HFE mutations and iron in hemodialysis patients

In chronic hemodialysis patients, a disruption in iron metabolism ranging from absolute to functional deficiency, with compartmentalization of this metal into macrophages, is often observed. Chronic inflammation indeed often causes an upregulation of the iron hormone hepcidin, thereby reducing iron absorption and availability to the erythron. We systematically reviewed the literature on the role of genetic risk factors on iron metabolism in hemodialysis. In this setting, mutations in the HFE gene of hereditary hemochromatosis may confer an adaptive benefit by decreasing hepcidin release, thus improving iron availability to erythropoiesis, anemia control, and the response to erythropoiesis stimulating agents and iron itself, and reducing the side effects of these therapies. The HFE protein together with Transferrin receptor-2 may also have a direct role on erythroid differentiation and iron uptake in erythroid cells. In addition, other genetic determinants of iron status, such as variants in Matriptase-2 (TMPRSS6), have been shown to influence iron metabolism in chronic hemodialysis patients, most likely acting through hepcidin regulation. Although data must be confirmed in larger prospective studies, this favorable shift in iron metabolism balance possibly results in reduced mortality, in particular because of cardiovascular and infective diseases. Further genetic studies may offer a valuable tool to test these hypotheses and guide personalized clinical management and the research of new therapies

Photonic chip based transmitter optimization and receiver demultiplexing of a 1.28 Tbit/s OTDM signal

We demonstrate chip-based Tbaud optical signal processing for all-optical performance monitoring, switching and demultiplexing based on the instantaneous Kerr nonlinearity in a dispersion-engineered As 2S 3 planar waveguide. At the Tbaud transmitter, we use a THz bandwidth radiofrequency spectrum analyzer to perform all-optical performance monitoring and to optimize the optical time division multiplexing stages as well as mitigate impairments, for example, dispersion. At the Tbaud receiver, we demonstrate error-free demultiplexing of a 1.28 Tbit/s single wavelength, return-to-zero signal to 10 Gbit/s via four-wave mixing with negligible system penalty (< 0.5 dB). Excellent performance, including high fourwave mixing conversion efficiency and no indication of an error-floor, was achieved. Our results establish the feasibility of Tbaud signal processing using compact nonlinear planar waveguides for Tbit/s Ethernet applications

Instantaneous frequency measurement system using optical mixing in highly nonlinear fiber

A broadband photonic instantaneous frequency measurement system utilizing four-wave mixing in highly nonlinear fiber is demonstrated. This new approach is highly stable and does not require any high-speed electronics or photodetectors. A first principles model accurately predicts the system response. Frequency measurement responses from 1 to 40 GHz are demonstrated and simple reconfiguration allows the system to operate over multiple bands

Adaptive Dispersion Compensation for Remote Fiber Delivery of NIR Femtosecond Pulses

We report on remote delivery of 25 pJ broadband near-infrared femtosecond light pulses from a Ti:sapphire laser through 150 meters of single-mode optical fiber. Pulse distortion due to dispersion is overcome with pre-compensation using adaptive pulse shaping techniques, while nonlinearities are mitigated using an SF10 rod for the final stage of pulse compression. Near transform limited pulse duration of 130 fs is measured after the final compression.Comment: 3 pages, 4 figure

Immune-related adverse events in the treatment of non-Hodgkin lymphoma with immune checkpoint inhibitors

Immune checkpoint inhibitors (ICIs) show efficacy in the treatment of non-Hodgkin lymphomas (NHL). However, these agents are associated with a unique group of side effects called immune-related adverse events (irAEs). We conducted an observational retrospective/prospective study on patients with relapsed/refractory NHL treated with ICI to determine the incidence of irAEs assessing the type, severity, and timing of onset, outcome and relationship with study drugs of these events. Thirty-two patients underwent ICI as single agent (N = 20) or in combination (N = 12). Ten patients (31.3%) developed at least one irAE for a total of 17 irAEs. Median time to presentation of irAEs was 69 days (range 0–407) with a median resolution time of 16 days (range 0–98). Progression free survival at 24 months for patients who developed an irAE was 40% and 31.8% for who did not. Overall survival for the two groups did not differ (at 24 months 40.0% and 62.5% for patients without and with irAE, respectively), but the median for who developed an irAE was not reached. The incidence of irAEs was associated with better long-term survival in NHL treated with ICIs but patients’ disease conditions need to be carefully evaluated to decide the optimal management

A Cooperative Emergency Navigation Framework using Mobile Cloud Computing

The use of wireless sensor networks (WSNs) for emergency navigation systems suffer disadvantages such as limited computing capacity, restricted battery power and high likelihood of malfunction due to the harsh physical environment. By making use of the powerful sensing ability of smart phones, this paper presents a cloud-enabled emergency navigation framework to guide evacuees in a coordinated manner and improve the reliability and resilience in both communication and localization. By using social potential fields (SPF), evacuees form clusters during an evacuation process and are directed to egresses with the aid of a Cognitive Packet Networks (CPN) based algorithm. Rather than just rely on the conventional telecommunications infrastructures, we suggest an Ad hoc Cognitive Packet Network (AHCPN) based protocol to prolong the life time of smart phones, that adaptively searches optimal communication routes between portable devices and the egress node that provides access to a cloud server with respect to the remaining battery power of smart phones and the time latency.Comment: This document contains 8 pages and 3 figures and has been accepted by ISCIS 2014 (29th International Symposium on Computer and Information Sciences

