FUS-mediated BBB opening leads to transient perfusion decrease and inflammation without acute or chronic brain lesion.

Impact: The permeabilization of the BBB to deliver therapeutics with MR-guided FUS redefines therapeutic strategies as it improves patient outcomes. To ensure the best translation towards clinical treatment, the evaluation of hemodynamic modifications in the CNS is necessary to refine treatment parameters. Methods: MR-guided FUS was applied at 1.5 MHz with a 50 ms burst every 1 s to open the BBB. CBF, BVf and ADC parameters were monitored with MRI. Cavitation was monitored with a PCD during the FUS sequence and classified with the IUD index into three cavitation levels. We distinctly applied the FUS in the cortex or the striatum. After the BBB permeabilization, neuroinflammation markers were quantified longitudinally. Results: The BBB was successfully opened in all animals in this study and only one animal was classified as "hard" and excluded from the rest of the study. 30 min after FUS-induced BBB opening in the cortex, we measured a 54% drop in CBF and a 13% drop in BVf compared to the contralateral side. After permeabilization of the striatum, a 38% drop in CBF and a 15% drop in BVf were measured. CBF values rapidly returned to baseline, and 90 min after BBB opening, no significant differences were observed. We quantified the subsequent neuroinflammation, noting a significant increase in astrocytic recruitment at 2 days and microglial activation at 1 day after FUS. After 7 days, no more inflammation was visible in the brain. Conclusion: FUS-induced BBB opening transiently modifies hemodynamic parameters such as CBF and BVf, suggesting limited nutrients and oxygen supply to the CNS in the hour following the procedure.

Ultrasound-guided serratus anterior plane block enhances postoperative analgesia and recovery in thoracoscopic surgery.

BACKGROUND: The serratus anterior muscle, located in the lateral aspect of the thorax, plays a crucial role in shoulder movement and stability. Thoracoscopic surgery, while minimally invasive, often results in significant postoperative pain, complicating patient recovery and potentially extending hospital stays. Traditional anesthesia methods may not adequately address this pain, leading to increased complications such as agitation due to inadequate pain management. AIM: To evaluate the application value of ultrasound-guided serratus anterior plane block (SAPB) in patients undergoing thoracoscopic surgery, focusing on its effects on postoperative analgesia and rehabilitation. METHODS: Eighty patients undergoing thoracoscopic surgery between August 2021 and December 2022 were randomly divided into two groups: An observation group receiving ultrasound-guided SAPB and a control group receiving standard care without SAPB. Both groups underwent general anesthesia and were monitored for blood pressure, heart rate (HR), oxygen saturation, and pulse. The primary outcomes measured included mean arterial pressure (MAP), HR, postoperative visual analogue scale (VAS) scores for pain, supplemental analgesic use, and incidence of agitation. RESULTS: The observation group showed significantly lower cortisol and glucose concentrations at various time points post-operation compared to the control group, indicating reduced stress responses. Moreover, MAP and HR levels were lower in the observation group during and after surgery. VAS scores were significantly lower in the observation group at 1 h, 4 h, 6 h, and 12 h post-surgery, and the rates of analgesic supplementation and agitation were significantly reduced compared to the control group. CONCLUSION: Ultrasound-guided SAPB significantly improves postoperative analgesia and reduces agitation in patients undergoing thoracoscopic surgery. This technique stabilizes perioperative vital signs, decreases the need for supplemental analgesics, and minimizes postoperative pain and stress responses, underscoring its high application value in enhancing patient recovery and rehabilitation post-thoracoscopy.

Evaluating the efficacy of percutaneous puncture biopsy guided by contrast-enhanced ultrasound for peripheral pulmonary lesions.

