What methods can the health care industry implement to reduce energy consumption and waste production from patient care to limit greenhouse gas emissions?

Purpose: Climate change is a growing issue all around the world and has negative impacts on the environment and human health. The health care industry is a significant contributor to greenhouse gas emissions amplifying climate change. Health care establishments are in place to improve health but are inadvertently harming it at the same time. Methods: A review of the literature was conducted to determine the impact the health care industry has on climate change and what can be done to limit the impacts on the environment. Resources were collected from trusted organizations databases such as Healthcare Without Harm, Alliance of Nurses for Healthy Environments, the Center for Disease Control and Prevention, and a selection of scholarly articles including The Lancet. Results: The literature indicated that the health care industry was a significant contributor to greenhouse gas emissions and correlated with the amount of expenditure. According to data collected in 2018, the U. S. health care system makes up 17.7% of the nation’s GDP, and therefore, produces a higher ratio of greenhouse gasses (Center for Medicare & Medicaid Services, 2019). Hospitals have been identified as the key contributor to greenhouse gasses from the healthcare industry. There are methods hospitals can implement to reduce their carbon footprint and it is possible to create a carbon-neutral healthcare system as Kaiser Permanente has achieved for the first time in the U.S. (Costa, 2020). Conclusion: As global temperatures rise, there is a dire need to make a change in the ways humans affect the environment. The health care industry has the power to make a significant impact to improve environmental health if correct methods were put in place. Nurses make up the majority of the workforce in health care and can kindle the movement to make a difference in how their community perceives the impacts health care facilities have on the environment

Controlled human malaria infection: applications, advances, and challenges

Controlled human malaria infection (CHMI) entails deliberate infection with malaria parasites either by mosquito bite or by direct injection of sporozoites or parasitized erythrocytes. When required, the resulting blood-stage infection is curtailed by the administration of antimalarial drugs. Inducing a malaria infection via inoculation with infected blood was first used as a treatment (malariotherapy) for neurosyphilis in Europe and the United States in the early 1900s. More recently, CHMI has been applied to the fields of malaria vaccine and drug development, where it is used to evaluate products in well-controlled early-phase proof-of-concept clinical studies, thus facilitating progression of only the most promising candidates for further evaluation in areas where malaria is endemic. Controlled infections have also been used to immunize against malaria infection. Historically, CHMI studies have been restricted by the need for access to insectaries housing infected mosquitoes or suitable malaria-infected individuals. Evaluation of vaccine and drug candidates has been constrained in these studies by the availability of a limited number of Plasmodium falciparum isolates. Recent advances have included cryopreservation of sporozoites, the manufacture of well-characterized and genetically distinct cultured malaria cell banks for blood-stage infection, and the availability of Plasmodium vivax-specific reagents. These advances will help to accelerate malaria vaccine and drug development by making the reagents for CHMI more widely accessible and also enabling a more rigorous evaluation with multiple parasite strains and species. Here we discuss the different applications of CHMI, recent advances in the use of CHMI, and ongoing challenges for consideration

Exploring opportunities in rural, primary care nursing: The student nurse perspective.

Abstract: Exploring opportunities in rural, primary care nursing: The student nurse perspective. Background: The demand for primary care services is outpacing the number of primary care providers in practice. This gap in primary care is projected to increase significantly within the next decade. Local Problem: The enhanced primary care RN role is a progressive role that optimizes the role of the RN within an interprofessional care team. Page County is a health professional shortage area, and until 2019 did not have RNs working in primary care settings. Purpose: This project aims to describe an innovation in nursing education and the outcomes of student engagement in the UPCARE program. Methods: The Undergraduate Primary Care and Rural Education (UPCARE) Project is a federally funded program focused on giving student nurses the opportunity to immerse themselves in rural primary care settings within Page County. Interventions: Student nurses in this program work side by side with RNs in the delivery of primary care nursing services. Scholars also participate in a variety of enriching clinical and co-curricular learning activities. Results: There are 25 student scholars participating in the UPCARE Project. The preliminary impact of the project demonstrated new revenue of over $78,000 for services generated by the primary care RNs. Through this collaboration, student scholars participating in UPCARE are able to help improve patient outcomes while gaining valuable experiences and education. Conclusion/Implications: UPCARE is a promising academic-practice partnership that can build on existing BSN curriculum, and leverage the strength of RNs practicing at the fullest scope of their license to provide holistic care to patients in primary care settings

Plasmodium Strain Determines Dendritic Cell Function Essential for Survival from Malaria

