Sustained telomere length in hepatocytes and cholangiocytes with increasing age in normal liver

Telomeres, a validated biomarker of aging, comprise multiple nucleotide repeats capping chromosomes that shorten with each cell cycle until a critical length is achieved, precipitating cell senescence. Only two previous studies focused on the effect of aging in "normal" liver tissue, but these studies were compromised by small sample size, limited age range, tissue derived from individuals with an increased risk of senescence, and the use of liver homogenates. We developed a robust large-volume, four-color quantitative fluorescent in situ hybridization technique to measure telomere length in large numbers of hepatocytes, Kupffer cells, hepatic stellate cells, CD4-positive and CD8-positive lymphocytes, and cholangiocytes. Following validation against the gold standard (Southern blotting), the technique was applied to normal archived paraffin-embedded liver tissue obtained following reperfusion of implanted donor liver. We studied 73 highly selected donors aged 5-79 years with a short medical illness preceding death and no history of liver disease, reperfusion injury, or steatosis and normal graft function 1-year posttransplantation. Cholangiocytes had significantly longer telomeres compared with all other intrahepatic lineages over a wide age range (P < 0.05). Age-related telomere attrition was restricted to sinusoidal cells (i.e., Kupffer cells [P = 0.0054] and stellate cells [P = 0.0001]). Cholangiocytes and hepatocytes showed no age-related telomere shortening. Conclusion: In normal liver and over a broad age range, cholangiocytes have longer telomeres than all other intrahepatic lineages. Age-related telomere length decline is restricted to Kupffer cells and stellate cells. (HEPATOLOGY 2012).     

Left-handedness is statistically linked to lifetime experimentation with illicit drugs

Handedness has been linked to an enhanced risk of alcohol abuse, while less is known about other drugs. A convenience sample of 1004 male and female Italian participants (females=58%) from the general community (18 to 65 years old: average age = 30; standard deviation = 10, median = 25) was asked about: handedness (preference in writing); lifetime use of alcohol, tobacco, and illicit drugs; levels of psychological distress, as measured by the General Health Questionnaire (GHQ); and levels of delusion proneness, as measured by the Peters et al. Delusions Inventory (PDI). Overall, 92 individuals (9.2%) were classified as left-handed, with no significant difference reported among genders. Lifetime use of illicit drugs, primarily cannabis, was reported by 20% of the sample. In a multiple logistic regression analysis, after taking into account sex, age, and caseness on GHQ and PDI, left-handed people in the sample were statistically more likely to report lifetime experimentation with heroin, ecstasy/amphetamine, and, marginally, hallucinogens, but not alcohol or tobacco. Different mechanisms might contribute to an explanation of greater lifetime experimentation with some illicit drugs among left-handed people as compared to right-handed people. However, replications with clinical samples are necessary before any definitive statements can be made.     

Adipose-derived stem cells and rabbit bone regeneration: histomorphometric, immunohistochemical and mechanical characterization

Background

In the last few years, several attempts have been made to treat large bone loss, including the use of tissue engineering with osteoinductive scaffolds and cells. This study highlights the role of mesenchymal stem cells from adipose tissue (ASCs; adipose-derived stem cells) in a rabbit bone regeneration model.

Methods

We compared the neoformed bone tissues achieved by treating critical tibial defects with either hydroxyapatite alone (HA, group I) or hydroxyapatite–autologous ASC constructs (ASCs-HA, group II), investigating their histomorphometric, immunohistochemical and biomechanical properties.

Results

After eight weeks of follow-up, we observed advanced maturation and a spatial distribution of new bone that was more homogeneous in the inner parts of the pores in group II, not just along the walls (as seen in group I). The new tissue expressed osteogenic markers, and biomechanical tests suggested that the newly formed bone in group II had a higher mineral content than that in group I. Although variability in differentiation was observed among the different cell populations in vitro, no differences in bone healing were observed in vivo; the variability seen in vitro was probably due to local microenvironment effects.

Conclusions

Tibial defects treated with rabbit ASCs-HA showed an improved healing process when compared to the process that occurred when only the scaffold was used. We suggest that implanted ASCs ameliorate the bone reparative process either directly or by recruiting resident progenitor cells.     

Transplantation of Autologous Cultivated Conjunctival Epithelium for the Restoration of Defects in the Ocular Surface

Ocular surface disorders are often characterised by partial or complete loss of corneo-conjunctival epithelium, which causes dramatic functional and cosmetic problems. Depletion of stem cells and the scarcity of donor tissue available make large or bilateral defects challenging to reconstruct, and usually require the transplantation of heterotopic or allogeneic grafts. We investigated the feasibility of restoring severely damaged ocular surfaces with autologous cultivated conjunctival epithelium. Conjunctival cells were harvested from the healthy eyelid bed of four patients with oculopalpebral diseases. An epithelial sheet reproducing the original conjunctival epithelium was generated by serial cell culture. This was transplanted for the first time ever to our knowledge on to the ocular surface of the same patients. Take was excellent and the cultivated epithelium was stable, resulting in great improvement of patient's symptoms and cosmesis. Transplantation of cultivated conjunctival cells opens new perspectives in the treatment of severe ocular surface disorders.     

