Short-term, supra-physiological rhGH administration induces transient DNA damage in peripheral lymphocytes of healthy women.

PURPOSE: While a good safety for recombinant human growth hormone (rhGH) therapy at replacement doses is recognized, a possible link between high concentration of the GH-IGF-I axis hormones and side negative effect has been reported. The aim of this pilot study was to assess whether a short-term exposure to supra-physiological doses of rhGH may affect DNA integrity in human lymphocytes (PBL). METHODS: Eighteen healthy Caucasian female (24.2 ± 3.5 years) were randomly included in a Control (n = 9) and rhGH administration group (n = 9, 3-week treatment). DNA damage (comet assay), chromosomal breaks, and mitotic index in phytohemagglutinin-stimulated PBL were evaluated before (PRE), immediately (POST), and 30 days (POST30) after the last rhGH administration (0.029 mg kg- 1 BW; 6 days/week), together with serum IGF-1 and IGFBP-3 concentrations. RESULTS: rhGH administration increased IGF-I, without evidence of persisting IGF-I and IGFBP-3 changes 30 days after withdrawal. Total DNA breakage (% DNA in tails) was not significantly different in subjects treated with rhGH in comparison with controls, although the rhGH-treated subjects showed an higher percentage of heavily damaged nuclei immediately after the treatment (POST30 vs. PRE: p = 0.003), with a lower mitogenic potential of lymphocytes, detectable up to the POST30 (PRE vs. POST: p = 0.02; PRE vs. POST30: p = 0.007). CONCLUSIONS: This pilot study showed that 3 weeks of short-term supra-physiological rhGH administration in healthy women induce a transient DNA damage and mitogenic impairment in PBL. The analysis of DNA damage should be explored as useful tool in monitoring the mid to long-term effects of high rhGH treatment or abuse.

Atypical Exciton-Phonon Interactions in WS2 and WSe2 Monolayers Revealed by Resonance Raman Spectroscopy.

Resonant Raman spectroscopy is a powerful tool for providing information about excitons and exciton-phonon coupling in two-dimensional materials. We present here resonant Raman experiments of single-layered WS2 and WSe2 using more than 25 laser lines. The Raman excitation profiles of both materials show unexpected differences. All Raman features of WS2 monolayers are enhanced by the first-optical excitations (with an asymmetric response for the spin-orbit related XA and XB excitons), whereas Raman bands of WSe2 are not enhanced at XA/B energies. Such an intriguing phenomenon is addressed by DFT calculations and by solving the Bethe-Salpeter equation. These two materials are very similar. They prefer the same crystal arrangement, and their electronic structure is akin, with comparable spin-orbit coupling. However, we reveal that WS2 and WSe2 exhibit quite different exciton-phonon interactions. In this sense, we demonstrate that the interaction between XC and XA excitons with phonons explains the different Raman responses of WS2 and WSe2, and the absence of Raman enhancement for the WSe2 modes at XA/B energies. These results reveal unusual exciton-phonon interactions and open new avenues for understanding the two-dimensional materials physics, where weak interactions play a key role coupling different degrees of freedom (spin, optic, and electronic).

Exciton antennas and concentrators from core-shell and corrugated carbon nanotube filaments of homogeneous composition.

There has been renewed interest in solar concentrators and optical antennas for improvements in photovoltaic energy harvesting and new optoelectronic devices. In this work, we dielectrophoretically assemble single-walled carbon nanotubes (SWNTs) of homogeneous composition into aligned filaments that can exchange excitation energy, concentrating it to the centre of core-shell structures with radial gradients in the optical bandgap. We find an unusually sharp, reversible decay in photoemission that occurs as such filaments are cycled from ambient temperature to only 357 K, attributed to the strongly temperature-dependent second-order Auger process. Core-shell structures consisting of annular shells of mostly (6,5) SWNTs (E(g)=1.21 eV) and cores with bandgaps smaller than those of the shell (E(g)=1.17 eV (7,5)-0.98 eV (8,7)) demonstrate the concentration concept: broadband absorption in the ultraviolet-near-infrared wavelength regime provides quasi-singular photoemission at the (8,7) SWNTs. This approach demonstrates the potential of specifically designed collections of nanotubes to manipulate and concentrate excitons in unique ways.

Contemplating Health Economics, Coding and Reimbursement in Orthotics, Prosthetics and Pedorthics.

