An Amperometric Sensor with Anti-Fouling Properties for Indicating Xylazine Adulterant in Beverages.

Amperometric electrochemical sensing schemes, which are easily fabricated and can directly relate measured current with analyte concentrations, remain a promising strategy for the development of the portable, in situ detection of commonly employed adulterants. Xylazine (XYL) is a non-narcotic compound designed for veterinary use as a sedative known as Rompun. XYL is increasingly being abused as a recreational drug, as an opioid adulterant and, because of its chemical properties, has found unfortunate prominence as a date rape drug spiked into beverages.

Fouling-Resistant Voltammetric Xylazine Sensors for Detection of the Street Drug "Tranq".

As the opioid crisis continues to wreak havoc on a global scale, it is increasingly critical to develop methodologies to detect the most dangerous drugs such as fentanyl and its derivatives, which have orders of magnitude higher potency than morphine. The scientific challenge for chemical detection of fentanyl and its derivatives is complicated by both the constantly increasing synthetic variations of the drug as well as the expanded use of adulterants. One tragically consequential example is the nocuous street drug known as "Tranq", which combines fentanyl or a fentanyl derivative with the veterinary sedative Rompun, chemically identified as xylazine (XYL).

Electronic Monitoring of Mom's Schedule (eMOMS™): A Feasibility Randomized Controlled Trial Targeting Postpartum Weight Retention and Breastfeeding Duration Among Populations With Overweight/Obesity.

Background: Globally, rising trends in gestational diabetes and body mass index contribute to maternal and neonatal morbidity and mortality. Lifestyle modifications and breastfeeding may reverse this effect, although few studies combine these into one intervention.

Research Aims: To measure postpartum weight retention, breastfeeding duration, hemoglobin A1C, and mean arterial blood pressure at 6 months postpartum among women with elevated pre-pregnancy body mass index.

Angiotensin-II drives changes in microglia-vascular interactions in rats with heart failure.

Activation of microglia, the resident immune cells of the central nervous system, leading to the subsequent release of pro-inflammatory cytokines, has been linked to cardiac remodeling, autonomic disbalance, and cognitive deficits in heart failure (HF). While previous studies emphasized the role of hippocampal Angiotensin II (AngII) signaling in HF-induced microglial activation, unanswered mechanistic questions persist. Evidence suggests significant interactions between microglia and local microvasculature, potentially affecting blood-brain barrier integrity and cerebral blood flow regulation.

Impaired oxytocin signalling in the central amygdala in rats with chronic heart failure.

Heart failure (HF) patients suffer from cognitive decline and mood impairments, but the molecular signals and brain circuits underlying these effects remain elusive. The hypothalamic neuropeptide oxytocin (OT) is critically involved in regulating mood, and OTergic signalling in the central amygdala (CeA) is a key mechanism that controls emotional responses including anxiety-like behaviours. Still, whether an altered OTergic signalling contributes to mood disorders in HF remains unknown.

Endoplasmic Reticulum and Mitochondrial Calcium Handling Dynamically Shape Slow Afterhyperpolarizations in Vasopressin Magnocellular Neurons.

Many neurons including vasopressin (VP) magnocellular neurosecretory cells (MNCs) of the hypothalamic supraoptic nucleus (SON) generate afterhyperpolarizations (AHPs) during spiking to slow firing, a phenomenon known as spike frequency adaptation. The AHP is underlain by Ca-activated K currents, and while slow component (sAHP) features are well described, its mechanism remains poorly understood. Previous work demonstrated that Ca influx through N-type Ca channels is a primary source of sAHP activation in SON oxytocin neurons, but no obvious channel coupling was described for VP neurons.

Blood flows from the SCN toward the OVLT within a new brain vascular portal pathway.

The suprachiasmatic nucleus (SCN) sets the phase of oscillation throughout the brain and body. Anatomical evidence reveals a portal system linking the SCN and the organum vasculosum of the lamina terminalis (OVLT), begging the question of the direction of blood flow and the nature of diffusible signals that flow in this specialized vasculature. Using a combination of anatomical and in vivo two-photon imaging approaches, we unequivocally show that blood flows unidirectionally from the SCN to the OVLT, that blood flow rate displays daily oscillations with a higher rate at night than in the day, and that circulating vasopressin can access portal vessels.

A vasopressin circuit that modulates mouse social investigation and anxiety-like behavior in a sex-specific manner.