BACKGROUND: The incidence and mortality of lung cancer have increased annually. Accurate diagnosis can help improve therapeutic efficacy of interventions and prognosis. Percutaneous lung biopsy is a reliable method for the clinical diagnosis of lung cancer. Ultrasound-guided percutaneous lung biopsy technology has been widely promoted and applied in recent years. AIM: To investigate the diagnostic value of contrast-enhanced ultrasound (CEUS)-guided percutaneous biopsy in peripheral pulmonary lesions. METHODS: We retrospectively collected data on 237 patients with peripheral thoracic focal lesions who underwent puncture biopsy at Wuxi People's Hospital. The patients were randomly divided into two groups: The CEUS-guided before lesion puncture group (contrast group) and conventional ultrasound-guided group (control group). Analyze the diagnostic efficacy of the puncture biopsy, impact of tumor size, and number of puncture needles and complications were analyzed and compared between the two groups. RESULTS: Accurate pathological results were obtained for 92.83% (220/237) of peripheral lung lesions during the first biopsy, with an accuracy rate of 95.8% (113/118) in the contrast group and 89.9% (107/119) in the control group. The difference in the area under the curve (AUC) between the contrast and the control groups was not statistically significant (0.952 vs 0.902, respectively; P > 0.05). However, when the lesion diameter ≥ 5 cm, the diagnostic AUC of the contrast group was higher than that of the control group (0.952 vs 0.902, respectively; P < 0.05). In addition, the average number of puncture needles in the contrast group was lower than that in the control group (2.58 ± 0.53 vs 2.90 ± 0.56, respectively; P < 0.05). CONCLUSION: CEUS guidance can enhance the efficiency of puncture biopsy of peripheral pulmonary lesions, especially for lesions with a diameter ≥ 5 cm. Therefore, CEUS guidance has high clinical diagnostic value in puncture biopsy of peripheral focal lung lesions.

['The knowledge I acquired at Ifsi and the support provided during the course helped me to develop my career plan']. / « Les connaissances acquises à l'Ifsi et le suivi proposé lors du stage ont participé à l'élaboration de mon projet professionnel ¼.

This interview explains how internships and nursing training institute training form part of a professional project. The nurse, who is committed to the development of her profession, talks about her first job in a clinical and research department at the Toulouse Oncopole. She stresses the importance of providing students and young graduates with sympathetic support. It's all about mobilizing resources for building skills, for nursing sciences and, ultimately, encouraging them to develop professionally.

Analysis of the Application Value of Dynamic Navigation Guidance in Oral Implantation.

OBJECTIVE: To investigate the application of dynamic navigation guidance technology in different implantation scenarios, and to provide a scientific basis for the innovation and advancement of implantation techniques. METHODS: Fifteen cases of patients with malocclusions admitted between January 2021 and February 2023 were selected as the study subjects. All patients underwent dynamic navigation-guided oral implantation interventions. CBCT scans were taken after implantation surgery to record deviations of implantation points, including implantation point deviation, endpoint deviation, and angle deviation. RESULTS: Dynamic navigation guidance effectively improves the reliability and stability of implantation in oral implant patients. CBCT effectively evaluated the state of the patient's periodontal implant, analyzed the state of the patient's lesion area, and improved the quality of implant intervention through CBCT guidance. The implantation point deviation was (0.407±0.193) mm, the endpoint deviation was (0.492±0.201) mm, and the implant angle deviation was (2.162±0.283)°. There was no significant difference in implantation point deviation in the anterior and posterior parts of the upper and lower jaws after intervention (P>0.05). However, there were significant differences in endpoint deviation and implant angle deviation among the anterior and posterior parts of the upper and lower jaws (P<0.05). CONCLUSION: Dynamic navigation guidance effectively improves the reliability and stability of implantation in oral implant patients. However, there is relatively greater endpoint deviation and implant angle deviation in the posterior part of the upper jaw.

Harnessing the power of infection prevention and public health data systems to support health care in Washington State during the COVID-19 pandemic.