Reimbursement to U.S. healthcare service providers is largely transitioning from fee for service to fee for value for those clinicians who code using current procedural terminology and through their coding, describe their professional services. The Orthotic, Prosthetic and Pedorthic profession (O&P), currently codes using a system that describes the devices they evaluate for, fabricate, fit and maintain and their professional services are incorporated into their codes. These O&P codes, in contrast to those for other healthcare disciplines, are predominantly product based rather than service based, focusing on product features and function more than clinical service. This editorial manuscript provides a brief overview of the system the US O&P profession uses currently, particularly in the context of other healthcare professions transitioning to value based coding and reimbursement and culminates in a call to action for the profession to academically consider the strengths and weaknesses of the current system relative to alternative systems.

Raman spectra of multilayer graphene under high temperatures.

For graphitic materials, Raman technique is a common method for temperature measurements through analysis of phonon frequencies. Temperature (T) induced downshift of the bond-stretching G mode (ΔG) is well known, but experimentally obtained thermal coefficients ΔG/ΔT vary considerably between diverse works. Further, ΔG/ΔT coefficients usually were evaluated for relatively low temperatures and found to differ strongly for mono, a few and multilayer graphene. We studied G band behavior in freely suspended multilayer graphene flakes (or graphite nanoflakes) under localized heating by a laser beam. Analysis of Stokes and anti-Stokes signals showed that G band has a complex structure and can be deconvoluted into several peaks that demonstrate distinctly different behavior under heating. A plausible assumption is that these peaks correspond to several groups of graphitic layers (surface, near-surface and bulk) and then different thermal coefficients were determined for these groups. This behavior can be explained by decreasing interaction between surface layers and underlying material at high temperatures that affects especially vibrational properties of a few outermost layers. Estimates of temperatures using anti-Stokes/Stokes intensity ratio (I aS/I S) were also done to give results comparable with those obtained from G band downshift, T ΔG ≈ T aS/S, supporting the proposed model. The range of temperatures obtained by laser heating, as evaluated by both methods, was from 450 to 1200 K.

Laparoscopic and open treatment of hepatocellular carcinoma in patients with cirrhosis.

BACKGROUND: Few studies have compared survival and recurrence rates between laparoscopic and open liver resection for hepatocellular carcinoma in patients with cirrhosis. METHODS: A retrospective analysis of a prospectively maintained database of 179 liver resections performed for HCC in cirrhotic liver between 2000 and 2007 was performed. RESULTS: Fifty-four patients underwent a laparoscopic resection and 125 patients had open surgery. Histopathological features were largely comparable in the two groups. Tumours operated laparoscopically were smaller than those removed at open operation and laparoscopic liver resection was less extensive. Laparoscopic surgery had a lower morbidity rate than open surgery (19 versus 36.0 per cent; P = 0.020), whereas 30-day mortality was similar (2 versus 4.0 per cent; P = 0.615). After a median follow-up of 24 months, 1- and 3-year survival rates were 94 and 67 per cent in the laparoscopic group. Recurrence rates were similar after laparoscopic and open procedures (45 versus 52.5 per cent; P = 0.381), as was disease-free survival (P = 0.864). CONCLUSION: Laparoscopic resection of HCC in cirrhotic liver is feasible and safe in selected patients. Adequate long-term survival and recurrence is achieved compared with open surgery, when stratified for tumour characteristics known to be related to survival outcome.

Laparoscopic versus open liver resection for hepatocellular carcinoma in patients with histologically proven cirrhosis: short- and middle-term results.

BACKGROUND: Liver surgery, especially for cirrhotic patients, is one of the last areas of resistance to progress in laparoscopic surgery. This study compares the postoperative results and the 2-year patient outcomes between laparoscopic and open resection for hepatocellular carcinoma in patients with histologically proven cirrhosis. METHODS: From May 2000 to October 2004, 23 consecutive cirrhotic patients who underwent laparoscopic hepatectomy (LH) for HCC were compared in a retrospective analysis with a historic group of 23 patients who underwent open hepatectomy (OH). The two groups were well matched for age, gender, American Society of Anesthesiology (ASA) class, tumor location and size, type of liver resection, and severity of cirrhosis. The selection criteria for both groups specified a small (size < 5 cm), exophytic, or subcapsular tumor located in the left or peripheral right segments of the liver (II-VI segments, Couinaud); a well-compensated cirrhosis (Child-Pugh A); and an ASA score lower than 3. In the LH group, 15 subsegmentectomies, 3 segmentectomies, and 5 left lateral sectionectomies were performed, as compared with 12 subsegmentectomies, 5 segmentectomies, and 6 left lateral sectionectomies in the OH group. RESULTS: One patient in the LH group (4.3%) underwent conversion to laparotomy for inadequate exposition. The mean operative time was statistically longer for the LH group (LH, 148 min; OH, 125 min; p = 0.016), whereas blood transfusions (LH, 0%; OH, 17.3%; p = 0.036), Pringle maneuver (LH, 0%; OH, 21.73%; p = 0.017), mean hospital stay (LH, 8.3 days; OH, 12 days; p = 0.047), and postoperative complications (LH, 13%; OH, 47.8%; p = 0.010) were significantly greater in OH group. There was no statistically significant difference in mortality and 2-year survival rates between the two groups. CONCLUSION: This study shows that LH for HCC in properly selected cirrhotic patients results in fewer early postoperative complications and a shorter hospital stay than the traditional OH. The 2-year survival rate was the same for LH and OH.

