ai Bridging brain and body in cancer [Special Section: Symposium Outlook] By genesdev.cshlp.org Published On :: 2024-10-16T07:18:56-07:00 Recent work has highlighted the central role the brain–body axis plays in not only maintaining organismal homeostasis but also coordinating the body's response to immune and inflammatory insults. Here, we discuss how science is poised to address the many ways that our brain is directly involved with disease. In particular, we feel that combining cutting-edge tools in neuroscience with translationally relevant models of cancer will be critical to understanding how the brain and tumors communicate and modulate each other's behavior. Full Article
ai The area postrema: a critical mediator of brain-body interactions [Special Section: Symposium Outlook] By genesdev.cshlp.org Published On :: 2024-10-16T07:18:56-07:00 The dorsal vagal complex contains three structures: the area postrema, the nucleus tractus solitarii, and the dorsal motor nucleus of the vagus. These structures are tightly linked, both anatomically and functionally, and have important yet distinct roles in not only conveying peripheral bodily signals to the rest of the brain but in the generation of behavioral and physiological responses. Reports on the new discoveries in these structures were highlights of the symposium. In this outlook, we focus on the roles of the area postrema in mediating brain–body interactions and its potential utility as a therapeutic target, especially in cancer cachexia. Full Article
ai Cancer neuroscience at the brain-body interface [Special Section: Symposium Outlook] By genesdev.cshlp.org Published On :: 2024-10-16T07:18:56-07:00 Our approaches toward understanding cancer have evolved beyond cell-intrinsic and local microenvironmental changes within the tumor to encompass how the cancer interfaces with the entire host organism. The nervous system is uniquely situated at the interface between the brain and body, constantly receiving and sending signals back and forth to maintain homeostasis and respond to salient stimuli. It is becoming clear that various cancers disrupt this dialog between the brain and body via both neuronal and humoral routes, leading to aberrant brain activity and accelerated disease. In this outlook, I discuss this view of cancer as a homeostatic challenge, emphasize cutting-edge work, and provide outstanding questions that need to be answered to move the field forward. Full Article
ai Dysregulating mTORC1-4E-BP2 signaling in GABAergic interneurons impairs hippocampus-dependent learning and memory [RESEARCH PAPERS] By learnmem.cshlp.org Published On :: 2024-10-28T08:52:55-07:00 Memory formation is contingent on molecular and structural changes in neurons in response to learning stimuli—a process known as neuronal plasticity. The initiation step of mRNA translation is a gatekeeper of long-term memory by controlling the production of plasticity-related proteins in the brain. The mechanistic target of rapamycin complex 1 (mTORC1) controls mRNA translation, mainly through phosphorylation of the eukaryotic initiation factor 4E (eIF4E)-binding proteins (4E-BPs) and ribosomal protein S6 kinases (S6Ks). mTORC1 signaling decreases throughout brain development, starting from the early postnatal period. Here, we discovered that in mice, the age-dependent decrease in mTORC1 signaling occurs selectively in excitatory but not inhibitory neurons. Using a gene conditional knockout (cKO) strategy, we demonstrate that either up- or downregulating the mTORC1-4E-BP2 axis in GAD65 inhibitory interneurons, but not excitatory neurons, results in long-term object recognition and object location memory deficits. Our data indicate that the mTORC1 pathway in inhibitory but not excitatory neurons plays a key role in memory formation. Full Article
ai The noninvasive ventilation outcomes score in patients requiring NIV for COPD exacerbation without prior evidence of airflow obstruction By beta.openres.ersjournals.com Published On :: 2024-11-11T01:50:25-08:00 Introduction Exacerbation of COPD complicated by respiratory acidaemia is the commonest indication for noninvasive ventilation (NIV). The NIV outcomes (NIVO) score offers the best estimate of survival for those ventilated. Unfortunately, two-thirds of cases of COPD are unrecognised, and patients may present without COPD having been confirmed by spirometry. Methods In the 10-centre NIVO validation study there was no pre-admission spirometry in 111 of 844 consecutive patients (termed "clinical diagnosis" patients). We compared the performance of the NIVO, DECAF and CURB-65 scores for in-hospital mortality in the clinical diagnosis cohort. Usual clinical practice was not influenced, but confirmation of COPD in the year following discharge was captured. Results In the clinical diagnosis cohort, in-hospital mortality was 19.8% and rose incrementally across the NIVO risk categories, consistent with the NIVO validation cohort. NIVO showed good discrimination in the clinical diagnosis cohort: area under the receiver operating curve 0.724, versus 0.79 in the NIVO validation cohort. At 1 year after discharge, 41 of 89 clinical diagnosis patients had undertaken diagnostic spirometry; 33 of 41 had confirmation of airflow obstruction (forced expiratory volume in 1 s/(forced) vital capacity <0.7), meaning the diagnosis of COPD was incorrect in 19.5% of cases. Discussion These data support the use of the NIVO score in patients with a "clinical diagnosis" of COPD. NIVO can help guide shared decision-making, assess risk-adjusted outcomes by centre and challenge prognostic pessimism. Accurate diagnosis is critical to ensure that acute and long-term treatment is optimised; this study highlights failings in the follow-up of such patients. Full Article
ai Longitudinal validation of King's Sarcoidosis Questionnaire in a prospective cohort with mild sarcoidosis By beta.openres.ersjournals.com Published On :: 2024-11-11T01:50:25-08:00 Background Quality of life is impaired in patients with sarcoidosis. The King's Sarcoidosis Questionnaire (KSQ) is a brief questionnaire assessing health-related quality of life in patients with sarcoidosis, comprising subdomains of General Health Status (GHS), Lung, Medication, Skin and Eyes. The aim of this study was to enhance the validation of the KSQ, incorporating longitudinal validation and known-groups validity in a cohort with mild sarcoidosis. Methods The KSQ was linguistically validated according to guidelines. Patients with sarcoidosis completed KSQ and other questionnaires at baseline, after 2 weeks and at 12 months. Forced vital capacity (FVC) was measured. Concurrent validity, reliability and responsiveness were assessed. Results In patients (n=150), the KSQ had moderate to strong correlations with the Short Form-12 (Mental Component Summary), the King's Brief Interstitial Lung Disease questionnaire and the Fatigue Assessment Scale (r=0.30–0.70) and weak correlations with the Short Form-12 (Physical Component Summary) and FVC (r=0.01–0.29). The KSQ GHS and Lung domains were able to discriminate between groups of patients stratified according to fatigue, treatment and FVC. The KSQ had high internal consistency (Cronbach's α=0.73–0.90) and repeatability (interclass correlation coefficients 0.72–0.81). Correlations to comparable questionnaires at baseline were moderate or strong for the GHS, Lung and GHS–Lung subdomains and weak or moderate for FVC. The KSQ was responsive to changes over time. Conclusion This study strengthened the validation of the KSQ by introducing known-groups validity and assessments of responsiveness over 12 months in patients with mild sarcoidosis. Full Article
