Pharmacokinetics and pharmacodynamics across infusion rates of intravenously administered nipocalimab: results of a phase 1, placebo-controlled study.

Introduction: Nipocalimab is a high-affinity, fully human, aglycosylated, effectorless, immunoglobulin G (IgG) 1 monoclonal antibody that targets the neonatal Fc receptor (FcRn), decreases systemic IgG including autoantibodies, and is under development in several IgG autoantibody- and alloantibody-mediated diseases, including generalized myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, maternal-fetal medicine, and multiple other therapeutic areas. An initial phase 1 study with single and multiple ascending doses of nipocalimab infused intravenously (IV) over 2 h demonstrated dose-dependent serum pharmacokinetics and IgG reductions, with an adverse event (AE) profile comparable to placebo.

Methods: The current investigation evaluates the safety, tolerability, pharmacokinetics, and pharmacodynamics of single doses of nipocalimab across various IV infusion rates in a randomized, double-blind, placebo-controlled, sequential-dose study.

Safety and Efficacy of Nipocalimab in Patients With Generalized Myasthenia Gravis: Results From the Randomized Phase 2 Vivacity-MG Study.

Background And Objectives: To evaluate in a phase 2 study the safety and efficacy of IV nipocalimab, a fully human, antineonatal Fc receptor monoclonal antibody, in patients with generalized myasthenia gravis (gMG).

Methods: Patients with gMG with inadequate response to stable standard-of-care (SOC) therapy were randomized 1:1:1:1:1 to receive either IV placebo every 2 weeks (Q2W) or one of 4 IV nipocalimab treatments: 5 mg/kg once every 4 weeks (Q4W), 30 mg/kg Q4W, 60 mg/kg Q2W each for 8 weeks, or a 60 mg/kg single dose, in addition to their background SOC therapy. Infusions (placebo or nipocalimab) were Q2W in all groups to maintain blinding.

Effect of ethanolic extracts from Piperaceae leaves on the reduction of skin necrosis and wound healing in an animal model of degloving injuries.

Purpose: To assess the effect of the ethanolic extract of the leaves of three species of plants from the Piperaceae family on reducing necrosis and enhancing wound healing in an animal model of degloving injuries.

Methods: The animals were divided into six groups, each consisting of six animals: sham, negative control, EEPA (Piper amalago ethanolic extract), EEPG (Piper glabratum ethanolic extract), EEPV (Piper vicosanum ethanolic extract), and positive control receiving hyperbaric oxygenation. The animals underwent surgery to induce excision wounds, and the extent of cutaneous necrosis was evaluated using graphic software, while wound healing was assessed through histopathology.

Emergence of preparatory dynamics in VIP interneurons during motor learning.

To determine what actions to perform in each context, animals must learn how to execute motor programs in response to sensory cues. In rodents, the interface between sensory processing and motor planning occurs in the secondary motor cortex (M2). Here, we investigate dynamics in vasointestinal peptide (VIP) and somatostatin (SST) interneurons in M2 during acquisition of a cue-based, reach-to-grasp (RTG) task in mice.

A monocular wide-field speed sensor inspired by the crabs' visual system for traffic analysis.

The development of visual sensors for traffic analysis can benefit from mimicking two fundamental aspects of the visual system of crabs: their panoramic vision and their visual processing strategy adapted to a flat world. First, the use of omnidirectional cameras in urban environments allows for analyzing the simultaneous movement of many objects of interest over broad areas. This would reduce the costs and complications associated with infrastructure: installation, synchronization, maintenance, and operation of traditional vision systems that use multiple cameras with a limited field of view.

Development of a dysphagia cup to improve patients' fluid intake and reduce caregiver burden.

Ensuring that the elderly drink adequate fluids to meet their recommended daily allowance is often a challenge, especially among the elderly in hospitals and long-term care settings. The complex interplay of biological, medical and psychosocial factors that cause the elderly to become dehydrated is difficult to tackle especially in care settings where there is a staff shortage and heavy workload. The team realised that 90% of the elderly inpatients in the general ward of a teaching hospital in Singapore were not drinking enough to meet their needs, despite the hot and humid weather.

