Systemic lupus erythematosus (lupus, SLE) is a chronic autoimmune disease characterized by the production of autoantibodies, which bind to antigens and are deposited within tissues to fix complement, ...resulting in widespread systemic inflammation. The studies presented herein are consistent with hyperpolarized, adenosine triphosphate (ATP)-deficient mitochondria being central to the disease process. These hyperpolarized mitochondria resist the depolarization required for activation-induced apoptosis. The mitochondrial ATP deficits add to this resistance to apoptosis and also reduce the macrophage energy that is needed to clear apoptotic bodies. In both cases, necrosis, the alternative pathway of cell death, results. Intracellular constituents spill into the blood and tissues, eliciting inflammatory responses directed at their removal. What results is “autoimmunity.” Ultraviolet (UV)-A1 photons have the capacity to remediate this aberrancy. Exogenous exposure to low-dose, full-body, UV-A1 radiation generates singlet oxygen. Singlet oxygen has two major palliative actions in patients with lupus and the UV-A1 photons themselves have several more. Singlet oxygen depolarizes the hyperpolarized mitochondrion, triggering non-ATP-dependent apoptosis that deters necrosis. Next, singlet oxygen activates the gene encoding heme oxygenase (HO-1), a major governor of systemic homeostasis. HO-1 catalyzes the degradation of the oxidant heme into biliverdin (converted to bilirubin), Fe, and carbon monoxide (CO), the first three of these exerting powerful antioxidant effects, and in conjunction with a fourth, CO, protecting against injury to the coronary arteries, the central nervous system, and the lungs. The UV-A1 photons themselves directly attenuate disease in lupus by reducing B cell activity, preventing the suppression of cell-mediated immunity, slowing an epigenetic progression toward SLE, and ameliorating discoid and subacute cutaneous lupus. Finally, a combination of these mechanisms reduces levels of anticardiolipin antibodies and protects during lupus pregnancy. Capping all of this is that UV-A1 irradiation is an essentially innocuous, highly manageable, and comfortable therapeutic agency.
Seliciclib (CYC202; R-roscovitine) is the first selective, orally bioavailable inhibitor of cyclin-dependent kinases 1, 2, 7 and 9 to enter clinical trial. Preclinical studies showed antitumour ...activity in a broad range of human tumour xenografts. A phase I trial was performed with a 7-day b.i.d. p.o. schedule. Twenty-one patients (median age 62 years, range: 39-73 years) were treated with doses of 100, 200 and 800 b.i.d. Dose-limiting toxicities were seen at 800 mg b.i.d.; grade 3 fatigue, grade 3 skin rash, grade 3 hyponatraemia and grade 4 hypokalaemia. Other toxicities included reversible raised creatinine (grade 2), reversible grade 3 abnormal liver function and grade 2 emesis. An 800 mg portion was investigated further in 12 patients, three of whom had MAG3 renograms. One patient with a rapid increase in creatinine on day 3 had a reversible fall in renal perfusion, with full recovery by day 14, and no changes suggestive of renal tubular damage. Further dose escalation was precluded by hypokalaemia. Seliciclib reached peak plasma concentrations between 1 and 4 h and elimination half-life was 2-5 h. Inhibition of retinoblastoma protein phosphorylation was not demonstrated in peripheral blood mononuclear cells. No objective tumour responses were noted, but disease stabilisation was recorded in eight patients; this lasted for a total of six courses (18 weeks) in a patient with ovarian cancer.
Multiple disease and treatment‐related factors contribute to intestinal insult and influence the nutritional status of children with cancer. Many children with cancer will experience intestinal ...dysfunction during their cancer journey and children with cancer are a common referral group for inpatient parenteral nutrition. Appropriate use of parenteral nutrition in children with cancer and intestinal failure may alleviate malnutrition and associated risks. However, proper selection of patients, correct parenteral nutrition prescription, and close monitoring is important to avoid unnecessary intestinal failure or parenteral nutrition–related complications, minimize long‐term nutritional sequelae or additional costs to health services, and optimize intestinal rehabilitation.
Flood is one of the most damaging natural hazards in urban areas in many places around the world as well as the city of Fredericton, New Brunswick, Canada. Recently, Fredericton has been flooded in ...two consecutive years in 2018 and 2019. Due to the complicated behaviour of water when a river overflows its bank, estimating the flood extent is challenging. The issue gets even more challenging when several different factors are affecting the water flow, like the land texture or the surface flatness, with varying degrees of intensity. Recently, machine learning algorithms and statistical methods are being used in many research studies for generating flood susceptibility maps using topographical, hydrological, and geological conditioning factors. One of the major issues that researchers have been facing is the complexity and the number of features required to input in a machine-learning algorithm to produce acceptable results. In this research, we used Random Forest to model the 2018 flood in Fredericton and analyzed the effect of several combinations of 12 different flood conditioning factors. The factors were tested against a Sentinel-2 optical satellite image available around the flood peak day. The highest accuracy was obtained using only 5 factors namely, altitude, slope, aspect, distance from the river, and land-use/cover with 97.57% overall accuracy and 95.14% kappa coefficient.
Background and Aim
Children with intestinal failure (IF) have abnormal intestinal anatomy, secretion, or motility, which impairs homeostatic mechanisms and can lead to small intestinal bacterial ...overgrowth (SIBO). We sought to describe clinical features at the time of clinically suspected SIBO by experienced clinicians in children with IF on home parenteral nutrition (PN), review specific challenges of diagnostic testing in this population, and describe potential new diagnostic surrogate markers.