ai TB or not TB: does AI have an answer for children? By erj.ersjournals.com Published On :: 2024-11-07T00:35:56-08:00 Extract In 2021, the World Health Organization (WHO) issued recommendations for the use of artificial intelligence (AI), affirming the technology could be used instead of human readers for the interpretation of chest radiograph (CXR) images for the screening and triage of tuberculosis (TB), marking a historic precedent for a guideline on AI in health [1]. The forward-looking guidance highlights the utility of CXR in TB, despite past reluctance from WHO to use it in TB programmes [2]. Employing CXR in a diagnostic algorithm can identify people with subclinical TB who are asymptomatic but have lung pathology suggestive of TB, and refer them for testing and diagnosis [3]. Full Article
ai Ensuring availability of respiratory medicines in times of European drug shortages By erj.ersjournals.com Published On :: 2024-11-07T00:35:56-08:00 Extract It is of utmost importance that medicines are available at all times for our patients. Historically, medication unavailability has typically, if not exclusively, affected low- and middle-income countries [1]. More recently however, drug shortages have also been reported in high-income European countries [2]. Drug shortages have negative health consequences for patients [3], and a profound economic impact, with the need to resort to more expensive alternatives and demands on healthcare professionals’ time to find, prescribe and dispense alternatives [4]. Full Article
ai Accuracy of CAD4TB (Computer-Aided Detection for Tuberculosis) on paediatric chest radiographs By erj.ersjournals.com Published On :: 2024-11-07T00:35:56-08:00 Background Computer-aided detection (CAD) systems hold promise for improving tuberculosis (TB) detection on digital chest radiographs. However, data on their performance in exclusively paediatric populations are scarce. Methods We conducted a retrospective diagnostic accuracy study evaluating the performance of CAD4TBv7 (Computer-Aided Detection for Tuberculosis version 7) using digital chest radiographs from well-characterised cohorts of Gambian children aged <15 years with presumed pulmonary TB. The children were consecutively recruited between 2012 and 2022. We measured CAD4TBv7 performance against a microbiological reference standard (MRS) of confirmed TB, and also performed Bayesian latent class analysis (LCA) to address the inherent limitations of the MRS in children. Diagnostic performance was assessed using the area under the receiver operating characteristic curve (AUROC) and point estimates of sensitivity and specificity. Results A total of 724 children were included in the analysis, with confirmed TB in 58 (8%), unconfirmed TB in 145 (20%) and unlikely TB in 521 (72%). Using the MRS, CAD4TBv7 showed an AUROC of 0.70 (95% CI 0.60–0.79), and demonstrated sensitivity and specificity of 19.0% (95% CI 11–31%) and 99.0% (95% CI 98.0–100.0%), respectively. Applying Bayesian LCA with the assumption of conditional independence between tests, sensitivity and specificity estimates for CAD4TBv7 were 42.7% (95% CrI 29.2–57.5%) and 97.9% (95% CrI 96.6–98.8%), respectively. When allowing for conditional dependence between culture and Xpert assay, CAD4TBv7 demonstrated a sensitivity of 50.3% (95% CrI 32.9–70.0%) and specificity of 98.0% (95% CrI 96.7–98.9%). Conclusion Although CAD4TBv7 demonstrated high specificity, its suboptimal sensitivity underscores the crucial need for optimisation of CAD4TBv7 for detecting TB in children. Full Article
ai Association between a recalled positive airway pressure device and incident cancer: a population-based study By erj.ersjournals.com Published On :: 2024-11-07T00:35:55-08:00 Background The real-world consequences of a Philips Respironics recall for positive airway pressure (PAP) devices distributed between 2009 and 2021 are unknown. Methods We conducted a retrospective population-based study using health administrative databases (Ontario, Canada) on all new adult PAP users identified through the provincial funding system, free of cancer at baseline, who initiated (claimed) PAP treatment between 2012 and 2018. Everyone was followed from the PAP claim date to the earliest of incident cancer diagnosis, death or end of follow-up (March 2022). We used inverse probability of treatment weighting to balance baseline characteristics between individuals on recalled devices and those on devices from other manufacturers. Weighted hazard ratios of incident cancer were compared between groups. Results Of 231 692 individuals identified, 58 204 (25.1%) claimed recalled devices and 173 488 (74.9%) claimed devices from other manufacturers. A meaningful baseline difference between groups (standardised difference ≥0.10) was noted only by location-relevant covariates; other variables were mostly equally distributed (standardised differences ≤0.06). Over a median (interquartile range) follow-up of 6.3 (4.9–8.0) years, 11 166 (4.8%) developed cancer: unadjusted rates per 10 000 person-years of 78.8 (95% CI 76.0–81.7) in the recall group versus 74.0 (95% CI 72.4–75.6) in others (p=0.0034). Propensity score weighting achieved excellent balance in baseline characteristics between groups (standardised differences ≤0.07). On a weighted sample, there was no statistical difference in the hazard of incident cancer between groups: cause-specific hazard ratio (recalled versus others) 0.97 (95% CI 0.89–1.06). Conclusion In our real-world population study, compared to other manufacturers and adjusting for confounders, recalled Philips Respironics PAP devices do not appear to be independently associated with developing cancer. Full Article
ai “Je suis desole, ȷe parle francais”: How English Hegemony Undermines Efforts to Shift Power in Global Health By ghspjournal.org Published On :: 2024-10-29T12:28:39-07:00 Le texte complet de l’article est aussi disponible en français. Full Article
ai Family Planning, Reproductive Health, and Progress Toward the Sustainable Development Goals: Reflections and Directions on the 30th Anniversary of the International Conference on Population and Development By ghspjournal.org Published On :: 2024-10-29T12:28:39-07:00 Full Article
ai Can the International Conference on Population and Development Programme of Action and Cairo Consensus Normalize the Discourse on Population? By ghspjournal.org Published On :: 2024-10-29T12:28:39-07:00 Full Article
ai Delays in Cardiovascular Emergency Responses in Africa: Health System Failures or Cultural Challenges? By ghspjournal.org Published On :: 2024-10-29T12:28:39-07:00 Full Article
ai Strengthening Capacity for Tailored Immunization Programs Using Adult Learning Principles: A Case Study from Nigeria By ghspjournal.org Published On :: 2024-10-29T12:28:39-07:00 ABSTRACTIntroduction: Nigeria has the highest number of children who have not received any vaccines in Africa. The training-of-trainers (TOT) model used to train program managers (PMs) and health care workers (HCWs) is ineffective for adult learning and limits immunization programs’ success. We incorporated adult learning principles (ALPs) in designing and delivering TOT for immunization PMs and HCWs to use data to engage communities for tailored immunization strategies.Methods: Our study was implemented in 3 local government areas (LGAs) of the Federal Capital Territory, Nigeria. A training curriculum was developed, integrating ALPs and technical and operational content based on best practices in delivering immunization training and the training needs assessment findings. State PMs (n=10), LGA PMs (n=30), and HCWs (n=42) were trained on the human-centered design for tailoring immunization programs (HCD-TIP) approaches using ALPs. We used interviews and surveys with purposively and conveniently sampled PMs and HCWs, respectively, and observations to assess participants’ satisfaction, knowledge and competence, behavior changes, and results. The interviews were analyzed thematically, and surveys were statistically.Results: There was a high level of satisfaction with the training among LGA PMs (100%), state PMs (91%), and HCWs (85%), with significant knowledge and competence improvements post-training (P<.001). The trained participants conducted 2 HCD sessions with 24 undervaccinated communities and co-designed 24 prototype solutions for testing. Results showed increased coverage of the pentavalent vaccine first dose (54%) and third dose (188%) across 12 participating communities. Improved community colaboration, communication skills, and data-driven approaches were the most cited behavior changes in practice.Conclusion: The application of ALPs in training, use of HCD-TIP approaches and tools, and supportive supervision enhanced PMs’ and HCWs’ capacity for tailored interventions. Countries should consider adopting a holistic approach that focuses on using these approaches in immunization programs to strengthen the health system for equitable vaccine coverage. Full Article