Clinical and structural brain correlates of hypomimia in early-stage Parkinson's disease.

Background And Purpose: Reduced facial expression of emotions is a very frequent symptom of Parkinson's disease (PD) and has been considered part of the motor features of the disease. However, the neural correlates of hypomimia and the relationship between hypomimia and other non-motor symptoms of PD are poorly understood.

Methods: The clinical and structural brain correlates of hypomimia were studied.

Increased homocysteine levels correlate with cortical structural damage in Parkinson's disease.

Background: Blood homocysteine appears to be increased in Parkinson's disease (PD) and may play a role in the development and progression of this disorder. However, the specific contribution of abnormal homocysteine levels to cortical degeneration in PD remains elusive.

Objective: To characterize the cortical structural correlates of homocysteine levels in PD.

Human-Specific Regulation of Neurotrophic Factors MANF and CDNF by microRNAs.

Mesencephalic astrocyte derived neurotrophic factor (MANF) and cerebral dopamine neurotrophic factor (CDNF) are novel evolutionary conserved trophic factors, which exhibit cytoprotective activity via negative regulation of unfolded protein response (UPR) and inflammation. Despite multiple reports demonstrating detrimental effect of MANF/CDNF downregulation, little is known about the control of their expression. miRNAs-small non-coding RNAs-are important regulators of gene expression.

In vivo cholinergic basal forebrain degeneration and cognition in Parkinson's disease: Imaging results from the COPPADIS study.

Introduction: We aimed to assess associations between multimodal neuroimaging measures of cholinergic basal forebrain (CBF) integrity and cognition in Parkinson's disease (PD) without dementia.

Methods: The study included a total of 180 non-demented PD patients and 45 healthy controls, who underwent structural MRI acquisitions and standardized neurocognitive assessment through the PD-Cognitive Rating Scale (PD-CRS) within the multicentric COPPADIS-2015 study. A subset of 73 patients also had Diffusion Tensor Imaging (DTI) acquisitions.

Computed tomography perfusion abnormalities after carotid endarterectomy help in the diagnosis of reversible cerebral vasoconstriction syndrome.

Acute neurologic deficits in the postoperative period after carotid endarterectomy (CEA) can prompt extensive diagnostic evaluation. Reversible cerebral vasoconstriction syndrome (RCVS) is an underrecognized cause of acute neurologic deficit after CEA. We present the case of RCVS in an 84-year-old male patient who had experienced left limb weakness after CEA, prompting multiple code stroke activations.

[Thoracic insufficiency syndrome].

The compendium of disorders that affect the normal growth or function of the thorax will cause Thoracic Insufficiency Syndrome (TIS). TIS is defined as the inability of the chest to sustain normal breathing and/or lung growth. The etiology of the syndrome may be secondary to spinal deformities, global deformities of the chest, neuromuscular dysfunction or the combination of any these.

A placebo-controlled proof-of-concept study of alirocumab on postprandial lipids and vascular elasticity in insulin-treated patients with type 2 diabetes mellitus.

Aim: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular disease (CVD) linked to atherogenic dyslipidaemia and postprandial hyperlipidaemia. Alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, improves CVD risk by reducing the concentration of low-density lipoprotein-cholesterol (LDL-C). However, effects of PCK9 inhibitors on other aspects of diabetic dyslipidaemia, particularly in the postprandial situation, are less clear.

Antimicrobial active edible coating of alginate and chitosan add ZnO nanoparticles applied in guavas (Psidium guajava L.).

Nanostructured coatings made with chitosan (100%Q), alginate (100%A) and blends of 50%Q-50%A; 90%Q-10%A and 90%A-10%Q, were added with (1%v/v) of nanoZnO and applied to guavas (Psidium guajava L.). After the coating application, fruits were stored for 15 days at 21 ± 1 °C and 80 ± 2% RH.

Stratification of cancer and diabetes based on circulating levels of formate and glucose.

Background: Serum and urine metabolites have been investigated for their use as cancer biomarkers. The specificity of candidate metabolites can be limited by the impact of other disorders on metabolite levels. In particular, the increasing incidence of obesity could become a significant confounding factor.

