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Introduction: Alzheimer's disease (AD) patients are at greater risk of focal seizures than similarly aged adults; these seizures, left untreated, may worsen functional decline. Older people with epilepsy generally respond well to antiseizure medications (ASMs). However, whether specific ASMs can differentially control seizures in AD is unknown. The corneal kindled mouse model of acquired chronic secondarily generalized focal seizures allows for precisely timed drug administration studies to quantify the efficacy and tolerability of ASMs in an AD-associated genetic model. Wh+e hypothesized that mechanistically distinct ASMs would exert differential anticonvulsant activity and tolerability in aged AD mice (8-15 months) to define whether rational ASM selection may benefit specific AD genotypes., Methods: Aged male and female PSEN2-N141I versus age-matched non-transgenic control (PSEN2 control) C57Bl/6J mice, and APP swe /PS1 dE9 versus transgene negative (APP control) littermates underwent corneal kindling to quantify latency to fully kindled criterion. Dose-related ASM efficacy was then compared in each AD model versus matched control over 1-2 months using ASMs commonly prescribed in older adults with epilepsy: valproic acid, levetiracetam, lamotrigine, phenobarbital, and gabapentin., Results: Sex and AD genotype differentially impacted seizure susceptibility. Male PSEN2-N141I mice required more stimulations to attain kindling criterion (X 2 =5.521; p<0.05). Male APP/PS1 mice did not differ in kindling rate versus APP control mice, but they did have more severe seizures. There were significant ASM class-specific differences in acute seizure control and dose-related tolerability. APP/PS1 mice were more sensitive than APP controls to valproic acid, levetiracetam, and gabapentin. PSEN2-N141I mice were more sensitive than PSEN2 controls to valproic acid and lamotrigine., Discussion: AD genotypes may differentially impact ASMs activity and tolerability in vivo with advanced biological age. These findings highlight the heterogeneity of seizure risk in AD and suggest that precisely selected ASMs may beneficially control seizures in AD, thus reducing functional decline., Competing Interests: Declaration of interest: None of the authors have any conflicts to disclose.

Introduction: Patients with early-onset Alzheimer's disease (EOAD) experience seizures and subclinical epileptiform activity, which may accelerate cognitive and functional decline. Antiseizure medicines (ASMs) may be a tractable disease-modifying strategy; numerous ASMs are marketed with well-established safety. However, little information is available to guide ASM selection as few studies have rigorously quantified ASM potency and tolerability in traditional seizure models in rodents with EOAD-associated risk factors. Presenilin 2 (PSEN2) variants evoke EOAD, and these patients experience seizures. This study thus established the anticonvulsant profile of mechanistically distinct ASMs in the frontline 6-Hz limbic seizure test evoked in PSEN2-knockout (KO) mice to better inform seizure management in EOAD., Methods: The median effective dose (ED50) of prototype ASMs was quantified in the 6-Hz test in male and female PSEN2-KO and wild-type (WT) C57BL/6J mice (3-4 months old). Minimal motor impairment (MMI) was assessed to estimate a protective index (PI). Immunohistological detection of cFos established the extent to which 6-Hz stimulation activates discrete brain regions in KO vs. WT mice., Results: There were significant genotype-related differences in the potency and tolerability of several ASMs. Valproic acid and levetiracetam were significantly more potent in male KO than in WT mice. Additionally, high doses of valproic acid significantly worsened MMI in KO mice. Conversely, carbamazepine was significantly less potent in female KO vs. WT mice. In both male and female KO mice vs. WTs, perampanel and lamotrigine were equally potent. However, there were marked genotype-related shifts in PI of both carbamazepine and perampanel, with KO mice exhibiting less MMI at the highest doses tested. Gabapentin was ineffective against 6-Hz seizures in KO mice vs. WTs without MMI changes. Neuronal activation 90 min following 6-Hz stimulation was significantly increased in the posterior parietal association cortex overlying CA1 and in the piriform cortex of WT mice, while stimulation-induced increases in cFos immunoreactivity were absent in KO mice., Discussion: Acute ASM potency and tolerability in the high-throughput 6-Hz test may be significantly altered with loss of normal PSEN2 function. Seizures in discrete EOAD populations may benefit from precisely selected medicines optimized for primary ASM pharmacological mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lehmann and Barker-Haliski.)