ai Effects of Dual Inhibition at Dopamine Transporter and {sigma} Receptors in the Discriminative-Stimulus Effects of Cocaine in Male Rats [Behavioral Pharmacology] By jpet.aspetjournals.org Published On :: 2024-10-18T07:04:15-07:00 Previous studies demonstrated that sigma receptor (R) antagonists alone fail to alter cocaine self-administration despite blocking various other effects of cocaine. However, R antagonists when combined with dopamine transporter (DAT) inhibitors substantially decrease cocaine self-administration. To better understand the effects of this combination, the present study examined the effects of R antagonist and DAT inhibitor combinations in male rats discriminating cocaine (10 mg/kg, i.p.) from saline injections. The DAT inhibitors alone [(–)-2-β-carbomethoxy-3-β-(4-fluorophenyl)tropane 1,5-naphthalenedisulfonate monohydrate (WIN 35,428) and methylphenidate] at low (0.1-mg/kg) doses that were minimally active failed to shift the dose-effect function for discriminative-stimulus effects of cocaine to the left more than 2-fold. At 0.32 mg/kg the DAT inhibitors alone shifted the cocaine dose-effect function leftward 24- or 6.6-fold, respectively. The R antagonists (BD1008, BD1047, and BD1063) failed to fully substitute for cocaine, although BD1008 and BD1047 substituted partially. At 10 mg/kg, BD1008, BD1047, or BD1063 alone shifted the cocaine dose-effect function leftward less than 6.0-fold. In combination with 0.1 mg/kg WIN 35,428, the 10 mg/kg doses of R antagonists shifted the cocaine dose-effect function from 12.3- to 36.7-fold leftward, and with 0.32 mg/kg WIN 35,428 from 14.3- to 440-fold leftward. In combination with 0.1 mg/kg methylphenidate, those R antagonist doses shifted the cocaine dose-effect function from 5.5- to 55.0-fold leftward, and with 0.32 mg/kg methylphenidate from 10.5- to 48.1-fold leftward. The present results suggest that dual DAT/R inhibition produces agonist-like subjective effects that may promote decreases in self-administration obtained in previous studies. SIGNIFICANCE STATEMENT There is currently no approved medication for treating stimulant abuse, although dopamine uptake inhibitors in combination with sigma receptor (R) antagonists decrease cocaine self-administration in laboratory animals. The present study assessed how this combination alters the discriminative-stimulus effects of cocaine in male rats. Results suggest that concurrent dopamine uptake inhibition and R antagonism together may promote decreases in self-administration, possibly by mimicking the subjective effects extant when subjects cease continued cocaine self-administration. Full Article
ai Cannabinoid 2 Receptor Activation Protects against Diabetic Cardiomyopathy through Inhibition of AGE/RAGE-Induced Oxidative Stress, Fibrosis, and Inflammasome Activation [Special Section: Cannabinoid Signaling in Human Health and Disease] By jpet.aspetjournals.org Published On :: 2024-10-18T07:04:15-07:00 Oxidative stress, fibrosis, and inflammasome activation from advanced glycation end product (AGE)–receptor of advanced glycation end product (RAGE) interaction contribute to diabetic cardiomyopathy (DCM) formation and progression. Our study revealed the impact of β-caryophyllene (BCP) on activating cannabinoid type 2 receptors (CB2Rs) against diabetic complication, mainly cardiomyopathy and investigated the underlying cell signaling pathways in mice. The murine model of DCM was developed by feeding a high-fat diet with streptozotocin injections. After the development of diabetes, the animals received a 12-week oral BCP treatment at a dose of 50 mg/kg/body weight. BCP treatment showed significant improvement in glucose tolerance and insulin resistance and enhanced serum insulin levels in diabetic animals. BCP treatment effectively reversed the heart remodeling and restored the phosphorylated troponin I and sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a expression. Ultrastructural examination showed reduced myocardial cell injury in DCM mice treated with BCP. The preserved myocytes were found to be associated with reduced expression of AGE/RAGE in DCM mice hearts. BCP treatment mitigated oxidative stress by inhibiting expression of NADPH oxidase 4 and activating phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor erythroid 2–related factor 2 (Nrf2) signaling. Also, BCP suppressed cardiac fibrosis and endothelial-to-mesenchymal transition in DCM mice by inhibiting transforming growth factor β (TGF-β)/suppressor of mothers against decapentaplegic (Smad) signaling. Further, BCP treatment suppressed nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 (NLRP3) inflammasome activation in DCM mice and alleviated cellular injury to the pancreatic tissues evidenced by significant elevation of the number of insulin-positive cells. To demonstrate a CB2R-dependent mechanism of BCP, another group of DCM mice were pretreated with AM630, a CB2R antagonist. AM630 was observed to abrogate the beneficial effects of BCP in DCM mice. Taken together, BCP demonstrated the potential to protect the myocardium and pancreas of DCM mice mediating CB2R-dependent mechanisms. SIGNIFICANCE STATEMENT BCP, a CB2R agonist, shows protection against DCM. BCP attenuates oxidative stress, inflammation, and fibrosis in DCM via activating CB2Rs. BCP mediating CB2R activation favorably modulates AGE/RAGE, PI3K/AKT/Nrf2β and TGF-β/Smad and (NLRP3) inflammasome in diabetic cardiomyopathy. Full Article
ai The Minor Phytocannabinoid Delta-8-Tetrahydrocannabinol Attenuates Collagen-Induced Arthritic Inflammation and Pain-Depressed Behaviors [Special Section: Cannabinoid Signaling in Human Health and Disease] By jpet.aspetjournals.org Published On :: 2024-10-18T07:04:15-07:00 Patients with arthritis report using cannabis for pain management, and the major cannabinoid delta-9-tetrahydrocannabinol (9-THC) has anti-inflammatory properties, yet the effects of minor cannabinoids on arthritis are largely unknown. The goal of the present study was to determine the antiarthritic potential of the minor cannabinoid delta-8-tetrahydrocannabinol (8-THC) using the collagen-induced arthritis (CIA) mouse model. Adult male DBA/1J mice were immunized and boosted 21 days later with an emulsion of collagen and complete Freund’s adjuvant. Beginning on the day of the booster, mice were administered twice-daily injections of 8-THC (3 or 30 mg/kg), the steroid dexamethasone (2 mg/kg), or vehicle for two weeks. Dorsal-ventral paw thickness and qualitative measures of arthritis were recorded daily, and latency to fall from an inverted grid was measured on alternating days, to determine arthritis severity and functional impairment. On the final day of testing, spontaneous wire-climbing behavior and temperature preference in a thermal gradient ring were measured to assess CIA-depressed behavior. The 8-THC treatment (30 mg/kg) reduced paw swelling and qualitative signs of arthritis. 8-THC also blocked CIA-depressed climbing and CIA-induced preference for a heated floor without producing locomotor effects but did not affect latency to fall from a wire grid. In alignment with the morphologic and behavioral assessments in vivo, histology revealed that 8-THC reduced synovial inflammation, proteoglycan loss and cartilage and bone erosion in the foot joints in a dose-dependent manner. Together, these findings suggest that 8-THC not only blocked morphologic changes but also prevented functional loss caused by collagen-induced arthritis. SIGNIFICANCE STATEMENT Despite increasing use of cannabis products, the potential effects of minor cannabinoids are largely unknown. Here, the minor cannabinoid delta-8-tetrahydrocannabinol blocked the development of experimentally induced arthritis by preventing both pathophysiological as well as functional effects of the disease model. These data support the development of novel cannabinoid treatments for inflammatory arthritis. Full Article
