disease (COPD) and their physiotherapists (PHTs) value an eHealth self-management intervention following a period of use.

Care Robot ZORA in Dutch Nursing Homes; An Evaluation Study.

From May 2016 - November 2016 the use of the ZORA robot was investigated in 15 long-term care facilities for older people. The ZORA robot is built as a social robot and used for pleasure and entertainment or to stimulate physical activities of the residents.

Foley catheter for induction of labour filled with 30mL or 60mL: A randomized controlled trial.

Objectives: One of the methods used to induce labour is the placement of a transcervical Foley catheter (FC). The aim of this randomized controlled study was to assess in term pregnant women with an unfavourable cervix, whether there is a difference in efficacy between the two most commonly used insufflation volumes of FC (30mL and 60mL).

Study Design: Randomized controlled trial.

A silent shift? The precarisation of the Dutch rental housing market.

The traditional Dutch rental contract is permanent (i.e. time unlimited), but there are indications that in recent years the number of temporary rental contracts has increased considerably.

Re-expression of Selected Epigenetically Silenced Candidate Tumor Suppressor Genes in Cervical Cancer by TET2-directed Demethylation.

DNA hypermethylation is extensively explored as therapeutic target for gene expression modulation in cancer. Here, we re-activated hypermethylated candidate tumor suppressor genes (TSGs) (C13ORF18, CCNA1, TFPI2, and Maspin) by TET2-induced demethylation in cervical cancer cell lines. To redirect TET2 to hypermethylated TSGs, we engineered zinc finger proteins (ZFPs), which were first fused to the transcriptional activator VP64 to validate effective gene re-expression and confirm TSG function.

Targeting Nrf2 in healthy and malignant ovarian epithelial cells: Protection versus promotion.

Risk factors indicate the importance of oxidative stress during ovarian carcinogenesis. To tolerate oxidative stress, cells activate the transcription factor Nrf2 (Nfe2l2), the master regulator of antioxidant and cytoprotective genes. Indeed, for most cancers, hyperactivity of Nrf2 is observed, and siRNA studies assigned Nrf2 as therapeutic target.

Biomarker profiling of steroid-resistant acute GVHD in patients after infusion of mesenchymal stromal cells.

We performed a prospective phase II study to evaluate clinical safety and outcome in 48 patients with steroid-refractory grade II-IV acute graft-versus-host disease (aGVHD) treated with mesenchymal stromal cells (MSCs). Clinical outcomes were correlated to comprehensive analyses of soluble and cellular biomarkers. Complete resolution (CR) of aGVHD at day 28 (CR-28) occurred in 12 (25%) patients, CR lasting >1 month (CR-B) occurred in 24 (50%) patients.

Prolonged re-expression of the hypermethylated gene EPB41L3 using artificial transcription factors and epigenetic drugs.

Epigenetic silencing of tumor suppressor genes (TSGs) is considered a significant event in the progression of cancer. For example, EPB41L3, a potential biomarker in cervical cancer, is often silenced by cancer-specific promoter methylation. Artificial transcription factors (ATFs) are unique tools to re-express such silenced TSGs to functional levels; however, the induced effects are considered transient.

Evaluation of Dutch guideline for just-in-time addition of plerixafor to stem cell mobilization in patients who fail with granulocyte-colony-stimulating factor.

Background: Plerixafor in combination with granulocyte-colony-stimulating factor (G-CSF) is approved for the use of stem cell collection in patients who fail to mobilize on G-CSF. In 2009 the Stem Cell Working Party of the Dutch-Belgian Cooperative Trial group for Hematology Oncology (HOVON) composed a guideline for the use of plerixafor. According to this guideline it is recommended to add plerixafor to G-CSF in patients with circulating CD34+ cell counts of fewer than 20 × 10(6) /L on 2 consecutive days accompanied by increasing white blood cells.

Rapid induction of single donor chimerism after double umbilical cord blood transplantation preceded by reduced intensity conditioning: results of the HOVON 106 phase II study.

Double umbilical cord blood transplantation is increasingly applied in the treatment of adult patients with high-risk hematological malignancies and has been associated with improved engraftment as compared to that provided by single unit cord blood transplantation. The mechanism of improved engraftment is, however, still incompletely understood as only one unit survives. In this multicenter phase II study we evaluated engraftment, early chimerism, recovery of different cell lineages and transplant outcome in 53 patients who underwent double cord blood transplantation preceded by a reduced intensity conditioning regimen.