BACKGROUND: State health departments' (SHD) role in infection prevention and control (IPC) includes robust educational and consultative services for various health care settings. During the COVID-19 pandemic, Washington-SHD (W-SHD) IPC staff conducted remote and on-site Infection Control Assessment and Response (ICAR) consultations for long-term care (LTC) and non-LTC health care facilities. METHODS: ICAR consultations were classified as "reactive" in response to a COVID-19 outbreak or "proactive" to help facilities improve IPC protocols. Facility addresses were geocoded to census tracks, classifying urban or rural areas. Facility types and characteristics were analyzed, assessing the impacts of repeat visits. All descriptive statistics, Pearson's χ2 tests, and odds ratios were calculated. RESULTS: Between March 2020 and December 2022, W-SHD conducted 3,093 ICARs at 1,703 health care facilities in 94.9% (37/39) of Washington counties. Of the total visits, most were in LTC (90.5%) and 48.9% were reactive. Facilities with initial on-site ICARs had 1.5 times the odds of having a repeat visit than facilities with initial remote visit (95% CI: 1.21, 1.87). DISCUSSION: Maintaining strong connections with health care facilities can help bolster infection prevention practices and minimize loss of information at the facility level. CONCLUSIONS: Evidence-based findings on the sustainability of the W-SHD's ICAR services during the COVID-19 pandemic illustrated the value of public health IPC programs.

How is tailored implementation undertaken using a self-guided toolkit? Qualitative study of the ItFits-toolkit in the ImpleMentAll project.

BACKGROUND: The process of tailored implementation is ill-defined and under-explored. The ItFits-toolkit was developed and subsequently tested as a self-guided online platform to facilitate implementation of tailored strategies for internet-based cognitive behavioural therapy (iCBT) services. In ImpleMentAll, ItFits-toolkit had a small but positive effect on the primary outcome of iCBT normalisation. This paper investigates, from a qualitative perspective, how implementation teams developed and undertook tailored implementation using the toolkit within the trial. METHODS: Implementation teams in thirteen sites from nine countries (Europe and Australia) used the ItFits-toolkit for six months minimum, consistent with the trial protocol. A qualitative process evaluation was conducted. Descriptive data regarding goals, barriers, strategies, and implementation plans collected within the toolkit informed qualitative data collection in real time. Qualitative data included remote longitudinal interviews (n = 55) with implementation team members (n = 30) and observations of support calls (n = 19) with study sites. Qualitative data were analysed thematically, using a team-based approach. RESULTS: Implementation teams developed and executed tailored implementation projects across all steps in the toolkit process. Working in a structured way but with room for flexibility, decisions were shaped by team members' ideas and goals, iterative stakeholder engagement, internal and external influences, and the context of the ImpleMentAll project. Although teams reported some positive impacts of their projects, 'time', both for undertaking the work, and for seeing project impacts, was described as a key factor in decisions about implementation strategies and assessments of success. CONCLUSION: This study responds directly to McHugh et al.'s (2022) call for empirical description of what implementation tailoring looks like in action, in service settings. Self-guided facilitation of tailored implementation enables implementers in service settings to undertake tailoring within their organisations. Implementation tailoring takes considerable time and involves detailed work but can be supported through the provision of implementation science informed guidance and materials, iterative and ongoing stakeholder engagement, and working reflectively in response to external influencing factors. Directions for advancement of tailored implementation are suggested.

External Oblique Intercostal Plane Block: A Case Report and Review of Literature.

Chronic low back pain (CLBP) and post-laminectomy syndrome (PLS) can pose significant therapeutic challenges, often refractory to conservative management. We present a case of a 52-year-old male with refractory CLBP and PLS who underwent spinal cord stimulation (SCS) lead placement, and subsequently developed chronic right anterior chest wall and upper abdominal pain. Despite using SCS and opioid therapy, the pain persisted until an ultrasound-guided external oblique intercostal plane block (EOIPB) was administered, resulting in complete pain relief. This case highlights the efficacy of EOIPB in managing chronic post-surgical neuropathic pain, underscoring its potential as a valuable intervention in such cases.

Molecular mechanism of contactin 2 homophilic interaction.

Contactin 2 (CNTN2) is a cell adhesion molecule involved in axon guidance, neuronal migration, and fasciculation. The ectodomains of CNTN1-CNTN6 are composed of six Ig domains (Ig1-Ig6) and four FN domains. Here, we show that CNTN2 forms transient homophilic interactions (KD ∼200 nM). Cryo-EM structures of full-length CNTN2 and CNTN2_Ig1-Ig6 reveal a T-shaped homodimer formed by intertwined, parallel monomers. Unexpectedly, the horseshoe-shaped Ig1-Ig4 headpieces extend their Ig2-Ig3 tips outwards on either side of the homodimer, while Ig4, Ig5, Ig6, and the FN domains form a central stalk. Cross-linking mass spectrometry and cell-based binding assays confirm the 3D assembly of the CNTN2 homodimer. The interface mediating homodimer formation differs between CNTNs, as do the homophilic versus heterophilic interaction mechanisms. The CNTN family thus encodes a versatile molecular platform that supports a very diverse portfolio of protein interactions and that can be leveraged to strategically guide neural circuit development.

