BACKGROUND: Drug consumption rooms (DCRs) are harm reduction facilities providing safer and hygienic setting for supervised administration of drugs aimed at decreasing negative health and social consequences of drug use. The first DCR in Czechia was opened in September 2023 in city of Brno in a mobile form operating in a socially excluded area (SEA). A research project informed the implementation of the DCR. METHODS: A mixed methods design was applied in the following phases: desk review, research before and after the launch of the mobile DCR, and routine monitoring of programme performance. Two cross-sectional questionnaire surveys among PWUDs (n = 131 and 135), ethnographic observation, focus group (n = 19), interviews with PWUDs (n = 26 and 19), with personnel of addiction services and local officials (n = 16 and 12), and residents (n = 7 and 6) were performed prior to and after the launch of the DCR. Thematic analysis of qualitative data, descriptive and regression analyses of quantitative data were performed. RESULTS: There was a need and high willingness to use the DCR among potential clients. The significant predictors were opioid use (adjusted odds ratio, AOR = 3.4 in survey 1 and 3.9 in survey 2), drug injection in the last 30 days (AOR 4.3 in survey 1), being in the probationary period during the previous 30 days (AOR 10.0 in survey 1), witnessing an overdose in the past 30 days (AOR 8.5 in survey 2), HCV positivity ever in life (AOR 2.9 in survey 2), living in SEA (AOR 2.7 in survey 2) and Roma ethnicity (AOR 2.8 in survey 2). The beginnings of the DCR were relatively slow with low initial number of clients and drug administrations. However, with time, and programme adjustments following research results, the attendance at the facility has grown. CONCLUSIONS: Research was instrumental in shaping the DCR in Brno before and during its implementation. The DCR showed a potential to attract the most vulnerable PWUDs from SEA. Despite a slow start, the DCR has become an integral part of low-threshold services for PWUDs in Brno and has proven its feasibility in the Czech settings.
- MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Mobile Health Units * organization & administration MeSH
- Substance-Related Disorders * MeSH
- Cross-Sectional Studies MeSH
- Surveys and Questionnaires MeSH
- Harm Reduction * MeSH
- Drug Users * statistics & numerical data MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
Intracranial human brain recordings from multiple implanted depth electrodes using stereo-EEG (sEEG) technology for seizure localization provide unique local field potential signals (LFP) sampled with standard macro- and special micro-electrode contacts. Over one hundred macro- and micro-contact LFP signals localized in particular brain regions were recorded from each sEEG monitoring case as patients engaged in an automated battery of verbal memory and non-verbal gaze movement tasks. Subject eye and vocal responses in both visual and auditory task versions were automatically detected in Polish, Czech, and Slovak languages with accurate timing of the correct and incorrect verbal responses using our web-based transcription tool. The behavioral events, LFP and pupillometric signals were synchronized and stored in a standard BIDS data structure with corresponding metadata. Each dataset contains recordings from at least one battery task performed over at least one day. The same set of 180 common nouns in the three languages was used across different battery tasks and recording days to enable the analysis of selective responses to specific word stimuli.