Development of a dual-functional conjugate of antigenic peptide and Fc-III mimetics (DCAF) for targeted antibody blocking.

Targeted antibody blocking enables characterization of binding sites on immunoglobulin G (IgG), and can efficiently eliminate harmful antibodies from organisms. In this report, we present a novel peptide-denoted as a dual-functional conjugate of antigenic peptide and Fc-III mimetics (DCAF)-for targeted blocking of antibodies. Synthesis of DCAF was achieved by native chemical ligation, and the molecule consists of three functional parts: a specific antigenic peptide, a linker and the Fc-III mimetic peptide, which has a high affinity toward the Fc region of IgG molecules.

M281, an Anti-FcRn Antibody: Pharmacodynamics, Pharmacokinetics, and Safety Across the Full Range of IgG Reduction in a First-in-Human Study.

M281 is a fully human, anti-neonatal Fc receptor (FcRn) antibody that inhibits FcRn-mediated immunoglobulin G (IgG) recycling to decrease pathogenic IgG while preserving IgG production. A randomized, double-blind, placebo-controlled, first-in-human study with 50 normal healthy volunteers was designed to probe safety and the physiological maximum for reduction of IgG. Intravenous infusion of single ascending doses up to 60 mg/kg induced dose-dependent serum IgG reductions, which were similar across all IgG subclasses.

Correlation of Synaptic Inputs in the Visual Cortex of Awake, Behaving Mice.

The subthreshold mechanisms that underlie neuronal correlations in awake animals are poorly understood. Here, we perform dual whole-cell recordings in the visual cortex (V1) of awake mice to investigate membrane potential (Vm) correlations between upper-layer sensory neurons. We find that the membrane potentials of neighboring neurons display large, correlated fluctuations during quiet wakefulness, including pairs of cells with disparate tuning properties.

[Multiple myeloma in systemic lupus erythematosus. Report of two cases].

There is an increased incidence of hematological malignancies, particularly non-Hodgkin lymphoma (NHL) in systemic lupus erythematosus (SLE). In contrast, the concurrence with Multiple Myeloma (MM) is very rare, and the possible pathogenetic mechanisms underlying this association remain unclear. We report two patients who developed MM 15 and four years after being diagnosed as having SLE.

GATA4 Directly Regulates Expression and Osteoblast Differentiation.

GATA4 is a zinc-finger transcription factor that is a pioneer factor in various tissues and regulates tissue-specific gene regulation. In vivo deletion of using Cre-recombinase under the control of the 2.3 kb promoter showed significantly reduced values for trabecular bone properties by microCT analysis of femur and tibia of 14-week-old male and female mice, suggesting GATA4 is necessary for maintaining normal adult bone phenotype.

Role of HLA-DR Alleles to Increase Genetic Susceptibility to Onychomycosis in Nail Psoriasis.

Background: Patients with nail psoriasis have an increased risk of onychomycosis. Previous studies suggest it may be due to structural changes of the nails. However, a genetic predisposition seems to be also at play.

Induced cytotoxic damage by exposure to gasoline vapors: a study in Sinaloa, Mexico.

Gasoline is a blend of organic compounds used in internal combustion engines. Gasoline-station attendants are exposed to gasoline vapors, which pose a potentially mutagenic risk. According to the International Agency for Research on Cancer, exposure to gasoline and engine exhaust is possibly carcinogenic to humans.

Acetylation of bacterial cellulose catalyzed by citric acid: Use of reaction conditions for tailoring the esterification extent.

Bacterial cellulose (BC) nanoribbons were partially acetylated by a simple direct solvent-free route catalyzed by citric acid. The assay of reaction conditions within chosen intervals (i.e.

Nonlinearity-induced synchronization enhancement in micromechanical oscillators.

An autonomous oscillator synchronizes to an external harmonic force only when the forcing frequency lies within a certain interval-known as the synchronization range-around the oscillator's natural frequency. Under ordinary conditions, the width of the synchronization range decreases when the oscillation amplitude grows, which constrains synchronized motion of micro- and nanomechanical resonators to narrow frequency and amplitude bounds. Here, we show that nonlinearity in the oscillator can be exploited to manifest a regime where the synchronization range increases with increasing oscillation amplitude.