Healthcare Provider-Related Factors in the Diagnostic Delay of Cervical Cancer: A Cross-Sectional Study.

Background and objective Cervical cancer is the second most common malignancy among Indian women. In 2018, the World Health Organization (WHO) called for global action toward the elimination of cervical cancer through the triple-intervention strategy. One of its pillars is ensuring 70% screening coverage of eligible women with a high-performance test at least twice in their lifetime. Various factors contribute to the delayed diagnosis of cervical cancer, increasing the burden of the disease. In this study, we aimed to determine the healthcare provider (HCP)-related factors in the diagnostic delay of advanced cervical cancer. Methods This prospective cross-sectional study was conducted over two months in the cancer clinic of the Department of Obstetrics and Gynecology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India. We interviewed 384 women diagnosed with advanced cervical cancer [the International Federation of Gynecology and Obstetrics (FIGO) stage IB3-IVB] by using a questionnaire to capture data inputs regarding the various healthcare services they had received in the past 10 years along with details of HCPs. The collected data were analyzed using the software STATA version 17.0. Results Among 384 participants, 185 (48.1%) had interacted with an HCP in the past 10 years; 157 (40.8%) of them had visited a healthcare facility. Among these 185 women, only 22.16% had been advised to undergo screening, and only 15.18% had been tested despite several having access to primary health centers within 10 km of their residence. The lack of screening guidance by HCPs accounted for 78% of delayed diagnoses of cervical cancer. Conclusions Based on our findings, a deficiency in screening guidance in the asymptomatic period by healthcare providers across various levels of our healthcare system contributed significantly to the delayed diagnosis of cervical cancer.

European Neuroendocrine Tumor Society (ENETS) 2024 guidance paper for the management of well-differentiated small intestine neuroendocrine tumours.

Both the incidence and prevalence of well-differentiated neuroendocrine tumours from the small intestine (Si-NET) are gradually increasing. Most patients have non-functioning tumours with subtle GI symptoms and tumours are often discovered incidentally by endoscopy or at advanced disease stages by imaging depicting mesenteric lymph node and /or liver metastases while around 30% of the patients present with symptoms of the carcinoid syndrome. Adequate biochemical assessment and staging including functional imaging is crucial for treatment-related decision-making that should take place in an expert multidisciplinary team setting. Preferably, patients should be referred to specialised ENETS Centres of Excellence or centres of high expertise in the field. This guidance paper provides the current evidence and best knowledge for the management of Si-NET grade (G) 1-3 following 10 key questions of practical relevance for the diagnostic and therapeutic decision making.

Prioritise safety, optimise success! Return to rugby postpartum.

Pregnancy and childbirth involve substantial physical, physiological and psychological changes. As such, postpartum rugby players should be supported and appropriately prepared to return to the demands of rugby alongside the additional demands of motherhood. This review aims to discuss specific perinatal considerations that inform a rugby player's readiness to return-to-sport postpartum and present an approach to rehabilitation. Before engaging in full rugby training and matchplay, postpartum players should have progressed through the initial phases of rehabilitation and graded sports-specific training to prepare them for the loads they will be exposed to. Additional rehabilitation considerations include minimising deconditioning during pregnancy; medical concerns; the abdominal wall; the pelvic floor; perinatal breast changes, breastfeeding and risk of contact breast injury; body mass; nutritional requirements; hormonal considerations; athlete identity and psychological considerations; joining team training; return to contact and tackle training; evaluating player load tolerance and future research, policy and surveillance needs. A whole-systems, biopsychosocial approach following an evidence informed return-to-sport framework is recommended when rehabilitating postpartum rugby players. Health and exercise professionals are encouraged to use the perinatal-specific recommendations in this review to guide the development of postpartum rehabilitation protocols and resources.

