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Signaling via N-methyl-d-aspartate receptors (NMDARs) is critical for the maturation of glutamatergic synapses, partly through a developmental switch from immature synapses expressing primarily GluN2B- and GluN3A-containing subtypes to GluN2A-rich mature ones. This subunit switch is thought to underlie the synaptic stabilization of NMDARs necessary for neural network consolidation. However, the cellular mechanisms controlling the NMDAR exchange remain unclear. Using a combination of single-molecule and confocal imaging and biochemical and electrophysiological approaches, we show that surface GluN3A-NMDARs form a highly diffusive receptor pool that is loosely anchored to synapses. Remarkably, changes in GluN3A subunit expression selectively alter the surface diffusion and synaptic anchoring of GluN2A- but not GluN2B-NMDARs, possibly through altered interactions with cell surface receptors. The effects of GluN3A on NMDAR surface diffusion are restricted to an early time window of postnatal development in rodents, allowing GluN3A subunits to control the timing of NMDAR signaling maturation and neuronal network refinements.

Primary familial brain calcification (PFBC) is a rare cerebral microvascular calcifying disorder with a wide spectrum of motor, cognitive, and neuropsychiatric symptoms. It is typically inherited as an autosomal-dominant trait with four causative genes identified so far: SLC20A2, PDGFRB, PDGFB, and XPR1. Our study aimed at screening the coding regions of these genes in a series of 177 unrelated probands that fulfilled the diagnostic criteria for primary brain calcification regardless of their family history. Sequence variants were classified as pathogenic, likely pathogenic, or of uncertain significance (VUS), based on the ACMG-AMP recommendations. We identified 45 probands (25.4%) carrying either pathogenic or likely pathogenic variants (n = 34, 19.2%) or VUS (n = 11, 6.2%). SLC20A2 provided the highest contribution (16.9%), followed by XPR1 and PDGFB (3.4% each), and PDGFRB (1.7%). A total of 81.5% of carriers were symptomatic and the most recurrent symptoms were parkinsonism, cognitive impairment, and psychiatric disturbances (52.3%, 40.9%, and 38.6% of symptomatic individuals, respectively), with a wide range of age at onset (from childhood to 81 years). While the pathogenic and likely pathogenic variants identified in this study can be used for genetic counseling, the VUS will require additional evidence, such as recurrence in unrelated patients, in order to be classified as pathogenic.

• A 6-month combined aerobic and resistance exercise program significantly improved walking ability and walking speed in people with peripheral arterial disease and claudication, as demonstrated by increased absolute claudication time, maximal walking time, and maximal walking distance during 6-minute walk test. • The supervised exercise program led to positive effects on physical fitness, including improvements in lower body and lower back flexibility, as well as favorable changes in body composition. • The exercise program was found to be safe and well-tolerated by people with peripheral arterial disease and claudication. Exercise therapy is a recognized non-pharmacological intervention for peripheral arterial disease (PAD); however, the effects of combined exercise remain under investigation. This study aimed to compare the effects of a 6-month combined supervised exercise program (SUP) with a usual care (UC) approach on walking ability, physical fitness, and peripheral blood flow in people with PAD and claudication. Twenty-three male participants (Age=64.1 ± 6.2years and ABI=0.58±0.07) with PAD and claudication were assigned to either the SUP group (n = 10), engaging in structured supervised treadmill walking combined with three resistance exercises, three times a week, or the UC group (n = 13), receiving advice to walk. The primary outcome measure was walking ability, with assessments conducted at baseline (M0), after 3 months (M3), and 6 months (M6). After the 6-month intervention, the SUP group exhibited significant improvements in absolute claudication time (ACT, p = 0.045), maximal walking time (MWT, p = 0.045), maximal walking distance (MWD, p = 0.027), and pause duration (p = 0.045) during the 6-minute walk test (6MWT), when compared to the UC group. Over time, a significant increase in walking speed during the 6MWT (Speed 6MWT , p = 0.001) and walking speed without claudication (Speed NoC , p < 0.001) was found, although no significant differences were found between the groups. The SUP group increased by 0.8 km/h in both Speed 6MWT and Speed NoC , while the UC group increased by 0.3 km/h and 0.6 km/h, respectively. Despite claudication consistently occurring at the same time, the SUP group demonstrated an improved tolerance to pain or a better understanding of pain, enabling them to walk longer distances at higher speeds. A positive effect of SUP was found for chair sit-and-reach test (p = 0.023), percentage of fat mass (p = 0.048), fat-free mass (p = 0.040), and total body water (p = 0.026), suggesting potential benefits attributed to the resistance strength exercises. A 6-month combined treadmill and resistance exercise program improved walking ability, walking speed, lower body and lower back flexibility, and body composition in people with PAD and claudication. [ABSTRACT FROM AUTHOR]

