The efficacy of a sumatriptan and naproxen combination pill in a patient with chronic migraines who discontinued triptan therapy in the past due to a self-reported poor response to sumatriptan monotherapy

A clinical decision report using: Mathew NT, Landy S, Stark S, et al. Fixed-dose sumatriptan and naproxen in poor responders to triptans with a short half-life. Headache. 2009;49(7):971-982. https://doi.org/10.1111/j.1526-4610.2009.01458.x for a patient with chronic migraines who had self-reported poor response to sumatriptan monotherapy

Detecting implausible social network effects in acne, height, and headaches: longitudinal analysis

Objective To investigate whether “network effects” can be detected for health outcomes that are unlikely to be subject to network phenomena

QUEnch assiSTed (QUEST) MRI Used as a Novel Approach to Identify Reactive Oxygen Species as a Result of Experimental TBI

Introduction: Traumatic brain injury (TBI) generates reactive oxygen species (ROS), promoting inflammatory processes and impeding TBI recovery. Within the VA population, over 70% of military personnel that sustain a TBI receive opioid-based pain relief, however, opiates may actually exacerbate post-TBI complications through its documented recruitment of oxidative and inflammatory systems. Thus, we hypothesize that TBI and opioid treatment act synergistically to worsen post-TBI oxidative stress. Methods: Mice were exposed to either TBI or sham injury and administered morphine or saline in the acute post-injury period. Afterwards, neuroimaging was conducted using a novel technique, QUEnch assiSTed (QUEST) MRI, which compares standard MRI signals across mice that acutely receive an antioxidant “quench” therapy and those receiving saline as control. Therefore, differential MRI signals between these groups are an index of ROS generation. Changes in hippocampus and cortex signals were measured, as these structures are most commonly affected by TBI. Methylene blue and α-lipoic acid were used as antioxidants in the quenching step as they halt mitochondrial ROS production and scavenge excess ROS, respectively. Results: No significant changes in ROS levels were detected as a result of TBI, opioid exposure or their combination using QUEST MRI in either the cortex or hippocampus. Conclusions and Future Directions: While QUEST imaging did not yield significant changes between experimental groups, future work will include ex-vivo biochemical ROS analyses from harvested tissues, which will provide higher resolution quantification of oxidative processes than that of QUEST MRI

Delayed Effects of Acute Radiation Exposure in a Murine Model of the H-ARS: Multiple-Organ Injury Consequent to <10 Gy Total Body Irradiation

The threat of radiation exposure from warfare or radiation accidents raises the need for appropriate animal models to study the acute and chronic effects of high dose rate radiation exposure. The goal of this study was to assess the late development of fibrosis in multiple organs (kidney, heart, and lung) in survivors of the C57BL/6 mouse model of the hematopoietic-acute radiation syndrome (H-ARS). Separate groups of mice for histological and functional studies were exposed to a single uniform total body dose between 8.53 and 8.72 Gy of gamma radiation from a Cs radiation source and studied 1-21 mo later. Blood urea nitrogen levels were elevated significantly in the irradiated mice at 9 and 21 mo (from ∼22 to 34 ± 3.8 and 69 ± 6.0 mg dL, p < 0.01 vs. non-irradiated controls) and correlated with glomerosclerosis (29 ± 1.8% vs. 64 ± 9.7% of total glomeruli, p < 0.01 vs. non-irradiated controls). Glomerular tubularization and hypertrophy and tubular atrophy were also observed at 21 mo post-total body irradiation (TBI). An increase in interstitial, perivascular, pericardial and peribronchial fibrosis/collagen deposition was observed from ∼9-21 mo post-TBI in kidney, heart, and lung of irradiated mice relative to age-matched controls. Echocardiography suggested decreased ventricular volumes with a compensatory increase in the left ventricular ejection fraction. The results indicate that significant delayed effects of acute radiation exposure occur in kidney, heart, and lung in survivors of the murine H-ARS TBI model, which mirrors pathology detected in larger species and humans at higher radiation doses focused on specific organs

Global change drivers and the risk of infectious disease

Anthropogenic change is contributing to the rise in emerging infectious diseases, but it remains unclear which global change drivers most increase disease and under what contexts. We amassed a dataset from the literature that includes 1,832 observations of infectious disease responses to global change drivers across 1,202 host-parasite combinations. We found that biodiversity loss, climate change, and introduced species were associated with increases in disease-related endpoints or harm (i.e., enemy release for introduced species), whereas urbanization was associated with decreases in disease endpoints. Natural biodiversity gradients, deforestation, forest fragmentation, and most classes of chemical contaminants had non-significant effects on these endpoints. Overall, these results were consistent across human and non-human diseases. Context-dependent effects of the global change drivers on disease were common and are discussed. These findings will help better target disease management and surveillance efforts towards global change drivers that increase disease.One-Sentence SummaryHere we quantify which global change drivers increase infectious diseases the most to better target global disease management and surveillance efforts

Feasibility of Frequent Patient-Reported Outcome Surveillance in Patients Undergoing Hematopoietic Cell Transplantation