[Psychological distress in applicants for genetic screening for colorectal cancer]. / Etude de la vulnérabilité psychologique des sujets inscrits à un dépistage génétique des cancers colorectaux héréditaires.

UNLABELLED: Introduction. The development of a DNA based diagnostic test has allowed for the genetic screening of many hereditary diseases. In addition to the identification of the deleterious gene, this screening process has led to the recognition of developing illnesses at high risk. In recent years, a number of genes predisposing to an inherited cancer syndrome have been identified. AIM OF THE STUDY: Our purpose in this study was to determine whether subjects at risk who test for inherited colorectal cancer, are likely to develop a higher level of psychological distress than the norm, taking into consideration the particular history of this familial disease. METHODS: The demographic and psychosocial aspects of our population was described using: 1) the State Trait Anxiety Inventory (STAI), 2) the Center for Epidemiologic Studies Depression (CES-D), 3) a perceived risk for the gene carrier, 4) subjective perception of personal vulnerability and 5) the role of the medical status (affected or not), which places the subject in either predisposition or predictive testing. RESULTS: Results show that our population had a higher predisposition for depressive disorders (chi2=9,3. p=0.002) and a significantly higher state of anxiety (chi2=9,3. p=0.002), prior to genetic counselling, compared with other populations. We found no evidence in the medical status, nor the perceived risk. However, the assessment of one's own personal vulnerability is related to psychological distress. DISCUSSION: These results highlight the particular vulnerability of subjects undergoing genetic testing as well as showing the pertinence of proposing psychological help throughout the process of these new specific diagnoses.

A new designed π conjugated molecule for stable single walled carbon nanotube dispersion in aqueous medium.

A molecule with a π conjugated backbone built from aromatic thiophene and dialkoxyphenylene units and substituted imidazolium groups (TPO) is designed to obtain ultra-stable single walled carbon nanotube (SWCNT) dispersion in aqueous medium. The proposed mechanism of non-covalent interaction is accompanied by individualization of SWCNT and comprises of dominant nondisruptive π-π and cation-π interaction between them and the TPO conjugated oligomer. The individualization of SWCNT and dispersibility and stability of the ultra-stable suspensions were estimated using high resolution transmission electron microscopy, UV-Visible-NIR absorption spectroscopy, Raman spectroscopy, photoluminescence and zeta potential measurement. Nuclear magnetic resonance data provides direct evidence toward possible cation-π interaction.

Kinetics of ultraweak light emission from human erythroleukemia K562 cells upon electroporation.

Electroporation involves the application of an electric pulse that creates transient aqueous channels (electropores) across the lipid bilayer membranes. Here, we describe an instrument set up suitable to record ultraweak light emission from human erythroleukemia K562 cells during and immediately after delivery of electric pulses. Most of light was emitted in the first seconds after each pulse, following a complex decay which can be fitted by a double exponential equation characterized by two different time constants (T1 and T2), both in the order of seconds. T1 was approximately 10-fold shorter than T2 and both time constants were dependent on field strength of the electric pulse. The effect of various antioxidants on the amount of emitted photons and on T1 and T2 values was investigated, in order to shed some light on the chemical species responsible for cellular luminescence.

Highly sensitive and simple SERS substrate based on photochemically generated carbon nanotubes-gold nanorods hybrids.

We report a simple and easy formation of hybrids between multi-wall carbon nanotubes and gold nanorods by one-pot in situ photochemical synthesis. Measurements of surface-enhanced Raman scattering (SERS) through the effect "coffee ring" in visible and near infrared (NIR) show high sensitivity with detection of nanomolar concentrations of aromatic dyes. The formation of nanocomposites between carbon nanotubes and gold nanorods without chemical binders simplifies the preparation. Photochemical synthesis is an advance over the techniques previously published.