One of the largest sex differences in brain neurochemistry is the expression of the neuropeptide arginine vasopressin (AVP) within the vertebrate brain, with males having more AVP cells in the bed nucleus of the stria terminalis (BNST) than females. Despite the long-standing implication of AVP in social and anxiety-like behaviors, the circuitry underlying AVP's control of these behaviors is still not well defined. Using optogenetic approaches, we show that inhibiting AVP BNST cells reduces social investigation in males, but not in females, whereas stimulating these cells increases social investigation in both sexes, but more so in males.

Angiotensin-II drives changes in microglia-vascular interactions in rats with heart failure.

Activation of microglia, the resident immune cells of the central nervous system, leading to the subsequent release of pro-inflammatory cytokines, has been linked to cardiac remodeling, autonomic disbalance, and cognitive deficits in heart failure (HF). While previous studies emphasized the role of hippocampal Angiotensin II (AngII) signaling in HF-induced microglial activation, unanswered mechanistic questions persist. Evidence suggests significant interactions between microglia and local microvasculature, potentially affecting blood-brain barrier integrity and cerebral blood flow regulation.

Tonic NMDAR Currents of NR2A-Containing NMDARs Represent Altered Ambient Glutamate Concentration in the Supraoptic Nucleus.

NMDA receptors (NMDARs) modulate glutamatergic excitatory tone in the brain via two complementary modalities: a phasic excitatory postsynaptic current and a tonic extrasynaptic modality. Here, we demonstrated that the tonic NMDAR-current ( ) mediated by NR2A-containing NMDARs is an efficient biosensor detecting the altered ambient glutamate level in the supraoptic nucleus (SON). of magnocellular neurosecretory cells (MNCs) measured by nonselective NMDARs antagonist, AP5, at holding potential ( ) -70 mV in low concentration of ECF Mg ([Mg]) was transiently but significantly increased 1-week post induction of a DOCA salt hypertensive model rat which was compatible with that induced by a NR2A-selective antagonist, PEAQX ( ) in both DOCA-HO and DOCA-salt groups.

Impaired oxytocin signaling in the central amygdala in rats with chronic heart failure.

Aims: Heart failure (HF) patients often suffer from cognitive decline, depression, and mood impairments, but the molecular signals and brain circuits underlying these effects remain elusive. The hypothalamic neuropeptide oxytocin (OT) is critically involved in the regulation of mood, and OTergic signaling in the central amygdala (CeA) is a key mechanism controlling emotional responses including anxiety-like behaviors. Based on this, we used in this study a well-established ischemic rat HF model and aimed to study alterations in the hypothalamus-to-CeA OTergic circuit.

Changes in neuropeptide large dense core vesicle trafficking dynamics contribute to adaptive responses to a systemic homeostatic challenge.

Neuropeptides are packed into large dense core vesicles (LDCVs) that are transported from the soma out into their processes. Limited information exists regarding mechanisms regulating LDCV trafficking, particularly during challenges to bodily homeostasis. Addressing this gap, we used 2-photon imaging in an preparation to study LDCVs trafficking dynamics in vasopressin (VP) neurons, which traffic and release neuropeptide from their dendrites and axons.

Raspberry polyphenols target molecular pathways of heart failure.

Approximately 650,000 new cases of heart failure (HF) are diagnosed annually with a 50% five-year mortality rate. HF is characterized by reduced left ventricular (LV) ejection fraction and hypertrophy of the LV wall. The pathophysiological remodeling of the heart is mediated by increased oxidative stress and inflammation.

A risk factor profile for placenta accreta spectrum in pregnancies conceived with assisted reproductive technology.

Objective: To identify independent risk factors for placenta accreta spectrum among pregnancies conceived with assisted reproductive technology.

Design: Retrospective cohort study.

Setting: Tertiary hospital.

Angiotensin II-Mediated Neuroinflammation in the Hippocampus Contributes to Neuronal Deficits and Cognitive Impairment in Heart Failure Rats.

Background: Heart failure (HF) is a debilitating disease affecting >64 million people worldwide. In addition to impaired cardiovascular performance and associated systemic complications, most patients with HF suffer from depression and substantial cognitive decline. Although neuroinflammation and brain hypoperfusion occur in humans and rodents with HF, the underlying neuronal substrates, mechanisms, and their relative contribution to cognitive deficits in HF remains unknown.

