Prostaglandin synthesis mediates the suppression of arcuate Kiss1 neuron activation and pulsatile luteinizing hormone secretion during immune/inflammatory stress in female mice.

Stress induces a series of compensatory mechanisms with the objective of restoration or adaptation of physiological function. A common casualty of the response to stress is impaired reproduction via the inhibition of pulsatile luteinizing hormone (LH) secretion; however, how stressors convey LH inhibition remains unclear and may be dependent on stress type. Immune/inflammatory stress, modeled with peripheral lipopolysaccharide (LPS) exposure, induces a systemic inflammatory response which may contrast with the neural mechanisms employed by psychosocial stressors.

TALEN-mediated intron editing of HSPCs enables transgene expression restricted to the myeloid lineage.

Gene therapy in hematopoietic stem and progenitor cells (HSPCs) shows great potential for the treatment of inborn metabolic diseases. Typical HSPC gene therapy approaches rely on constitutive promoters to express a therapeutic transgene, which is associated with multiple disadvantages. Here, we propose a novel promoterless intronic gene editing approach that triggers transgene expression only after cellular differentiation into the myeloid lineage.

Mysterious Arm Swelling in a Patient With Non-Hodgkin Lymphoma Complicated by Superior Vena Cava Syndrome.

Hematologic malignancies often create difficult venous complications. Specifically, with lymphoma, the risk of venous thromboembolism (VTE) is high, often requiring highly specialized accuracy in balancing this coagulopathy. This case study demonstrates a situation where the advanced practitioner participated in the differential diagnosis of VTEs, management, and workup of subsequent central venous complications in a patient with non-Hodgkin lymphoma and superior vena cava syndrome.

Nonoperative Treatment of Periprosthetic Humeral Shaft Fractures After Reverse Total Shoulder Arthroplasty.

Few studies report on periprosthetic humeral shaft fractures after reverse total shoulder arthroplasty (RTSA). The authors evaluated outcomes of 5 patients with this complication who were initially treated nonoperatively. Of 152 patients who underwent RTSA at the authors' institution from 2012 to 2017, 4 experienced periprosthetic humeral shaft fractures.

Association Between Delays in Radiography and Surgery With Hip Fracture Outcomes in Elderly Patients.

Appropriate waiting time for hip fracture surgery is disputed. The American Academy of Orthopaedic Surgeons recommends surgery within 48 hours of presentation, although evidence suggests that earlier surgery (within 24 hours) reduces the risks of complications and death. The authors asked: (1) Do patients who receive earlier radiographic evaluation of hip fracture undergo surgery earlier? and (2) Is "surgery delay" (time from presentation to surgery) associated with postoperative opioid use, duration of hospital stay, and 30-day and 1-year mortality rates? The authors identified 511 adults 60 years or older who were admitted to their emergency department with hip fractures from 2015 through 2017.

Racial Disparities are Present in the Timing of Radiographic Assessment and Surgical Treatment of Hip Fractures.

Background: Hip fractures are associated with 1-year mortality rates as high as 19% to 33%. Nonwhite patients have higher mortality and lower mobility rates at 6 months postoperatively than white patients. Studies have extensively documented racial disparities in hip fracture outcomes, but few have directly assessed racial disparities in the timing of hip fracture care.

Three- and 4-part proximal humeral fracture fixation with an intramedullary cage: 1-year clinical and radiographic outcomes.

Background: Reverse total shoulder arthroplasty is a treatment option for 3- and 4-part proximal humeral fractures in elderly patients. However, arthroplasty has drawbacks in younger patients because of their greater activity level and more likely need for revision surgery. In such patients, an intramedullary cage may allow for reconstruction of the proximal humerus.

Host- and Helminth-Derived Endocannabinoids That Have Effects on Host Immunity Are Generated during Infection.

Helminths have coevolved with their hosts, resulting in the development of specialized host immune mechanisms and parasite-specific regulatory products. Identification of new pathways that regulate helminth infection could provide a better understanding of host-helminth interaction and may identify new therapeutic targets for helminth infection. Here we identify the endocannabinoid system as a new mechanism that influences host immunity to helminths.

Continuous Inhalation Exposure to Fungal Allergen Particulates Induces Lung Inflammation While Reducing Innate Immune Molecule Expression in the Brainstem.

