Reframing Dutch drug policies: a new era for harm reduction.

In this article the authors offer their perspective on the changes in the Dutch harm reduction field. From the 1970s to the 1990s, the Netherlands emerged as a leader in harm reduction services, driven by grassroots movements like the Medisch-sociale Dienst Heroïne Gebruikers (MDHG) (Medisch-sociale Dienst Heroïne Gebruikers (MDHG) translates to Medical-Social Service Heroin Users in English) in Amsterdam and Junkiebond in Rotterdam. These organisations advocated for health-centred policies, initiated needle exchange programmes, and created safe consumption spaces.

Mitochondrial Dysfunction Inhibits Hypoxia-Induced HIF-1α Stabilization and Expression of Its Downstream Targets.

mtDNA variations often result in bioenergetic dysfunction inducing a metabolic switch toward glycolysis resulting in an unbalanced pH homeostasis. In hypoxic cells, expression of the tumor-associated carbonic anhydrase IX (CAIX) is enhanced to maintain cellular pH homeostasis. We hypothesized that cells with a dysfunctional oxidative phosphorylation machinery display elevated CAIX expression levels.

Distinct radiation responses after in vitro mtDNA depletion are potentially related to oxidative stress.

Several clinically used drugs are mitotoxic causing mitochondrial DNA (mtDNA) variations, and thereby influence cancer treatment response. We hypothesized that radiation responsiveness will be enhanced in cellular models with decreased mtDNA content, attributed to altered reactive oxygen species (ROS) production and antioxidant capacity. For this purpose BEAS-2B, A549, and 143B cell lines were depleted from their mtDNA (ρ0).

Mitochondrial DNA copy number in colorectal cancer: between tissue comparisons, clinicopathological characteristics and survival.

Low mitochondrial DNA (mtDNA) copy number in tumors has been associated with worse prognosis in colorectal cancer (CRC). This study further deciphers the role of mtDNA copy number in CRC by comparing mtDNA copy number between healthy, adenoma and carcinoma tissue, by investigating its association according to several clinicopathological characteristics in CRC, and by relating it to CRC-specific survival in CRC patients. A hospital-based series of samples including cancer, adenoma and adjacent histologically normal tissue from primary CRC patients (n = 56) and recurrent CRC (n = 16) was studied as well as colon mucosa samples from healthy subjects (n = 76).

How do changes in the mtDNA and mitochondrial dysfunction influence cancer and cancer therapy? Challenges, opportunities and models.

Several mutations in nuclear genes encoding for mitochondrial components have been associated with an increased cancer risk or are even causative, e.g. succinate dehydrogenase (SDHB, SDHC and SDHD genes) and iso-citrate dehydrogenase (IDH1 and IDH2 genes).

An Overview of HIV Prevention Interventions for People Who Inject Drugs in Tanzania.

In the past decade, Tanzania has seen a rapid rise in the number of people who inject drugs (PWID), specifically heroin. While the overall HIV prevalence in Tanzania has declined recently to 5.6%, in 2009, the HIV prevalence among PWID remains alarmingly high at 35%.

No association between TGF-β1 polymorphisms and radiation-induced lung toxicity in a European cohort of lung cancer patients.

This study aimed at validating the previously published association between TGF-β1 single nucleotide polymorphisms and a reduced risk for radiation-induced lung toxicity. We were not able to confirm the reported association, neither using maximum dyspnea score nor after correction for baseline dyspnea score.

Patient-derived fibroblasts indicate oxidative stress status and may justify antioxidant therapy in OXPHOS disorders.

Oxidative phosphorylation disorders are often associated with increased oxidative stress and antioxidant therapy is frequently given as treatment. However, the role of oxidative stress in oxidative phosphorylation disorders or patients is far from clear and consequently the preventive or therapeutic effect of antioxidants is highly anecdotic. Therefore, we performed a systematic study of a panel of oxidative stress parameters (reactive oxygen species levels, damage and defense) in fibroblasts of twelve well-characterized oxidative phosphorylation patients with a defect in the POLG1 gene, in the mitochondrial DNA-encoded tRNA-Leu gene (m.