- MeSH
- Electroencephalography MeSH
- Language MeSH
- Cognition * MeSH
- Humans MeSH
- Brain * physiology MeSH
- Eye Movements MeSH
- Eye-Tracking Technology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Dataset MeSH
BACKGROUND: Temporal interference stimulation (TIS) is a novel noninvasive electrical stimulation technique to focally modulate deep brain regions; a minimum of two high-frequency signals (f1 and f2 > 1 kHz) interfere to create an envelope-modulated signal at a deep brain target with the frequency of modulation equal to the difference frequency: Δf = |f2 - f1|. OBJECTIVE: The goals of this study were to verify the capability of TIS to modulate the subthalamic nucleus (STN) with Δf and to compare the effect of TIS and conventional deep brain stimulation (DBS) on the STN beta oscillations in patients with Parkinson's disease (PD). METHODS: DBS leads remained externalized after implantation, allowing local field potentials (LFPs) recordings in eight patients with PD. TIS was performed initially by two pairs (f1 = 9.00 kHz; f2 = 9.13 kHz, 4 mA peak-peak per pair maximum) of scalp electrodes placed in temporoparietal regions to focus the envelope signal maximum (Δf = 130 Hz) at the motor part of the STN target. RESULTS: The comparison between the baseline LFPs and recordings after TIS and conventional DBS sessions showed substantial suppression of high beta power peak after both types of stimulation in all patients. CONCLUSIONS: TIS has the potential to effectively modulate the STN and reduce the beta oscillatory activity in a completely noninvasive manner, as is traditionally possible only with intracranial DBS. Future studies should confirm the clinical effectiveness of TIS and determine whether TIS could be used to identify optimal DBS candidates and individualize DBS targets. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
- MeSH
- Beta Rhythm * physiology MeSH
- Deep Brain Stimulation * methods MeSH
- Middle Aged MeSH
- Humans MeSH
- Subthalamic Nucleus * physiopathology MeSH
- Parkinson Disease * therapy physiopathology MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Temporal lobe epilepsy is a common neurological disease characterized by recurrent seizures that often originate within limbic networks involving amygdala and hippocampus. The limbic network is involved in crucial physiologic functions involving memory, emotion and sleep. Temporal lobe epilepsy is frequently drug-resistant, and people often experience comorbidities related to memory, mood and sleep. Deep brain stimulation targeting the anterior nucleus of the thalamus (ANT-DBS) is an established therapy for temporal lobe epilepsy. However, the optimal stimulation parameters and their impact on memory, mood and sleep comorbidities remain unclear. We used an investigational brain sensing-stimulation implanted device to accurately track seizures, interictal epileptiform spikes (IES), and memory, mood and sleep comorbidities in five ambulatory subjects. Wireless streaming of limbic network local field potentials (LFPs) and subject behaviour were captured on a mobile device integrated with a cloud environment. Automated algorithms applied to the continuous LFPs were used to accurately cataloged seizures, IES and sleep-wake brain state. Memory and mood assessments were remotely administered to densely sample cognitive and behavioural response during ANT-DBS in ambulatory subjects living in their natural home environment. We evaluated the effect of continuous low-frequency and duty cycle high-frequency ANT-DBS on epileptiform activity and memory, mood and sleep comorbidities. Both low-frequency and high-frequency ANT-DBS paradigms reduced seizures. However, continuous low-frequency ANT-DBS showed greater reductions in IES, electrographic seizures and better sleep and memory outcomes. These results highlight the potential of synchronized brain sensing and dense behavioural tracking during ANT-DBS for optimizing neuromodulation therapy. While studies with larger patient numbers are needed to validate the benefits of low-frequency ANT-DBS, these findings are potentially translatable to individuals currently implanted with ANT-DBS systems.
- Publication type
- Journal Article MeSH
Social withdrawal and deficits in social cognition are hallmarks of Alzheimer's disease (AD). While early deficits in social behavior and memory have been documented in mouse AD models, they remain understudied in rat models. Early-stage AD is accompanied by dysfunction of parvalbumin-positive (PV+) interneurons, implicating their potential connection to early symptoms. In this study, we employed a 5-trial social memory task to investigate early deficits in social cognition in 6-month-old TgF344-AD male and female rats. We counted the number of PV+ interneurons and recorded local field potentials during social interactions in the hippocampal CA2 - a region critical for social information processing. Our results show decreased social interest and novelty preference in TgF344-AD male and female rats. However, reduced PV+ interneuron numbers were observed only in female rats and specific to the CA2 area. The electrophysiological recordings revealed reduced theta-gamma phase-amplitude coupling in the CA2 during direct social interactions. We conclude that deficits in social cognition accompany early-stage AD in TgF344-AD rats and are potentially linked to PV+ interneuron and brain oscillatory dysfunction in the CA2 region of the hippocampus.
