Neurovascular mechanisms of cognitive aging: Sex-related differences in the average progression of arteriosclerosis, white matter atrophy, and cognitive decline.

Arterial stiffness (arteriosclerosis) has been linked to heightened risks for cognitive decline, and ultimately for Alzheimer's disease and other forms of dementia. Importantly, neurovascular outcomes generally vary according to one's biological sex. Here, capitalizing on a large sample of participants with neuroimaging and behavioral data (N = 203, age range = 18-87 years), we aimed to provide support for a hierarchical model of neurocognitive aging, which links age-related declines in cerebrovascular health to the rate of cognitive decline via a series of intervening variables, such as white matter integrity.

Non-Surgical Bleeding and Transurethral Resection of the Prostate (TURP) Syndrome after TURP Surgery: A Case Report and Literature Review.

Patients undergoing transurethral resection of the prostate (TURP) surgery can develop TURP syndrome and post-TURP bleeding. Post-TURP bleeding can be surgical, from arteries or venous sinuses, or non-surgical, due to coagulopathy preventing clot formation. Non-surgical post-TURP bleeding may be due to high concentrations of urokinase and tissue plasminogen activator (tPA) in the urine that cause fibrinolytic changes and increase bleeding risk.

Neurovascular Mechanisms of Cognitive Aging: Sex-Related Differences in the Average Progression of Arteriosclerosis, White Matter Atrophy, and Cognitive Decline.

Arterial stiffness (arteriosclerosis) has been linked to heightened risks for cognitive decline, and ultimately for Alzheimer's disease and other forms of dementia. Importantly, neurovascular outcomes generally vary according to one's biological sex. Here, capitalizing on a large sample of participants with neuroimaging and behavioral data ( = 203, age range = 18-87 years), we aimed to provide support for a hierarchical model of neurocognitive aging, which links age-related declines in cerebrovascular health to the rate of cognitive decline via a series of intervening variables, such as white matter integrity.

Morphologic features of prostate cancer-encased native vessels: An image analysis study.

Background: Vasculature plays a crucial role in the progression of prostate cancer (PC). Changes to the prostatic native vessels have not been studied since 2000 when Garcia et al. demonstrated marked media hypercellularity and increased artery thickness in prostatic native arteries within PC.

Clinicopathologic Characterization of Kaposi Sarcoma on the Foot and Ankle: Analysis of 11 Patients Seen in Our Clinics.

Background: Kaposi sarcoma (KS) has multiple clinical variants, and most frequently presents on the lower extremities. Anti-human immunodeficiency virus (HIV) therapy has significantly reduced the incidence of KS. However, KS is still prevalent in both HIV-infected and HIV-uninfected patients.

The association between trial of labor after cesarean in obese patients and adverse maternal outcomes.

Purpose: We hypothesized that among obese patients with a history of cesarean birth, a TOLAC is associated with decreased composite maternal adverse outcomes (CMAO) compared to planned repeat low transverse cesarean section (RLTCS).

Methods: In this population-based cross-sectional study using the National Birth Certificate database from 2016 to 2020, we compared obese patients who attempted TOLAC at term (≥ 37 weeks estimated gestational age) to planned RLTCS. The primary outcome was a CMAO, defined as delivery complications, including intensive care unit (ICU) admission, uterine rupture, unplanned hysterectomy, or maternal blood transfusion.

Influence of social-normative information on the modeling of food-related decisions.

Social modeling is a powerful influence on people's food intake: When there is a clear and consistent norm, people eat more when eating with someone who eats a lot and eat less when eating with someone who eats only a little. In three studies, the present research examined how clear versus ambiguous social-normative information influences the modeling of food-related decisions. Using a novel online decision-making paradigm, female participants (total N = 1042) were provided with information about how many cookies previous participants had supposedly selected (no information was provided in the control condition), and then decided how many cookies they would choose for a snack.

COVID-19 in Pediatric Inpatients: A Multi-Center Observational Study of Factors Associated with Negative Short-Term Outcomes.

Most cases of COVID-19 in children and adolescents are mild or asymptomatic, but a small number of individuals may develop severe disease, requiring PICU admission and/or mechanical ventilation. We assessed the factors associated with negative short-term outcomes of COVID-19 in 82 pediatric patients at three hospitals within the United States during the spring and summer of 2020 using medical records, laboratory data, and imaging studies of all patients admitted with a positive RT-PCR test for SARS-CoV-2. We found that older patients were more likely to have an extended hospital stay, and those with high BMIs (over 25) were more likely to be admitted to the PICU during the early pandemic.

Quality Improvement to Address Surgical Burden of Disease at a Large Tertiary Public Hospital in Peru.

Background: In resource-limited settings, there is a unique opportunity for using process improvement strategies to address the lack of access to surgical care. By implementing organizational changes in the surgical admission process, we aimed to decrease wait times, increase surgical volume, and improve patient satisfaction for elective general surgery procedures at a public tertiary hospital in Lima, Peru.

Methods: During the first phase of the intervention, Plan-Do-Study-Act (PDSA) cycles were performed to ensure the surgery waitlist included up-to-date clinical information.