Transcriptional changes in OXPHOS complex I deficiency are related to anti-oxidant pathways and could explain the disturbed calcium homeostasis.

Defective complex I (CI) is the most common type of oxidative phosphorylation disease, with an incidence of 1 in 5000 live births. Here, whole genome expression profiling of fibroblasts from CI deficient patients was performed to gain insight into the cell pathological mechanism. Our results suggest that patient fibroblasts responded to oxidative stress by Nrf2-mediated induction of the glutathione antioxidant system and Gadd45-mediated activation of the DNA damage response pathway.

Large scale mtDNA sequencing reveals sequence and functional conservation as major determinants of homoplasmic mtDNA variant distribution.

The mitochondrial DNA (mtDNA) is highly variable, containing large numbers of pathogenic mutations and neutral polymorphisms. The spectrum of homoplasmic mtDNA variation was characterized in 730 subjects and compared with known pathogenic sites. The frequency and distribution of variants in protein coding genes were inversely correlated with conservation at the amino acid level.

Inherited mitochondrial variants are not a major cause of age-related hearing impairment in the European population.

Mitochondrial DNA (mtDNA) mutations have been implicated in various age-related diseases. To further clarify the role of mtDNA variants in age-related hearing impairment (ARHI), we determined the DNA sequence of the entire mitochondrial genome of 400 individuals using the Affymetrix Human Mitochondrial Resequencing Array. These were the 200 worst hearing and the 200 best hearing from a collection of 947 Belgian samples.

Enumeration of probiotic bacilli spores in animal feed: interlaboratory study.

Fourteen out of 17 laboratories completed an interlaboratory study comparing 2 pretreatment protocols of feed samples containing authorized probiotic bacilli spores. Both methods used tryptone soy agar for enumeration. Pretreatment A involved preparation of a suspension of the feed sample in 50% ethanol.

Percutaneous removal of a knotted pulmonary artery catheter using a tracheostomy dilator.

STATEMENT OF FINDINGS: This case report describes removal of a knotted, subclavian, pulmonary artery catheter using a tracheostomy dilator. With this simple method an invasive procedure might be averted.

The influence of open-heart surgery on survival of patients with co-existent surgically amenable lung cancer (stages I and II).

Objective: The evaluation of the influence of open-heart surgery on the survival of patients with co-existent surgically amenable lung cancer stages I and II.

Methods: A retrospective, observational study was conducted in a tertiary centre for cardiothoracic surgery. From 1988 to 1995, 121 consecutive patients underwent pulmonary resection for stages I-II primary non-small cell bronchogenic carcinoma.

Synchroneously occurring lung cancer (stages I-II) and coronary artery disease: concomitant versus staged surgical approach.

Objective: The assessment of the best surgical approach in patients with synchroneously occurring lung cancer (stages I and II) and coronary artery disease: concomitant or staged.

Methods: A retrospective, observational study was conducted in a tertiary centre for cardiothoracic surgery. From 1988-1995, 34 patients underwent pulmonary resection for stages I-II primary bronchogenic carcinoma and open-heart surgery (almost always coronary-artery bypass grafting), either concomitantly (n = 24) or in a staged procedure (n = 10).

Immunosenescence revisited. Does it have any clinical significance?

Immunosenescence refers to the influence of aging on the immune system. Numerous problems are encountered in studying this topic, the main one being the influence of concomitant disease. Despite the great efforts that have been devoted to research in this field, the results of studies performed to date have not been convincing and, until now, no sound scientific evidence has emerged to show that immunosenescence is clinically significant.

[Special attention intensive care in the Netherlands once again].

The organizational structure of intensive care departments is still under debate. 'Open' (without) or 'closed format' (with intensivists), that is the question. However, various studies establish that the presence of full-time intensivists reduces mortality rates in intensive care units substantially.