Hypoxia-inducible factor 1alpha and vascular endothelial growth factor in Glioblastoma Multiforme:a systematic review going beyond pathologic implications

Glioblastoma multiforme(GBM)is an aggressive primary brain tumor characterized by extensive heterogeneity and vascular proliferation.Hypoxic conditions in the tissue microenvironment are considered a pivotal player leading tumor progression.Specifically,hypoxia is known to activate inducible factors,such as hypoxia-inducible factor 1alpha(HIF-1α),which in turn can stimulate tumor neo-angiogenesis through activation of various downward mediators,such as the vascular endothelial growth factor(VEGF).Here,we aimed to explore the role of HIF-1α/VEGF immunophenotypes alone and in combination with other prognostic markers or clinical and image analysis data,as potential biomarkers of GBM prognosis and treatment efficacy.We performed a systematic review(Medline/Embase,and Pubmed database search was completed by 16th of April 2024 by two independent teams;PRISMA 2020).We evaluated methods of immunoassays,cell viability,or animal or patient survival methods of the retrieved studies to assess unbiased data.We used inclusion criteria,such as the evaluation of GBM prognosis based on HIF-1α/VEGF expression,other biomarkers or clinical and imaging manifestations in GBM related to HIF-1α/VEGF expression,application of immunoassays for protein expression,and evaluation of the effectiveness of GBM therapeutic strategies based on HIF-1α/VEGF expression.We used exclusion criteria,such as data not reporting both HIF-1αand VEGF or prognosis.We included 50 studies investigating in total 1319 GBM human specimens,18 different cell lines or GBM-derived stem cells,and 6 different animal models,to identify the association of HIF-1α/VEGF immunophenotypes,and with other prognostic factors,clinical and macroscopic data in GBM prognosis and therapeutic approaches.We found that increased HIF-1α/VEGF expression in GBM correlates with oncogenic factors,such as miR-210-3p,Oct4,AKT,COX-2,PDGF-C,PLDO3,M2 polarization,or ALK,leading to unfavorable survival.Reduced HIF-1α/VEGF expression correlates with FIH-1,ADNP,or STAT1 upregulation,as well as with clinical manifestations,like epileptogenicity,and a favorable prognosis of GBM.Based on our data,HIF-1αor VEGF immunophenotypes may be a useful tool to clarify MRI-PET imaging data distinguishing between GBM tumor progression and pseudoprogression.Finally,HIF-1α/VEGF immunophenotypes can reflect GBM treatment efficacy,including combined first-line treatment with histone deacetylase inhibitors,thimerosal,or an active metabolite of irinotecan,as well as STAT3 inhibitors alone,and resulting in a favorable tumor prognosis and patient survival.These data were supported by a combination of variable methods used to evaluate HIF-1α/VEGF immunophenotypes.Data limitations may include the use of less sensitive detection methods in some cases.Overall,our data support HIF-1α/VEGF’s role as biomarkers of GBM prognosis and treatment efficacy.

Pathophysiology of pulmonary complications of acute pancreatitis

Acute pancreatitis in its severe form is complicated by multiple organ system dysfunction, most importantly by pulmonary complications which include hypoxia, acute respiratory distress syndrome, atelectasis, and pleural effusion. The pathogenesis of some of the above complications is attributed to the production of noxious cytokines. Clinically significant is the early onset of pleural effusion, which heralds a poor outcome of acute pancreatitis. The role of circulating trypsin, phospholipase A2, platelet activating factor, release of free fatty acids, chemoattractants such as tumor necrsosis factor （TNF）- alpha, interleukin （IL）-1, IL-6, IL-8, fMet-leu-phe （a bacterial wall product）, nitric oxide, substance P, and macrophage inhlbitor factor is currently studied. The hope is that future management of acute pancreatitis with a better understanding of the pathogenesis of lung injury will be directed against the production of noxious cytokines.

Developing nursing curriculum to facilitate the delivery of holistic care to the military veteran

Daily media coverage tells the story of challenges facing returning members of the United States Military. High rates of suicide, more than twenty per day,?horrific traumatic injuries necessitating challenging physical and emotional healing, and lingering post-traumatic stress disorders warranting the most advanced methods of treatment are reported daily. As America recoils from two prolonged oversea wars, the need for prepared healthcare providers is essential not only for the Veterans Administration (VA), but also for civilian based healthcare systems. The bulk of nursing education literature seems to evidence a void regarding this segment of the population. What seems like a prime education focus remains yet to be enacted in most nursing programs. The authors have responded to this challenge, by creating curricula developed to increase nursing student awareness of veterans’ unique needs, and to prepare undergraduate nursing students to provide quality care to veterans. Through the creation of a laboratory simulation scenario, students learned how to holistically view and respond to the needs of a veteran client. Debriefing allowed for reviewing the experience and discussing concerns. Outcomes measured via pre- and post- testing survey reflected the complexity of patient care needs. Students were asked to rate their ability to identify and prioritize appropriate nursing interventions. Anecdotal feedback was positive in that students consistently expressed a need to have additional simulation experiences.