The severity of malaria can range from asymptomatic to lethal infections involving severe anaemia and cerebral disease. However, the molecular and cellular factors responsible for these differences in disease severity are poorly understood. Identifying the factors that mediate virulence will contribute to developing antiparasitic immune responses. Since immunity is initiated by dendritic cells (DCs), we compared their phenotype and function following infection with either a nonlethal or lethal strain of the rodent parasite, Plasmodium yoelii, to identify their contribution to disease severity. DCs from nonlethal infections were fully functional and capable of secreting cytokines and stimulating T cells. In contrast, DCs from lethal infections were not functional. We then transferred DCs from mice with nonlethal infections to mice given lethal infections and showed that these DCs mediated control of parasitemia and survival. IL-12 was necessary for survival. To our knowledge, our studies have shown for the first time that during a malaria infection, DC function is essential for survival. More importantly, the functions of these DCs are determined by the strain of parasite. Our studies may explain, in part, why natural malaria infections may have different outcomes

Chemically attenuated blood-stage Plasmodium yoelii parasites induce long-lived and strain-transcending protection

The development of a vaccine is essential for the elimination of malaria. However, despite many years of effort, a successful vaccinehas not been achieved. Most subunit vaccine candidates tested in clinical trials have provided limited efficacy, and thus attenuatedwhole-parasite vaccines are now receiving close scrutiny. Here, we test chemically attenuated Plasmodium yoelii 17Xand demonstrate significant protection following homologous and heterologous blood-stage challenge. Protection againstblood-stage infection persisted for at least 9 months. Activation of both CD4+ and CD8+ T cells was shown after vaccination;however, in vivo studies demonstrated a pivotal role for both CD4+ T cells and B cells since the absence of either cell type led toloss of vaccine-induced protection. In spite of significant activation of circulating CD8+ T cells, liver-stage immunity was notevident. Neither did vaccine-induced CD8+ T cells contribute to blood-stage protection; rather, these cells contributed to pathogenesis,since all vaccinated mice depleted of both CD4+ and CD8+ T cells survived a challenge infection. This study providescritical insight into whole-parasite vaccine-induced immunity and strong support for testing whole-parasite vaccines in humans

Chemically attenuated blood-stage Plasmodium yoelii parasites induce long-lived and strain-transcending protection

The development of a vaccine is essential for the elimination of malaria. However, despite many years of effort, a successful vaccine has not been achieved. Most subunit vaccine candidates tested in clinical trials have provided limited efficacy, and thus attenuated whole-parasite vaccines are now receiving close scrutiny. Here, we test chemically attenuated Plasmodium yoelii 17X and demonstrate significant protection following homologous and heterologous blood-stage challenge. Protection against blood-stage infection persisted for at least 9 months. Activation of both CD4+ and CD8+ T cells was shown after vaccination; however, in vivo studies demonstrated a pivotal role for both CD4+ T cells and B cells since the absence of either cell type led to loss of vaccine-induced protection. In spite of significant activation of circulating CD8+ T cells, liver-stage immunity was not evident. Neither did vaccine-induced CD8+ T cells contribute to blood-stage protection; rather, these cells contributed to pathogenesis, since all vaccinated mice depleted of both CD4+ and CD8+ T cells survived a challenge infection. This study provides critical insight into whole-parasite vaccine-induced immunity and strong support for testing whole-parasite vaccines in humans

Cross-species Malaria Immunity Induced By Chemically Attenuated Parasites

Vaccine development for the blood stages of malaria has focused on the induction of antibodies to parasite surface antigens, most of which are highly polymorphic. An alternate strategy has evolved from observations that low-density infections can induce antibody-independent immunity to different strains. To test this strategy, we treated parasitized red blood cells from the rodent parasite Plasmodium chabaudi with secocyclopropyl pyrrolo indole analogs. These drugs irreversibly alkylate parasite DNA, blocking their ability to replicate. After administration in mice, DNA from the vaccine could be detected in the blood for over 110 days and a single vaccination induced profound immunity to different malaria parasite species. Immunity was mediated by CD4(+) T cells and was dependent on the red blood cell membrane remaining intact. The human parasite, Plasmodium falciparum, could also be attenuated by treatment with seco-cyclopropyl pyrrolo indole analogs. These data demonstrate that vaccination with chemically attenuated parasites induces protective immunity and provide a compelling rationale for testing a blood-stage parasite-based vaccine targeting human Plasmodium species

Infectivity of Plasmodium falciparum in malaria-naive individuals is related to knob expression and cytoadherence of the parasite

