Electroencephalographic evoked pain response is suppressed by spinal cord stimulation in complex regional pain syndrome: a case report

Spinal cord stimulation (SCS) is considered as an option for the management of complex regional pain syndrome (CRPS). Hyperalgesia, an increased pain response to a mechanical or thermal stimulus at normal or increased threshold is a common feature of CRPS. Animal studies have demonstrated that SCS significantly reduces mechanical hyperalgesia. These studies suggest that SCS mechanisms may involve reduction of glial activation at spinal cord level and/or activation of μ-opioid and δ-opioid receptors. However, in humans it has been observed that SCS had no effect on experimental pain thresholds and did not produce decreased sensitivity for pressure, warmth, and cold induced pain in CRPS patients. The majority of currently available studies on the effectiveness of SCS, including those using quantitative sensory testing (QST) rely on patient reported outcomes such as visual analogue or numerical rating scales. The current case report investigates the effectiveness of SCS based on electroencephalogram (EEG) analysis of contact heat evoked potentials following experimental induction of thermal stimuli

Integrating Weight Bias Awareness and Mental Health Promotion Into Obesity Prevention Delivery: A Public Health Pilot Study

Abstract Introduction Promoting healthy weight is a top priority in Canada. Recent federal guidelines call for sustained, multisectoral partnerships that address childhood obesity on multiple levels. Current healthy weight messaging does not fully acknowledge the influence of social determinants of health on weight

Analysis of the Ex Vivo and In Vivo Antiretroviral Activity of Gemcitabine

Replication of retroviral and host genomes requires ribonucleotide reductase to convert rNTPs to dNTPs, which are then used as substrates for DNA synthesis. Inhibition of ribonucleotide reductase by hydroxyurea (HU) has been previously used to treat cancers as well as HIV. However, the use of HU as an antiretroviral is limited by its associated toxicities such as myelosuppression and hepatotoxicity. In this study, we examined the ribonucleotide reductase inhibitor, gemcitabine, both in cell culture and in C57Bl/6 mice infected with LP-BM5 murine leukemia virus (LP-BM5 MuLV, a murine AIDS model). Gemcitabine decreased infectivity of MuLV in cell culture with an EC50 in the low nanomolar range with no detectable cytotoxicity. Similarly, gemcitabine significantly decreased disease progression in mice infected with LP-BM5. Specifically, gemcitabine treatment decreased spleen size, plasma IgM, and provirus levels compared to LP-BM5 MuLV infected, untreated mice. Gemcitabine efficacy was observed at doses as low as 1 mg/kg/day in the absence of toxicity. Higher doses of gemcitabine (3 mg/kg/day and higher) were associated with toxicity as determined by a loss in body mass. In summary, our findings demonstrate that gemcitabine has antiretroviral activity ex vivo and in vivo in the LP-BM5 MuLV model. These observations together with a recent ex vivo study with HIV-1[1], suggest that gemcitabine has broad antiretroviral activity and could be particularly useful in vivo when used in combination drug therapy

Functional abilities, respiratory and cardiac function in a large cohort of adults with Duchenne muscular dystrophy treated with glucocorticoids

\ua9 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.Background and purpose: The transition to adult services, and subsequent glucocorticoid management, is critical in adults with Duchenne muscular dystrophy. This study aims (1) to describe treatment, functional abilities, respiratory and cardiac status during transition to adulthood and adult stages; and (2) to explore the association between glucocorticoid treatment after loss of ambulation (LOA) and late-stage clinical outcomes. Methods: This was a retrospective single-centre study on individuals with Duchenne muscular dystrophy (≥16 years old) between 1986 and 2022. Logistic regression, Cox proportional hazards models and survival analyses were conducted utilizing data from clinical records. Results: In all, 112 individuals were included. Mean age was 23.4 \ub1 5.2 years and mean follow-up was 18.5 \ub1 5.5 years. At last assessment, 47.2% were on glucocorticoids; the mean dose of prednisone was 0.38 \ub1 0.13 mg/kg/day and of deflazacort 0.43 \ub1 0.16 mg/kg/day. At age 16 years, motor function limitations included using a manual wheelchair (89.7%), standing (87.9%), transferring from a wheelchair (86.2%) and turning in bed (53.4%); 77.5% had a peak cough flow <270 L/min, 53.3% a forced vital capacity percentage of predicted <50% and 40.3% a left ventricular ejection fraction <50%. Glucocorticoids after LOA reduced the risk and delayed the time to difficulties balancing in the wheelchair, loss of hand to mouth function, forced vital capacity percentage of predicted <30% and forced vital capacity <1 L and were associated with lower frequency of left ventricular ejection fraction <50%, without differences between prednisone and deflazacort. Glucocorticoid dose did not differ by functional, respiratory or cardiac status. Conclusion: Glucocorticoids after LOA preserve late-stage functional abilities, respiratory and cardiac function. It is suggested using functional abilities, respiratory and cardiac status at transition stages for adult services planning

Global cooling as a driver of diversification in a major marine clade

Climate is a strong driver of global diversity and will become increasingly important as human influences drive temperature changes at unprecedented rates. Here we investigate diversification and speciation trends within a diverse group of aquatic crustaceans, the Anomura. We use a phylogenetic framework to demonstrate that speciation rate is correlated with global cooling across the entire tree, in contrast to previous studies. Additionally, we find that marine clades continue to show evidence of increased speciation rates with cooler global temperatures, while the single freshwater clade shows the opposite trend with speciation rates positively correlated to global warming. Our findings suggest that both global cooling and warming lead to diversification and that habitat plays a role in the responses of species to climate change. These results have important implications for our understanding of how extant biota respond to ongoing climate change and are of particular importance for conservation planning of marine ecosystems