ai Select Minor Cannabinoids from Cannabis sativa Are Cannabimimetic and Antinociceptive in a Mouse Model of Chronic Neuropathic Pain [Special Section: Cannabinoid Signaling in Human Health and Disease] By jpet.aspetjournals.org Published On :: 2024-10-18T07:04:15-07:00 Chronic pain conditions affect nearly 20% of the population in the United States. Current medical interventions, such as opioid drugs, are effective at relieving pain but are accompanied by many undesirable side effects. This is one reason increased numbers of chronic pain patients have been turning to Cannabis for pain management. Cannabis contains many bioactive chemical compounds; however, current research looking into lesser-studied minor cannabinoids in Cannabis lacks uniformity between experimental groups and/or excludes female mice from investigation. This makes it challenging to draw conclusions between experiments done with different minor cannabinoid compounds between laboratories or parse out potential sex differences that could be present. We chose five minor cannabinoids found in lower quantities within Cannabis: cannabinol (CBN), cannabidivarin (CBDV), cannabigerol (CBG), 8-tetrahydrocannabinol (8-THC), and 9-tetrahydrocannabivarin (THCV). These compounds were then tested for their cannabimimetic and pain-relieving behaviors in a cannabinoid tetrad assay and a chemotherapy-induced peripheral neuropathy (CIPN) pain model in male and female CD-1 mice. We found that the minor cannabinoids we tested differed in the cannabimimetic behaviors evoked, as well as the extent. We found that CBN, CBG, and high-dose 8-THC evoked some tetrad behaviors in both sexes, while THCV and low-dose 8-THC exhibited cannabimimetic tetrad behaviors only in females. Only CBN efficaciously relieved CIPN pain, which contrasts with reports from other researchers. Together these findings provide further clarity to the pharmacology of minor cannabinoids and suggest further investigation into their mechanism and therapeutic potential. SIGNIFICANCE STATEMENT Minor cannabinoids are poorly studied ligands present in lower levels in Cannabis than cannabinoids like THC. In this study, we evaluated five minor cannabinoids (CBN, CBDV, CBG, THCV, and 8-THC) for their cannabimimetic and analgesic effects in mice. We found that four of the five minor cannabinoids showed cannabimimetic activity, while one was efficacious in relieving chronic neuropathic pain. This work is important in further evaluating the activity of these drugs, which are seeing wider public use with marijuana legalization. Full Article
ai Low-Efficacy Mu Opioid Agonists as Candidate Analgesics: Effects of Novel C-9 Substituted Phenylmorphans on Pain-Depressed Behavior in Mice [Behavioral Pharmacology] By jpet.aspetjournals.org Published On :: 2024-10-18T07:04:15-07:00 Low-efficacy mu opioid receptor (MOR) agonists may serve as novel candidate analgesics with improved safety relative to high-efficacy opioids. This study used a recently validated assay of pain-depressed behavior in mice to evaluate a novel series of MOR-selective C9-substituted phenylmorphan opioids with graded MOR efficacies. Intraperitoneal injection of dilute lactic acid (IP acid) served as a noxious stimulus to depress locomotor activity by mice in an activity chamber composed of two compartments connected by an obstructed door. Behavioral measures included (1) crosses between compartments (vertical activity over the obstruction) and (2) movement counts quantified as photobeam breaks summed across compartments (horizontal activity). Each drug was tested alone and as a pretreatment to IP acid. A charcoal-meal test and whole-body-plethysmography assessment of breathing in 5% CO2 were also used to assess gastrointestinal (GI) inhibition and respiratory depression, respectively. IP acid produced a concentration-dependent depression in crosses and movement that was optimally alleviated by intermediate- to low-efficacy phenylmorphans with sufficient efficacy to produce analgesia with minimal locomotor disruption. Follow-up studies with two low-efficacy phenylmorphans (JL-2-39 and DC-1-76.1) indicated that both drugs produced naltrexone-reversible antinociception with a rapid onset and a duration of ~1 h. Potency of both drugs increased when behavior was depressed by a lower IP-acid concentration, and neither drug alleviated behavioral depression by a non-pain stimulus (IP lithium chloride). Both drugs produced weaker GI inhibition and respiratory depression than fentanyl and attenuated fentanyl-induced GI inhibition and respiratory depression. Results support further consideration of selective, low-efficacy MOR agonists as candidate analgesics. SIGNIFICANCE STATEMENT This study used a novel set of mu opioid receptor (MOR)-selective opioids with graded MOR efficacies to examine the lower boundary of MOR efficacy sufficient to relieve pain-related behavioral depression in mice. Two novel low-efficacy opioids (JL-2-39, DC-1-76.1) produced effective antinociception with improved safety relative to higher- or lower-efficacy opioids, and results support further consideration of these and other low-efficacy opioids as candidate analgesics. Full Article
ai Minor Cannabinoids as an Emerging Frontier for Pain Relief [Viewpoint] By jpet.aspetjournals.org Published On :: 2024-10-18T07:04:15-07:00 Full Article
ai Glatiramer Acetate for the Treatment of Multiple Sclerosis: From First-Generation Therapy to Elucidation of Immunomodulation and Repair [Review Article] By pharmrev.aspetjournals.org Published On :: 2024-10-16T07:40:25-07:00 Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS), with a putative autoimmune origin and complex pathogenesis. Modification of the natural history of MS by reducing relapses and slowing disability accumulation was first attained in the 1990 s with the development of the first-generation disease-modifying therapies. Glatiramer acetate (GA), a copolymer of L-alanine, L-lysine, L-glutamic acid, and L-tyrosine, was discovered due to its ability to suppress the animal model of MS, experimental autoimmune encephalomyelitis. Extensive clinical trials and long-term assessments established the efficacy and the safety of GA. Furthermore, studies of the therapeutic processes induced by GA in animal models and in MS patients indicate that GA affects various levels of the innate and the adaptive immune response, generating deviation from proinflammatory to anti-inflammatory pathways. This includes competition for binding to antigen presenting cells; driving dendritic cells, monocytes, and B-cells toward anti-inflammatory responses; and stimulating T-helper 2 and T-regulatory cells. The immune cells stimulated by GA reach the CNS and secrete in situ anti-inflammatory cytokines alleviating the pathological processes. Furthermore, cumulative findings reveal that in addition to its immunomodulatory effect, GA promotes neuroprotective repair processes such as neurotrophic factors secretion, remyelination, and neurogenesis. This review aims to provide an overview of MS pathology diagnosis and treatment as well as the diverse mechanism of action of GA. Significance Statement Understanding the complex MS immune pathogenesis provided multiple targets for therapeutic intervention, resulting in a plethora of agents, with various mechanisms of action, efficacy, and safety profiles. However, promoting repair beyond the body’s limited spontaneous extent is still a major challenge. GA, one of the first approved disease-modifying therapies, induces diverse immunomodulatory effects. Furthermore, GA treatment results in elevated neurotrophic factors secretion, remyelination and neurogenesis, supporting the notion that immunomodulatory treatment can support in situ a growth-promoting and repair environment. Full Article
