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Gary Berman,1 Alexandra Thiry,2 Robert Croop3 1Clinical Research Institute, Minneapolis, MN, USA; 2Pfizer Inc., New York, NY, USA; 3Biohaven Pharmaceuticals, New Haven, CT, USACorrespondence: Gary Berman, Clinical Research Institute, 825 Nicollet Mall Suite 1135, Minneapolis, MN, 55402, USA, Tel + 1 612-333-2200, Email gdb@allergy-asthma-docs.comPurpose: To evaluate the safety and tolerability of rimegepant 75 mg for the acute treatment of migraine in participants concurrently using a preventive migraine medication.Patients and Methods: This long-term, open-label safety study (NCT03266588) enrolled adults with a history of 2– 14 moderate or severe migraine attacks per month. Participants self-administered rimegepant 75 mg (1) up to once daily as needed for 52 weeks to treat attacks of any pain intensity or (2) every other day plus as needed for 12 weeks. Preventive migraine medications were allowed if dosing was stable for ≥ 2 months prior to the baseline visit.Results: Of 1800 rimegepant-treated participants, 243 (13.5%) took a concomitant preventive medication. The most common preventive medication was topiramate (26.3%). Rimegepant exposure was comparable in both groups (mean [SD] number of doses per 4 weeks was 7.8 [4.5] in those taking preventives and 7.7 [4.7] in those not taking preventives). The proportion of participants experiencing ≥ 1 on-treatment adverse event (AE) was 68.7% among those using preventive medication and 59.2% among those not using preventives. Serious AEs occurred in 4.5% of those using preventive medication and 2.3% of those who were not using preventives. AEs leading to study drug discontinuation occurred in 4.5% of those taking preventive medication and 2.4% of those not taking preventives. AEs occurring in ≥ 5% of participants in either cohort (with preventives vs without preventives) were upper respiratory tract infection (7.4% vs 9.0%), nasopharyngitis (7.8% vs 6.6%), sinusitis (7.0% vs 4.8%), urinary tract infection (5.3% vs 3.6%), and back pain (5.3% vs 2.8%).Conclusion: Acute treatment of migraine with rimegepant 75 mg for up to 52 weeks was well tolerated and had a favorable safety profile in adults who were concomitantly using preventive migraine medication.Keywords: rimegepant, migraine, preventive, concomitant, safety, clinical trial

We consider two types of joins of graphs G1{G}_{1} and G2{G}_{2}, G1⊻G2{G}_{1}\hspace{0.33em}⊻\hspace{0.33em}{G}_{2} – the neighbors splitting join and G1∨=G2{G}_{1}\mathop{\vee }\limits_{=}{G}_{2} – the nonneighbors splitting join, and compute the adjacency characteristic polynomial, the Laplacian characteristic polynomial, and the signless Laplacian characteristic polynomial of these joins. When G1{G}_{1} and G2{G}_{2} are regular, we compute the adjacency spectrum, the Laplacian spectrum, the signless Laplacian spectrum of G1∨=G2{G}_{1}\mathop{\vee }\limits_{=}{G}_{2}, and the normalized Laplacian spectrum of G1⊻G2{G}_{1}\hspace{0.33em}⊻\hspace{0.33em}{G}_{2} and G1∨=G2{G}_{1}\mathop{\vee }\limits_{=}{G}_{2}. We use these results to construct nonregular, nonisomorphic graphs that are cospectral with respect to the four matrices: adjacency, Laplacian, signless Laplacian and normalized Laplacian.

