"I was very scared when I found out my son had sickle cell": Caregiver knowledge and attitudes toward early intervention for young children with sickle cell disease: Implications for policy and practice from a multi-site study.

Objective: This study characterized caregivers' beliefs related to early intervention services for children with sickle cell disease (SCD) to gain an indepth understanding of caregivers' experiences and desires for early intervention services.

Methods: Both qualitative and quantitative data were collected from caregivers of children aged 0-4 years with SCD across two sites in the United States. Caregivers completed the Knowledge of Infant Development Inventory, a custom survey about their experiences with early intervention, and a qualitative interview.

Addressing Inequities in SARS-CoV-2 Vaccine Uptake: The Boston Medical Center Health System Experience.

Academic medical centers could play an important role in increasing access to and uptake of SARS-CoV-2 vaccines, especially in Black and Latino communities that have been disproportionately affected by the pandemic. This article describes the vaccination program developed by the Boston Medical Center (BMC) health system (New England's largest safety-net health system), its affiliated community health centers (CHCs), and community partners. The program was based on a conceptual framework for community interventions and aimed to increase equitable access to vaccination in the hardest-hit communities through community-based sites in churches and community centers, mobile vaccination events, and vaccination on the BMC campus.

Integrating physical activity promotion into UK medical school curricula: testing the feasibility of an educational tool developed by the Faculty of Sports and Exercise Medicine.

Background: At present education on exercise medicine and physical activity (PA) promotion does not feature heavily within the medical curriculum.

Objectives: The purpose of this study was to test the feasibility of a self-directed educational tool (Faculty of Sports and Exercise Medicine (FSEM) exercise prescription booklet) on medical students' understanding of PA in disease management.

Methods: Students from 22 UK medical schools were invited to complete a brief online questionnaire before and after being provided access to the FSEM exercise prescription booklet.

Effectiveness of the probiotic Streptococcus salivarius K12 for the treatment and/or prevention of sore throat: a systematic review.

Background: Sore throat resulting from pharyngotonsillitis is one of the commonest reasons for primary care consultation and inappropriate antibiotic prescription and finding effective alternative treatments is important.

Objectives: To review the evidence for using the probiotic Streptococcus salivarius K12 (SsK12) for the prevention or treatment of pharyngotonsillitis.

Data Sources: PubMed, Embase, CINAHL and Cochrane Library.

Systematic Review and Meta-Analysis of Individual Patient Data to Assess the Sensitivity of Cervical Cytology for Diagnosis of Cervical Cancer in Low- and Middle-Income Countries.

Purpose: To assess the sensitivity of cervical cytology to cancer by pooling individual patient cytology results from cancers diagnosed in studies that assessed cervical screening in low- and middle-income countries.

Methods: Two authors reviewed studies identified through PubMed and Embase databases. We included studies that reported cervical cytology in which at least one woman was diagnosed with cervical cancer and in which abnormal cytology results were investigated at colposcopy and through a histologic sample (if appropriate).

Fixed bimonthly aflibercept in naïve and switched neovascular age-related macular degeneration patients: one year outcomes.

Aim: To determine real life clinical outcomes in poorly responsive and treatment-naïve neovascular age related macular degeneration (nvAMD) patients using bimonthly fixed dosing aflibercept regimen.

Methods: This was a retrospective study of 165 eyes with nvAMD started on aflibercept at Southampton Eye Unit between June 2013 and June 2014. Patients were either switched from pro re nata (PRN) ranibizumab/bevacizumab due to poor response (107 eyes), or treatment-naïve (58 eyes).

Arachidonic acid induces brain endothelial cell apoptosis via p38-MAPK and intracellular calcium signaling.

Arachidonic acid (AA), a bioactive fatty acid whose levels increase during neuroinflammation, contributes to cerebral vascular damage and dysfunction. However, the mode of injury and underlying signaling mechanisms remain unknown. Challenge of primary human brain endothelial cells (HBECs) with AA activated a stress response resulting in caspase-3 activation, poly(ADP-ribose) polymerase cleavage, and disruption of monolayer integrity.

Preoperative serum C-reactive protein levels and post-operative lymph node ratio are important predictors of survival after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma.

Context: There is paucity of data on the prognostic value of pre-operative inflammatory response and post-operative lymph node ratio on patient survival after pancreatic-head resection for pancreatic ductal adenocarcinoma.

Objectives: To evaluate the role of the preoperative inflammatory response and postoperative pathology criteria to identify predictive and/or prognostic variables for pancreatic ductal adenocarcinoma.

Design: All patients who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma between 2002 and 2008 were reviewed retrospectively.

Therapeutic implications of disorders of cell death signalling: membranes, micro-environment, and eicosanoid and docosanoid metabolism.

Disruptions of cell death signalling occur in pathological processes, such as cancer and degenerative disease. Increased knowledge of cell death signalling has opened new areas of therapeutic research, and identifying key mediators of cell death has become increasingly important. Early triggering events in cell death may provide potential therapeutic targets, whereas agents affecting later signals may be more palliative in nature.

Lichtenstein hernia repair under different anaesthetic techniques with special emphasis on outcomes in older people.

Background: This study compared local (LA) and general anaesthesia (GA) for elective inguinal hernia repair with specific reference to older people (≥70 years).

Methods: A total of 470 inguinal hernia repairs were compared for demographics, operating time, day case rates and complications. Subgroup analysis was performed to evaluate outcomes in <70 and >70 years.

Glioma cell death: cell-cell interactions and signalling networks.

