Anti-seizure therapy with a long-term, implanted intra-cerebroventricular delivery system for drug-resistant epilepsy: A first-in-man study.

Background: A clinical feasibility study was undertaken at a single center of long-term intra-cerebroventricular drug delivery of the anti-seizure medication valproic acid, into the cerebrospinal fluid (CSF) in order to treat drug resistant focal seizures, using an implantable infusion system. The primary objective was to establish the dose range of VPA administered in this manner. Secondarily, safety, pharmacokinetics (PK) and a preliminary estimate of effectiveness were evaluated.

Sex Differences in Oral Anticoagulation and Outcomes of Stroke and Intracranial Bleeding in Newly Diagnosed Atrial Fibrillation.

Background Female sex is an independent predictor of stroke in patients with atrial fibrillation (AF). Older data suggest undertreatment with anticoagulation among women compared with men. However, it is unknown if novel therapies and updated guidelines have impacted sex differences in AF treatment and outcomes.

Correlations of Calf Muscle Macrophage Content With Muscle Properties and Walking Performance in Peripheral Artery Disease.

Background Peripheral artery disease (PAD) is a manifestation of atherosclerosis characterized by reduced blood flow to the lower extremities and mobility loss. Preliminary evidence suggests PAD damages skeletal muscle, resulting in muscle impairments that contribute to functional decline. We sought to determine whether PAD is associated with an altered macrophage profile in gastrocnemius muscles and whether muscle macrophage populations are associated with impaired muscle phenotype and walking performance in patients with PAD.

Heterogeneity of Treatment and Outcomes Among Asians With Coronary Artery Disease in the United States.

Background Prior data demonstrate significant heterogeneity regarding coronary artery disease risk factors and outcomes among Asians in the United States, but no studies have yet examined coronary artery disease treatment patterns or outcomes among disaggregated Asian American subgroups. Methods and Results From a total of 772 882 patients with known race/ethnicity and sex who received care from a mixed-payer healthcare organization in Northern California between 2006 and 2015, a retrospective analysis was conducted on 6667 adults with coronary artery disease. Logistic regression was used to examine medical and procedural therapies and outcomes by race/ethnicity, with adjustment for age, sex, income, and baseline comorbidities.

Prognostic Implications of Early and Midrange Readmissions After Acute Heart Failure Hospitalizations: A Report From a Japanese Multicenter Registry.

Background Although 30-day readmission is thought to be an important quality indicator in patients with hospitalized heart failure, its prognostic impact and comparison of patients who were readmitted beyond 30 days has not been investigated. We assessed early (0-30 days) versus midrange (31-90 days) readmission in terms of incidence and distribution, and elucidated whether the timing of readmission could have a different prognostic significance. Methods and Results We examined patients with hospitalized heart failure registered in the WET-HF (West Tokyo Heart Failure) registry.

Long-term Outcome of Pulmonary Vein Isolation Versus Amiodarone Therapy in Patients with Coexistent Persistent AF and Congestive Heart Failure.

Although pharmacological rhythm control of AF in patients with heart failure with reduced ejection fraction (HFrEF) does not seem to provide any benefit over rate control, catheter ablation of AF has been shown to improve clinical outcomes. These results can be explained with higher success rates of catheter ablation in restoring and maintaining sinus rhythm compared with antiarrhythmic drugs. In addition, pharmacotherapy is not void of side-effects, which are thought to offset its potential antiarrhythmic benefits.

The use of platelet-rich plasma in treatment of olfactory dysfunction: A pilot study.

Background: Olfactory dysfunction is a prevalent problem with a significant impact on quality of life and increased mortality. Limited effective therapies exist. Platelet-rich plasma (PRP) is an autologous biologic product with anti-inflammatory and neuroprotective effects.

Single-Cell Encapsulation via Click-Chemistry Alters Production of Paracrine Factors from Neural Progenitor Cells.

Extracellular matrix (ECM) properties affect multiple cellular processes such as cell survival, proliferation, and protein synthesis. Thus, a polymeric-cell delivery system with the ability to manipulate the extracellular environment can act as a fundamental regulator of cell function. Given the promise of stem cell therapeutics, a method to uniformly enhance stem cell function, in particular trophic factor release, can prove transformative in improving efficacy and increasing feasibility by reducing the total number of cells required.

Outcomes and Care Quality Metrics for Women of Reproductive Age Living With Rheumatic Heart Disease in Uganda.