Inorganic matter in rice husk derived carbon and its effect on the capacitive performance

Porous carbons were obtained from rice husk using two different chemical activation methods and they were investigated as supercapacitors.Their properties were studied using X-ray photoelectron spectroscopy,thermal analysis,potentiometric titration,and nitrogen adsorption isotherm.The specific capacitance measured in both H_(2) SO_(4) and KOH electrolytes in two-electrode cell was up to-150 F/g.The activation method used affected the resulting carbons’features.As expected,the dependence of the capacitance on porosity was found.The ash content reached 36 wt.%and that inorganic mater blocked some pores and limited their accessibility to electrolyte ions and increased the charge transfer resistance.Nevertheless,the main ash constituents such as CaCO_(3),MgCO_(3),Ca_(3)(PO_(4))2(or P_(2)O_(5)),and Fe-and Zn-containing species did not affect the specific capacitance to a large extent.Especially SiO2,even in a relatively large amount(~20 wt.%)T did not play a detrimental role in the capacitance behavior.The results showed that in spite of a high ash content,carbon can exhibit a good capacitive performance provided that it has a favorable porosity and is rich in sp_(2) configurations.

Influence of hospital volume and outcomes of adult structural heart procedures

Hospital volume is regarded amongst many in the medical community as an important quality metric. This is especially true in more complicated and less commonly performed procedures such as structural heart disease interventions. Seminal work on hospital volume relationships was done by Luft et al more than 4 decades ago, when they demonstrated that hospitals performing > 200 surgical procedures a year had 25%-41% lower mortality than those performing fewer procedures. Numerous volume-outcome studies have since been done for varied surgical procedures. An old adage "practice makes perfect" indicating superior operator and institutional experience at higher volume hospitals is believed to primarily contribute to the volume outcome relationship. Compelling evidence from a slew of recent publications has also highlighted the role of hospital volume in predicting superior post-procedural outcomes following structural heart disease interventions. These included transcatheter aortic valve repair, transcatheter mitral valve repair, septal ablation and septal myectomy for hypertrophic obstructive cardiomyopathy, left atrial appendage closure and atrial septal defect/patent foramen ovale closure. This is especially important since these structural heart interventions are relatively complex with evolving technology and a steep learning curve. The benefit was demonstrated both in lower mortality and complications as well as better economics in terms of lower length of stay and hospitalization costs seen at high volume centers. We present an overview of the available literature that underscores the importance of hospital volume in complex structural heart disease interventions.

Utilizing simulation curriculum to decentralize mental health concepts

The International Society of Psychiatric Nurses as well as The American Psychiatric Nurses Association called for decentralization of psychiatric concepts in undergraduate nursing education. The author developed a series of simulation scenarios to address therapeutic communication and psychosocial needs in a variety of patient care settings. In terms of holistic care, psychological well-being is relevant to all realms of nursing practice. Mental health assessment and intervention need to be included in all areas of an undergraduate-nursing curriculum. The purpose of this project was to create a BSN curriculum that reflects the mental health needs of patients not only in acute care psychiatric facilities but also in medical-surgical disciplines, maternity units, and community settings. The curriculum is designed to also cover mental health throughout the lifespan-from infancy to end of life. A goal was to develop educational techniques, which translate into safe practice. A series of five simulations have been created with additional scenarios to be established in the following academic year. Topics include: alcohol withdrawal, end of life care, post-traumatic stress disorder, post-partum depression, serotonin syndrome, benzodiazepine over dose, elder abuse, depression in military veterans, and geriatric depression. All incorporate QSEN competencies [1]. The overall learning objectives are for undergraduate nursing students to initiate and implement an appropriate mental status assessment using therapeutic communication, and also to provide safe care by identifying risk factors and using clinical decision making to establish requisite nursing interventions. The methodology included relevant documentation through the use of appropriate assessment tools. Learning objectives were assessed through pre-simulation and post-simulation ten-question inventory and anecdotal feedback. QSEN competencies were utilized in creating scenarios as well as pre and post testing. Students voiced an ability to connect the didactic material to their clinical experiences following simulation.

