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. Their efforts led to significant public health improvements and policy shifts towards harm reduction, reducing HIV and hepatitis rates among people who use drugs. By the 1980s, harm reduction became institutionalised within local health and social care systems, leading to notable declines in drug-related harm and crime. However, from the 2000s, a shift towards security and crime prevention emerged, influenced by socio-political changes. Increased criminal justice measures and budget cuts for harm reduction services strained the system, making it harder to address emerging drug trends and the complex needs of people who use drugs. Despite challenges, there is renewed momentum for reform, particularly at the local level, advocating for the responsible regulation of psychoactive substances. Amsterdam Mayor Femke Halsema's 2024 conference on drug regulation exemplifies this shift, calling for policies that address prohibition failures and centre harm reduction. International bodies like the UN High Commissioner for Human Rights support this approach, emphasising a health and rights-based framework. As the Netherlands navigates these evolving dynamics, there is a pressing need to reinvest in harm reduction infrastructure, ensuring it meets diverse community needs and reaffirms its foundational rights-affirming principles.

Actor-network analysis of community-based organisations in health pandemics: evidence from the COVID-19 response in Freetown, Sierra Leone.

Freetown, Sierra Leone, is confronted with health risks that are compounded by rapid unplanned urbanisation and weak capacities of local government institutions. Addressing them implies a shared responsibility between government and non-state actors. In low-income areas, the role of community-based organisations (CBOs) in combating health disasters is well-recognised. Yet, empirical evidence on how they have utilised their networks and coordinated community-level strategies in responding to the COVID-19 pandemic is scant. This paper, based on a qualitative study in two informal settlements in Freetown, employs actor-network theory to understand how CBOs problematise COVID-19 as a health risk, interact with other entities, and the subsequent tensions that arise. The findings show that community vulnerabilities and past experiences of health disasters informed CBOs' perception of COVID-19 as a communal emergency. In response, they coordinated sensitisation and mobilisation programmes by relying on a network of actors to support COVID-19 risk reduction strategies. Nonetheless, misunderstandings among them caused friction.

Simultaneous recording of fluorescence and electrical signals by photometric patch electrode in deep brain regions in vivo.

Despite its widespread use, high-resolution imaging with multiphoton microscopy to record neuronal signals in vivo is limited to the surface of brain tissue because of limited light penetration. Moreover, most imaging studies do not simultaneously record electrical neural activity, which is, however, crucial to understanding brain function. Accordingly, we developed a photometric patch electrode (PME) to overcome the depth limitation of optical measurements and also enable the simultaneous recording of neural electrical responses in deep brain regions. The PME recoding system uses a patch electrode to excite a fluorescent dye and to measure the fluorescence signal as a light guide, to record electrical signal, and to apply chemicals to the recorded cells locally. The optical signal was analyzed by either a spectrometer of high light sensitivity or a photomultiplier tube depending on the kinetics of the responses. We used the PME in Oregon Green BAPTA-1 AM-loaded avian auditory nuclei in vivo to monitor calcium signals and electrical responses. We demonstrated distinct response patterns in three different nuclei of the ascending auditory pathway. On acoustic stimulation, a robust calcium fluorescence response occurred in auditory cortex (field L) neurons that outlasted the electrical response. In the auditory midbrain (inferior colliculus), both responses were transient. In the brain-stem cochlear nucleus magnocellularis, calcium response seemed to be effectively suppressed by the activity of metabotropic glutamate receptors. In conclusion, the PME provides a powerful tool to study brain function in vivo at a tissue depth inaccessible to conventional imaging devices.

Transcriptome Analysis of Sweet Cherry (Prunus avium L.) Cultivar 'Lapins' upon Infection of Pseudomonas syringae pv. syringae.

Bacterial canker caused by Pseudomonas syringae pv. syringae (Pss) is responsible for substantial loss to the production of sweet cherry in Chile. To date, the molecular mechanisms of the Pss-sweet cherry interaction and the disease-related genes in the plant are poorly understood. In order to gain insight into these aspects, a transcriptomic analysis of the sweet cherry cultivar 'Lapins' for differentially expressed genes (DEGs) in response to Pss inoculation was conducted. Three Pss strains, A1M3, A1M197, and 11116_b1, were inoculated in young twigs, and RNA was extracted from tissue samples at the inoculation site and distal sections. RNA sequencing and transcriptomic expression analysis revealed that the three strains induced different patterns of responses in local and distal tissues. In the local tissues, A1M3 triggered a much more extensive response than the other two strains, enriching DEGs especially involved in photosynthesis. In the distal tissues, the three strains triggered a comparable extent of responses, among which 11116_b1 induced a group of DEGs involved in defense responses. Furthermore, tissues from various inoculations exhibited an enrichment of DEGs related to carbohydrate metabolism, terpene metabolism, and cell wall biogenesis. This study opened doors to future research on the Pss-sweet cherry interaction, immunity responses, and disease control.