La cetosis es un desbalance metabólico que disminuye la producción, reduce la fertilidad y predispone a las vacas lecheras a otras enfermedades. Con el objetivo de determinar la frecuencia de aparición de cetosis subclínica se estudiaron 52 vacas lecheras durante tres etapas productivas (13 en periparto, 17 en lactancia temprana y 22 en lactancia media); haciendo uso de tiras colorimétricas (Jorvet URS1k®) se realizaron mediciones de cuerpos cetónicos en orina, considerando negativas las vacas que presentaron una concentración menor a 5 mg de cuerpos cetónicos por decilitro (dl). Los casos positivos se clasificaron en leves (entre 5 mg·dl-1 y 50 mg·dl-1) y graves (entre 51 mg·dl-1 y 150 mg·dl-1), considerando la etapa productiva, condición corporal y número de partos. Se registró una prevalencia de 27 % y se determinó que la lactancia media es la etapa con más casos positivos. Los casos positivos corresponden a cetosis primaria, debido a que, en la etapa postparto e inicio de la lactancia, las vacas presentan un balance energético negativo (BEN), que las vuelve susceptible a desarrollar la enfermedad. La proporción de casos graves fue similar en las etapas de lactancia temprana y lactancia media. El total de casos graves se encontraron en vacas de al menos tres partos con condición corporal entre 3 y 3.7. No se determinó una vinculación clara entre el número de partos y los casos leves y graves de cetosis subclínica. La prevalencia de la cetosis subclínica es baja en relación con otras reportadas en la región y está influenciada por factores de riesgo como la etapa productiva (periparto, lactancia temprana y lactancia media), número de partos y condición corporal de los animales, producto de una mayor concentración de cuerpos cetónicos debido al marcado balance energético negativo.

Tim Cheok,1– 3 Matthew Jennings,1,4 Morgan Berman,1 Kanihska Williams,1,3 Jaideep Singh Rawat,1,5,6 Bruce K Foster1,5 1Department of Trauma and Orthopaedics, Alice Springs Hospital, Alice Springs, Northern Territory, Australia; 2Department of Orthopaedic Surgery, Palmerston North Hospital, Palmerston North, New Zealand; 3College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia; 4Department of Plastics and Reconstructive Surgery, Women’s and Children’s Hospital, Adelaide, South Australia, Australia; 5Department of Orthopaedic Surgery, Flinders Medical Centre, Adelaide, South Australia, Australia; 6Department of Orthopaedic Surgery, Women’s and Children’s Hospital, Adelaide, South Australia, AustraliaCorrespondence: Tim Cheok, Email tim.cheok@flinders.edu.auCase: We present a case of acute unstable valgus slipped capital femoral epiphysis (SCFE) in an 8-year-old female who presented after a trip and fall. The patient was managed with emergent closed reduction and percutaneous screw fixation and prophylactic fixation of contralateral side after 6 weeks. At 18-month follow-up, the patient was symptom free with a good range of movement and no evidence of slip progression, chondrolysis or avascular necrosis of the femoral head.Conclusion: We demonstrate that, in this case, closed reduction and percutaneous fixation provided satisfactory outcome at 18-month follow-up. This case highlights the need for both anteroposterior and lateral radiographs.Keywords: SCFE, closed reduction, percutaneous pinning, valgus slip