Motivation and guidance of college students' low-carbon behavior: evidence from Chinese colleges and universities.

In the context of the global implementation of the emission peak and carbon-neutral strategic goal, guiding residents' low-carbon behavior is of great significance for the realization of the dual carbon goal. However, existing studies have paid less attention to the low-carbon behavior of college students. Based on the theory of planned behavior, this paper constructs a theoretical model of influencing factors of college students' low-carbon behavior. Combined with 612 questionnaires from Chinese colleges and universities, this study uses a structural equation model and multi-group analysis method to explore the motivation of college students' low-carbon behavior and guiding education strategies. The results show that low-carbon attitude, subjective norms, low-carbon values, and perceived behavior control have significant positive effects on low low-carbon behavior intention of college students, and influence their low-carbon behavior through low-carbon behavior intention. Further research found that gender and growth environment (urban vs. rural) presented heterogeneity in different influence paths, and the perceived cost had a significant negative moderating effect during the transition from low-carbon intention to low-carbon behavior. These research findings provide a theoretical basis and policy inspiration for explaining and guiding the low-carbon behavior of college students.

Puncture Cube Patient-Mounted Navigation System versus Freehand Method for CT-Guided Needle Placement: Study on a Neoprene Covered Elliptical Cylinder Gelatin Phantom.

PURPOSE: The study aims to show how the "Puncture Cube" (PC) (Medical Templates, Egg, Switzerland) compares to the freehand method (FHM) for CT-guided punctures. METHODS: The PC is a patient-mounted disassemblable cube consisting of an upper and lower template with multiple holes each to predefine puncture trajectory. A total of 80 punctures (FHM in-plane, FHM off-plane, PC in-plane, PC off-plane) was performed by 4 radiologists on a target 9.1 cm below surface level of a neoprene covered elliptical cylinder gelatin phantom. The PC was never disassembled. Evaluated parameters were procedure time, number of CT-scans, euclidean distance (ED) and normal distance (ND). Respective parameters of FHM and PC were compared using the Wilcoxon signed-rank test and Levene test with significance levels of 5%. RESULTS: PC achieved smaller ED and ND values after initial needle insertion without corrections for both in-plane and off-plane punctures (P > 0.05). Variance of initial NDs was off-plane significantly larger for FHM. Final ED after needle path corrections was smaller for FHM both in- and off-plane (P < 0.05). Final off-plane ND was significantly lower for FHM with no significant difference in final in-plane ND. FHM off-plane punctures were significantly faster. There was no significant difference in CT-scans between both methods. CONCLUSION: Utilizing the PC may improve initial needle positioning and safety especially off-plane. However, better final needle positioning after correction with the greater freedom of movement method may suggest need for disassembly of the cube.

Anaesthesia Considerations in a Case of Alkaptonuria Posted for Total Knee Arthroplasty.

Alkaptonuria is a rare hereditary condition in which homogentisic acid is deposited in collagenous tissues, leading to blackish discoloration, degenerative changes, restricted mobility, and pain in the affected part. The skeletal system is commonly affected, resulting in the stiffening of the vertebral spine, shoulders, knees, hip joints, and thoracic cage. Additionally, the degenerative process involves heart valves, endocardium, and kidneys, with associated pathophysiological changes. These patients present significant challenges in neuraxial anesthesia, airway management, and postoperative pain relief. In this report, we present the anesthetic management of a case of alkaptonuria undergoing total knee arthroplasty and discuss the encountered difficulties. We conclude that the perioperative anesthesia management of alkaptonuria patients requires thorough planning to effectively address the various challenges associated with the administration of anesthesia.

Gestational VPA exposure reduces the density of juxtapositions between TH+ axons and calretinin or calbindin expressing cells in the ventrobasal forebrain of neonatal mice.