Culturally tailored DSMES:A new key for South Asian patients with Type 2 Diabetes Mellitus

South Asians have an exceptionally high risk for developing Type 2 diabetes mellitus.It is very challenging for healthcare providers to successfully manage diabetes and control glucose levels at target due to the unique lifestyle of the South Asian population.Culturally tailored diabetes self-management education and support(DSMES)can be more effective in guiding South Asian patients with Type 2 diabetes.Unique considerations to address lifestyle modification for South Asians include a diet that typically consists of a high carbohydrate to lipids/proteins ratio,preference for high glucose index fruits,regular intake of traditional sweets or desserts,late afternoon tea break followed by late dinner,lack of vigorous exercise(yoga or walking being the preferred activity),lack of DSMES knowledge and skills,and poor access to culturally appropriate resources for diabetes care.We present a 38-year-old male diagnosed with diabetes four years ago who showed poor glucose control before our intervention.Our interventions included education on the importance of blood glucose monitoring,exercise,and diet.Based on our experience with this case,we propose the following recommendations for a tailored approach to DSMES for South Asian patients with Type 2 diabetes:make appropriate dietary changes(decrease total daily caloric intake,decrease the percentage of carbohydrates,add low glucose index fruits and vegetables,avoid late afternoon tea breaks,eat dinner before 8 PM);incorporate appropriate daily physical activity;and monitor blood glucose daily for prompt feedback.

Dietary pyruvate targets cytosolic phospholipase A2 to mitigate inflammation and obesity in mice

Obesity has a multifactorial etiology and is known to be a state of chronic low-grade inflammation,known as meta-inflammation.This state is associated with the development of metabolic disorders such as glucose intolerance and nonalcoholic fatty liver disease.Pyruvate is a glycolytic metabolite and a crucial node in various metabolic pathways.However,its role and molecular mechanism in obesity and associated complications are obscure.In this study,we reported that pyruvate substantially inhibited adipogenic differentiation in vitro and its administration significantly prevented HFD-induced weight gain,white adipose tissue inflammation,and metabolic dysregulation.To identify the target proteins of pyruvate,drug affinity responsive target stability was employed with proteomics,cellular thermal shift assay,and isothermal drug response to detect the interactions between pyruvate and its molecular targets.Consequently,we identified cytosolic phospholipase A2(cPLA2)as a novel molecular target of pyruvate and demonstrated that pyruvate restrained diet-induced obesity,white adipose tissue inflammation,and hepatic steatosis in a cPLA2-dependent manner.Studies with global ablation of cPLA2 in mice showed that the protective effects of pyruvate were largely abrogated,confirming the importance of pyruvate/cPLA2 interaction in pyruvate attenuation of inflammation and obesity.Overall,our study not only establishes pyruvate as an antagonist of cPLA2 signaling and a potential therapeutic option for obesity but it also sheds light on the mechanism of its action.Pyruvate’s prior clinical use indicates that it can be considered a safe and viable alternative for obesity,whether consumed as a dietary supplement or as part of a regular diet.

NAFLD Epidemiology, Emerging Pharmacotherapy, Liver Transplantation Implications and the Trends in the United States

Nonalcoholic fatty liver disease (NAFLD) is a hepatic mani-festation of metabolic syndrome. The spread of obesity worldwide in pandemic proportions has led to a rapid rise of NAFLD in developed and developing countries alike. There are no approved pharmacological agents to treat steatohepatitis or advanced fibrosis but obeticholic acid recently has shown some promise in phase III trial. Currently, NAFLD is the number one etiology for simultaneous liver and kidney trans-plantation in the USA, second most common indication for liver transplantation (LT) and projected to become number one very soon. LT for NAFLD poses unique challenges, as these patients are generally older, obese and more likely to have a number of metabolic risk factors. Bariatric surgery is an option and can be considered if a structured weight loss program does not achieve the sustained weight loss goal. Comprehensive cardiovascular risk assessment and aggres-sive management of comorbid conditions are crucial in the LT evaluation process to improve post-transplant survival. Re-current nonalcoholic steatohepatitis after LT is not uncom-mon, and thus warrants primary and secondary prevention strategies through a multidisciplinary approach. Prevalence of NAFLD in a donor population is a unique and growing concern that limits the access to quality liver grafts.