Assessment of Local and Systemic Changes in Plant Gene Expression and Aphid Responses during Potato Interactions with Arbuscular Mycorrhizal Fungi and Potato Aphids.

This research examined aphid and plant responses to distinct levels (none, low, and high) of arbuscular mycorrhizal (AM) fungal root colonization by studying the association between potato aphids (Macrosiphum euphorbiae), potatoes (Solanum tuberosum), and AM fungi (Rhizophagus intraradices). It extends knowledge on gene expression changes, assessed by RT-qPCR, of ten defense-related genes at two time-points post-herbivory (24 h and 10 days), focusing on aphid-infested local leaves, non-infested systemic leaves, and roots. The results showed that aphid fitness was not altered by AM symbiosis. At 24 h, ETHYLENE RECEPTOR 1 gene expression was repressed in roots of aphid-infested non-mycorrhizal plants and aphid-infested plants with a high level of AM fungal root colonization, but not on aphid-infested plants with a low level of AM fungal root colonization. At 10 days, ALLENE OXIDE CYCLASE and POTATO TYPE I PROTEASE INHIBITOR were upregulated exclusively in local leaves of aphid-infested plants with a low level of AM fungal root colonization. In addition, local and systemic changes in plant gene expression appeared to be regulated exclusively by AM status and aphid herbivory. In summary, the gene expression data provide insights on mycorrhizal potato responses to aphid herbivory and serve as a starting point for future studies using this system.

Induced Local and Systemic Defense Responses in Tomato Underlying Interactions Between the Root-Knot Nematode Meloidogyne incognita and the Potato Aphid Macrosiphum euphorbiae.

Plants mediate interactions between different herbivores that attack simultaneously or sequentially aboveground (AG) and belowground (BG) organs. The local and systemic activation of hormonal signaling pathways and the concomitant accumulation of defense metabolites underlie such AG-BG interactions. The main plant-mediated mechanisms regulating these reciprocal interactions via local and systemic induced responses remain poorly understood. We investigated the impact of root infection by the root-knot nematode (RKN) Meloidogyne incognita at different stages of its infection cycle, on tomato leaf defense responses triggered by the potato aphid Macrosiphum euphorbiae. In addition, we analyzed the reverse impact of aphid leaf feeding on the root responses triggered by the RKN. We focused specifically on the signaling pathways regulated by the phytohormones jasmonic acid (JA), salicylic acid (SA), abscisic acid (ABA), and indole-3-acetic acid (IAA) as well as steroidal glycoalkaloids as induced defense compounds. We found that aphid feeding did not induce AG hormonal signaling, but it repressed steroidal glycoalkaloids related responses in leaves, specifically when feeding on plants in the vegetative stage. Root infection by the RKN impeded the aphid-triggered repression of the steroidal glycoalkaloids-related response AG. In roots, the RKN triggered the SA pathway during the entire infection cycle and the ABA pathway specifically during its reproduction stage. RKN infection also elicited the steroidal glycoalkaloids related gene expression, specifically when it was in the galling stage. Aphid feeding did not systemically alter the RKN-induced defense responses in roots. Our results point to an asymmetrical interaction between M. incognita and Ma. euphorbiae when co-occurring in tomato plants. Moreover, the RKN seems to determine the root defense response regardless of a later occurring attack by the potato aphid AG.

A Correlation with Retinal Thickness Using Retinal Thickness Analyzer and the Responses of Multifocal Electroretinogram in Patients with Diabetic Macular Edema

PURPOSE: To assess the correlation between retinal thickness determined with a retinal thickness analyzer (RTA) and the responses of multifocal electroretinogram (mfERG) in patients with diabetic macular edema. METHODS: RTA and mfERG were performed in patients with diabetic macular edema (20eyes, 10 patients) and normal subjects (10eyes, 10 patients). The measured retina of RTA and mfERG overlapped based on the anatomical landmarks of the fundus. The center of macula was defined as "Area 1", and the central 5 degree retina including the center of macula was defined as "Area 2". The correlations between retinal thickness and the local responses in each area were assessed. RESULTS: The mean retinal thickness of patients with diabetic macular edema was significantly greater than that of normal subject, and the results of mfERG typically represented decreased amplitudes and delayed latencies. In the matching of retinal thickness and local responses in Area 2, amplitudes of N1 & P1 decreased and latency of P1 delayed as the retinal thickness increased. The correlation was prominent in patients with diabetic macular edema. CONCLUSIONS: In the matching of RTA and mfERG of patients with diabetic macular edema, retinal thickness and local responses were significantly correlated.