N-methyl D-aspartate (NMDA) receptor antagonists and memantine treatment for Alzheimer's disease, vascular dementia and Parkinson's disease

Memantine, a partial antagonist of N-methyl-D-aspartate receptor (NMDAR), approved for moderate to severe Alzheimer's disease (AD) treatment within the U.S. and Europe under brand name Namenda (Forest), Axura and Akatinol (Merz), and Ebixa and Abixa (Lundbeck), may have potential in alleviating additional neurological conditions, such as vascular dementia (VD) and Parkinson's disease (PD). In various animal models, memantine has been reported to be a neuroprotective agent that positively impacts both neurodegenerative and vascular processes. While excessive levels of glutamate result in neurotoxicity, in part through the over-activation of NMDARs, memantine-as a partial NMDAR antagonist, blocks the NMDA glutamate receptors to normalize the glutamatergic system and ameliorate cognitive and memory deficits. The key to memantine's therapeutic action lies in its uncompetitive binding to the NMDAR through which low affinity and rapid off-rate kinetics of memantine at the level of the NMDAR-channel preserves the physiological function of the receptor, underpinning memantine's tolerability and low adverse event profile. As the biochemical pathways evoked by NMDAR antagonism also play a role in PD and since no other drug is sufficiently effective to substitute for the first-line treatment of L-dopa despite its side effects, memantine may be useful in PD treatment with possibly fewer side effects. In spite of the relative modest nature of its adverse effects, memantine has been shown to provide only a moderate decrease in clinical deterioration in AD and VD, and hence efforts are being undertaken in the design of new and more potent memantine-based drugs to hopefully provide greater efficacy

Molecular Characterization of Cryptosporidium Species and Giardia duodenalis from Symptomatic Cambodian Children

Background: In a prospective study, 498 single faecal samples from children aged under 16 years attending an outpatient clinic in the Angkor Hospital for Children, northwest Cambodia, were examined for Cryptosporidium oocysts and Giardia cysts using microscopy and molecular assays. Methodology/Principal Findings: Cryptosporidium oocysts were detected in 2.2% (11/498) of samples using microscopy and in 7.7% (38/498) with molecular tests. Giardia duodenalis cysts were detected in 18.9% (94/498) by microscopy and 27.7% (138/498) by molecular tests; 82% of the positive samples (by either method) were from children aged 1–10 years. Cryptosporidium hominis was the most common species of Cryptosporidium, detected in 13 (34.2%) samples, followed by Cryptosporidium meleagridis in 9 (23.7%), Cryptosporidium parvum in 8 (21.1%), Cryptosporidium canis in 5 (13.2%), and Cryptosporidium suis and Cryptosporidium ubiquitum in one sample each. Cryptosporidium hominis and C. parvum positive samples were subtyped by sequencing the GP60 gene: C. hominis IaA16R6 and C. parvum IIeA7G1 were the most abundant subtypes. Giardia duodenalis was typed using a multiplex real-time PCR targeting assemblages A and B. Assemblage B (106; 76.8% of all Giardia positive samples) was most common followed by A (12.3%) and mixed infections (5.1%). Risk factors associated with Cryptosporidium were malnutrition (AOR 9.63, 95% CI 1.67–55.46), chronic medical diagnoses (AOR 4.51, 95% CI 1.79–11.34) and the presence of birds in the household (AOR 2.99, 95% CI 1.16–7.73); specifically C. hominis (p = 0.03) and C. meleagridis (p<0.001) were associated with the presence of birds. The use of soap was protective against Giardia infection (OR 0.74, 95% CI 0.58–0.95). Conclusions/Significance: This is the first report to describe the different Cryptosporidium species and subtypes and Giardia duodenalis assemblages in Cambodian children. The variety of Cryptosporidium species detected indicates both anthroponotic and zoonotic transmission in this population. Interventions to improve sanitation, increase hand washing after defecation and before preparing food and promote drinking boiled water may reduce the burden of these two parasites

