High prevalence of a screening-detected,HFE-unrelated,mild idiopathic iron overload in Northern Italy

BACKGROUND AND OBJECTIVES: In Italy, typical HFE mutations account for only 64% of the cases with overt hereditary hemochromatosis (HH), and a common HFE-unrelated disease was hypothesized. DESIGN AND METHODS: One thousand and fifty potential blood donors were screened by iron tests, C282Y and H63D HFE mutation analysis in a region in North Italy. Subjects with repeated fasting transferrin saturation of 45% or more and no secondary iron overload were defined as probands with idiopathic iron overload. To assess the inheritance of iron overload, relatives of probands were screened. RESULTS: The overall frequency of probands with idiopathic iron overload was 3.43% (95% confidence interval, 2.32 to 4.52). Of these, 8.4% had genotypes associated with HH (compound heterozygous for H63D/C282Y or homozygous for H63D HFE mutations), and 91.6% had atypical genotypes: 47.2% were heterozygous for C282Y or H63D HFE mutations, and 44.4% had wild type/wild type genotype. A family history of iron overload was proven in 33.3% of probands with atypical genotypes (1.04% of the overall population). Pedigree analysis excluded linkage of heterozygous HFE mutations with iron overload (cumulative lod score 2.41) and documented a recessive non-HLA-linked locus accounting for iron overload in wild type/wild type genotypes. None of the probands had clinical signs of iron accumulation; in males, serum ferritin positively correlated with age (r=0.63, p<0.01), and the regression model predicted a serum ferritin of 700 ng/mL at the age of 58. INTERPRETATION AND CONCLUSIONS: In Northern Italy an HFE-unrelated, mild idiopathic iron overload is highly prevalent. A recessive locus accounts for iron overload in at least 1.04% of the overall population.     

Optimization of 3D ZnO brush-like nanorods for dye-sensitized solar cells

In a dye-sensitized solar cell (DSSC) the amount of adsorbed dye on the photoanode surface is a key factor that must be maximized in order to obtain enhanced DSSC performance. In this study 3D ZnO nanostructures, named brush-like, are demonstrated as alternative photoanodes. In these structures, long ZnO nanorods are covered with a metal–organic precursor, known as a layered-hydroxide zinc salt (LHZS), which is subsequently converted to crystalline ZnO using two-step annealing. The LHZS is able to easily grow on any surface, such as the ZnO nanorod surface, without needing the assistance of a seed-layer. Brush-like structures synthesized using different citrate concentrations in the growth solutions and different annealing conditions are characterized and tested as DSSC photoanodes. The best-performing structure reported in this study was obtained using the highest citrate concentration (1.808 mM) and the lowest temperature annealing condition in an oxidative environment. Conversion efficiency as high as 1.95% was obtained when these brush-like structures were employed as DSSC photoanodes. These results are extremely promising for the implementation of these innovative structures in enhanced DSSCs, as well as in other applications that require the maximization of surface area exposed by ZnO or similar semiconductors, such as gas- or bio-sensing or photocatalysis.

Optimized 3D ZnO brush-like nanorods showing large surface area are presented as the photoanode in enhanced high-current-density DSSCs.     

From the Cover: Sleep homeostasis in the rat is preserved during chronic sleep restriction

Sleep is homeostatically regulated in all animal species that have been carefully studied so far. The best characterized marker of sleep homeostasis is slow wave activity (SWA), the EEG power between 0.5 and 4 Hz during nonrapid eye movement (NREM) sleep. SWA reflects the accumulation of sleep pressure as a function of duration and/or intensity of prior wake: it increases after spontaneous wake and short-term (3–24 h) sleep deprivation and decreases during sleep. However, recent evidence suggests that during chronic sleep restriction (SR) sleep may be regulated by both allostatic and homeostatic mechanisms. Here, we performed continuous, almost completely artifact-free EEG recordings from frontal, parietal, and occipital cortex in freely moving rats (n = 11) during and after 5 d of SR. During SR, rats were allowed to sleep during the first 4 h of the light period (4S⁺) but not during the following 20 h (20S⁻). During the daily 20S⁻ most sleep was prevented, whereas the number of short (<20 s) sleep attempts increased. Low-frequency EEG power (1–6 Hz) in both sleep and wake also increased during 20S⁻, most notably in the occipital cortex. In all animals NREM SWA increased above baseline levels during the 4S⁺ periods and in post-SR recovery. The SWA increase was more pronounced in frontal cortex, and its magnitude was determined by the efficiency of SR. Analysis of cumulative slow wave energy demonstrated that the loss of SWA during SR was compensated by the end of the second recovery day. Thus, the homeostatic regulation of sleep is preserved under conditions of chronic SR.     

