Multitargeting Pt(IV) Derivatives of Cisplatin or Oxaliplatin Inhibit Tumor Growth in Mice without Inducing Neuropathic Pain.

Cisplatin and oxaliplatin are Pt(II) anticancer agents that are used to treat several cancers, usually in combination with other drugs. Their efficacy is diminished by dose-limiting peripheral neuropathy (PN) that affects ∼70% of patients. PN is caused by selective accumulation of the platinum drugs in the dorsal root ganglia (DRG), which overexpress transporters for cisplatin and oxaliplatin.

Glycemic control contributes to the neuroprotective effects of Mediterranean and green-Mediterranean diets on brain age: the DIRECT PLUS brain-magnetic resonance imaging randomized controlled trial.

Background: We recently reported that Mediterranean (MED) and green-MED diets significantly attenuated age-related brain atrophy by ∼50% within 18 mo.

Objective: The objective of this study was to explore the contribution of specific diet-induced parameters to brain-volume deviation from chronologic age.

Methods: A post hoc analysis of the 18-mo DIRECT PLUS trial, where participants were randomly assigned to the following groups: 1) healthy dietary guidelines, 2) MED diet, or 3) green-MED diet, high in polyphenols, and low in red meat.

Age-dependent decrease in inhibitory drive on the excitatory superficial spinal dorsal horn neurons.

The excitatory and inhibitory interneurons of superficial laminae I-II of the spinal dorsal horn (SDH) receive and process pain-related information from the primary afferents and transmit it to the brain via the projection neurons. Thus, the interaction between excitatory and inhibitory SDH interneurons is crucial in determining the output from the spinal cord network. Disruption of this interaction in pathological conditions leads to increased SDH output to the higher brain centers, which could underlie pathological pain.

Kinesin family member 2A gates nociception.

Nociceptive axons undergo remodeling as they innervate their targets during development and in response to environmental insults and pathological conditions. How is nociceptive morphogenesis regulated? Here, we show that the microtubule destabilizer kinesin family member 2A (Kif2a) is a key regulator of nociceptive terminal structures and pain sensitivity. Ablation of Kif2a in sensory neurons causes hyperinnervation and hypersensitivity to noxious stimuli in young adult mice, whereas touch sensitivity and proprioception remain unaffected.

Epidural Analgesia for Labour: Comparing the Effects of Continuous Epidural Infusion (CEI) and Programmed Intermittent Epidural Bolus (PIEB) on Obstetric Outcomes.

Objective: In the last few years there is a trend of transiting from the continuous epidural infusion (CEI) method for epidural analgesia to a new method - programmed intermittent epidural analgesia (PIEB). This change improves the quality of epidural analgesia, thanks to an increased spread of the anaesthetic in the epidural space and higher maternal satisfaction. Nevertheless, we must make sure that such change of method does not lead to worse obstetric and neonatal outcomes.

Neonatal intensive care admission for term neonates and subsequent childhood mortality: a retrospective linkage study.

Background: Neonatal intensive care unit (NICU) admission among term neonates is a rare event. The aim of this study was to study the association of the NICU admission of term neonates on the risk of long-term childhood mortality.

Methods: A single-center case-control retrospective study between 2005 and 2019, including all in-hospital ≥ 37 weeks' gestation singleton live-born neonates.

Efficacy of oral versus long-acting antipsychotic treatment in patients with early-phase schizophrenia in Europe and Israel: a large-scale, open-label, randomised trial (EULAST).

Background: Schizophrenia is a severe psychiatric disorder with periods of remission and relapse. As discontinuation of antipsychotic medication is the most important reason for relapse, long-term maintenance treatment is key. Whether intramuscular long-acting (depot) antipsychotics are more efficacious than oral medication in preventing medication discontinuation is still unresolved.

Structural plasticity of axon initial segment in spinal cord neurons underlies inflammatory pain.

