On the impact of controlled wall roughness shape on the flow of a soft-material

We explore the impact of geometrical corrugations on the near-wall flow properties of a soft-material driven in a confined rough microchannel. By means of numerical simulations, we perform a quantitative analysis of the relation between the flow rate $\Phi$ and the wall stress $\sigma_w$ for a number of setups, by changing both the roughness values as well as the roughness shape. Roughness suppresses the flow, with the existence of a characteristic value of $\sigma_w$ at which flow sets in. Just above the onset of flow, we quantitatively analyze the relation between $\Phi$ and $\sigma_w$. While for smooth walls a linear dependency is observed, steeper behaviours are found to set in by increasing wall roughness. The variation of the steepness, in turn, depends on the shape of the wall roughness, wherein gentle steepness changes are promoted by a variable space localization of the roughness

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

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

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

Juvenile hemochromatosis associated with heterozygosity for novel hemojuvelin mutations and with unknown cofactors

Background & Aims. Juvenile hemochromatosis (JH) is a rare autosomal recessive disorder characterized by severe early-onset iron overload, caused by mutations in hemojuvelin (HJV), hepcidin (HAMP), or a combination of genes regulating iron metabolism. Here we describe two JH cases associated with simple heterozygosity for novel HJV mutations and unknown genetic factors. Case 1: A 12 year-old male from Central Italy with beta-thalassemia trait, increased aminotransferases, ferritin 9035 ng/ml and transferrin saturation 84%, massive hepatocellular siderosis and hepatic bridging fibrosis. Case 2: A 12 year-old female from Northern Italy with ferritin 467 ng/ml, transferrin saturation 87-95%, and moderate hepatic iron overload. Material and methods. Direct sequencing of hemochromatosis genes (HFE-TfR2-HJV-HAMP-FPN-1) was performed in the children and siblings. Results. In case 1, we detected heterozygosity for a novel HJV mutation (g.3659_3660insG), which was inherited together with the beta thalassemia trait from the father, who (as well as the mother) had normal iron parameters. In case 2, we detected another novel HJV mutation (g.2297delC) in heterozygosity, which was inherited from the mother, affected by mild iron deficiency. The father had normal iron stores. Both mutations are frameshifts determining premature stop codons. No other disease causing variant was detected. Conclusion. Although beta-thalassemia trait was a possible cofactor of iron overload in case 1, iron overload cannot be explained by simple heterozygosity for HJV mutations in both cases. Other genetic factors should be investigated, and further studies are needed to understand genotype-phenotype correlations in JH

Prevalence and Determinants of Liver Disease in Relatives of Italian Patients With Advanced MASLD

Background &amp; Aims: Metabolic dysfunction associated steatotic liver disease (MASLD) has a strong genetic component. The aim of this study was to examine noninvasively the prevalence of MASLD and of advanced fibrosis in relatives of patients with advanced MASLD and the risk factors for liver involvement, with a focus on the contribution of common genetic risk variants. Methods: We prospectively enrolled 98 consecutive probands with advanced fibrosis and/or hepatocellular carcinoma caused by MASLD and 160 nontwin first-degree relatives noninvasively screened for MASLD and advanced fibrosis at 4 Italian centers. We evaluated common genetic determinants and polygenic risk scores of liver disease. Results: Among relatives, prevalence of MASLD was 56.8% overall, whereas advanced fibrosis was observed in 14.4%. At multivariable analysis in relatives, MASLD was associated with body mass index (odds ratio [OR], 1.31 [1.18–1.46]) and tended to be associated with diabetes (OR, 5.21 [0.97–28.10]), alcohol intake (OR, 1.32 [0.98–1.78]), and with female sex (OR, 0.54 [0.23–1.15]), whereas advanced fibrosis was associated with diabetes (OR, 3.13 [1.16–8.45]) and nearly with body mass index (OR, 1.09 [1.00–1.19]). Despite that the PNPLA3 risk variant was enriched in probands (P =.003) and overtransmitted to relatives with MASLD (P =.045), evaluation of genetic risk variants and polygenic risk scores was not useful to guide noninvasive screening of advanced fibrosis in relatives. Conclusions: We confirmed that about 1 in 7 relatives of patients with advanced MASLD has advanced fibrosis, supporting clinical recommendations to perform family screening in this setting. Genetic risk variants contributed to liver disease within families but did not meaningfully improve fibrosis risk stratification

Prevalence and Determinants of Liver Disease in Relatives of Italian Patients With Advanced MASLD

Background & Aims: Metabolic dysfunction associated steatotic liver disease (MASLD) has a strong genetic component. The aim of this study was to examine noninvasively the prevalence of MASLD and of advanced fibrosis in relatives of patients with advanced MASLD and the risk factors for liver involvement, with a focus on the contribution of common genetic risk variants. Methods: We prospectively enrolled 98 consecutive probands with advanced fibrosis and/or hepatocellular carcinoma caused by MASLD and 160 nontwin first-degree relatives noninvasively screened for MASLD and advanced fibrosis at 4 Italian centers. We evaluated common genetic determinants and polygenic risk scores of liver disease. Results: Among relatives, prevalence of MASLD was 56.8% overall, whereas advanced fibrosis was observed in 14.4%. At multivariable analysis in relatives, MASLD was associated with body mass index (odds ratio [OR], 1.31 [1.18–1.46]) and tended to be associated with diabetes (OR, 5.21 [0.97–28.10]), alcohol intake (OR, 1.32 [0.98–1.78]), and with female sex (OR, 0.54 [0.23–1.15]), whereas advanced fibrosis was associated with diabetes (OR, 3.13 [1.16–8.45]) and nearly with body mass index (OR, 1.09 [1.00–1.19]). Despite that the PNPLA3 risk variant was enriched in probands (P =.003) and overtransmitted to relatives with MASLD (P =.045), evaluation of genetic risk variants and polygenic risk scores was not useful to guide noninvasive screening of advanced fibrosis in relatives. Conclusions: We confirmed that about 1 in 7 relatives of patients with advanced MASLD has advanced fibrosis, supporting clinical recommendations to perform family screening in this setting. Genetic risk variants contributed to liver disease within families but did not meaningfully improve fibrosis risk stratification

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