The prognosis for patients with malignant gliomas is poor, but improvements may emerge from a better understanding of the pathophysiology of glioma signalling. Recent therapeutic developments have implicated lipid signalling in glioma cell death. Stress signalling in glioma cell death involves mitochondria and endoplasmic reticulum.

Brain endothelial cell death: modes, signaling pathways, and relevance to neural development, homeostasis, and disease.

Emerging evidence indicates that brain microvascular endothelial cells play a critical role in brain development, maturation, and homeostasis. Acute or chronic insults, including oxidative stress, oxygen-glucose deprivation, trauma, infections, inflammatory cytokines, DNA damaging agents, beta-amyloid deposition, and endoplasmic reticulum stress induce brain endothelial cell dysfunction and damage, which can result in cell death. The homeostatic balance between endothelial cell survival and endothelial cell death is critical for brain development, remodeling, and repair.

Prostaglandin E2 activates cAMP response element-binding protein in glioma cells via a signaling pathway involving PKA-dependent inhibition of ERK.

Prostaglandin E(2) (PGE(2)) plays a critical role in influencing the biological behavior of tumor cells. We previously demonstrated that PGE(2) stimulates human glioma cell growth via activation of protein kinase A (PKA) type II. This study was undertaken to further elucidate the intracellular pathways activated by PGE(2) downstream to PKA.

Compliance to recommended liver function monitoring in patients on statin therapy.

Product information and national guidelines consistently recommend the estimation of serum alanine aminotranferase (ALT) before and after approximately 3 months as part of risk management following initiation of statin therapy. The aim of this study was to determine compliance to the recommendations for monitoring ALT in patients initiated on statin therapy. The prevalence of abnormal serum ALT levels was also evaluated and compared with current data.

Immunologic and stress responses following video-assisted thoracic surgery and open pulmonary lobectomy in early stage lung cancer.

Conventional open major surgery evokes an injury response involving endocrine, neural, and immunologic mechanisms. The immunologic responses are characterized by release of cytokines, inflammatory mediators, and acute-phase proteins and by adverse disturbances in immune cell function. The use of a minimal access approach strategy is associated with a significant reduction in the cytokine response, as exemplified by reduced interleukin-6 levels and a corresponding reduction in acute-phase protein generation with reduced C-reactive protein levels.

c-jun amino-terminal kinase and mitogen activated protein kinase 1/2 mediate hepatocyte growth factor-induced migration of brain endothelial cells.

Hepatocyte growth factor (HGF) influences several components of the angiogenic response, including endothelial cell migration. While recent studies indicate a crucial role of HGF in brain angiogenesis, the signaling pathways that regulate brain endothelial cell migration by HGF remain uncharacterized. Herein, we report that HGF stimulated human brain microvascular endothelial cell (HBMEC) migration in a dose- and time-dependent manner.

Calcium-sensitive mitochondrial membrane potential in human platelets and intrinsic signals of cell death.

The mechanisms involved in storage-induced damage in platelets are not well understood, but membrane signalling via Ca2+ ion flux may affect mitochondrial H+ gradients and metabolism and the intrinsic pathways of cell death, platelet survival and function. In this study, the effects of blood bank storage conditions, including reduced plasma concentration and interrupted agitation, were evaluated in platelets from 136 healthy donors. Mitochondrial membrane potential (DeltaPsim), an indicator of intrinsic cell death, and its sensitivity to Ca2+ ionophore A23187, were monitored using JC-1 by flow cytometry and fluorescence microscopy.

Microsomal prostaglandin E synthase-1 regulates human glioma cell growth via prostaglandin E(2)-dependent activation of type II protein kinase A.

Dysregulation of enzymes involved in prostaglandin biosynthesis plays a critical role in influencing the biological behavior and clinical outcome of several tumors. In human gliomas, overexpression of cyclooxygenase-2 has been linked to increased aggressiveness and poor prognosis. In contrast, the role of prostaglandin E synthase in influencing the biological behavior of human gliomas has not been established.

Intracellular oxidation by human glioma cell populations: effect of arachidonic acid.

Arachidonic acid (AA) and Gamma linolenic acid have been shown to limit glioma cell growth, stimulate apoptosis and lipid peroxidation. However, brain tumours are characterised by cellular heterogeneity and responding cell populations have not been identified. Brain tumour samples from patients were disaggregated.

Highly unsaturated fatty acid induced tumour regression in glioma pharmacodynamics and bioavailability of gamma linolenic acid in an implantation glioma model: effects on tumour biomass, apoptosis and neuronal tissue histology.

Highly unsaturated fatty acids (HUFAs) are naturally occurring anti-tumour agents. HUFAs act as intracellular signalling molecules in cell proliferation and death. In human glioma, HUFAs may stimulate tumour regression and apoptosis.

Antitumour and pro-apoptotic actions of highly unsaturated fatty acids in glioma.

The highly unsaturated fatty acids (HUFA) of the n-6 and n-3 series are involved in cell signalling in normal and transformed cells and have recently been associated with pathways leading to tumour cell death. The antitumour activity of three HUFA (arachidonic acid, gamma linolenic acid and eicosapentaenoic acid) were studied in glioma cells and tissue. Using five glioma models, including primary cell suspensions prepared from 46 human glioma samples and an in vivo rat C6 glioma model, we obtained evidence that, following exposure to HUFA, either administered into the medium surrounding human glioma cells or in 16 preparations of multicellular spheroids derived from human and rodent glioma cell lines (C6, MOG, U87, U373) or administered intra-tumourally by infusion using osmotic mini-pumps in 48 rats, glioma regression and apoptosis were detected.