Physiological or pathology-mediated changes in neuronal activity trigger structural plasticity of the action potential generation site-the axon initial segment (AIS). These changes affect intrinsic neuronal excitability, thus tuning neuronal and overall network output. Using behavioral, immunohistochemical, electrophysiological, and computational approaches, we characterized inflammation-related AIS plasticity in rat's superficial (lamina II) spinal cord dorsal horn (SDH) neurons and established how AIS plasticity regulates the activity of SDH neurons, thus contributing to pain hypersensitivity.

Does ultrasound guidance during dilation and curettage for first trimester missed abortion reduce complication rates?

Background: Dilation and curettage (D&C) may be performed with or without transabdominal ultrasound guidance. The aim of this study was to evaluate the association between the use of ultrasound guidance during D&C for first trimester missed abortion (MA) and D&C related complication rates.

Methods: A retrospective cohort study included women in the age of 20-45 years, who underwent D&C for first-trimester MA in a hospital-based setting between 2013-2019.

Encoding of inflammatory hyperalgesia in mouse spinal cord.

Inflammation modifies the input-output properties of peripheral nociceptive neurons such that the same stimulus produces enhanced nociceptive firing. This increased nociceptive output enters the superficial dorsal spinal cord (SDH), an intricate neuronal network composed largely of excitatory and inhibitory interneurons and a small percentage of projection neurons. The SDH network comprises the first central nervous system network integrating noxious information.

Application of Prospect Theory in Obstetrics by Evaluating Mode of Delivery and Outcomes in Neonates Born Small or Appropriate for Gestational Age.

Importance: Antenatal diagnosis of fetal weight is challenging, and the detection rate of fetal growth restriction (FGR) is low. Neonates with FGR are known to have an increased rate of obstetric intervention during labor, but the association of antenatal fetal weight estimation with mode of delivery and neonatal outcomes among neonates who are small and appropriate for gestational age (SGA and AGA) has not been reported.

Objective: To evaluate the association of antenatal fetal weight estimation with mode of delivery and neonatal outcomes among neonates who are SGA and AGA, applying psychological concepts of cognitive bias and prospect theory to a model of clinical behavior.

Long-Standing Corneal Edema and Endothelial Decompensation due to Ecballium elaterium.

Purpose: The purpose of this study was to report the most severe documented ocular injury caused by Ecballium elaterium , an invasive and toxic herb characterized by an explosive seed dispersal.

Methods: A 55-year-old man presented to the emergency department several hours after direct exposure to the contents of E. elaterium to his left eye.

Primary risk stratification for neonatal jaundice among term neonates using machine learning algorithm.

Background: Neonatal jaundice occurs in approximately 60% of term newborns. Although risk factors for neonatal jaundice have been studied, all the suggested strategies are based on various newborn tests for bilirubin levels. We aim to stratify neonates into risk groups for clinically significant neonatal jaundice using a combined data analysis approach, without serum bilirubin evaluation.

The effect of a high-polyphenol Mediterranean diet (Green-MED) combined with physical activity on age-related brain atrophy: the Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed Study (DIRECT PLUS).

Background: The effect of diet on age-related brain atrophy is largely unproven.

Objectives: We aimed to explore the effect of a Mediterranean diet (MED) higher in polyphenols and lower in red/processed meat (Green-MED diet) on age-related brain atrophy.

Methods: This 18-mo clinical trial longitudinally measured brain structure volumes by MRI using hippocampal occupancy score (HOC) and lateral ventricle volume (LVV) expansion score as neurodegeneration markers.

Anxiety and pain perception using a speculum-free eyelid retraction technique for intravitreal injection.

Purpose: This study compared pain and anxiety levels in individuals receiving intravitreal injections (IVIs) using a speculum-free injection technique, the lid splinting eyelid retraction technique, or using a speculum.

Methods: This was a prospective study of individuals receiving IVI at a single tertiary care medical center who responded to a questionnaire and visual analog scale (VAS) between December 2019 and January 2020. In one group, a speculum was used prior to injection, whereas in the other group, a speculum-free injection technique was used.

Effect of Music Selection on Anxiety Level during Intravitreal Injections for Individuals of Varying Cultures.