Predictors of Unilateral Arm Lymphedema in Non-obese Locoregionally Advanced Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy, Modified Radical Mastectomy, and Postoperative Irradiation

Objective: The most dreaded long-term complication of axillary lymph node dissection remains upper arm lymphedema. Our study has strategized the three most common identified causes of post treatment arm lymphedema, i.e., obesity, radiation, and neoadjuvant chemotherapy and tried to identify the histopathological and clinical or surgical factors which can predict arm lymphedema. Materials and Methods: This is a prospective observational study was conducted at a tertiary care referral centre in India, with strict inclusion criteria of BMI <30 kg/m2, age <75 years, presence of metastatic axillary node proven by FNAC, received anthracycline based neoadjuvant chemotherapy and postoperative nodal irradiation, and completed 24 months of regular follow-up. Results: Total of 70 patients were included in the study. The mean age of the patients was 50.3 years (±12.9). lymphovascular invasion, total number of lymph nodes removed from level III, total number of days drain was left in situ and maximum drain output were found to be significantly (p<0.05) associated with arm lymphedema. Conclusion: In patients undergoing modified radical mastectomy with level III dissection, and postoperative irradiation, the incidence of unilateral arm lymphedema is significantly influenced by several clinicopathological factors like the total number of lymph nodes removed in level III, higher maximal drain output, prolonged duration of drain placement and the presence of lymphovascular invasion

Report of the Topical Group on Physics Beyond the Standard Model at Energy Frontier for Snowmass 2021

This is the Snowmass2021 Energy Frontier (EF) Beyond the Standard Model (BSM) report. It combines the EF topical group reports of EF08 (Model-specific explorations), EF09 (More general explorations), and EF10 (Dark Matter at Colliders). The report includes a general introduction to BSM motivations and the comparative prospects for proposed future experiments for a broad range of potential BSM models and signatures, including compositeness, SUSY, leptoquarks, more general new bosons and fermions, long-lived particles, dark matter, charged-lepton flavor violation, and anomaly detection

Report of the Topical Group on Physics Beyond the Standard Model at Energy Frontier for Snowmass 2021

International audienceThis is the Snowmass2021 Energy Frontier (EF) Beyond the Standard Model (BSM) report. It combines the EF topical group reports of EF08 (Model-specific explorations), EF09 (More general explorations), and EF10 (Dark Matter at Colliders). The report includes a general introduction to BSM motivations and the comparative prospects for proposed future experiments for a broad range of potential BSM models and signatures, including compositeness, SUSY, leptoquarks, more general new bosons and fermions, long-lived particles, dark matter, charged-lepton flavor violation, and anomaly detection

Report of the Topical Group on Physics Beyond the Standard Model at Energy Frontier for Snowmass 2021

International audienceThis is the Snowmass2021 Energy Frontier (EF) Beyond the Standard Model (BSM) report. It combines the EF topical group reports of EF08 (Model-specific explorations), EF09 (More general explorations), and EF10 (Dark Matter at Colliders). The report includes a general introduction to BSM motivations and the comparative prospects for proposed future experiments for a broad range of potential BSM models and signatures, including compositeness, SUSY, leptoquarks, more general new bosons and fermions, long-lived particles, dark matter, charged-lepton flavor violation, and anomaly detection

Report of the topical group on physics beyond the standard model at energy frontier for snowmass 2021

This is the Snowmass2021 Energy Frontier (EF) Beyond the Standard Model (BSM) report. It combines the EF topical group reports of EF08 (Model-specific explorations), EF09 (More general explorations), and EF10 (Dark Matter at Colliders). The report includes a general introduction to BSM motivations and the comparative prospects for proposed future experiments for a broad range of potential BSM models and signatures, including compositeness, SUSY, leptoquarks, more general new bosons and fermions, long-lived particles, dark matter, charged-lepton flavor violation, and anomaly detection