Continuous exposure to aerosolized fine (particle size ≤2.5 µm) and ultrafine (particle size ≤0.1 µm) particulates can trigger innate inflammatory responses in the lung and brain depending on particle composition.

Hematopoietic cell-derived RELMα regulates hookworm immunity through effects on macrophages.

Resistin-like molecule α (RELMα) is a highly secreted protein in type 2 (Th2) cytokine-induced inflammation including helminth infection and allergy. In infection with Nippostrongylus brasiliensis (Nb), RELMα dampens Th2 inflammatory responses. RELMα is expressed by immune cells, and by epithelial cells (EC); however, the functional impact of immune versus EC-derived RELMα is unknown.

Human resistin protects against endotoxic shock by blocking LPS-TLR4 interaction.

Helminths trigger multiple immunomodulatory pathways that can protect from sepsis. Human resistin (hRetn) is an immune cell-derived protein that is highly elevated in helminth infection and sepsis. However, the function of hRetn in sepsis, or whether hRetn influences helminth protection against sepsis, is unknown.

CD103 CD8 T Cells in the -Infected Brain Exhibit a Tissue-Resident Memory Transcriptional Profile.

During chronic infection, memory T cells acquire a unique phenotype and become dependent on different survival signals than those needed for memory T cells generated during an acute infection. The distinction between the role of effector and memory T cells in an environment of persistent antigen remains unclear. Here, in the context of chronic infection, we demonstrate that a population of CD8 T cells exhibiting a tissue-resident memory (T) phenotype accumulates within the brain.

Comparison of RELMα and RELMβ Single- and Double-Gene-Deficient Mice Reveals that RELMα Expression Dictates Inflammation and Worm Expulsion in Hookworm Infection.

Resistin-like molecules (RELMs) are highly expressed following helminth infection, where they impact both the host and helminth. While RELMα (Retnla) impairs helminth expulsion by inhibiting protective Th2 immunity, RELMβ (Retnlb) can promote its expulsion. We employed Retnla(-/-) and Retnlb(-/-) mice to delineate the function of both proteins following infection with Nippostrongylus brasiliensis, a hookworm that infects the lung and intestine.

Macrophage-derived human resistin is induced in multiple helminth infections and promotes inflammatory monocytes and increased parasite burden.

Parasitic helminth infections can be associated with lifelong morbidity such as immune-mediated organ failure. A better understanding of the host immune response to helminths could provide new avenues to promote parasite clearance and/or alleviate infection-associated morbidity. Murine resistin-like molecules (RELM) exhibit pleiotropic functions following helminth infection including modulating the host immune response; however, the relevance of human RELM proteins in helminth infection is unknown.

Polarizing the T helper 17 response in Citrobacter rodentium infection via expression of resistin-like molecule α.

Citrobacter rodentium infection is a murine model of pathogenic Escherichia coli infection that allows investigation of the cellular and molecular mechanisms involved in host-protective immunity and bacterial-induced intestinal inflammation. We recently demonstrated that following C. rodentium infection, the absence of Resistin-Like Molecule (RELM) α resulted in attenuated Th17 cell responses and reduced intestinal inflammation with minimal effects on bacterial clearance.

Alternatively Activated Macrophages Revisited: New Insights into the Regulation of Immunity, Inflammation and Metabolic Function following Parasite Infection.

The role of macrophages in homeostatic conditions and the immune system range from clearing debris to recognizing and killing pathogens. While classically activated macrophages (CAMacs) are induced by T helper type 1 (Th1) cytokines and exhibit microbicidal properties, Th2 cytokines promote alternative activation of macrophages (AAMacs). AAMacs contribute to the killing of helminth parasites and mediate additional host-protective processes such as regulating inflammation and wound healing.

Current state of palliative and end-of-life care in home versus inpatient facilities and urban versus rural settings in Africa.

Objective: Because palliative care in sub-Saharan Africa may not fit the style of delivery of palliative care in the global north, exploring the evidence can serve to reduce existing barriers and help streamline national policies that determine the optimal setting to implement formal palliative and end-of-life services.

Method: A search was conducted in Ovid MEDLINE®, PubMed, and Google Scholar databases using the search terms nursing care, terminal care, end of life care, palliative care, dying, death, hospice, opioids, morphine, Africa, sub-Saharan Africa, caregivers, and place of death. Eighty-seven relevant articles were found using the search terms.