Magnitude and Correlates of Intimate Partner Violence against Women and Its Outcome in Southwest Ethiopia

BACKGROUND: Intimate Partner Violence (IPV) is a major public health problem with serious consequences. This study was conducted to assess the magnitude of IPV in Southwest Ethiopia in predominantly rural community. METHODS: This community based cross-sectional study was conducted in May, 2009 in Southwest Ethiopia using the World Health Organization core questionnaire to measure violence against women. Trained data collectors interviewed 851 ever-married women. Stata version 10.1 software and SPSS version 12.0.1 for windows were used for data analysis. RESULT: In this study the life time prevalence of sexual or physical partner violence, or both was 64.7% (95%CI: 61.4%-67.9%). The lifetime sexual violence [50.1% (95% CI: 46.7%-53.4%)] was considerably more prevalent than physical violence [41.1% (95%:37.8-44.5)]. A sizable proportion [41.5%(95%CI: 38.2%-44.8%)] of women reported physical or sexual violence, or both, in the past year. Men who were controlling were more likely to be violent against their partner. CONCLUSION: Physical and sexual violence is common among ever-married women in Southwest Ethiopia. Interventions targeting controlling men might help in reducing IPV. Further prospective longitudinal studies among ever-married women are important to identify predictors and to study the dynamics of violence over time

Differential Impact of Tumor Suppressor Pathways on DNA Damage Response and Therapy-Induced Transformation in a Mouse Primary Cell Model

The RB and p53 tumor suppressors are mediators of DNA damage response, and compound inactivation of RB and p53 is a common occurrence in human cancers. Surprisingly, their cooperation in DNA damage signaling in relation to tumorigenesis and therapeutic response remains enigmatic. In the context of individuals with heritable retinoblastoma, there is a predilection for secondary tumor development, which has been associated with the use of radiation-therapy to treat the primary tumor. Furthermore, while germline mutations of the p53 gene are critical drivers for cancer predisposition syndromes, it is postulated that extrinsic stresses play a major role in promoting varying tumor spectrums and disease severities. In light of these studies, we examined the tumor suppressor functions of these proteins when challenged by exposure to therapeutic stress. To examine the cooperation of RB and p53 in tumorigenesis, and in response to therapy-induced DNA damage, a combination of genetic deletion and dominant negative strategies was employed. Results indicate that loss/inactivation of RB and p53 is not sufficient for cellular transformation. However, these proteins played distinct roles in response to therapy-induced DNA damage and subsequent tumorigenesis. Specifically, RB status was critical for cellular response to damage and senescence, irrespective of p53 function. Loss of RB resulted in a dramatic evolution of gene expression as a result of alterations in epigenetic programming. Critically, the observed changes in gene expression have been specifically associated with tumorigenesis, and RB-deficient, recurred cells displayed oncogenic characteristics, as well as increased resistance to subsequent challenge with discrete therapeutic agents. Taken together, these findings indicate that tumor suppressor functions of RB and p53 are particularly manifest when challenged by cellular stress. In the face of such challenge, RB is a critical suppressor of tumorigenesis beyond p53, and RB-deficiency could promote significant cellular evolution, ultimately contributing to a more aggressive disease

Clinical Heterogeneity of Duchenne Muscular Dystrophy (DMD): Definition of Sub-Phenotypes and Predictive Criteria by Long-Term Follow-Up

International audienceBACKGROUND: To explore clinical heterogeneity of Duchenne muscular dystrophy (DMD), viewed as a major obstacle to the interpretation of therapeutic trials METHODOLOGY/PRINCIPAL FINDINGS: A retrospective single institution long-term follow-up study was carried out in DMD patients with both complete lack of muscle dystrophin and genotyping. An exploratory series (series 1) was used to assess phenotypic heterogeneity and to identify early criteria predicting future outcome; it included 75 consecutive steroid-free patients, longitudinally evaluated for motor, respiratory, cardiac and cognitive functions (median follow-up: 10.5 yrs). A validation series (series 2) was used to test robustness of the selected predictive criteria; it included 34 more routinely evaluated patients (age>12 yrs). Multivariate analysis of series 1 classified 70/75 patients into 4 clusters with distinctive intellectual and motor outcomes: A (early infantile DMD, 20%): severe intellectual and motor outcomes; B (classical DMD, 28%): intermediate intellectual and poor motor outcome; C (moderate pure motor DMD, 22%): normal intelligence and delayed motor impairment; and D (severe pure motor DMD, 30%): normal intelligence and poor motor outcome. Group A patients had the most severe respiratory and cardiac involvement. Frequency of mutations upstream to exon 30 increased from group A to D, but genotype/phenotype correlations were restricted to cognition (IQ>71: OR 7.7, 95%CI 1.6-20.4, p6 at 8 yrs" with "normal or borderline mental status" reliably assigned patients to group C (sensitivity: 1, specificity: 0.94). These criteria were also predictive of "early infantile DMD" and "moderate pure motor DMD" in series 2. CONCLUSIONS/SIGNIFICANCE: DMD can be divided into 4 sub-phenotypes differing by severity of muscle and brain dysfunction. Simple early criteria can be used to include patients with similar outcomes in future therapeutic trials