ai Probabilistic Presurgical Language fMRI Atlas of Patients with Brain Tumors [CLINICAL PRACTICE] By www.ajnr.org Published On :: 2024-11-07T15:14:12-08:00 BACKGROUND AND PURPOSE: Patients with brain tumors have high intersubject variation in putative language regions, which may limit the utility of straightforward application of healthy subject brain atlases in clinical scenarios. The purpose of this study was to develop a probabilistic functional brain atlas that consolidates language functional activations of sentence completion and Silent Word Generation language paradigms using a large sample of patients with brain tumors. MATERIALS AND METHODS: The atlas was developed using retrospectively collected fMRI data from patients with brain tumors who underwent their first standard-of-care presurgical language fMRI scan at our institution between July 18, 2015, and May 13, 2022. Three hundred seventeen patients (861 fMRI scans) were used to develop the language functional atlas. An independent presurgical language fMRI data set of 39 patients with brain tumors from a previous study was used to evaluate our atlas. Family-wise error–corrected binary functional activation maps from sentence completion, letter fluency, and category fluency presurgical fMRI were used to create probability overlap maps and pooled probabilistic overlap maps in Montreal Neurological Institute standard space. The Wilcoxon signed-rank test was used to determine a significant difference in the maximum Dice coefficient for our atlas compared with a meta-analysis-based template with respect to expert-delineated primary language area activations. RESULTS: Probabilities of activating the left anterior primary language area and left posterior primary language area in the temporal lobe were 87.9% and 91.5%, respectively, for sentence completion, 88.5% and 74.2%, respectively, for letter fluency, and 83.6% and 67.6%, respectively, for category fluency. Maximum Dice coefficients for templates derived from our language atlas were significantly higher than the meta-analysis-based template in the left anterior primary language area (0.351 and 0.326, respectively, P < .05) and the left posterior primary language area in the temporal lobe (0.274 and 0.244, respectively, P < .005). CONCLUSIONS: Brain tumor patient- and paradigm-specific probabilistic language atlases were developed. These atlases had superior spatial agreement with fMRI activations in individual patients compared with the meta-analysis-based template. Full Article
ai Neuroimaging Correlates with Clinical Severity in Wilson Disease: A Multiparametric Quantitative Brain MRI [RESEARCH] By www.ajnr.org Published On :: 2024-11-07T15:14:12-08:00 BACKGROUND AND PURPOSE: Previous studies have reported metal accumulation and microstructure changes in deep gray nuclei (DGN) in Wilson disease (WD). However, there are limited studies that investigate whether there is metal accumulation and microstructure changes in DGN of patients with WD with normal-appearing routine MRI. This study aimed to evaluate multiparametric changes in DGN of WD and whether the findings correlate with clinical severity in patients with WD. MATERIALS AND METHODS: The study enrolled 28 patients with WD (19 with neurologic symptoms) and 25 controls. Fractional anisotropy (FA), mean diffusivity (MD), and magnetic susceptibility in globus pallidus, pontine tegmentum, dentate nucleus, red nucleus, head of caudate nucleus, putamen, substantia nigra, and thalamus were extracted. Correlations between imaging data and the Unified Wilson’s Disease Rating Scale (UWDRS) neurologic subitems were explored. RESULTS: FA, MD, and susceptibility values were higher in multiple DGN of patients with WD than controls (P < .05). Patients with WD without abnormal signals in DGN on routine MRI also had higher FA, MD, and susceptibility values than controls (P < .017). We found that UWDRS neurologic subscores correlated with FA and susceptibility values of DGN (P < .05). In addition, we also found that FA and susceptibility values in specific structures correlated with specific neurologic symptoms of WD (ie, tremor, parkinsonism, dysarthria, dystonia, and ataxia) (P < .05). CONCLUSIONS: Patients with WD have increased FA, MD, and susceptibility values even before the lesion is morphologically apparent on routine MRI. The increased FA and susceptibility values correlate with clinical severity of WD. Full Article
ai Stent Retriever AssIsted Lysis Technique with Tirofiban: A Potential Bailout Alternative to Angioplasty and Stenting [CLINICAL PRACTICE] By www.ajnr.org Published On :: 2024-11-07T15:14:12-08:00 BACKGROUND AND PURPOSE: Angioplasty and stent placement have been described as a bailout technique in individuals with failed thrombectomy. We aimed to investigate Stent retriever AssIsted Lysis (SAIL) with tirofiban before angioplasty and stent placement. MATERIALS AND METHODS: Patients from 2 comprehensive stroke centers were reviewed (2020–2023). We included patients with failed thrombectomy and/or underlying intracranial stenosis who received SAIL with tirofiban before the intended angioplasty and stent placement. SAIL consisted of deploying a stent retriever through the occluding lesion to create a bypass channel and infuse 10 mL of tirofiban for 10 minutes either intra-arterially or IV. The stent retriever was re-sheathed before retrieval. The primary end points were successful reperfusion (expanded TICI 2b–3) and symptomatic intracerebral hemorrhage. Additional end points included 90-day mRS 0–2 and mortality. RESULTS: After a median of 3 (interquartile range, 2–4) passes, 44 patients received the SAIL bridging protocol with tirofiban, and later they were considered potential candidates for angioplasty and stent placement bailout (43.2%, intra-arterial SAIL). Post-SAIL successful reperfusion was obtained in 79.5%. A notable residual stenosis (>50%) after successful SAIL was observed in 45.7%. No significant differences were detected according to post-SAIL: successful reperfusion (intra-arterial SAIL, 80.0% versus IV-SAIL, 78.9%; P = .932), significant stenosis (33.3% versus 55.0%; P = .203), early symptomatic re-occlusion (0% versus 8.0%; P = .207), or symptomatic intracerebral hemorrhage (5.3% versus 8.0%; P = .721). Rescue angioplasty and stent placement were finally performed in 15 (34.1%) patients (intra-arterial SAIL 21.0% versus IV-SAIL 44%; P = .112). At 90 days, mRS 0–2 (intra-arterial SAIL 50.0% versus IV-SAIL 43.5%; P = .086) and mortality (26.3% versus 12.0%; P = .223) were also similar. CONCLUSIONS: In patients with stroke in which angioplasty and stent placement are considered, SAIL with tirofiban, either intra-arterial or IV, seems to safely induce sustained recanalization, offering a potential alternative to definitive angioplasty and stent placement. Full Article