Hypereosinophilic syndrome is a rare systemic condition characterized by eosinophil-mediated organ damage. Cardiac involvement is common and typically occurs in sequential stages. We present two cases that demonstrate these different stages and presentations of eosinophilia-mediated myocardial disease, where multimodality imaging was essential for the diagnosis. More importantly, they demonstrate, for the first time, the dissociation between the eosinophil count and patients' clinical evolution, suggesting the need for close follow up even after the eosinophilia has been controlled. Cardiac involvement in hypereosinophilic syndrome typically occurs in three stages – necrotic, thrombotic, and fibrotic. Although cardiac damage is mediated by eosinophils, the blood eosinophil count and patients' clinical evolution are dissociated. Therefore, eosinophil count on its own is not an adequate marker of clinical evolution, and cardiac follow up should be continued even after the eosinophilia has been controlled. [ABSTRACT FROM AUTHOR]

ObjectiveTo assess the potential connection between PCDH12 and brain calcifications in a patient carrying a homozygous nonsense variant in PCDH12 and in adult patients with brain calcifications.MethodsWe performed a CT scan in 1 child with a homozygous PCDH12 nonsense variant. We screened DNA samples from 53 patients with primary familial brain calcification (PFBC) and 26 patients with brain calcification of unknown cause (BCUC).ResultsWe identified brain calcifications in subcortical and perithalamic regions in the patient with a homozygous PCDH12 nonsense variant. The calcification pattern was different from what has been observed in PFBC and more similar to what is described in in utero infections. In patients with PFBC or BCUC, we found no protein-truncating variant and 3 rare (minor allele frequency

Objectives. Hungry bone syndrome (HBS) is a severe and underdiagnosed complication of parathyroidectomy in the treatment of primary hyperparathyroidism (PHP) and secondary hyper-parathyroidism to chronic kidney disease (SHP-CKD).

Despite an increase in the reporting of rape, convictions in England and Wales have fallen significantly in recent years. Previous research has found high rape myth acceptance among police officers. Given that the police act as gatekeepers to the criminal justice system, subscribing to rape myths may have significant effects upon victim attrition and conviction rates. This study explores police officers' use of rape myths and how these may impact investigations and prosecutions. A total of 17 semi-structured interviews were conducted with police officers from a large English police force. The interview data were analysed using the qualitative method of thematic analysis. Although there were instances where officers demonstrated some awareness of the need to dispel or counter rape myths, rape myths were employed by most officers, with the most common relating to (1) victim fabrication ('women lie') and (2) victim precipitation ('women ask for it'). Recommendations are made around screening and training for police officers. [ABSTRACT FROM AUTHOR]

A cytogenetic map of common bean was built by in situ hybridization of 35 bacterial artificial chromosomes (BACs) selected with markers mapping to eight linkage groups, plus two plasmids for 5S and 45S ribosomal DNA and one bacteriophage. Together with three previously mapped chromosomes (chromosomes 3, 4, and 7), 43 anchoring points between the genetic map and the cytogenetic map of the species are now available. Furthermore, a subset of four BAC clones was proposed to identify the 11 chromosome pairs of the standard cultivar BAT93. Three of these BACs labelled more than a single chromosome pair, indicating the presence of repetitive DNA in their inserts. A repetitive distribution pattern was observed for most of the BACs; for 38% of them, highly repetitive pericentromeric or subtelomeric signals were observed. These distribution patterns corresponded to pericentromeric and subtelomeric heterochromatin blocks observed with other staining methods. Altogether, the results indicate that around half of the common bean genome is heterochromatic and that genes and repetitive sequences are intermingled in the euchromatin and heterochromatin of the species.