Background Rheumatic heart disease disproportionately affects women of reproductive age, as it increases the risk of cardiovascular complications and death during pregnancy and childbirth. In sub-Saharan Africa, clinical outcomes and adherence to guideline-based therapies are not well characterized for this population. Methods and Results In a retrospective cohort study of the Uganda rheumatic heart disease registry between June 2009 and May 2018, we used multivariable regression and Cox proportional hazards models to compare comorbidities, mortality, anticoagulation use, and treatment cascade metrics among women versus men aged 15 to 44 with clinical rheumatic heart disease.

Chemical control of competing electron transfer pathways in iron tetracyano-polypyridyl photosensitizers.

Photoinduced intramolecular electron transfer dynamics following metal-to-ligand charge-transfer (MLCT) excitation of [Fe(CN)(2,2'-bipyridine)] (), [Fe(CN)(2,3-bis(2-pyridyl)pyrazine)] () and [Fe(CN)(2,2'-bipyrimidine)] () were investigated in various solvents with static and time-resolved UV-Visible absorption spectroscopy and Fe 2p3d resonant inelastic X-ray scattering (RIXS). This series of polypyridyl ligands, combined with the strong solvatochromism of the complexes, enables the MLCT vertical energy to be varied from 1.64 eV to 2.

Atomic layer deposition of metal oxides for efficient perovskite single-junction and perovskite/silicon tandem solar cells.

Aluminum-doped and undoped zinc oxide films were investigated as potential front and rear contacts of perovskite single and perovskite/silicon tandem solar cells. The films were prepared by atomic layer deposition (ALD) at low (<200 °C) substrate temperatures. The deposited films were crystalline with a single-phase wurtzite structure and exhibit excellent uniformity and low surface roughness which was confirmed by XRD and SEM measurements.

Probing competing relaxation pathways in malonaldehyde with transient X-ray absorption spectroscopy.

Excited-state intramolecular hydrogen transfer (ESIHT) is a fundamental reaction relevant to chemistry and biology. Malonaldehyde is the simplest example of ESIHT, yet only little is known experimentally about its excited-state dynamics. Several competing relaxation pathways have been proposed, including internal conversion mediated by ESIHT and C[double bond, length as m-dash]C torsional motion as well as intersystem crossing.

Associations of Peripheral Artery Disease With Calf Skeletal Muscle Mitochondrial DNA Heteroplasmy.

Background Patients with peripheral artery disease (PAD) undergo frequent episodes of ischemia-reperfusion in lower extremity muscles that may negatively affect mitochondrial health and are associated with impaired mobility. We hypothesized that skeletal muscle from PAD patients will show high mitochondrial DNA heteroplasmy, especially in regions more susceptible to oxidative damage, such as the displacement loop, and that the degree of heteroplasmy will be correlated with the severity of ischemia and mobility impairment. Methods and Results Mitochondrial mutations and deletions and their relative abundance were identified by targeted mitochondrial DNA sequencing in biopsy specimens of gastrocnemius muscle from 33 PAD (ankle brachial index <0.

Cumulative Lifetime Burden of Cardiovascular Disease From Early Exposure to Air Pollution.

The disease burden associated with air pollution continues to grow. The World Health Organization (WHO) estimates ≈7 million people worldwide die yearly from exposure to polluted air, half of which-3.3 million-are attributable to cardiovascular disease (CVD), greater than from major modifiable CVD risks including smoking, hypertension, hyperlipidemia, and diabetes mellitus.

A Global Bibliometric Analysis of Services for Children Affected by HIV/AIDS: Implications for Impact Mitigation Programs (GAPRESEARCH).

Tremendous progress has been made over the past three decades in the fight against the HIV epidemic; however, children experienced substantial physical and psychosocial effects of HIV infection. To inform services and policy development, we analyzed research growth and current trends in studies on children with HIV/AIDS. A total of 17,598 research papers and reviews in English, which were published on Web of Science, were downloaded.

Alcoholics Anonymous and other 12-step programs for alcohol use disorder.

Background: Alcohol use disorder (AUD) confers a prodigious burden of disease, disability, premature mortality, and high economic costs from lost productivity, accidents, violence, incarceration, and increased healthcare utilization. For over 80 years, Alcoholics Anonymous (AA) has been a widespread AUD recovery organization, with millions of members and treatment free at the point of access, but it is only recently that rigorous research on its effectiveness has been conducted.

Objectives: To evaluate whether peer-led AA and professionally-delivered treatments that facilitate AA involvement (Twelve-Step Facilitation (TSF) interventions) achieve important outcomes, specifically: abstinence, reduced drinking intensity, reduced alcohol-related consequences, alcohol addiction severity, and healthcare cost offsets.