ai Artificial Intelligence Efficacy as a Function of Trainee Interpreter Proficiency: Lessons from a Randomized Controlled Trial [RESEARCH] By www.ajnr.org Published On :: 2024-11-07T15:14:12-08:00 BACKGROUND AND PURPOSE: Recently, artificial intelligence tools have been deployed with increasing speed in educational and clinical settings. However, the use of artificial intelligence by trainees across different levels of experience has not been well-studied. This study investigates the impact of artificial intelligence assistance on the diagnostic accuracy for intracranial hemorrhage and large-vessel occlusion by medical students and resident trainees. MATERIALS AND METHODS: This prospective study was conducted between March 2023 and October 2023. Medical students and resident trainees were asked to identify intracranial hemorrhage and large-vessel occlusion in 100 noncontrast head CTs and 100 head CTAs, respectively. One group received diagnostic aid simulating artificial intelligence for intracranial hemorrhage only (n = 26); the other, for large-vessel occlusion only (n = 28). Primary outcomes included accuracy, sensitivity, and specificity for intracranial hemorrhage/large-vessel occlusion detection without and with aid. Study interpretation time was a secondary outcome. Individual responses were pooled and analyzed with the t test; differences in continuous variables were assessed with ANOVA. RESULTS: Forty-eight participants completed the study, generating 10,779 intracranial hemorrhage or large-vessel occlusion interpretations. With diagnostic aid, medical student accuracy improved 11.0 points (P < .001) and resident trainee accuracy showed no significant change. Intracranial hemorrhage interpretation time increased with diagnostic aid for both groups (P < .001), while large-vessel occlusion interpretation time decreased for medical students (P < .001). Despite worse performance in the detection of the smallest-versus-largest hemorrhages at baseline, medical students were not more likely to accept a true-positive artificial intelligence result for these more difficult tasks. Both groups were considerably less accurate when disagreeing with the artificial intelligence or when supplied with an incorrect artificial intelligence result. CONCLUSIONS: This study demonstrated greater improvement in diagnostic accuracy with artificial intelligence for medical students compared with resident trainees. However, medical students were less likely than resident trainees to overrule incorrect artificial intelligence interpretations and were less accurate, even with diagnostic aid, than the artificial intelligence was by itself. Full Article
ai ITPR1-associated spinocerebellar ataxia with craniofacial features--additional evidence for germline mosaicism [RESEARCH ARTICLE] By molecularcasestudies.cshlp.org Published On :: 2024-01-10T08:13:38-08:00 Inositol 1,4,5-triphosphate receptor type 1 (ITPR1) is an endoplasmic reticulum–bound intracellular inositol triphosphate receptor involved in the regulation of intracellular calcium. Pathogenic variants in ITPR1 are associated with spinocerebellar ataxia (SCA) types 15/16 and 29 and have recently been implicated in a facial microsomia syndrome. In this report, we present a family with three affected individuals found to have a heterozygous missense c.800C > T (predicted p.Thr267Met) who present clinically with a SCA29-like syndrome. All three individuals presented with varying degrees of ataxia, developmental delay, and apparent intellectual disability, as well as craniofacial involvement—an uncommon finding in patients with SCA29. The variant was identified using clinical exome sequencing and validated with Sanger sequencing. It is presumed to be inherited via parental germline mosaicism. We present our findings to provide additional evidence for germline mosaic inheritance of SCA29, as well as to expand the clinical phenotype of the syndrome. Full Article
ai Rapid genome diagnosis of alveolar capillary dysplasia leading to treatment in a child with respiratory and cardiac failure [RESEARCH REPORT] By molecularcasestudies.cshlp.org Published On :: 2024-01-10T08:13:38-08:00 Alveolar capillary dysplasia (ACD) is a fatal disorder that typically presents in the neonatal period with refractory hypoxemia and pulmonary hypertension. Lung biopsy is traditionally required to establish the diagnosis. We report a 22-mo-old male who presented with anemia, severe pulmonary hypertension, and right heart failure. He had a complicated hospital course resulting in cardiac arrest and requirement for extracorporeal membrane oxygenation. Computed tomography of the chest showed a heterogenous pattern of interlobular septal thickening and pulmonary edema. The etiology of his condition was unknown, lung biopsy was contraindicated because of his medical fragility, and discussions were held to move to palliative care. Rapid whole-genome sequencing (rWGS) was performed. In 2 d it resulted, revealing a novel FOXF1 gene pathogenic variant that led to the presumptive diagnosis of atypical ACD. Cases of atypical ACD have been reported with survival in patients using medical therapy or lung transplantation. Based on the rWGS diagnosis and more favorable potential of atypical ACD, aggressive medical treatment was pursued. The patient was discharged home after 67 d in the hospital; he is currently doing well more than 30 mo after his initial presentation with only one subsequent hospitalization and no requirement for lung transplantation. Our case reveals the potential for use of rWGS in a critically ill child in which the diagnosis is unknown. rWGS and other advanced genetic tests can guide clinical management and expand our understanding of atypical ACD and other conditions. Full Article
ai The importance of escalating molecular diagnostics in patients with low-grade pediatric brain cancer [PRECISION MEDICINE IN PRACTICE] By molecularcasestudies.cshlp.org Published On :: 2024-01-10T08:13:38-08:00 Pilocytic astrocytomas are the most common pediatric brain tumors, typically presenting as low-grade neoplasms. We report two cases of pilocytic astrocytoma with atypical tumor progression. Case 1 involves a 12-yr-old boy with an unresectable suprasellar tumor, negative for BRAF rearrangement but harboring a BRAF p.V600E mutation. He experienced tumor size reduction and stable disease following dabrafenib treatment. Case 2 describes a 6-yr-old boy with a thalamic tumor that underwent multiple resections, with no actionable driver detected using targeted next-generation sequencing. Whole-genome and RNA-seq analysis identified an internal tandem duplication in FGFR1 and RAS pathway activation. Future management options include FGFR1 inhibitors. These cases demonstrate the importance of escalating molecular diagnostics for pediatric brain cancer, advocating for early reflexing to integrative whole-genome sequencing and transcriptomic profiling when targeted panels are uninformative. Identifying molecular drivers can significantly impact treatment decisions and improve patient outcomes. Full Article
ai CGRP therapy in primary care for migraine: prevention and acute medication By bjgp.org Published On :: 2024-10-31T16:05:26-07:00 Full Article
ai Yonder: Improving connections, AI in reflective practice, lung cancer diagnosis, and euthanasia aftercare By bjgp.org Published On :: 2024-10-31T16:05:26-07:00 Full Article
ai The Changing Role of a Chair and DA: Follow-Up from the 2023 ADFM Annual Conference Session [Family Medicine Updates] By www.annfammed.org Published On :: 2024-09-23T14:00:14-07:00 Full Article
ai Chest Pain in Primary Care: A Systematic Review of Risk Stratification Tools to Rule Out Acute Coronary Syndrome [Systematic Review] By www.annfammed.org Published On :: 2024-09-23T14:00:14-07:00 PURPOSE Chest pain frequently poses a diagnostic challenge for general practitioners (GPs). Utilizing risk stratification tools might help GPs to rule out acute coronary syndrome (ACS) and make appropriate referral decisions. We conducted a systematic review of studies evaluating risk stratification tools for chest pain in primary care settings, both with and without troponin assays. Our aims were to assess the performance of tools for ruling out ACS and to provide a comprehensive review of the current evidence. METHODS We searched PubMed and Embase for articles up to October 9, 2023 concerning adult patients with acute chest pain in primary care settings, for whom risk stratification tools (clinical decision rules [CDRs] and/or single biomarker tests) were used. To identify eligible studies, a combination of active learning and backward snowballing was applied. Screening, data extraction, and quality assessment (following the Quality Assessment of Diagnostic Accuracy Studies-2 tool) were performed independently by 2 researchers. RESULTS Of the 1,204 studies screened, 14 were included in the final review. Nine studies validated 7 different CDRs without troponin. Sensitivities ranged from 75.0% to 97.0%, and negative predictive values (NPV) ranged from 82.4% to 99.7%. None of the CDRs outperformed the unaided judgment of GP’s. Five studies reported on strategies using troponin measurements. Studies using high-sensitivity troponin showed highest diagnostic accuracy with sensitivity 83.3% to 100% and NPV 98.8% to 100%. CONCLUSION Clinical decision rules without troponin and the use of conventional troponin showed insufficient sensitivity to rule out ACS in primary care and are not recommended as standalone tools. High-sensitivity troponin strategies are promising, but studies are limited. Further prospective validation in primary care is needed before implementation. Full Article