Gestational exposure to valproic acid (VPA) is a valid rodent model of human autism spectrum disorder (ASD). VPA treatment is known to bring about specific behavioral deficits of sociability, matching similar alterations in human autism. Previous quantitative morphometric studies from our laboratory showed a marked reduction and defasciculation of the mesotelencephalic dopaminergic pathway of VPA treated mice, along with a decrease in tissue dopamine in the nucleus accumbens (NAc), but not in the caudatoputamen (CPu). In the present study, the correlative distribution of tyrosine hydroxylase positive (TH+) putative axon terminals, presynaptic to the target neurons containing calretinin (CR) or calbindin (CB), was assessed using double fluorescent immunocytochemistry and confocal laser microscopy in two dopamine recipient forebrain regions, NAc and olfactory tubercle (OT) of neonatal mice (mothers injected with VPA on ED13.5, pups investigated on PD7). Representative image stacks were volumetrically analyzed for spatial proximity and abundance of presynaptic (TH+) and postsynaptic (CR+, CB+) structures with the help of an Imaris (Bitplane) software. In VPA mice, TH/CR juxtapositions were reduced in the NAc, whereas the TH/CB juxtapositions were impoverished in OT. Volume ratios of CR+ and CB+ elements remained unchanged in NAc, whereas that of CB+ was markedly reduced in OT; here the abundance of TH+ axons was also diminished. CR and CB were found to partially colocalize with TH in the VTA and SN. In VPA exposed mice, the abundance of CR+ (but not CB+) perikarya increased both in VTA and SN, however, this upregulation was not mirrored by an increase of the number of CR+/TH+ double labeled cells. The observed reduction of total CB (but not of CB+ perikarya) in the OT of VPA exposed animals signifies a diminished probability of synaptic contacts with afferent TH+ axons, presumably by reducing the available synaptic surface. Altered dopaminergic input to ventrobasal forebrain targets during late embryonic development will likely perturb the development and consolidation of neural and synaptic architecture, resulting in lasting changes of the neuronal patterning (detected here as reduced synaptic input to dopaminoceptive interneurons) in ventrobasal forebrain regions specifically involved in motivation and reward.

A novel simplified sonographic approach with fluoroscopy-controlled L5 transforaminal epidural injections in patients with high iliac crest: a retrospective study.

BACKGROUND: To explore a novel ultrasound (US) modality for lumbar transforaminal epidural injections (TFEIs) in patients with low back pain (LBP) and L5 radicular pain combined with high iliac crest (HIC). METHODS: One-hundred and forty-one patients were retrospectively stratified into two groups based on the treatment they received: novel group, receiving US-guided and fluoroscopy (FL)-controlled TFEIs using a sagittal oblique approach between the superior articular process of L5 and S1, and control group, receiving US-guided TFEIs with conventional transverse approach combined with FL confirmation. Accuracy of contrast dispersing into lumbar epidural space was set as the primary endpoint. Radiation dosages, procedure time, numeric rating scale (NRS) scores, Modified Oswestry Disability Questionnaire (MODQ) scores, adverse events, and rescue analgesic requirement were also recorded. The generalized liner mixed model (GLMMs) was employed to compare the repeatedly measured variables between groups, taking individual confounding factors as covariance. RESULTS: The accuracy of TFEIs was 92.8% and 65.2% in novel and control group, with a significant difference of 26.7% (95% CI: 15.4%, 39.8%) between two modalities (p < 0.001). Significant pain relief was observed in novel group as opposed to control group after one injection. Procedure time in novel group (8.4 ± 1.6 min) was shorter than control group (15.8 ± 3.5 min) (p < 0.001) with less radiation dosage (3047 ± 5670 vs. 8808 ± 1039 µGy/m2, p < 0.001). Significantly, lower incidence of L5 paresthesia occurred in novel group. Statistical differences of NRS scores between the novel and control group were reached at 1 week after procedure (1 (IQR: - 1-3) vs. 3 (IQR: - 1-7), p = 0.006), while not reached at both 1- (1 (IQR: 0-2) vs. 1 (IQR: - 1-3), p = 0.086) or 3-month follow-up (0 (IQR: - 1-1) vs. 1 (IQR: 0-2), p = 0.094). Both groups showed similar functional improvement (F = 0.103, p = 0.749) during follow-up. CONCLUSIONS: The novel sonographic technique provided superior accuracy needle placement and better pain-relieving effect through one injection as compared to the routine transverse approach. Consequently, in situations where the HIC imposed limitations for TFEIs performance on L5, the novel technique should be recommended to consider increasing accurate puncture, minimizing radiation exposure, consuming procedure time, and reducing the risk of neuraxial injury.