Camille Robichaux,1 Jordan Aron,2 Chris H Wendt,1,3 Jesse D Berman,4 Austin Rau,4 Ann Bangerter,5 R Adams Dudley,1,3,5 Arianne K Baldomero1,3,5 1Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Minnesota, Minneapolis, MN, USA; 2Division of Biostatistics, University of Minnesota School of Public Health, Minneapolis, MN, USA; 3Pulmonary, Allergy, Critical Care, and Sleep Medicine, Minneapolis VA Health Care System, Minneapolis, MN, USA; 4Division of Environmental Health Sciences, University of Minnesota School of Public Health, Minneapolis, MN, USA; 5Center for Care Delivery and Outcomes Research, Minneapolis VA Health Care System, Minneapolis, MN, USACorrespondence: Camille Robichaux, Division of Pulmonary, Allergy, Critical Care, and Sleep, University of Minnesota, 420 Delaware Street SE, MMC 276, Minneapolis, MN, 55455, USA, Tel +1 612 624-0999, Email robic020@umn.eduBackground: Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. Identifying both individual and community risk factors associated with higher mortality is essential to improve outcomes. Few population-based studies of mortality in COPD include both individual characteristics and community risk factors.Objective: We used geocoded, patient-level data to describe the associations between individual demographics, neighborhood socioeconomic status, and all-cause mortality.Methods: We performed a nationally representative retrospective cohort analysis of all patients enrolled in the Veteran Health Administration with at least one ICD-9 or ICD-10 code for COPD in 2016– 2019. We obtained demographic characteristics, comorbidities, and geocoded residential address. Area Deprivation Index and rurality were classified using individual geocoded residential addresses. We used logistic regression models to assess the association between these characteristics and age-adjusted all-cause mortality.Results: Of 1,106,163 COPD patients, 33.4% were deceased as of January 2021. In age-adjusted models, having more comorbidities, Black/African American race (OR 1.09 [95% CI: 1.08– 1.11]), and higher neighborhood disadvantage (OR 1.30 [95% CI: 1.28– 1.32]) were associated with all-cause mortality. Female sex (OR 0.67 [95% CI: 0.65– 0.69]), Asian race (OR 0.64, [95% CI: 0.59– 0.70]), and living in a more rural area were associated with lower odds of all-cause mortality. After adjusting for age, comorbidities, neighborhood socioeconomic status, and rurality, the association with Black/African American race reversed.Conclusion: All-cause mortality in COPD patients is disproportionately higher in patients living in poorer neighborhoods and urban areas, suggesting the impact of social determinants of health on COPD outcomes. Black race was associated with higher age-adjusted all-cause mortality, but this association was abrogated after adjusting for gender, socioeconomic status, comorbidities, and urbanicity. Future studies should focus on exploring mechanisms by which disparities arise and developing interventions to address these.Keywords: chronic obstructive pulmonary disease, social determinants, race, geography, socioeconomic status

Todd Schlesinger,1 Eggert Stockfleth,2 Ayman Grada,3 Brian Berman4 1Clinical Research Center of the Carolinas, Charleston, SC, USA; 2Department of Dermatology, Venereology and Allergology, Ruhr-University Bochum, Bochum, Germany; 3Department of Dermatology, Case Western Reserve University School of Medicine, Cleveland, OH, USA; 4Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, USACorrespondence: Ayman Grada, Email ayman.grada@case.eduAbstract: Actinic keratosis (AK) is a common pre-neoplastic skin lesion constituted by uncontrolled proliferation of atypical keratinocytes that may evolve to squamous cell carcinoma. With global prevalence increasing, AK is expected to be the most common carcinoma of the skin. Tirbanibulin is a reversible tubulin polymerization inhibitor with potent anti-proliferative and anti-tumoral effects. In-vivo and in-vitro studies have shown that tirbanibulin significantly inhibits cell proliferation, tumor growth and downregulates Src signaling with no overt toxicity. Early phase and Phase III trials have shown high lesion clearance, compliance, and few side effects of once daily tirbanibulin treatment. This review discusses tirbanibulin anti-cancer activity, focusing on tubulin polymerization and Src signaling inhibitory effects, highlighting relevant literature and novel preclinical results from the ATNXUS-KX01-001 study. Furthermore, we address the relevant findings obtained in recent clinical trials to evaluate the safety, efficacy, pharmacokinetics, clearance efficacy, and side effects of the 1% tirbanibulin ointment applied once daily. In summary, we highlight preclinical and clinical evidence on the use of tirbanibulin as an effective and safe treatment option for AK.Keywords: actinic keratosis, tirbanibulin, microtubules, Src kinase inhibitor

Este artículo busca avanzar en la comprensión sobre la participación política y electoral de las mujeres en las elecciones ejecutivas en siete provincias argentinas de 1983 a 2015. A partir del análisis de 958 candidaturas en 62 comicios provinciales durante 32 años de democracia ininterrumpida y de la aplicación de veintiún entrevistas a profundidad a informantes provinciales clave; se estudiaron los tipos de liderazgo partidario y los procesos de selección de candidaturas en los partidos políticos más relevantes de cada elección para determinar los contextos favorables para candidaturas de mujeres en este nivel de gobierno. Liderazgos fuertes, procesos de selección de candidaturas cerrados y cercanía al líder son tres elementos que, al combinarse, muestran un contexto favorable para que las mujeres sean candidatas.

See the retraction notice BIO Web of Conferences 84, 00001 (2024), https://doi.org/10.1051/bioconf/20248400001