ai A Few Doctors Will See Some of You: The Critical Role of Underrepresented in Medicine (URiM) Family Physicians in the Care of Medicaid Beneficiaries [Original Research] By www.annfammed.org Published On :: 2024-09-23T14:00:14-07:00 PURPOSE Despite being key to better health outcomes for patients from racial and ethnic minority groups, the proportion of underrepresented in medicine (URiM) physicians remains low in the US health care system. This study linked a nationally representative sample of family physicians (FPs) with Medicaid claims data to explore the relative contributions to care of Medicaid populations by FP race and ethnicity. METHODS This descriptive cross-sectional study used 2016 Medicaid claims data from the Transformed Medicaid Statistical Information System and from 2016-2017 American Board of Family Medicine certification questionnaire responses to examine the diversity and Medicaid participation of FPs. We explored the diversity of FP Medicaid patient panels and whether they saw ≥150 beneficiaries in 2016. Using logistic regression models, we controlled for FP demographics, practice characteristics, and characteristics of the communities in which they practiced. RESULTS Of 13,096 FPs, Latine, Hispanic, or of Spanish Origin (LHS) FPs and non-LHS Black FPs saw more Medicaid beneficiaries compared with non-LHS White and non-LHS Asian FPs. The patient panels of URiM FPs had a much greater proportion of Medicaid beneficiaries from racial and ethnic minority groups. Overall, non-LHS Black and LHS FPs had greater odds of seeing ≥150 Medicaid beneficiaries in 2016. CONCLUSIONS These findings clearly show the critical role URiM FPs play in caring for Medicaid beneficiaries, suggesting physician race and ethnicity are correlated with Medicaid participation. Diversity in the health care workforce is essential for addressing racial health inequities. Policies need to address problems in pathways to medical education, including failures to recruit, nurture, and retain URiM students. Full Article
ai Des politiques pour mieux soutenir les chirurgiennes enceintes [Commentaire] By www.cmaj.ca Published On :: 2024-11-11T21:05:15-08:00 Full Article
ai Highlights from the Respiratory Failure and Mechanical Ventilation Conference 2024 By breathe.ersjournals.com Published On :: 2024-11-12T00:25:08-08:00 The Respiratory Intensive Care Assembly of the European Respiratory Society gathered in Berlin to organise the third Respiratory Failure and Mechanical Ventilation Conference in February 2024. The conference covered key points of acute and chronic respiratory failure in adults. During the 3-day conference ventilatory strategies, patient selection, diagnostic approaches, treatment and health-related quality of life topics were addressed by a panel of international experts. In this article, lectures delivered during the event have been summarised by early career members of the Assembly and take-home messages highlighted. Full Article
ai An elderly woman with acute respiratory failure and diffuse pulmonary changes By breathe.ersjournals.com Published On :: 2024-11-12T00:25:08-08:00 Full Article
ai You Have Less Than a Week to File a Claim for Cash App’s $2,500 Payouts By gizmodo.com Published On :: Tue, 12 Nov 2024 17:03:40 +0000 The deadline to claim part of the $15 million Cash App settlement is November 18. Here's what to know. Full Article Privacy and Security
ai Waymo Drops Waitlist, Opens Robotaxis to Anyone in Los Angeles By gizmodo.com Published On :: Tue, 12 Nov 2024 19:00:28 +0000 The driverless vehicles still can't take L.A.'s notorious highways. Full Article Transportation Cruise driverless cars robotaxis Waymo Zoox
ai Airman Who Leaked Classified Documents on Discord Sentenced to 15 Years By gizmodo.com Published On :: Tue, 12 Nov 2024 21:08:10 +0000 The leak caught national intelligence officials by surprise and led to an embarrassing Air Force Inspector General investigation. Full Article News Discord Jack Teixeira
ai City of Vancouver to lowest paid workers: Let them eat cuts! By rabble.ca Published On :: Tue, 07 Nov 2023 16:50:27 +0000 The City of Vancouver council has reneged on a previous commitment to a living wage for its employees. The post City of Vancouver to lowest paid workers: Let them eat cuts! appeared first on rabble.ca. Full Article Canadian Politics Economy
ai Far-right groups gain ground in Sweden and Germany amid migrant influx By www.pbs.org Published On :: Tue, 17 Oct 2017 22:30:37 +0000 Watch Video | Listen to the AudioJUDY WOODRUFF: But first: Sunday’s elections Austria were the latest ample of a shift to the right Europe’s politics, as 31-year-old Christian Kurz was elected chancellor on an anti-immigration platform. He may now form a government with a far-right party founded in the 1950s by former Nazis. That follows recent elections in Germany, where a far-right party roiled the race and dealt a blow to returning leader Angela Merkel. In Sweden, too, there is a strong challenge from the right and a neo-Nazi group that looks stand in elections next year. Special correspondent Malcolm Brabant ha been surveying the political landscape in Germany and Sweden, and he begins his report in Scandinavia. MALCOLM BRABANT, Special Correspondent: In a Gothenburg parking lot, supporters of the Nordic Resistance Movement form up for what they hope will be their biggest-ever march, to propagate an ideology espoused by mother of eight Paulina Forslund. PAULINA FORSLUND, Nordic Resistance Movement: When white becomes the minority, they will be destroyed. I want my children to have a secure future. I want them not only for them to have a secure Sweden. I want them to have a secure world. And I want other people to fight for the same thing. MALCOLM BRABANT: When addressing her fellow neo-Nazis, Forslund’s rhetoric sharpens. PAULINA FORSLUND (through interpreter): I’m the welder’s daughter, the forester’s grandchild. My line consists of hardworking men and women. It’s people like them we can thank for the welfare system that our lying politicians are now giving away to imported scum. MALCOLM BRABANT: Clearly expecting trouble, the movement’s leaders have a muscular protection detail, marching past a silent protest. The sign reads “No Nazis on our streets.” This protester would only give her name as Johanna. JOHANNA, Anti-Nazi Protester: They are racist people. They are people who think that certain people are better than others, and I will not stand for that. It’s not something I think has a place in a modern society. MALCOLM BRABANT: Experts say the resistance movement is recruiting aggressively, and believe this demonstration is emblematic of the rise of the far right. It took place on Yom Kippur, the Jewish day of atonement. Allan Stutzinky is leader of Gothenburg’s Jewish community. ALLAN STUTZINKY, Jewish Community Leader (through interpreter): Nazism has returned. The descendants of the murderers are organizing the same marches today, waving the same flags, shouting the same slogans, and have the same racist agenda. MALCOLM BRABANT: Anna Johansson is a member of the governing Social Democrat Party. It’s considering outlawing the Nordic Resistance Movement. ANNA JOHANSSON, Swedish Social Democratic Party: In Sweden and in Denmark, and in other countries, extreme parties are growing, and the hatred is spreading around. MALCOLM BRABANT: “Go home to mama,” he shouts. “Nazi pigs,” chant the anti- fascist