The auditory stimulus facilitates memory guidance in distractor suppression in males with substance use disorder.

Introduction: Representations in working memory can affect distractor suppression in human visual search, and this process is modulated by a separate top-down cognitive control. An increasing body of research has demonstrated that patients with substance use disorder (SUD) have deficits in cognitive control over filtering interference by perceptual distractors. However, their ability to resist proactive interference from working memory has received comparatively less attention. Methods: Here, we investigate this issue by employing a working memory/visual search dual-task paradigm. An intervening gap-location search task was instructed to be performed while participants memorized a written color word, with congruent auditory information present during the memory encoding phase on half of the trials. Results: Results showed that there was a reliable response time (RT) advantage when the meaning of the memory sample agreed with the color of one of the distractors under the visual alone condition. However, such a result was only found in the control group. More importantly, both groups exhibited comparable facilitation under the audiovisual condition, with the facilitation effect appearing later in the SUD group. Furthermore, the facilitation effect was superior in magnitude and time course under the audiovisual condition to the visual alone condition. Discussion: These findings highlight how patients with SUD resist distractor interference at the memory level and extend our understanding of how working memory, selective attention, and audiovisual enhancement interact to optimize perceptual decisions in patients with SUD.

Regulatory systems and requirements for clinical trials of AAV-based gene therapies - Perspectives from six Asian countries or regions: Report from the 6th Asia Partnership Conference of Regenerative Medicine - April 20, 2023.

Gene therapies, which include viral-vector gene delivery, genome editing, and genetically modified cell therapy, are innovative treatments with the potential to address the underlying genetic causes of disorders and to provide life-changing value in terms of curing disease. Although adeno-associated virus (AAV)-based gene therapy is one of the most advanced types of gene therapy, far fewer AAV-based gene therapy studies have been conducted in Asia than in North America and Europe. The 6th Asia Partnership Conference of Regenerative Medicine (APACRM) was held on April 20, 2023 in Tokyo, Japan. APACRM Working Group 3 comprehensively analyzed the regulatory processes that occur prior to the initiation of clinical trials as well as the regulatory requirements for AAV-based gene therapies for six Asian countries or regions (China, India, Japan, Singapore, South Korea, and Taiwan). In this article, we report the outcomes of this conference, summarizing the regulatory requirements for initiating clinical trials for AAV-based gene therapies in terms of the laws, regulations, and guidelines for gene therapy; consultations or reviews required by the health authorities; points to consider for scientific reviews by the health authorities; and specific challenges to address when developing gene therapy products in these locations. Finally, we present several policy recommendations, including simplifying the regulatory review system for multiple scientific review areas; simplifying the regulatory consultation system; and providing training programs and regulatory guidance to support the advancement of gene therapy development in Asia.

Technical considerations and strategies for generating and optimizing humanized mouse tumor models in immuno-oncology research.

The field of cancer immunotherapy has experienced significant progress, resulting in the emergence of numerous biological drug candidates requiring in vivo efficacy testing and a better understanding of their mechanism of action (MOA). Humanized immune system (HIS) models are valuable tools in this regard. However, there is a lack of systematic guidance on HIS modeling. To address this issue, the present study aimed to establish and optimize a variety of HIS models for immune-oncology (IO) study, including genetically engineered mouse models and HIS models with human immune components reconstituted in severely immunocompromised mice. The efficacy and utility of these models were tested with several marketed or investigational IO drugs according to their MOA, followed by immunophenotypic analysis and efficacy evaluation. The results of the present study demonstrated that the HIS models responded to various IO drugs as expected and that each model had unique niches, utilities and limitations. Researchers should carefully choose the appropriate models based on the MOA and the targeted immune cell populations of the investigational drug. The present study provides valuable methodologies and actionable technical guidance on designing, generating or utilizing appropriate HIS models to address specific questions in translational IO.