Voluntary Restoration: Mitigation's Silent Partner in the Quest to Reverse Coastal Wetland Loss in the USA.

Coastal ecosystems are under pressure from a vast array of anthropogenic stressors, including development and climate change, resulting in significant habitat losses globally Conservation policies are often implemented with the intent of reducing habitat loss. However, losses already incurred will require restoration if ecosystem functions and services are to be recovered. The United States has a long history of wetland loss and recognizes that averting loss requires a multi-pronged approach including mitigation for regulated activities and non-mitigation (voluntary herein) restoration.

Diagnostic yield of pulmonary embolism testing in patients presenting to the emergency department with syncope.

Background: Syncope occurs in 1 in 4 people during their lifetime and accounts for 1% to 1.5% of emergency department (ED) visits. Most causes of syncope are benign, but syncope may be caused by life-threatening conditions including pulmonary embolism (PE) in up to 2% of cases.

Machine learning to predict venous thrombosis in acutely ill medical patients.

Background: The identification of acutely ill patients at high risk for venous thromboembolism (VTE) may be determined clinically or by use of integer-based scoring systems. These scores demonstrated modest performance in external data sets.

Objectives: To evaluate the performance of machine learning models compared to the IMPROVE score.

Synthesis and mechanistic investigations of pH-responsive cationic poly(aminoester)s.

The synthesis and degradation mechanisms of a class of pH-sensitive, rapidly degrading cationic poly(α-aminoester)s are described. These reactive, cationic polymers are stable at low pH in water, but undergo a fast and selective degradation at higher pH to liberate neutral diketopiperazines. Related materials incorporating oligo(α-amino ester)s have been shown to be effective gene delivery agents, as the charge-altering degradative behavior facilitates the delivery and release of mRNA and other nucleic acids and .

Hypoglycemia in CDG patients due to PMM2 mutations: Follow up on hyperinsulinemic patients.

Background: Phosphomannomutase 2 deficiency (PMM2-CDG) is the most common congenital disorder of glycosylation (CDG). Hypoglycemia has been reported in various CDG including PMM2-CDG. The frequency and etiology of hypoglycemia in PMM2-CDG are not well studied.

PMI's heated tobacco products marketing claims of reduced risk and reduced exposure may entice youth to try and continue using these products.

Importance: Philip Morris International (PMI) is seeking Food and Drug Administration's (FDA) authorisation to market IQOS as a modified risk tobacco product and to make marketing claims of reduced risk and reduced exposure. Such claims may be misunderstood by youth, thereby increasing their risk for tobacco initiation.

Objective: To assess youth (mean age 19.

Injectable supramolecular polymer-nanoparticle hydrogels enhance human mesenchymal stem cell delivery.

Stem cell therapies have emerged as promising treatments for injuries and diseases in regenerative medicine. Yet, delivering stem cells therapeutically can be complicated by invasive administration techniques, heterogeneity in the injection media, and/or poor cell retention at the injection site. Despite these issues, traditional administration protocols using bolus injections in a saline solution or surgical implants of cell-laden hydrogels have highlighted the promise of cell administration as a treatment strategy.

Advances in screening instruments for Alzheimer's disease.

At its fundamental basis, Alzheimer's disease (AD) is a pathological process that affects neuroplasticity, leading to a specific disruption of episodic memory. This review will provide a rationale for calls to screen for the early detection of AD, appraise the currently available cognitive instruments for AD detection, and focus on the development of the MemTrax test, which provides a new approach to detect the early manifestations and progression of the dementia associated with AD. MemTrax assesses metrics that reflect the effects of neuroplastic processes on learning, memory, and cognition, which are affected by age and AD, particularly episodic memory functions, which cannot presently be measured with enough precision for meaningful use.

A borane-mediated palladium-catalyzed reductive allylic alkylation of α,β-unsaturated carbonyl compounds.

The development of the palladium-catalyzed allylic alkylation of generated boron enolates tandem 1,4-hydroboration is reported. Investigation of the reaction revealed insights into specific catalyst electronic features as well as a profound leaving group effect that proved crucial for achieving efficient allylic alkylation of ester enolates at room temperature and ultimately a highly preparatively useful synthesis of notoriously challenging acyclic all-carbon quaternary stereocenters. The method demonstrates boron enolates as viable pro-nucleophiles in transition-metal catalyzed allylic alkylation, potentially opening up further transformations outside their traditional use.