Nipple-sparing mastectomy--is it worth the risk?

Nipple-sparing mastectomy (NSM) is a surgical protocol designed to reduce the disabling psychological effects of radical or skin-sparing mastectomy. The preservation of the nipple-areola complex produces a more-natural result of the breast reconstruction, but this preservation is suspected of increasing tumor local recurrence. To reduce this risk, different approaches have been proposed: restrict the inclusion criteria and/or add localized radiation therapy. The local recurrence rate in recent series of patients receiving NSM is comparable with the local recurrence rate in modified radical or skin-sparing mastectomies. Today, the quality of the subcutaneous mastectomy technique allows for a more radical glandular removal, especially in the retroareolar area; therefore, local recurrence is observed in 3-6% of patients at 5 years, consistent with traditional mastectomy.     

The low level laser therapy in the management of neurological burning mouth syndrome. A pilot study

BACKGROUND AND OBJECTIVE.: Burning Mouth Syndrome (BMS) is a common disease but still a diagnostic and therapeutic challenge for clinicians. Despite many studies its nature remains obscure and controversial; nowadays there is no consensus about definition, diagnosis and classification. BMS is characterized clinically by burning sensations in the tongue or other oral sites, often without clinical and laboratory findings. According to the etiology, BMS cases should be subdivided into three subtypes: BMS by local factors (lfBMS), BMS by systemic factors (sfBMS) and neurological BMS (nBMS), the most frequent, in which the symptom is caused by central or peripheral neurological malfunctions affecting in particular the taste pathway. To establish the type of BMS, both anamnesis and clinical examination, including laboratory tests, are necessary; nBMS cases will be recognized by exclusion of any other type. In case of lfBMS or sfBMS, the treatment of the main pathology will be resolutive; in nBMS cases many Authors proposed different pharmacological trials without satisfactory results and the current opinion is that a multidisciplinary approach is required to keep the condition under control. This pilot study aimed to investigate whether the biostimulative effect of Low Level Laser Therapy (LLLT) could enhance the symptoms of nBMS cases, improving patients' quality of life. STUDY DESIGN/MATERIALS AND METHODS.: Among 160 patients affected by oral burning sensation attending to the Oral Pathology Complex Operative Unit of the Department of Stomatological Sciences of Sapienza University of Rome, 77 resulted affected by nBMS. Twenty-five of these patients, 16 females and 9 males, were randomly selected for low level laser applications. All the patients were irradiated with a double diode laser (Lumix 2 Prodent, Italy) emitting contemporarily at 650 nm and 910 nm, with a fluence of 0.53 J/cm(2) for 15 minutes twice a week for 4 weeks. The areas of irradiation were the sides of the tongue on the path of taste fibers. A NRS (numerical rating scale) evaluation of maximum and minimum pain was registered before and after the treatment. In each case to the total value of NRS rates registered before the treatment was deducted the total NRS rate registered after the treatment. The difference was estimated effective if over two points. The Kruskall-Wallis test revealed the significance of the study (p<0.0001) and the Dunn's Multiple Comparison test, applied to compare NRS rates before and after the treatment, showed that there is not a statistically relevant difference between min NRS ratings before and after treatment, while there are statistically significant differences between max NRS ratings (p<0.05). RESULTS: All the patients agreed the treatment confirming the general good compliance related to laser treatments. No side effects were registered and all the patients completed the therapy without interruption. Seventeen patients (68%) had relevant benefits from the treatment with valid reduction of NRS ratings. In 8 cases the differences of NRS rates were not relevant being under the limit of reliability established in study design. In no case there was a worsening of the symptoms. CONCLUSIONS: According to the results of this pilot study it is reasonable to suppose that LLLT may play an important role in the management of nBMS cases, more investigations are needed to clarify, by a greater number of cases and a placebo control group, the real effectiveness of this innovative LLLT application.     