Occlus-o-Guide? versus Andresen activator appliance: neuromuscular evaluation

Background

The aim of the present study was to assess the muscular variations at the electromyography (EMG) level for the anterior temporalis muscles and masseter muscles during treatment with Occlus-o-Guide^® and Andresen activator appliances.

Methods

Eighty-two patients (35 males and 47 females) aged between 8 and 12 years (mean age, 10.5 ± 0.8 years) participated in the study. Fifty patients underwent treatment with an Occlus-o-Guide^® and 32 patients with an Andresen activator. All patients underwent EMG examination using a Freely EMG (De Gotzen, Legnano, Italy) and surface bipolar electrodes when the appliances were worn for the first time (T0), and after 6 months (T1) and after 12 months (T2) of appliance use.

Results

Statistical analysis showed that both at T0 and T2, the percent overlapping coefficient (POC) of the anterior temporalis muscles was not statistically different between the appliance groups. At T0, the POC of the masseter muscles was significantly lower for the Andresen appliance as compared to the Occlus-o-Guide^® (p = 0.02), while at T2 this significance was lost.

Conclusions

At insertion of an appliance, all patients show neuromuscular balance that does not correspond to orthognathic occlusion. Both appliances work by creating muscular imbalance. With the appliances in situ, EMG responses were generally analogous for the Occlus-o-Guide^® and the Andresen activator; however, the imbalance was greater and the recovery of the orthological muscular balance was slower in patients under treatment with the Andresen activator as compared to those with the Occlus-o-Guide^®.     

Foreign Accent Syndrome: In the ear of the beholder?

Background: The identification of accent type in patients with acquired accent change following brain damage (Foreign Accent Syndrome; FAS), may vary depending on the judge. Aims: This experiment tests the accent identification abilities of naive judges listening to speech samples from FAS patients versus healthy controls. Method & Procedures: A total of 52 naive judges listened to speech samples from speakers of British English, which were presented over audio CD. They were asked to identify the accent type, but were blind as to the identity of the participants vis-a-vis FAS versus control, and foreign versus native UK. Accuracy, variability, and confidence ratings were assessed as a function of participant and of accent type. Outcomes & Results: The naive judges displayed greater accuracy, consistency, and confidence in typing the control versus the FAS accents. There was a positive familiarity effect for the control, but not the FAS accents. Conclusions: The data provide preliminary support for the view that FAS is not exclusively “in the ear of the beholder”.     

Hypo-fractionated IMRT for patients with newly diagnosed glioblastoma multiforme: A 6 year single institutional experience

Objectives

Glioblastoma (GBM) is the most common malignant primary brain tumour in adults. Surgery and radiotherapy constitute the cornerstones for the therapeutic management of GBM. The standard treatment today is maximal surgical resection followed by concomitant chemo-radiation therapy followed by adjuvant TMZ according to Stupp protocol. Despite the progress in neurosurgery, radiotherapy and oncology, the prognosis still results poor.In order to reduce the long time of standard treatment, maintaining or improving the clinical results, in our institute we have investigated the effects of hypo-fractionated radiation therapy for patients with GBM.

Patients and methods

Sixty-seven patients affected by GBM who had previously undergone surgical resection (total, subtotal or biopsy) were enrolled between October 2005 and December 2011 in a single institutional study of hypo-fractionated intensity modulated radiation therapy (IMRT) followed or not by adjuvant chemotherapy with TMZ (6–12 cycles). The most important eligibility criteria were: biopsy-proven GBM, KPS ≥ 60, age ≥ 18 years, no previous brain irradiation, informed consensus. Hypo-fractionated IMRT was delivered to a total dose of 25 Gy in 5 fractions prescribed to 70% isodose. Response to treatment, OS, PFS, toxicity and patterns of recurrence were evaluated, and sex, age, type of surgery, Karnofsky performance status, Recursive Partitioning Analysis (RPA) classification, time between surgery and initiation of radiotherapy were evaluated as potential prognostic factors for survival.

Results

All patients have completed the treatment protocol. Median age was 64.5 years (range 41–82 years) with 31 females (46%) and 36 males (54%). Median KPS at time of treatment was 80. The surgery was gross total in 38 patients and subtotal in 14 patients; 15 patients underwent only biopsy.No grade 3–4 acute or late neurotoxicity was observed. With median follow-up of 14.9 months, the median OS and PFS were 13.4 and 7.9 months, respectively.

Conclusions

The hypo-fractionated radiation therapy can be used for patients with GBM, resulting in favourable overall survival, low rates of toxicity and satisfying QoL. Future investigations are needed to determine the optimal fractionation for GBM.