Efficacy, Indications, and Safety of Intrathecal Baclofen Pump: A Narrative Review.

Purpose Of Review: Baclofen, a muscle relaxant that reduces the release of excitatory neurotransmitters in the pre-synaptic neurons stimulating inhibitory neuronal signals in post-synaptic neurons, has been around for over 5 decades. Baclofen is used primarily for spasticity and since 1982, has had a role as an intrathecal agent. In the present investigation, we review research trends and updates on safety and efficacy of intrathecal baclofen (ITB) pumps.

Validation Assessment of Privacy-Preserving Synthetic Electronic Health Record Data: Comparison of Original Versus Synthetic Data on Real-World COVID-19 Vaccine Effectiveness.

Purpose: To assess the validity of privacy-preserving synthetic data by comparing results from synthetic versus original EHR data analysis.

Methods: A published retrospective cohort study on real-world effectiveness of COVID-19 vaccines by Maccabi Healthcare Services in Israel was replicated using synthetic data generated from the same source, and the results were compared between synthetic versus original datasets. The endpoints included COVID-19 infection, symptomatic COVID-19 infection and hospitalization due to infection and were also assessed in several demographic and clinical subgroups.

Implementation of medication for opioid use disorder treatment during a natural disaster: The PROUD-LA study.

Background: The impacts of climate change-related extreme weather events (EWEs) on Medication for Opioid Use Disorders (MOUD) implementation for Medicaid beneficiaries are relatively unknown. Such information is critical to disaster planning and other implementation strategies. In this study we examined implementation determinants and strategies for MOUD during EWEs.

Macrophage Migration Inhibitory Factor Promotes Thromboinflammation and Predicts Fast Progression of Aortic Stenosis.

Background: Aortic stenosis (AS) is driven by progressive inflammatory and fibrocalcific processes regulated by circulating inflammatory and valve resident endothelial and interstitial cells. The impact of platelets, platelet-derived mediators, and platelet-monocyte interactions on the acceleration of local valvular inflammation and mineralization is presently unknown.

Methods: We prospectively enrolled 475 consecutive patients with severe symptomatic AS undergoing aortic valve replacement.

Extracorporeal membrane oxygenation aggravates platelet glycoprotein V shedding and δ-granule deficiency in COVID-19-associated acute respiratory distress syndrome.

Background: Extracorporeal membrane oxygenation (ECMO) is a lifesaving therapy in patients with acute respiratory distress syndrome (ARDS). Hemostatic complications are frequently observed in patients on ECMO and limit the success of this therapy. Platelets are key mediators of hemostasis enabling activation, aggregation, and thrombus formation by coming in contact with exposed matrix proteins via their surface receptors such as glycoprotein (GP) VI or GPIb/V/IX.

Utility of parentage-based tagging for monitoring Coho salmon () in the interior Columbia River basin.

By the 1980s, after decades of declining numbers in the mid-1900s, Coho salmon () were considered extirpated from the interior Columbia River. In the mid-1990s, the Confederated Tribes of the Umatilla Indian Reservation, the Confederated Tribes and Bands of the Yakama Nation, and the Nez Perce Tribe began successful reintroduction programs of Coho salmon upstream of Bonneville Dam, but which were initially sourced from lower Columbia River hatcheries. Here we present the first Coho salmon parentage-based tagging (PBT) baseline from seven hatchery programs located in the interior Columbia River basin, and two sites at or downstream of Bonneville Dam, composed of over 32,000 broodstock samples.

Binding of herpesvirus entry mediator (HVEM) and HSV-1 gD affect reactivation but not latency levels.

Previously we reported that the HSV-1 latency associated transcript (LAT) specifically upregulates the cellular herpesvirus entry mediator (HVEM) but no other known HSV-1 receptors. HSV-1 glycoprotein D (gD) binds to HVEM but the effect of this interaction on latency-reactivation is not known. We found that the levels of latent viral genomes were not affected by the absence of gD binding to HVEM.

Thrombocytopenia Absent Radius (TAR)-Syndrome: From Current Genetics to Patient Self-Empowerment.

Thrombocytopenia absent radius (TAR) syndrome is a rare form of hereditary thrombocytopenia associated with a bilateral radial aplasia. TAR syndrome is genetically defined by the combination of a microdeletion on chromosome 1 which includes the gene , and a single nucleotide polymorphism (SNP) in the second allele. While most patients with TAR syndrome harbor a SNP in either the 5' UTR region or in intron 1 of , further SNPs associated with TAR syndrome are still being identified.

State-of-the-Art Targeted High-Throughput Sequencing for Detecting Inherited Platelet Disorders.

Inherited platelet disorders (IPDs) are a heterogeneous group of rare entities caused by molecular divergence in genes relevant for platelet formation and function. A rational diagnostic approach is necessary to counsel and treat patients with IPDs. With the introduction of high-throughput sequencing at the beginning of this millennium, a more accurate diagnosis of IPDs has become available.

Loss of zinc transporters ZIP1 and ZIP3 augments platelet reactivity in response to thrombin and accelerates thrombus formation .

Zinc (Zn) is considered as important mediator of immune cell function, thrombosis and haemostasis. However, our understanding of the transport mechanisms that regulate Zn homeostasis in platelets is limited. Zn transporters, ZIPs and ZnTs, are widely expressed in eukaryotic cells.

Isolation, In Vitro Differentiation, and Culture of Murine Megakaryocytes From Fetal Liver and Adult Bone Marrow.

