Optimal management of oropharyngeal and esophageal candidiasis in patients living with HIV infection

Mucocutaneous candidiasis is frequently one of the first signs of human immunodeficiency virus (HIV) infection. Over 90% of patients with AIDS will develop oropharyngeal candidiasis (OPC) at some time during their illness. Although numerous antifungal agents are available, azoles, both topical (clotrimazole) and systemic (fluconazole, itraconazole, voriconazole, posaconazole) have replaced older topical antifungals (gentian violet and nystatin) in the management of oropharyngeal candidiasis in these patients. The systemic azoles, are generally safe and effective agents in HIV-infected patients with oropharyngeal candidiasis. A constant concern in these patients is relapse, which is dependent on the degree of immunosuppression commonly seen after topical therapy, rather than with systemic azole therapy. Candida esophagitis (CE) is also an important concern since it occurs in more than 10% of patients with AIDS and can lead to a decrease in oral intake and associated weight loss. Fluconazole has become the most widely used antifungal in the management of mucosal candidiasis. However, itraconazole and posaconazole have similar clinical response rates as fluconazole and are also effective alternative agents. In patients with fluconazole-refractory mucosal candidiasis, treatment options now include itraconazole solution, voriconazole, posaconazole, and the newer echinocandins (caspofungin, micafungin, and anidulafungin)

Magnetization pinning in modulated nanowires: from topological protection to the "corkscrew" mechanism

Diameter-modulated nanowires offer an important paradigm to design the magnetization response of 3D magnetic nanostructures by engineering the domain wall pinning. With the aim to understand its nature and to control the process, we analyze the magnetization response in FeCo modulated polycrystalline two-segment nanowires varying the minor diameter. Our modelling indicates a very complex behavior with a strong dependence on the disorder distribution and an important role of topologically non-trivial magnetization structures. We demonstrate that modulated nanowires with a small diameter difference are characterized by an increased coercive field in comparison to the straight ones which is explained by a formation of topologically protected walls formed by two 3D skyrmions with opposite chiralities. For a large diameter difference we report the occurrence of a novel pinning type called here the "corkscrew": the magnetization of the large diameter segment forms a skyrmion tube with a core position in a helical modulation along the nanowire. This structure is pinned at the constriction and in order to penetrate the narrow segments the vortex/skyrmion core size should be reduced

Insulin and GLP-1 infusions demonstrate the onset of adipose-specific insulin resistance in a large fasting mammal: potential glucogenic role for GLP-1.

Prolonged food deprivation increases lipid oxidation and utilization, which may contribute to the onset of the insulin resistance associated with fasting. Because insulin resistance promotes the preservation of glucose and oxidation of fat, it has been suggested to be an adaptive response to food deprivation. However, fasting mammals exhibit hypoinsulinemia, suggesting that the insulin resistance-like conditions they experience may actually result from reduced pancreatic sensitivity to glucose/capacity to secrete insulin. To determine whether fasting results in insulin resistance or in pancreatic dysfunction, we infused early- and late-fasted seals (naturally adapted to prolonged fasting) with insulin (0.065 U/kg), and a separate group of late-fasted seals with low (10 pM/kg) or high (100 pM/kg) dosages of glucagon-like peptide-1 (GLP-1) immediately following a glucose bolus (0.5g/kg), and measured the systemic and cellular responses. Because GLP-1 facilitates glucose-stimulated insulin secretion, these infusions provide a method to assess pancreatic insulin-secreting capacity. Insulin infusions increased the phosphorylation of insulin receptor and Akt in adipose and muscle of early and late fasted seals; however the timing of the signaling response was blunted in adipose of late fasted seals. Despite the dose-dependent increases in insulin and increased glucose clearance (high dose), both GLP-1 dosages produced increases in plasma cortisol and glucagon, which may have contributed to the glucogenic role of GLP-1. Results suggest that fasting induces adipose-specific insulin resistance in elephant seal pups, while maintaining skeletal muscle insulin sensitivity, and therefore suggests that the onset of insulin resistance in fasting mammals is an evolved response to cope with prolonged food deprivation

Influence of Body Weight Category on Outcomes in Candidemia Patients Treated With Anidulafungin

BACKGROUND: Case reports and pharmacokinetic data suggest off-label echinocandin dosing may be needed to reach adequate serum concentrations in obese patients. Few outcome studies exist evaluating this population. OBJECTIVES: Of this study were to (1) determine the association of body mass index (BMI) with clinical outcomes of candidemia patients on standard doses of anidulafungin and (2) characterize fungal infections by body weight. METHODS: A retrospective cohort was conducted to evaluate hospitalized patients treated for candidemia with anidulafungin at Food and Drug Administration-labeled dosing for at least 72 hours from January 1, 2014, through January 31, 2018. Candidemia was diagnosed by blood culture or T2 magnetic resonance (T2MR). Patients were compared according to BMI category. RESULTS: One hundred seventy-three patients were included. CONCLUSION: There was no difference detected in mortality among patients with candidemia across BMI category. Larger studies are needed to confirm whether standard doses of anidulafungin are sufficient for candidemia in obese patients

High Motor Vibration On A Screw Compressor Linked To Natural Frequency Excitation

Case Stud