Testosterone decreases adiponectin levels in female to male transsexuals

Aim: To evaluate the effect of testosterone (T) on adiponectin serum levels in transsexual female patients. Methods: We measured adiponectin, leptin, luteinizing hormone and follicle stimulating hormone, T, estradiol, lipid profile, biochemical parameters and body composition in 16 transsexual female patients at baseline and after 6 months of T treatment (100 mg Testoviron Depot /10 days, i.m.). Results: Adiponectin levels were 16.9 ± 7.3 mg/mL at baseline and 13.5 ± 7.4 mg/mL at month 6 of T treatment (P < 0.05). Leptin and high-density lipoprotein cholesterol decreased significantly, whereas body mass index, waist circumference and lean body mass increased significantly after 6 months of T treatment. No changes in insulin or Homeostasis Model Assessment were detected. Conclusion: T can significantly reduce adiponectin serum levels in transsexual female patients

Hepcidin levels in chronic hemodialysis patients : A critical evaluation

Altered systemic iron metabolism is a key element of uremia, and functional iron deficiency mainly related to subclinical inflammation makes it difficult to maintain proper control of anemia in chronic hemodialysis patients (CHD). In the last decade, the hepatic hormone hepcidin has been progressively recognized as the master regulator of circulating iron levels through the modulation of cellular iron fluxes in response to iron stores, as well as to erythroid and inflammatory stimuli. Hepcidin is cleared by the kidney and progression of renal disease has been associated to increased serum hepcidin levels. This, in turn, reduces iron availability for erythropoiesis, suggesting anti-hepcidin strategies for improving anemia control. Moreover, hepcidin has been recently implicated in the pathogenesis of long-term complications of dialysis, like accelerated atherosclerosis. Initial studies almost invariably reported a sustained increase of serum hepcidin in chronic hemodialysis patients. Noteworthy, such studies included relatively few patients and controls that were poorly matched for major determinants of serum hepcidin at population level, i.e., age and gender. More recent data based on accurately matched larger series challenge the view that hepcidin is intrinsically increased in hemodialysis patients, showing a marked inter-and intra-individual variability of hormone levels. Here we take a critical look to the data published so far on hepcidin levels in CHD, analyze the reasons underlying the discrepancies in available studies and the hepcidin variability in CHD, and point out the need for further studies in large series of well-characterized CHD patients and controls

Exploring the human chorionic gonadotropin induced steroid secretion profile of mouse Leydig tumor cell line 1 by a 20 steroid LC-MS/MS panel

The canonical androgen synthesis in Leydig cells involves Delta 5 and Delta 4 steroids. Besides, the backdoor pathway, eompassing 5 alpha and 5 alpha,3 alpha steroids, is gaining interest in fetal and adult pathophysiology. Moreover, the role of androgen epimers and progesterone metabolites is still unknown. We developed a liquid chromatographytandem mass spectrometry (LC-MS/MS) method for measuring 20 steroids and used it to investigate the steroid secretion induced by human chorionic gonadotropin (hCG) in the mouse Leydig tumor cell line 1 (mLTC1). Steroids were extracted from 500 mu L supernatants from unstimulated or 100 pM hCG-exposed mLTC1 cells, separated on a Luna C8 100 x 3 mm, 3 mu m column, with 100 mu M NH4F and methanol as mobile phases, and analyzed by positive electrospray ionization and multiple reaction monitoring. Sensitivity ranged within 0.012-38.0 nmol/L. Intra-assay and inter-assay imprecision were &lt; 9.1% and 10.0%, respectively. Trueness, recovery and matrix factor were within 93.4-122.0, 55.6-104.1 and 76.4-106.3%, respectively. Levels of 16OH-progesterone, 11-deoxycortisol, androstenedione, 11-deoxycorticosterone, testosterone, 17OH-progesterone, androstenedione, epitestosterone, dihydrotestosterone, progesterone, androsterone and 17OH-allopregnanolone were effectively measured. Traces of 17OH-dihydroprogesterone, androstanediol and dihydroprogesterone were found, whereas androstenediol, 17OH-pregnenolone, dehydroepiandrosterone, pregnenolone and allopregnanolone showed no peak. hCG induced an increase of 80.2-102.5 folds in 16OH-progesterone, androstenedione and testosterone, 16.6 in dihydrotestosterone, 12.2-27.5 in epitestosterone, progesterone and metabolites, 8.1 in 17OH-allopregnanolone and &lt;= 3.3 in 5 alpha and 5 alpha,3 alpha steroids