Plasmodium falciparum is the most virulent human malaria parasite because of its ability to cytoadhere in the microvasculature. Nonhuman primate studies demonstrated relationships among knob expression, cytoadherence, and infectivity. This has not been examined in humans. Cultured clinical-grade P. falciparum parasites (NF54, 7G8, and 3D7B) and ex vivo-derived cell banks were characterized. Knob and knob-associated histidine-rich protein expression, CD36 adhesion, and antibody recognition of parasitized erythrocytes (PEs) were evaluated. Parasites from the cell banks were administered to malaria-naive human volunteers to explore infectivity. For the NF54 and 3D7B cell banks, blood was collected from the study participants for in vitro characterization. All parasites were infective in vivo. However, infectivity of NF54 was dramatically reduced. In vitro characterization revealed that unlike other cell bank parasites, NF54 PEs lacked knobs and did not cytoadhere. Recognition of NF54 PEs by immune sera was observed, suggesting P. falciparum erythrocyte membrane protein 1 expression. Subsequent recovery of knob expression and CD36-mediated adhesion were observed in PEs derived from participants infected with NF54. Knobless cell bank parasites have a dramatic reduction in infectivity and the ability to adhere to CD36. Subsequent infection of malaria-naive volunteers restored knob expression and CD36-mediated cytoadherence, thereby showing that the human environment can modulate virulence

De novo DHDDS variants cause a neurodevelopmental and neurodegenerative disorder with myoclonus

Subcellular membrane systems are highly enriched in dolichol, whose role in organelle homeostasis and endosomal-lysosomal pathway remains largely unclear besides being involved in protein glycosylation. DHDDS encodes for the catalytic subunit (DHDDS) of the enzyme cis-prenyltransferase (cis-PTase), involved in dolichol biosynthesis and dolichol-dependent protein glycosylation in the endoplasmic reticulum. An autosomal recessive form of retinitis pigmentosa (retinitis pigmentosa 59) has been associated with a recurrent DHDDS variant. Moreover, two recurring de novo substitutions were detected in a few cases presenting with neurodevelopmental disorder, epilepsy, and movement disorder. We evaluated a large cohort of patients (n=25) with de novo pathogenic variants in DHDDS and provided the first systematic description of the clinical features and long-term outcome of this new neurodevelopmental and neurodegenerative disorder. The functional impact of the identified variants was explored by yeast complementation system and enzymatic assay. Patients presented during infancy or childhood with a variable association of neurodevelopmental disorder, generalized epilepsy, action myoclonus/cortical tremor, and ataxia. Later in the disease course they experienced a slow neurological decline with the emergence of hyperkinetic and/or hypokinetic movement disorder, cognitive deterioration, and psychiatric disturbances. Storage of lipidic material and altered lysosomes were detected in myelinated fibers and fibroblasts, suggesting a dysfunction of the lysosomal enzymatic scavenger machinery. Serum glycoprotein hypoglycosylation was not detected and, in contrast to retinitis pigmentosa and other congenital disorders of glycosylation involving dolichol metabolism, the urinary dolichol D18/D19 ratio was normal. Mapping the disease-causing variants into the protein structure revealed that most of them clustered around the active site of the DHDDS subunit. Functional studies using yeast complementation assay and in vitro activity measurements confirmed that these changes affected the catalytic activity of the cis-PTase and showed growth defect in yeast complementation system as compared with the wild-type enzyme and retinitis pigmentosa-associated protein. In conclusion, we characterized a distinctive neurodegenerative disorder due to de novo DHDDS variants, which clinically belongs to the spectrum of genetic progressive encephalopathies with myoclonus. Clinical and biochemical data from this cohort depicted a condition at the intersection of congenital disorders of glycosylation and inherited storage diseases with several features akin to of progressive myoclonus epilepsy such as neuronal ceroid lipofuscinosis and other lysosomal disorders

B cell–intrinsic signaling through IL-21 receptor and STAT3 is required for establishing long-lived antibody responses in humans

Engagement of cytokine receptors by specific ligands activate Janus kinase–signal transducer and activator of transcription (STAT) signaling pathways. The exact roles of STATs in human lymphocyte behavior remain incompletely defined. Interleukin (IL)-21 activates STAT1 and STAT3 and has emerged as a potent regulator of B cell differentiation. We have studied patients with inactivating mutations in STAT1 or STAT3 to dissect their contribution to B cell function in vivo and in response to IL-21 in vitro. STAT3 mutations dramatically reduced the number of functional, antigen (Ag)-specific memory B cells and abolished the ability of IL-21 to induce naive B cells to differentiate into plasma cells (PCs). This resulted from impaired activation of the molecular machinery required for PC generation. In contrast, STAT1 deficiency had no effect on memory B cell formation in vivo or IL-21–induced immunoglobulin secretion in vitro. Thus, STAT3 plays a critical role in generating effector B cells from naive precursors in humans. STAT3-activating cytokines such as IL-21 thus underpin Ag-specific humoral immune responses and provide a mechanism for the functional antibody deficit in STAT3-deficient patients