- MeSH
- Alzheimer Disease * physiopathology pathology metabolism MeSH
- CA2 Region, Hippocampal * physiopathology metabolism pathology MeSH
- Interneurons * metabolism pathology MeSH
- Rats MeSH
- Disease Models, Animal MeSH
- Parvalbumins * metabolism MeSH
- Sex Characteristics MeSH
- Rats, Inbred F344 MeSH
- Rats, Transgenic MeSH
- Social Behavior * MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Despite enormous progress, advanced cancers are still one of the most serious medical problems in current society. Although various agents and therapeutic strategies with anticancer activity are known and used, they often fail to achieve satisfactory long-term patient outcomes and survival. Recently, immunotherapy has shown success in patients by harnessing important interactions between the immune system and cancer. However, many of these therapies lead to frequent side effects when administered systemically, prompting treatment modifications or discontinuation or, in severe cases, fatalities. New therapeutic approaches like intratumoral immunotherapy, characterized by reduced side effects, cost, and systemic toxicity, offer promising prospects for future applications in clinical oncology. In the context of locally advanced or metastatic cancer, combining diverse immunotherapeutic and other treatment strategies targeting multiple cancer hallmarks appears crucial. Such combination therapies hold promise for improving patient outcomes and survival and for promoting a sustained systemic response. This review aims to provide a current overview of immunotherapeutic approaches, specifically focusing on the intratumoral administration of drugs in patients with locally advanced and metastatic cancers. It also explores the integration of intratumoral administration with other modalities to maximize therapeutic response. Additionally, the review summarizes recent advances in intratumoral immunotherapy and discusses novel therapeutic approaches, outlining future directions in the field.
- MeSH
- Immunotherapy * methods MeSH
- Combined Modality Therapy MeSH
- Humans MeSH
- Neoplasm Metastasis MeSH
- Tumor Microenvironment immunology MeSH
- Neoplasms * therapy immunology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Skin and soft tissue infections (SSTIs) represent a significant healthcare challenge, particularly in the context of increasing antibiotic resistance. This study investigates the efficacy of a novel therapeutic approach combining bacteriophage (phage) therapy with a gum Karaya (GK)-based hydrogel delivery system in a porcine model of deep staphylococcal SSTIs. The study exploits the lytic activity and safety of the Staphylococcus phage 812K1/420 of the Kayvirus genus, which is active against methicillin-resistant Staphylococcus aureus (MRSA). The GK injectable hydrogels and hydrogel films, developed by our research group, serve as effective, non-toxic, and easy-to-apply delivery systems, supporting moist wound healing and re-epithelialization. In the porcine model, the combined treatment showed asynergistic effect, leading to a significant reduction in bacterial load (2.5 log CFU/gram of tissue) within one week. Local signs of inflammation were significantly reduced by day 8, with clear evidence of re-epithelialization and wound contraction. Importantly, no adverse effects of the GK-based delivery system were observed throughout the study. The results highlight the potential of this innovative therapeutic approach to effectively treat deep staphylococcal SSTIs, providing a promising avenue for further research and clinical application in the field of infections caused by antibiotic-resistant bacteria.