Purpose: To investigate music selection as a treatment for anxiety during Intravitreal injections (IVI) for individuals of varying cultures.

Methods: 106 individuals were enrolled in this randomized controlled study. Individuals were randomized into one to three categories: (1) a control group in which the IVI procedure was performed without music (n = 35), (2) an experimental group in which the music was selected by the physician (n = 36), (3) an experimental group in which the music was selected by the patient (n = 35).

Muscarinic regulation of the neuronal Na /K -ATPase in rat hippocampus.

Key Points: Stimulation of postsynaptic muscarinic receptors was shown to excite principal hippocampal neurons by modulating several membrane ion conductances. We show here that activation of postsynaptic muscarinic receptors also causes neuronal excitation by inhibiting Na /K -ATPase activity. Muscarinic Na /K -ATPase inhibition is mediated by two separate signalling pathways that lead downstream to enhanced Na /K -ATPase phosphorylation by activating protein kinase C and protein kinase G.

Polycations and polyanions in SARS-CoV-2 infection.

We hypothesize that polycations, such as nuclear histones, released by neutrophils COVID-19 aggravate COVID-19 by multiple mechanisms: (A) Neutralization of the electrostatic repulsion between the virus particles and the cell membrane, thereby enhancing receptor-mediated entry. (B) Binding to the virus particles, thereby inducing opsonin-mediated endocytosis. (C) Adding to the cytotoxicity, in conjunction with oxidants, cytokines and other pro-inflammatory substances secreted by cells of the innate immunity system.

The Impact of COVID-19 on Intravitreal Injection Compliance.

Intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF) agents have become the most prevalent intraocular procedure as they represent the major therapeutic modality for prevalent retinal conditions such as age-related macular degeneration (AMD) and diabetic retinopathy. Effective therapy requires adherence to a schedule of iterative IVI as well as routine clinic appointments. The ongoing coronavirus disease 2019 (COVID-19) pandemic has resulted in the reduction of attendance at scheduled clinic visits and IVI.

The Input-Output Relation of Primary Nociceptive Neurons is Determined by the Morphology of the Peripheral Nociceptive Terminals.

The output from the peripheral terminals of primary nociceptive neurons, which detect and encode the information regarding noxious stimuli, is crucial in determining pain sensation. The nociceptive terminal endings are morphologically complex structures assembled from multiple branches of different geometry, which converge in a variety of forms to create the terminal tree. The output of a single terminal is defined by the properties of the transducer channels producing the generation potentials and voltage-gated channels, translating the generation potentials into action potential (AP) firing.

Ocular involvement in coronavirus disease 2019 (COVID-19): a clinical and molecular analysis.

Purpose: Coronavirus disease 2019 (COVID-19) caused a global pandemic with millions infected worldwide. Little is known on the ocular involvement associated with the disease. The aim of this study was to assess the clinical and molecular ocular involvement among patients with confirmed COVID-19 admitted to a tertiary care facility.

Intrapartum fetal monitoring and perinatal risk factors of neonatal hypoxic-ischemic encephalopathy.

Background: Neonatal hypoxic-ischemic encephalopathy (HIE) in term infants, is a major cause of neonatal mortality and severe neurologic disability.

Objectives: To identify in labor fetal monitoring characteristic patterns and perinatal factors associated with neonatal HIE.

Study Design: Single-center retrospective case-control study between 2010 and 2017.

Choriocapillaris flow deficit associated with intraretinal hyperreflective foci in intermediate age-related macular degeneration.

Purpose: To evaluate the choriocapillaris (CC) flow deficit (FD) beneath drusen associated with overlying intraretinal hyperreflective foci (HRF).

Methods: Patients with intermediate age-related macular degeneration (AMD) who had structural spectral-domain optical coherence tomography (SD-OCT) and OCT angiography (OCTA) using the Cirrus HD-OCT with AngioPlex software were retrospectively evaluated. A 6 × 6-mm-volume scan was used for the SD-OCT and OCTA.