Microgeometrical dendritic factors predict electrical decoupling between somatic and dendritic compartments in magnocellular neurosecretory neurons.

It is generally assumed that dendritic release of neuropeptides from magnocellular neurosecretory neurons (MNNs), a critical process involved in homeostatic functions, is an activity-dependent process that requires backpropagating action potentials (APs). Still, growing evidence indicates that dendritic release can occur in the absence of APs, and axonal APs have been shown to fail to evoke dendritic release. These inconsistencies strongly suggest that APs in MNNs may fail to backpropagating into dendrites.

Examining attention-deficit/hyperactivity disorder and related behavioral disorders by fertility treatment exposure in a prospective cohort.

Purpose: To evaluate whether underlying infertility and mode of conception are associated with childhood behavioral disorders.

Methods: Oversampling on fertility treatment exposure using vital records, the Upstate KIDS Study followed 2057 children (of 1754 mothers) from birth to 11 years. Type of fertility treatment and time to pregnancy (TTP) were self-reported.

Parallel trajectories in the discovery of the SCN-OVLT and pituitary portal pathways: Legacies of Geoffrey Harris.

A map of central nervous system organization based on vascular networks provides a layer of organization distinct from familiar neural networks or connectomes. As a well-established example, the capillary networks of the pituitary portal system enable a route for small amounts of neurochemical signals to reach local targets by traveling along specialized pathways, thereby avoiding dilution in the systemic circulation. The first evidence of such a pathway in the brain came from anatomical studies identifying a portal pathway linking the hypothalamus and the pituitary gland.

An analgesic pathway from parvocellular oxytocin neurons to the periaqueductal gray in rats.

The hypothalamic neuropeptide oxytocin (OT) exerts prominent analgesic effects via central and peripheral action. However, the precise analgesic pathways recruited by OT are largely elusive. Here we discovered a subset of OT neurons whose projections preferentially terminate on OT receptor (OTR)-expressing neurons in the ventrolateral periaqueductal gray (vlPAG).

Assisted Reproductive Technology or Infertility: What underlies adverse outcomes? Lessons from the Massachusetts Outcome Study of Assisted Reproductive Technology.

Numerous studies have demonstrated that assisted reproductive technology (ART: defined here as including only fertilization and related technologies) is associated with increased adverse pregnancy, neonatal, and childhood developmental outcomes, even in singletons. The comparison group for many had often been a fertile population that conceived without assistance. The Massachusetts Outcome Study of Assisted Reproductive Technology (MOSART) was initiated to define a subfertile population with which to compare ART outcomes.

Analysis of the hypothalamic oxytocin system and oxytocin receptor-expressing astrocytes in a mouse model of Prader-Willi syndrome.

Prader-Willi syndrome (PWS) is a neurodevelopmental disorder characterized by hyperphagia, obesity, developmental delay and intellectual disability. Studies suggest dysfunctional signaling of the neuropeptide oxytocin as one of the key mechanisms in PWS, and administration of oxytocin via intranasal or systemic routes yielded promising results in both humans and mouse models. However, a detailed assessment of the oxytocin system in mouse models of PWS such as the Magel2-deficient Magel2 mouse, is lacking.

Hypothalamic astrocytes control systemic glucose metabolism and energy balance.

The hypothalamus is key in the control of energy balance. However, strategies targeting hypothalamic neurons have failed to provide viable options to treat most metabolic diseases. Conversely, the role of astrocytes in systemic metabolic control has remained largely unexplored.

Polycystic ovary syndrome and risk of adverse pregnancy outcomes: a registry linkage study from Massachusetts.

Study Question: Do women with polycystic ovary syndrome (PCOS) have a greater risk of adverse pregnancy complications (gestational diabetes, preeclampsia, cesarean section, placental abnormalities) and neonatal outcomes (preterm birth, small for gestational age, prolonged delivery hospitalization) compared to women without a PCOS diagnosis and does this risk vary by BMI, subfertility and fertility treatment utilization?

Summary Answer: Deliveries to women with a history of PCOS were at greater risk of complications associated with cardiometabolic function, including gestational diabetes and preeclampsia, as well as preterm birth and prolonged length of delivery hospitalization.

What Is Known Already: Prior research has suggested that women with PCOS may be at increased risk of adverse pregnancy outcomes. However, findings have been inconsistent possibly due to lack of consistent adjustment for confounding factors, small samples size and other sources of bias.