- MeSH
- Phage Therapy * methods MeSH
- Wound Healing drug effects MeSH
- Hydrogels * administration & dosage chemistry MeSH
- Wound Infection * therapy microbiology drug therapy MeSH
- Methicillin-Resistant Staphylococcus aureus * drug effects MeSH
- Disease Models, Animal * MeSH
- Swine MeSH
- Plant Gums chemistry MeSH
- Staphylococcus Phages MeSH
- Staphylococcal Infections * therapy drug therapy MeSH
- Animals MeSH
- Check Tag
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Nicotinic acetylcholine receptors (nAChRs) are widely expressed in the central nervous system and play an important role in the control of neural functions including neuronal activity, transmitter release and synaptic plasticity. Although the common subtypes of nAChRs are abundantly expressed throughout the brain, their expression in different brain regions and by individual neuronal types is not homogeneous or incidental. In recent years, several studies have emerged showing that particular subtypes of nAChRs are expressed by specific neuronal populations in which they have major influence on the activity of local circuits and behavior. It has been demonstrated that even nAChRs expressed by relatively rare neuronal types can induce significant changes in behavior and contribute to pathological processes. Depending on the identity and connectivity of the particular nAChRs-expressing neuronal populations, the activation of nAChRs can have distinct or even opposing effects on local neuronal signaling. In this review, we will summarize the available literature describing the expression of individual nicotinic subunits by different neuronal types in two crucial brain regions, the striatum and the prefrontal cortex. The review will also briefly discuss nicotinic expression in non-neuronal, glial cells, as they cannot be ignored as potential targets of nAChRs-modulating drugs. The final section will discuss options that could allow us to target nAChRs in a neuronal-type-specific manner, not only in the experimental field, but also eventually in clinical practice.
- MeSH
- Corpus Striatum metabolism MeSH
- Humans MeSH
- Neurons * metabolism MeSH
- Receptors, Nicotinic * metabolism MeSH
- Prefrontal Cortex * metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
PURPOSE OF REVIEW: Oligometastatic tumors illustrate a distinct state between localized and systematic disease and might harbor unique biologic features. Moreover, these tumors represent a different clinical entity, with a potential of long-term disease control or even cure, therefore they receive growing attention in the field of urologic oncology. RECENT FINDINGS: Currently, there is no consensus on the definition of oligometastatic prostate cancer, most experts limit it to a maximum of three to five lesions and involvement of no more than two organs, excluding visceral metastases. Quality data on oligometastatic bladder cancer is scarce, however, a consensus of experts defined it as a maximum of three metastatic lesions, either resectable or suitable for stereotactic therapy, without restrictions to the number of organs involved. As for kidney cancer, a maximum number of five metastases, without limitations to the location are defined as oligometastatic, with an important implication of timing of developing metastases since diagnosis of the primary tumor. SUMMARY: Defining oligometastatic state among urological tumors reflecting their distinct biological and clinical behavior is crucial to establish a sound framework for future clinical trials, and to facilitate guideline and policy formulation for improved patient care. Advancements in molecular imaging are expected to transform the field of oligometastatic urologic tumors in the future.
- MeSH
- Humans MeSH
- Neoplasm Metastasis * MeSH
- Kidney Neoplasms * pathology therapy MeSH
- Urinary Bladder Neoplasms * pathology therapy MeSH
- Prostatic Neoplasms pathology therapy MeSH
- Urologic Neoplasms pathology therapy diagnosis MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
We present a case of a 32-year-old male with a history of palpitations and preexcitation on ECG who underwent altogether four failed catheter ablations using different approaches in the two other electrophysiology centers within two years. ECG showed overt preexcitation with a positive delta wave in lead I and negative in leads V1-V3, suggesting a right free wall accessory pathway. During the electrophysiological study, the accessory pathway was localized on the free lateral wall. However, the electrograms and mapping during atrial and ventricular pacing suggested the presence of true epicardial accessory pathway. Repeated radiofrequency energy delivery with the support of the steerable sheath and excellent contact (as assessed by intracardiac echocardiography) at the earliest ventricular activation was not successful. Therefore, the Farawave catheter (Boston Scientific, Inc) was used, and a flower configuration with the intention to cover the entire atrial attachment of the pathway during ventricular pacing was selected. Application of pulsed field resulted in interruption of accessory pathway conduction. An electrophysiological study one year later confirmed the persistent effect of ablation. This case illustrates the potential utility of pulsed field energy for the ablation of atrial insertion of the accessory pathway with an epicardial course. Such an approach can avoid epicardial mapping and access and may improve the safety of the procedure.
- Publication type
- Case Reports MeSH