Patient-reported outcomes (PROs), including symptoms and health-related quality of life (HRQOL), provide a patient-centered description of hematopoietic cell transplantation (HCT)-related toxicity. These data characterize the patient experience after HCT and may have prognostic usefulness for long-term outcomes after HCT. We conducted a study of 32 patients after HCT (10 autologous HCT recipients, 11 full-intensity conditioning allogeneic HCT recipients, and 11 reduced-intensity conditioning allogeneic HCT recipients) to determine the feasibility of weekly electronic PRO collection from HCT until day (D) +100. We used questions from the PRO version of the Common Terminology Criteria for Adverse Events to capture symptoms, and the Patient-Reported Outcomes Measurement Information System Global Health scale to measure physical and mental HRQOL. The vast majority (94%) of patients used the electronic PRO system, with only 6% opting for paper-and-pencil only. The median weekly percentage of participants who completed the surveys was 100% in all cohorts through hospital discharge, and remained 100% for the autologous HCT and reduced-intensity allogeneic HCT cohorts through D+100. Patients were satisfied with the electronic system, giving high marks for readability, comfort, and questionnaire length. Symptom severity varied by absolute level and type of symptom across the 3 cohorts, with the full-intensity allogeneic HCT cohort exhibiting the greatest median overall symptom severity, peaking at D+7. Median physical health HRQOL scores decreased with time in the 3 cohorts, and HRQOL was generally correlated with overall symptom severity. Our results demonstrate the feasibility of frequent electronic PROs in the early post-HCT period. Future studies in larger populations to explore predictive models using frequent PRO data for outcomes, including long-term HRQOL and survival, are warranted

Serum Adiponectin in Relation to Body Mass Index and Other Correlates in Black and White Women

Adiponectin is a promising biomarker linking obesity and disease risk; however, limited data are available regarding adiponectin in black women among whom obesity is highly prevalent

Adherence to Highly Active Antiretroviral Treatment in HIV-Infected Rwandan Women

Scale-up of highly active antiretroviral treatment therapy (HAART) programs in Rwanda has been highly successful but data on adherence is limited. We examined HAART adherence in a large cohort of HIV+ Rwandan women.The Rwanda Women's Interassociation Study Assessment (RWISA) was a prospective cohort study that assessed effectiveness and toxicity of ART. We analyzed patient data 12±3 months after HAART initiation to determine adherence rates in HIV+ women who had initiated HAART.Of the 710 HIV+ women at baseline, 490 (87.2%) initiated HAART. Of these, 6 (1.2%) died within 12 months, 15 others (3.0%) discontinued the study and 80 others (19.0%) remained in RWISA but did not have a post-HAART initiation visit that fell within the 12±3 month time points leaving 389 subjects for analysis. Of these 389, 15 women stopped their medications without being advised to do so by their doctors. Of the remaining 374 persons who reported current HAART use 354 completed the adherence assessment. All women, 354/354, reported 100% adherence to HAART at the post-HAART visit. The high self-reported level of adherence is supported by changes in laboratory measures that are influenced by HAART. The median (interquartile range) CD4 cell count measured within 6 months prior to HAART initiation was 185 (128, 253) compared to 264 (182, 380) cells/mm(3) at the post-HAART visit. Similarly, the median (interquartile range) MCV within 6 months prior to HAART initiation was 88 (83, 93) fL compared to 104 (98, 110) fL at the 12±3 month visit.Self-reported adherence to antiretroviral treatment 12±3 months after initiating therapy was 100% in this cohort of HIV-infected Rwandan women. Future studies should explore country-specific factors that may be contributing to high levels of adherence to HAART in this population

ADIPOQ, ADIPOR1, and ADIPOR2 Polymorphisms in Relation to Serum Adiponectin Levels and BMI in Black and White Women

Adiponectin is an adipose-secreted protein with influence on several physiologic pathways including those related to insulin sensitivity, inflammation, and atherogenesis. Adiponectin levels are highly heritable and several single nucleotide polymorphisms (SNPs) in adiponectin-related genes (ADIPOQ, ADIPOR1, ADIPOR2) have been examined in relation to circulating adiponectin levels and obesity phenotypes, but despite differences in adiponectin levels and obesity prevalence by race, few studies have included black participants. Using cross-sectional interview data and blood samples collected from 990 black and 977 white women enrolled in the Southern Community Cohort Study from 2002 to 2006, we examined 25 SNPs in ADIPOQ, 19 in ADIPOR1, and 27 in ADIPOR2 in relation to serum adiponectin levels and body mass index (BMI) using race-stratified linear regression models adjusted for age and percentage African ancestry. SNP rs17366568 in ADIPOQ was significantly associated with serum adiponectin levels in white women only (adjusted mean adiponectin levels = 15.9 for G/G genotype, 13.7 for A/G, and 9.3 for A/A, p=0.00036). No other SNPs were associated with adiponectin or BMI among blacks or whites. Because adiponectin levels as well as obesity are highly heritable and vary by race but associations with polymorphisms in the ADIPOQ, ADIPOR1, and ADIPOR2 genes have been few in this and other studies, future work including large populations from diverse racial groups is needed to detect additional genetic variants that influence adiponectin and BMI

Impact of SARS-CoV-2 ORF6 and its variant polymorphisms on host responses and viral pathogenesis

: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encodes several proteins that inhibit host interferon responses. Among these, ORF6 antagonizes interferon signaling by disrupting nucleocytoplasmic trafficking through interactions with the nuclear pore complex components Nup98-Rae1. However, the roles and contributions of ORF6 during physiological infection remain unexplored. We assessed the role of ORF6 during infection using recombinant viruses carrying a deletion or loss-of-function (LoF) mutation in ORF6. ORF6 plays key roles in interferon antagonism and viral pathogenesis by interfering with nuclear import and specifically the translocation of IRF and STAT transcription factors. Additionally, ORF6 inhibits cellular mRNA export, resulting in the remodeling of the host cell proteome, and regulates viral protein expression. Interestingly, the ORF6:D61L mutation that emerged in the Omicron BA.2 and BA.4 variants exhibits reduced interactions with Nup98-Rae1 and consequently impairs immune evasion. Our findings highlight the role of ORF6 in antagonizing innate immunity and emphasize the importance of studying the immune evasion strategies of SARS-CoV-2