Methods
A descriptive single‐center retrospective chart review was performed during all episodes of clinically suspected SIBO over 33 months. Information was recorded on clinical symptoms, and diagnostic tests performed.
Results
Of all patients on home PN, 71% (12/17) had at least one episode of clinically suspected SIBO (mean 1 episode/year, range 1–7); 50% of patients had short bowel syndrome (SBS), and 50% had non‐SBS IF. The average reported symptoms per episode were 1.9 (range 1–5). Children with SBS reported fewer symptoms per episode (1.5) than children with non‐SBS IF (2.3). Diarrhea was the most commonly reported symptom, particularly in children with SBS.
Conclusions
Children with IF on home PN are a high‐risk group for SIBO. Clinical features of SIBO vary depending on the cause of IF and may mimic symptoms of the underlying condition. Diagnostic tests have innate challenges in this group, and a strong index of clinical suspicion is paramount. Further research is recommended into potential new surrogate markers (urinary metabolite screen, gastric aspirate) for this diagnostically challenging population.
Children with intestinal failure (IF) on home parenteral nutrition are a high‐risk group for small intestinal bacterial overgrowth. We identified clinical features during episodes of clinically suspected small intestinal bacterial overgrowth and found variation depending on the underlying cause of IF. Diagnostic tests have innate challenges in children with IF on home parenteral nutrition, and we discuss potential new surrogate markers for this diagnostically challenging population.
Children with cancer are at risk of treatment related gastrointestinal toxicity and malnutrition. Intestinal dysfunction may preclude or limit use of enteral nutrition, and parenteral nutrition (PN) ...may be required. Published indications for PN use in children with cancer are generally nonspecific. We sought to describe patterns of use, indications, and frequency of PN prescription in children with cancer and propose indicators to guide appropriate PN use.
Retrospective chart review of children with cancer receiving inpatient PN in a tertiary referral pediatric hospital over 12 months was performed using electronic medical record search and paper records. Data were summarized using descriptive statistics.
PN was prescribed to 88 patients in 111 episodes. Total use (2377 days) represented 24% of annual inpatient days in all children with cancer. Primary clinical indications were mucositis (40%), feed intolerance (29%), postoperative (16%), or "other" (15%), (including nasogastric tube refusal (n = 6)). Patients with hematological cancer had longer median episodes (19 vs 12.5 days) and earlier commencement of PN after diagnosis (50 vs 80 days) than children with nonhematological cancer. Most PN episodes longer than 28 days were in children with hematopoietic stem cell transplant (HSCT).
Inpatient PN use is common in childhood cancer. Indications include mucositis, feed intolerance, and surgical management. Patterns of use are influenced by cancer diagnosis and treatment, with greater use in children with hematological cancer and HSCT. Improved understanding and specific indications may guide appropriate PN prescription and minimize unnecessary risk, cost, and inconsistency in care.
Gastrostomy tube use in children with cancer McGrath, Kathleen H.; Hardikar, Winita
Pediatric blood & cancer,
July 2019, 2019-07-00, 20190701, Letnik:
66, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Children with cancer are at risk of malnutrition, which can impair critical childhood processes of growth and development and contribute to poor health outcomes. Enteral nutrition can effectively ...ameliorate malnutrition or weight loss in children with cancer; however, published nutrition support algorithms contain minimal specific information on gastrostomy tube use, and current literature is limited. Decisions about gastrostomy tube insertion in children with cancer can be challenging. Consideration of gastrostomy tube insertion is only appropriate in children with long‐term dependence on enteral nutrition, particularly when nasogastric tube insertion is predicted or proven to be problematic. Specific indications for patient selection are unclear, and referring clinicians may be unaware of important absolute and relative contraindications. Complications are predominantly minor in nature; however, reported rates are high. Morbidity must be weighed carefully against the need and anticipated duration of enteral nutrition support, and further research in this area is needed.
Memory regulatory T cells reside in human skin Sanchez Rodriguez, Robert; Pauli, Mariela L; Neuhaus, Isaac M ...
The Journal of clinical investigation,
03/2014, Letnik:
124, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Regulatory T cells (Tregs), which are characterized by expression of the transcription factor Foxp3, are a dynamic and heterogeneous population of cells that control immune responses and prevent ...autoimmunity. We recently identified a subset of Tregs in murine skin with properties typical of memory cells and defined this population as memory Tregs (mTregs). Due to the importance of these cells in regulating tissue inflammation in mice, we analyzed this cell population in humans and found that almost all Tregs in normal skin had an activated memory phenotype. Compared with mTregs in peripheral blood, cutaneous mTregs had unique cell surface marker expression and cytokine production. In normal human skin, mTregs preferentially localized to hair follicles and were more abundant in skin with high hair density. Sequence comparison of TCRs from conventional memory T helper cells and mTregs isolated from skin revealed little homology between the two cell populations, suggesting that they recognize different antigens. Under steady-state conditions, mTregs were nonmigratory and relatively unresponsive; however, in inflamed skin from psoriasis patients, mTregs expanded, were highly proliferative, and produced low levels of IL-17. Taken together, these results identify a subset of Tregs that stably resides in human skin and suggest that these cells are qualitatively defective in inflammatory skin disease.
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