protesters, as a bottle flies through the air. DAMON, Nordic Resistance Movement: If someone calls themselves a Nazi, most of us would dissociate with that person. That’s nothing we stand for ourselves. I never call myself a Nazi. I’m a national socialist. MALCOLM BRABANT: Hitler’s party was also called National Socialist, but Damon, a 40-year-old welder, insists he’s a nonviolent family man. DAMON: The demographic landscape of our — of the whole of Europe is changing, so, basically, it’s a concern on preserving my heritage for my family and our kin. MALCOLM BRABANT: This demonstration has been stopped short of its destination. The Nordic Resistance Movement is currently trapped between a line of police and anti-fascist protesters. And it looks as though this demonstration isn’t going any further. Violence briefly erupts as the resistance movement tries to break through police lines, and several marchers are arrested. PAULINA FORSLUND: We are not your enemy. We are the government’s enemy. They say we live in a democracy, but we have never had an election about if we want to take all these people in. MALCOLM BRABANT: When Europe’s refugee crisis began in 2015, Sweden copied Germany’s open-door policy, and 160,000 migrants entered the country. Two years on, Sweden has tighter borders and has begun deporting some of the newcomers. The new atmosphere alarms Floid Gumbo, entertaining an anti-Nazi rally. FLOID GUMBO, Singer Originally from Zimbabwe: I came to Sweden over 20 years ago. The climate in Sweden, the people were so friendly, and things were completely different, more welcoming. And I feel like things have sort of gradually changed. I’m very concerned, because I have children, because I’m thinking what I experienced here is not the same kind of climate, atmosphere that they are going to experience here. ANNA JOHANSSON: It’s not so long ago that the Nazis ruined Europe. And that makes me very worried. The German elections were terrifying, I think. MALCOLM BRABANT: Johansson is referring to last month’s success of the right-wing Alternative For Germany Party, or AFD, when it entered Parliament for the first time with 13 percent of the vote. HUGH BRONSON, Alternative For Germany Party: The AFD only came into existence because Merkel deserted the traditional conservative Christian voters. They were looking for a home, and the AFD has offered them a safe place. MALCOLM BRABANT: Hugh Bronson is deputy leader of the AFD in Berlin. Now his party, the third largest in Parliament, is demanding that Angela Merkel imposes tougher immigration rules. Your opponents claim that you are a party of hate. What’s your response to that? HUGH BRONSON: We embrace foreigners who respect our laws, pay their taxes, send their children to school, and go about their normal life. The problem is with people who abuse the system to have a better life, or let others pay for their better lives, or who are criminals. MALCOLM BRABANT: Outside the opera house in Dresden, former East Germany, singer Luca Bergelt is dismayed by the political landscape shifting to the right. LUCA BERGELT, Singer: My fear is that they will tear Europe apart. They are going to raise up the walls again. They’re going to build new walls between the countries, and that Europe will get more close into itself. MALCOLM BRABANT: Anti-immigrant sentiment is strong in Dresden. The city was the birthplace of a pan-European anti-Islamic movement, and it delivered the largest number of votes for the right-wing party. On a holiday to celebrate German unification after the fall of communism, retired engineer Wilfried Schmidt explained why he sent a message to Angela Merkel. WILFRIED SCHMIDT, Retired Engineer (through interpretor): Let’s put it this way. We all need to recognize that Germany is undergoing social changes that are becoming harder to control. For one, there is mass immigration from difficult regions that is increasingly uncontrollable, of people with entirely different concepts of life, from fundamental differently structured societies that are problematic. MALCOLM BRABANT: About one million migrants poured into Germany in 2015. Chancellor Merkel consistently defended her pro-refugee policies, but now she has been punished by voters who believe she ignored their concerns. Chancellor Merkel has promised to listen to the people who voted for the AFD, and she says she’s going to try to win them over with what she calls good politics. But she will not countenance having the party in her coalition. But the chancellor needs to find new partners who are prepared to be tough on immigration. As she tries to forge a coalition, the chancellor has agreed to put an annual cap of 200,000 on the number of immigrants, something she previously refused to do. But will it be enough to woo back people who deserted her at the election? A question for Werner Patzelt, a political scientist at Dresden University. WERNER PATZELT, Dresden University: Since Chancellor Merkel has made so many U-turns in German domestic politics, it wouldn’t be a surprise if she would try to do a U-turn, also winning back AFD voters. But this is a really hard political task, because so many of them are so much disappointed by the Christian Democratic Union in general, and by Chancellor Merkel in particular, that they will do anything to avoid going back. MALCOLM BRABANT: Back in Sweden, the governing party is horrified at the concept of conceding ground to right-wingers, and is trying to isolate them. ANNA JOHANSSON: Experience shows that, when you adopt the ideas from these right-wing parties, they spread. These parties have their agenda implemented by other parties. And I wouldn’t want to see that happen in Sweden. FLOID GUMBO: We’re all human beings. We share this world. We’re all here. There’s enough space for us all. MALCOLM BRABANT: But that’s an appeal that an increasing number of Swedes are rejecting, as the country and much of Europe go through a crisis of identity. For the PBS NewsHour, I’m Malcolm Brabant in Gothenburg. The post Far-right groups gain ground in Sweden and Germany amid migrant influx appeared first on PBS NewsHour. Full Article Austria elections europe Far-Right Politics
ai Tigerair chaos as Bali flights cancelled By www.dailytelegraph.com.au Published On :: Wed, 11 Jan 2017 23:52:00 GMT HUNDREDS of travellers’ holiday plans are in disarray after all Tigerair flights in and out of Bali were cancelled again today and early tomorrow. Full Article
ai Pauline Hanson’s ‘pain in her backside’ By www.dailytelegraph.com.au Published On :: Thu, 12 Jan 2017 00:47:00 GMT PAULINE Hanson has described Rod Culleton as a “pain in the backside”, and despite being disqualified from the Senate he’s continuing to cause her pain. Full Article
ai PM preps for campaign launch By www.dailytelegraph.com.au Published On :: Sat, 25 Jun 2016 07:30:00 GMT ROLLING UPDATES:Malcolm Turnbull heads into tomorrow’s Liberal Party campaign launch with the economy and stability firmly front and centre. Full Article
ai Dundee ice hockey player jailed for rape of teen girl in his car By www.heraldscotland.com Published On :: Mon, 11 Nov 2024 14:34:23 +0000 A Dundee ice hockey player has been jailed after being found guilty of raping a teenage girl in his car. Full Article
ai Mhairi Black rules out standing for Holyrood in 2026 By www.heraldscotland.com Published On :: Tue, 12 Nov 2024 15:37:01 +0000 "I hear journalists are wondering if I’ve put my name in for the Scottish Parliament. Big news re 2026 coming in the next hour…watch this space." Full Article
ai Scottish family-run dairy wins major listing with world’s third largest retailer By www.heraldscotland.com Published On :: Tue, 12 Nov 2024 04:33:00 +0000 Family business Graham’s Family Dairy has secured a multinational listing Full Article
ai Scottish airport chief 'thrilled' as airline giant launches first advanced aircraft By www.heraldscotland.com Published On :: Tue, 12 Nov 2024 04:34:00 +0000 The plane is hailed as 'one of the most advanced aircraft available on the market' Full Article