Stroke in COVID-19: a single-centre initial experience in a hotspot of the pandemic.

Background: COVID-19, caused by SARS-CoV-2, is a global pandemic that has been an immense burden on healthcare systems all over the world. These patients may be at higher risk for acute ischaemic stroke (AIS). We present our experience with AIS in patients with COVID-19.

Final safety and efficacy results from the CPX-351 early access program for older patients with high-risk or secondary acute myeloid leukemia.

CPX-351, a dual-drug liposomal encapsulation of cytarabine and daunorubicin at a synergistic 5:1 molar drug ratio, achieved superior efficacy compared with conventional chemotherapy in older adults with newly diagnosed, high-risk/secondary acute myeloid leukemia (AML) in phase 2 and 3 studies. Prior to CPX-351 commercialization, an expanded access program (EAP) provided CPX-351 access for this population in the United States. In this phase 4, single-arm, open-label study (NCT02533115), 52 patients were treated with CPX-351 for 1-2 induction cycles and ≤4 consolidation cycles.

Acral Lentiginous Melanoma of Foot and Ankle: A Clinicopathological Study of 7 Cases.

Background/aim: Acral lentiginous melanoma (ALM) is a rare entity on the foot. This study aimed to reveal its clinical presentations, histopathology and treatment options.

Materials And Methods: Seven cases of ALM involving foot were treated in our Institute in a 3-year period.

Melanoma and Thyroid Carcinoma: Our Current Understanding.

Melanoma is listed among the most common cancers in the United States, with new cases increasing steadily.1 Due to the aggressive nature of melanoma and its high risk of metastasis, early detection and treatment is essential. It is noted that the majority of unresectable and metastatic melanomas are BRAF V600-mutated.

Anemia in the emergency department: evaluation and treatment.

Anemia is a common worldwide problem that is associated with nonspecific complaints. The initial focus for the emergency evaluation of anemia is to determine whether the problem is acute or chronic. Acute anemia is most commonly associated with blood loss, and the patient is usually symptomatic.

Discovery of 6-phenylpyrimido[4,5-b][1,4]oxazines as potent and selective acyl CoA:diacylglycerol acyltransferase 1 (DGAT1) inhibitors with in vivo efficacy in rodents.

The discovery and optimization of a series of acyl CoA:diacylglycerol acyltransferase 1 (DGAT1) inhibitors based on a pyrimido[4,5-b][1,4]oxazine scaffold is described. The SAR of a moderately potent HTS hit was investigated resulting in the discovery of phenylcyclohexylacetic acid 1, which displayed good DGAT1 inhibitory activity, selectivity, and PK properties. During preclinical toxicity studies a metabolite of 1 was observed that was responsible for elevating the levels of liver enzymes ALT and AST.

Inhibiting NF-κB-inducing kinase (NIK): discovery, structure-based design, synthesis, structure-activity relationship, and co-crystal structures.

The discovery, structure-based design, synthesis, and optimization of NIK inhibitors are described. Our work began with an HTS hit, imidazopyridinyl pyrimidinamine 1. We utilized homology modeling and conformational analysis to optimize the indole scaffold leading to the discovery of novel and potent conformationally constrained inhibitors such as compounds 25 and 28.

Discovery of INT131: a selective PPARγ modulator that enhances insulin sensitivity.

PPARγ is a member of the nuclear hormone receptor family and plays a key role in the regulation of glucose homeostasis. This Letter describes the discovery of a novel chemical class of diarylsulfonamide partial agonists that act as selective PPARγ modulators (SPPARγMs) and display a unique pharmacological profile compared to the thiazolidinedione (TZD) class of PPARγ full agonists. Herein we report the initial discovery of partial agonist 4 and the structure-activity relationship studies that led to the selection of clinical compound INT131 (3), a potent PPARγ partial agonist that displays robust glucose-lowering activity in rodent models of diabetes while exhibiting a reduced side-effects profile compared to marketed TZDs.

Immune activation and neuropsychiatric symptoms in HIV infection.

This study examined the role of biological processes in the development of specific neuropsychiatric complications in HAART-naive adults with HIV/AIDS. Depressive symptoms were modestly associated with elevated IL-6 mRNA expression (r(s)=0.40, p<0.

Impact of social support on cognitive symptom burden in HIV/AIDS.

As many as 50% of people living with HIV/AIDS report cognitive difficulties, which can be associated with objective neuropsychological impairments and depression. A number of studies have demonstrated an association between higher social support and lower rates of depression. Using a cross-sectional design, we examined the role social support may play in attenuating the effects of both neuropsychological status and depression on cognitive difficulties.

Discovery of potent LPA2 (EDG4) antagonists as potential anticancer agents.

The LPA(2) protein is overexpressed in many tumor cells. We report the optimization of a series of LPA(2) antagonists using calcium mobilization assay (aequorin assay) that led to the discovery of the first reported inhibitors selective for LPA(2). Key compounds were evaluated in vitro for inhibition of LPA(2) mediated Erk activation and proliferation of HCT-116 cells.