Response to Therapy as a Criterion for Awarding Priority to Patients With Hepatocellular Carcinoma Awaiting Liver Transplantation

Background

How to prioritize patients with hepatocellular carcinoma (HCC) for liver transplantation (LT) remains controversial. This study was designed to assess the effectiveness of a policy for prioritizing HCC patients according to their response to pre-LT therapy.

Methods

The study period was from 2000 to 2008. Dropout criteria included macroscopic vascular invasion, metastases, and poorly differentiated grade at pre-LT biopsy. A specific treatment algorithm was adopted to treat HCC before LT, and the effect of treatment was evaluated 3 months after listing or after the diagnosis of HCC for patients diagnosed while already on the waiting list. Patients were divided into two groups: group 1, patients with disease that completely or partially responded to therapy; and group 2, patients with stable, progressive, or untreatable disease. Group 2 patients were prioritized for LT unless full restaging and repeat biopsy identified dropout criteria.

Results

At the 3-month visit, 62 HCC patients (42%) were assigned to group 2 and 85 (58%) to group 1. Eleven of 12 dropouts due to tumor progression came from group 2 (P < 0.01). Response to therapy was the sole predictor of dropout probability, independent of tumor stage (competing risk analysis). The 42 patients in group 2 who were transplanted had much the same 3-year post-LT survival rate as the 57 transplanted patients in group 1 (with survival rates of 82% and 83%, respectively; P > 0.05), but a slightly higher risk of post-LT HCC recurrence (13% and 2%, respectively; P = 0.04).

Conclusions

Response to therapy is a potentially effective tool for prioritizing HCC patients for LT.     

p53 expression in patients with advanced urothelial cancer of the urinary bladder

Study Type – Prognosis (inception cohort)
Level of Evidence 1b

OBJECTIVE

To test whether assessing p53 expression could improve the ability to predict disease recurrence and disease‐specific survival in a multi‐institutional cohort of patients with advanced urothelial carcinoma of the urinary bladder (UCB).

PATIENTS AND METHODS

The study comprised 692 patients with pT3–4 N0 or pTany N+ UCB treated with radical cystectomy and lymphadenectomy. The predictive accuracy (PA) was quantified using the 200 bootstrap‐corrected concordance index. The base model comprised age, gender, stage, grade, lymphovascular invasion, number of lymph nodes removed, number of lymph nodes positive, concomitant carcinoma in situ, and adjuvant chemotherapy.

RESULTS

p53 expression was altered in 341 (49.3%) patients. In multivariable analyses, p53 expression was independently associated with disease recurrence (hazard ratio, 1.66; P < 0.001) and cancer‐specific mortality (hazard ratio 1.65, P < 0.001). Overall, adding p53 did not significantly improve the PA of the base model (recurrence +0.7%, P = 0.085, and cancer‐specific mortality +1.2%, P = 0.050). In the subgroups of pT3N0 (280) and pT4N0 (83) patients, p53 slightly improved the PA of the base model by a statistically significant degree (recurrence +1.7% and +3.6%, respectively; cancer‐specific mortality +1.9% and +3.5%, respectively; all P < 0.001). In 329 patients with pTany N+ disease p53 status did not improve the PA of the base model.

CONCLUSION

While assessing p53 expression has limited utility in patients with lymph node‐positive UCB, it marginally improves prognostication in patients with advanced non‐metastatic UCB. Integration of p53 into a panel of biomarkers might be necessary to capture a more accurate picture of the biological potential of advanced UCB.