Activation of nitric oxide synthase is involved in tamoxifen-induced apoptosis of human erythroleukemia K562 cells.

Tamoxifen induces apoptosis (programmed cell death) in human erythroleukemia K562 cells. Nitric oxide synthase activity and expression increased in apoptotic cells by 315% and 280%, respectively, compared to controls. The specific inhibitor of nitric oxide synthase, L-NAME, protected K562 cells from tamoxifen-induced apoptosis, whereas the nitric oxide donor, sodium nitroprusside (SNP), potentiated the apoptotic effect of the drug. In addition, 5-lipoxygenase was activated by tamoxifen and the specific enzyme inhibitor, MK886, protected K562 cells against the drug. Conversely, the 5-lipoxygenase product, 5-hydroperoxyeicosatetraenoic acid, enhanced the tamoxifen-induced apoptosis. Finally, tamoxifen altered also membrane properties of K562 cells.

Selective changes in DNA binding activity of transcription factors in UM-X7.1 cardiomyopathic hamsters.

UM-X7.1 hamsters (CH) are considered a representative model for human cardiomyopathy. CH display the loss of the cytoskeletal delta-sarcoglycan protein, associated with myocardium remodeling and fatal reduction of heart functional efficiency. Even though altered redox balance and calcium homeostasis have already been reported to affect cardiomyocyte function, the molecular mechanisms underlying this pathology are largely unknown. We found no significant differences in DNA binding activity of redox-related (NF-kappaB, Sp1, AP-1 and AP-2) transcription factors in heart ventricles of 90 day-old CH, compared to normal animals. On the other hand, DNA binding activity of calcium-dependent transcription factors NF-AT3 and CREB were increased and decreased respectively in CH vs. normal ventricles. Western blot experiments confirmed the down regulation of CREB levels and suggest a novel regulation mechanism for this transcription factor in the heart. Our results are consistent with recent studies on NF-AT3, GATA4 and CREB transgenic mice, and provide clues for the comprehension of pathogenetic mechanisms of hamster hereditary cardiomyopathy.

Sister chromatid exchanges and DNA topoisomerase II inhibitors: effect of low concentrations of etoposide (VP-16) in ataxia telangiectasia lymphoblastoid cell lines.

The correlation between etoposide (VP-16) cytotoxicity and the induction of sister chromatid exchanges (SCEs) suggested that the promotion of DNA recombination events may be crucial for the activity of antitopoisomerase drugs. To further evaluate this hypothesis, we investigated the correlation between VP-16 induction of SCEs, chromosomal aberrations and cell cycle alterations in lymphoblastoid cell lines derived from patients affected by ataxia telangiectasia (AT), whose cells are known as hypersensitive to the cytotoxic and clastogenic activity of DNA topoisomerase II inhibitors. Our present study has shown that AT homozygous and heterozygous cell lines exposed to low VP-16 concentrations, although hypersensitive to the induction of chromosomal aberrations, exhibit an induction of SCEs comparable to that found in normal cell lines. Moreover, while the clastogenic effect of the drug was directly correlated to the reduction of the mitotic index, the enhancement of SCE frequencies, obtained over the same range of VP-16 concentrations, was not paralleled by a modification of proliferation index. Thus, these results suggest that etoposide retains in AT cells a strong clastogenic and cytostatic activity which is independent from DNA recombination events and which may be important for the induction of cell death by this kind of drug.

Banded karyotypes of 20 Papionini species reveal no necessary correlation with speciation.

The G-banded karyotypes of 20 species of the tribe Papionini are remarkably similar, and the amount of phylogenetic interpretation permitted is limited. The genera Mandrillus and Cercocebus may be linked by a derived chromosome 10. T. gelada may be linked to the macaques by chromosome 2. Chromosome 5, which differs in M. fascicularis, makes this species an unlikely ancestor of the Sulawesi (Celebes) macaques. An alternate hypothesis, which takes into consideration the possibility that ancestral populations may be polymorphic for these chromosome variants, suggests that different chromosome variants have become fixed in different lines. These chromosomes would therefore not reflect phylogenetic relations. In the Papionini the karyotype has not played a major role in diversification and speciation.

[Use of compression anastomosis devices in digestive surgery]. / L'uso delle suturatrici a pressione in chirurgia digestiva.