Megakaryocytes (MKs) are the source of circulating platelets and are readily recognized by their large size and distinctive morphology. Their poor representation in hematopoietic tissues often requires enrichment or considerable ex vivo expansion to generate cells for biochemical and cell biological studies. These experimental protocols describe the enrichment of primary MKs directly from the murine bone marrow as well as in vitro differentiation of fetal liver- or bone marrow-derived hematopoietic stem cells into MKs.

Contribution of Comorbid Conditions to the Diagnosis of Insomnia: A Database Study in a Commercially Insured Population.

Insomnia is a common sleep disorder characterized as dissatisfaction with sleep quantity or quality resulting in distress or impairment of social, occupational, or other daily functioning. It is unknown if there are medical conditions that have strong associations with insomnia but are unrecognized in previous literature. In this cross-sectional study based on IBM Marketscan Research Databases, we measured insomnia and 78 medical conditions in patients with 2-year continuous enrollment during 2018-2019.

Ontogenesis of functional platelet subpopulations from preterm and term neonates to adulthood: The PLINIUS study.

Erythrocytes undergo a well-defined switch from fetal to postnatal circulation, which is mainly reflected by the stage-specific expression of hemoglobin chains. Perinatal alterations in thrombopoiesis are poorly understood. We assessed the ontogenesis of platelet phenotype and function from early prematurity to adulthood.

Rapid isolation of mature murine primary megakaryocytes by size exclusion via filtration.

Megakaryocytes (MKs), the largest and rarest cells of the hematopoietic system, differentiate by increasing their size, DNA and cytoplasmic contents during maturation in order to release high numbers of blood platelets into the circulation. The gold-standard to study these complex cells is the isolation of primary MKs from the native bone marrow (BM). This is typically achieved by using fluorescence- or magnetic-activated cell sorting.

Stomatal patchiness and cellular computing.

Control of carbon dioxide and water vapor exchange between a leaf's interior and the surrounding air is accomplished by variations in the turgor pressures in the small epidermal and guard cells that cover the leaf's surface. These pressures respond to changes in light intensity and wavelength, temperature, CO concentration, and air humidity. The dynamical equations that describe such processes are formally identical to those that define computation in a two-layer, adaptive, cellular nonlinear network.

Uncoupling of platelet granule release and integrin activation suggests GPIIb/IIIa as a therapeutic target in COVID-19.

Thromboembolic events are frequent and life-threating complications of COVID-19 but are also observed in patients with sepsis. Disseminated thrombosis can occur despite anticoagulation, suggesting that platelets play a direct but incompletely understood role. Several studies demonstrated altered platelet function in COVID-19 with some controversial findings, while underlying disease-specific mechanisms remain ill defined.

Impaired microtubule dynamics contribute to microthrombocytopenia in RhoB-deficient mice.

Megakaryocytes are large cells in the bone marrow that give rise to blood platelets. Platelet biogenesis involves megakaryocyte maturation, the localization of the mature cells in close proximity to bone marrow sinusoids, and the formation of protrusions, which are elongated and shed within the circulation. Rho GTPases play important roles in platelet biogenesis and function.

"Hurry up and wait": Stigma, Poverty, and Contractual Citizenship.

The emergence of welfare contractualism in the United States in the 1970s marked a shift from viewing welfare as an entitlement to viewing welfare as a right to be earned through work. Combined with the continual degradation of labor markets since the 1970s, the rise of neoliberal ideology emphasizing individualism, and the passage of the 1996 Personal Responsibility and Work Opportunity Reconciliation Act, the devolved welfare system - most often managed by a myriad of social service nonprofits - has exacerbated the difficulties of the poor. Scholars have noted, for instance, the loss of civil rights and the proliferation of administrative burdens - including incessant waiting - with which poor people seeking aid are increasingly faced.

Small Noncoding RNA (sncRNA1) within the Latency-Associated Transcript Modulates Herpes Simplex Virus 1 Virulence and the Host Immune Response during Acute but Not Latent Infection.

The HSV-1 latency-associated transcript (LAT) locus contains two small noncoding RNA (sncRNA) sequences (sncRNA1 and sncRNA2) that are not microRNAs (miRNAs). We recently reported that sncRNA1 is more important for activation of the herpesvirus entry mediator than sncRNA2, but its function is not known. To determine the role, if any, of sncRNA1 during herpes simplex virus 1 (HSV-1) infection , we deleted the 62-bp sncRNA1 sequence in HSV-1 strain McKrae using dLAT2903 (LAT-minus) virus, creating ΔsncRNA1 recombinant virus.

G6b-B regulates an essential step in megakaryocyte maturation.

G6b-B is a megakaryocyte lineage-specific immunoreceptor tyrosine-based inhibition motif-containing receptor, essential for platelet homeostasis. Mice with a genomic deletion of the entire Mpig6b locus develop severe macrothrombocytopenia and myelofibrosis, which is reflected in humans with null mutations in MPIG6B. The current model proposes that megakaryocytes lacking G6b-B develop normally, whereas proplatelet release is hampered, but the underlying molecular mechanism remains unclear.

Interprofessional education in the clinical learning environment: a mixed-methods evaluation of a longitudinal experience in the primary care setting.

Team collaboration in our healthcare workforce is necessary to effectively address multifaceted medical and social needs, especially for those impacted by systemic inequities. Effective interprofessional practice and education models including curricula are needed to prepare a practice ready healthcare workforce for team collaboration. Most healthcare trainee interprofessional experiences take place episodically in classroom settings.