Introduction: The progressive nature of type 2 diabetes necessitates treatment intensification. This often involves intensification with oral antidiabetic drugs (OADs) initially, followed by other agents, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), with the majority of patients eventually requiring insulin therapy. Therefore, this trial aimed to investigate the efficacy of IDegLira (combination of insulin degludec and liraglutide) in controlling glycemia in adults with type 2 diabetes who were inadequately controlled on a GLP-1RA and OADs., Methods: In this 26-week open-label phase 3b trial, patients on maximum-dose GLP-1RA therapy (liraglutide once daily or exenatide twice daily) with metformin alone or with pioglitazone and/or sulfonylurea were randomized 2:1 to IDegLira once daily (n = 292) or to unchanged GLP-1RA therapy (n = 146), continuing OADs at the pre-trial dose., Results: After 26 weeks, HbA 1c reductions were superior with IDegLira versus unchanged GLP-1RA; estimated treatment difference -0.94% (-10.3 mmol/mol), p < 0.001. Mean HbA 1c reduced from 7.8% to 6.4% (61.5 to 46.9 mmol/mol) with IDegLira and from 7.7 to 7.4% (60.8 to 57.1 mmol/mol) with unchanged GLP-1RA. With IDegLira, 75% and 63% of patients achieved HbA 1c <7% and ≤6.5%, compared with 36% and 23% on unchanged GLP-1RA, respectively. Fasting plasma glucose and 9-point self-monitored blood glucose profiles improved significantly more with IDegLira versus unchanged GLP-1RA. The mean change in weight was +2.0 kg with IDegLira, versus -0.8 kg with unchanged GLP-1RA. Rates of confirmed hypoglycemia were low, but higher with IDegLira versus unchanged GLP-1RA. The safety profile of IDegLira was consistent with previous findings; both treatments were well tolerated and the rate of nausea was low in both groups. IDegLira improved patient-reported outcomes versus unchanged GLP-1RA., Conclusions: IDegLira provided superior glycemic control versus unchanged GLP-1RA and represents an efficacious intensification approach in patients inadequately controlled on GLP-1RAs., Trial Registration: ClinicalTrials.gov #NCT01676116., Funding: Novo Nordisk.

Introduction  Toxoplasmosis a parasitic zoonosis of global distribution, responsible for disorders during gestation can cause fetal death or congenital anomalies. Objective  To evaluate the knowledge of toxoplasmosis among pregnant and postpartum women treated at the University Hospital of the city of Rio Grande, Rio Grande do Sul, Brazil. Methods  This was a cross-sectional study of 100 pregnant and postpartum women at the University Hospital. Participants answered a self-administered questionnaire and gave consent for data relating to serological examinations to be abstracted from their medical records. Results  The proportion of women who received information about toxoplasmosis was higher among those who received care in the private health care system (52.9%) than among those cared for in the public health care system (25.0%). Only 55.7% of women reported having some knowledge about toxoplasmosis. Of these, 53.7% received information during the prenatal period. However, most participants were unable to answer questions about preventive measures and modes of infection. Of the 100 patients in the study, only 46 underwent serologic testing for toxoplasmosis, 65.2% of whom tested negative (IgG). Conclusion  Findings from this study are relevant to the training of health professionals regarding toxoplasmosis education and prevention. Improved education for health care providers and patients can lead to earlier diagnoses and reductions in adverse outcomes., (Thieme Publicações Ltda Rio de Janeiro, Brazil.)

Background: Human toxocariasis is a parasitic zoonosis with a worldwide distribution but is underdiagnosed with an underestimated impact on human health. The ingestion of embryonated eggs of Toxocara spp. present on the hands or in contaminated food or water is the main mode of infection. The only record of Toxocara congenital infection in humans occurred in a premature infant. Helminth infections during pregnancy may be associated with reproductive disorders. Studies investigating the occurrence of toxocariasis in pregnancy are scarce, as is research on the possible implications of these parasites in reproductive health. The aim of this study was to determine the seroprevalence of antibodies to Toxocara spp. in pregnant women and to identify risk factors associated with its infection., Methodology/principal Findings: The cross-sectional study of the seropositivity of specific antibodies for Toxocara spp. was performed on 280 pregnant women. Serum samples were examined with enzyme-linked immunoassay. Epidemiological data were obtained through a questionnaire containing information about obstetric history, general life style choices, and the social and economic status of the women. The prevalence of Toxocara spp. IgG in pregnant women was 6.4%. Some of the risk factors associated with the infection were owning dogs (p = 0.003), living in the city centre (p = 0.028), living at the city beach (p = 0.003), and having a family income at or below minimum wage (p < 0.001). There was no association between reproductive disorders and Toxocara seropositivity., Conclusions/significance: The seroprevalence of 6.4% for Toxocara spp. in pregnant women shows that there was exposure to the parasite. The study demonstrates the need for attention for the completion of clinical diagnosis parameters, as well as the expansion of highly specific serological studies in different regions to understand the impact of toxocariasis in pregnancy.