In this summary the authors report their experience of the clinical utilization in digestive surgery of a new compression anastomosis device consisting of a biofragmentable ring (BAR-Valtrac). From January 1993 through August 1994 26 patients underwent operations with Valtrac application: 22 for malignant colo-rectal neoplasms, 3 for diverticular disease and 1 for Crohn disease. The authors have performed 8 ileo-colic, 16 colo-colic and 2 colo-rectal anastomoses. There was no perioperatively mortality. Valtrac was discharged post-operatively between XVI and XXVIII days. There were no anastomotic leakage, bleeding or obstruction. Six months postoperatively an endoscopic control carried out in the 50% of the patients showed no anastomotic stenoses. These results, in association with those ones reported by the literature, confirm that anastomoses performed with Valtrac are safe, reliable and allow the same of better results than stapled anastomoses.

[Peritoneal innervation and post-laparoscopic course. Role of CO2]. / Terminazioni nervose peritoneali e decorso post-laparoscopia. Ruolo della CO2.

BACKGROUND: 30-67% of patients undergoing laparoscopic surgery reports shoulder pain. Besides, post-surgical course of patients undergoing converted laparoscopic procedures is similar to the course of patients who received a completely laparoscopic procedure. It is supposed that there is a temporary neurotoxic damage of the peritoneal sensitive nervous fibres defined by CO2. METHODS: A prospective review has been carried out by histologically analyzing 38 peritoneal biopsies from 10 selected patients, during different laparoscopic surgical procedures (6 cholecystectomies, 2 appendectomies, 1 selective bilateral ligature of the spermatic vessles) and at different times during each operation. Patients whom anamnesis, clinical or local conditions were suggestive for peritoneal flogosis were excluded from the study: therefore only 29 biopsies from 8 patients have been considered useful to the study. RESULTS: Histological analysis has been carried out with different methods of coloration (hematoxylin eosin, argentic staining) and at different magnifications (30x, 60x, 100x), without electronical microscopy or immunohistochemical studies. No biopsy showed signs of damage of the nervous structures. CONCLUSIONS: Certainly, the realization of a pneumoperitoneum at CO2 doesn't cause damages of the peritoneal sensitive fibres. It has been demonstrated that the abdominal introduction of CO2 causes a "relative peritoneal acidosis", directly depending from the percentage of CO2 employed: the peritoneal pH decreases to 6.9 after 15 min of pneumoperitoneum with CO2 at 100% and to 7.35% with CO2 at 5% of air. Probably this condition causes a temporary biochemical change that defines reduction of the nervous impulses and, therefore, the "peritoneization" of the patient subjected to laparoscopic procedure. The "biochemical hypoesthesia", based on a change of the peritoneal homeostasis, would translate itself in a beneficial effect for the patient, persisting also when converted to laparotomic operation due the impossibility to proceed under laparoscopy, held up by the residual pneumoperitoneum.

[Non-surgical treatment of liver trauma]. / Il trattamento non operatorio dei traumi epatici.

The aim of the study was to assess the role of non-operative treatment in haemodynamically stable patients with liver trauma. Over the period from 1996 to July 2000, out of a total of 2,048 patients with abdominal trauma, 124 open and 1,924 closed, we observed 77 hepatic lesions, consisting of 55 closed traumas and 22 penetrating traumas. Non-operative treatment was implemented in 18 patients (32.7%) with closed liver traumas. In addition to serial clinical examinations of the abdomen, the patients receiving non-operative treatment were submitted to thorough haemodynamic monitoring and complete blood counts in the intensive care unit. After an abdominal CT scan at entry, patients were submitted to abdominal ultrasonography 6, 12 and 24 hours after admission. Only two patients required transfusions, one presenting a pelvic fracture and the other a triple fracture of the femur, tibia and fibula. There was no mortality. A biloma was present in one case, successfully treated by means of a US-guided drainage puncture. It is patients with major cranial traumas that pose most problems for conservative treatment. Fifty percent of non-therapeutic laparotomies in our series were performed in patients with severe cranial traumas. It is precisely in these patients that an improvement in diagnostic capability is most desirable.

[Use of the Ravo bypass in high-risk colonic anastomoses]. / L'uso del by-pass di Ravo nelle anastomosi coliche a rischio.

The Authors report a case of high risk colonic anastomosis treated by intracolonic by-pass procedure. The technique of Coloshield application is described. Its use prevents fecal contamination of the anastomotic site and, in case of dehiscence, anastomotic fistula formation.