Relationship between self-perceived driving ability and neuropsychological performance in neurological and psychiatric patients

Neurological Sciences - Neurological and psychiatric patients want to keep driving but several sensory, motor, and cognitive deficits could limit this purpose. However, some drivers...     

Characteristics and time-dependence of cut marks and blunt force fractures on costal cartilages: an experimental study

Purpose

The distinction between cut marks and blunt force injuries on costal cartilages is a crucial issue in the forensic field. Moreover, a correct distinction may further be complicated by decomposition, so the need arises to investigate the distinctive features of lesions on cartilage and their changes over time.

Methods

This study aimed to assess the stereomicroscopic features of cut marks (performed with six different knives) and blunt fractures (performed with a hammer and by means of manual bending) on 48 fragments of human costal cartilages. Moreover, in order to simulate decomposition, the cut and fractured surfaces were checked with stereomicroscopy and through casts after 1 and 2 days, 1 week, and 1, 2 and 4 months of drying in ambient air.

Results

In fresh samples, for single and unique cuts, striations were observed in between 44 and 88 % of cases when non-serrated blades were used, and between 77 and 88 % for serrated blades; in the case of “repeated” (back and forth movement) cuts, striations were detected in between 56 and 89 % of cases for non-serrated blades, and between 66 and 100 % for serrated blades. After only 1 week of decomposition the detection rates fell to percentages of between 28 and 39 % for serrated blades and between 17 and 33 % for non-serrated blades. Blunt force injuries showed non-specific characteristics, which, if properly assessed, may lead to a reliable distinction between different cut marks in fresh samples. The most evident alterations of the structure of the cartilage occurred in the first week of decomposition in ambient air. After one week of drying, the characteristics of cut marks were almost undetectable, thereby making it extremely challenging to distinguish between cut marks, blunt force fractures and taphonomic effects.

Conclusion

The study represents a contribution to the correct assessment and distinction of cut marks and blunt force injuries on cartilages, providing a glimpse on the modifications such lesions may undergo with decomposition.

     

Prognostic role of ERCC1 protein expression in upper tract urothelial carcinoma following radical nephroureterectomy with curative intent

Background

Excision repair cross-complementing 1 (ERCC1) has been associated with outcomes of urothelial carcinoma of the bladder, but was not yet studied in upper tract urothelial carcinoma (UTUC). The aim of this study was to assess the prognostic role of ERCC1 expression in a large international cohort of UTUC patients.

Methods

Immunohistochemical ERCC1 expression was evaluated in 716 UTUC patients who underwent radical nephroureterectomy with curative intent. ERCC1 was considered positive when the H-score was >1.0. Associations with overall survival and cancer-specific survival were assessed using univariable and multivariable Cox models.

Results

ERCC1 was expressed in 303 tumors (42.3 %) and linked with the presence of tumor necrosis (16.2 vs. 10.4 %, p = 0.023), but not with any other clinical or pathological variable. ERCC1 status did not predict cancer-specific survival and overall survival on both univariable (p = 0.70 and 0.32, respectively) and multivariable analyses (p = 0.48 and 0.33, respectively).

Conclusions

ERCC1 is expressed in a significant proportion of UTUC and is linked with tumor necrosis, but its expression appears not to be associated with prognosis following radical nephroureterectomy.

     

Age estimation in the Mediterranean bottlenose dolphin Tursiops truncatus (Montagu 1821) by bone density of the thoracic limb

The determination of age is an important step in defining the life history traits of individuals and populations. Age determination of odontocetes is mainly based on counting annual growth layer groups in the teeth. However, this useful method is always invasive, requiring the cutting of at least one tooth, and sometimes the results are difficult to interpret. Based on the concept that bone matrix is constantly deposited throughout life, we analysed the bone mineral density of the arm and forearm of a series of bottlenose dolphins (Tursiops truncatus, Montagu 1821) stranded along the Italian coast of the Adriatic Sea or maintained in confined waters. The bone mineral density values we obtained were evaluated as possible age predictors of the Mediterranean population of this species, considering age as determined by counting growth layer groups in sections of the teeth and the total body length of the animal as references. Comparisons between left and right flipper showed no difference. Our results show that bone mineral density values of the thoracic limb are indeed reliable age predictors in Tursiops truncatus. Further investigations in additional odontocete species are necessary to provide strong evidence of the reliability of bone mineral density as an indicator of growth and chronological wear and tear in toothed-whales.     

Pneumo- and neurotropism of avian origin Italian highly pathogenic avian influenza H7N1 isolates in experimentally infected mice

An experimental infection of mice was performed in order to investigate the potential for interspecies transmission in mammals of Italian HPAI viruses of the H7N1 subtype. Three avian origin isolates were selected, two strains obtained from ostrich (one of which contained a PB2-627 Lysine residue) and one from a chicken. Following intranasal infection of mice, clinical signs and mortality were recorded in the experimental groups challenged with the two ostrich isolates, while only weight loss was observed in those receiving the chicken strain. Viruses were recovered to a varying extent from respiratory and nervous tissues of infected animals. These results suggest that HPAI viruses, other than H5N1 and H7N7, may have zoonotic implications, and support the consensus that AI infections in poultry are to be eradicated rather than contained.     

Selective induction of apoptosis in MCF7 cancer-cell by targeted liposomes functionalised with mannose-6-phosphate

Liposomes are versatile platforms to carry anticancer drugs in targeted drug delivery; they can be surface modified by different strategies and, when coupled with targeting ligands, are able to increase cellular internalisation and organelle-specific drug delivery. An interesting strategy of antitumoral therapy could involve the use of lysosomotropic ligand-targeted liposomes loaded with molecules, which can induce lysosomal membrane permeabilization (LMP), leakage of cathepsins into the cytoplasm and subsequent apoptosis. We have previously demonstrated the ability of liposomes functionalised with a mannose-6-phosphate to reach lysosomes; in this research we compare the behaviour of M6P-modified and non-functionalised liposomes in MCF7 tumour cell and in HDF normal cells. With this aim, we first demonstrated by Western blotting the overexpression of mannose-6-phosphate/insulin-like growth factor (M6P/IGF-II) receptor in MCF7. Then, we prepared calcein-loaded liposomes and we revealed the increased uptake of M6P-functionalised liposomes in MCF7 cells respect to HDF cells by flow cytometry analysis. Finally, we loaded functionalised and not functionalised liposomes with N-hexanoyl-d-erythro-sphingosine (C6Cer), able to initiate LMP-induced apoptosis; after having studied the stability of both vesicles in the presence of serum by Dynamic Light Scattering and Spectrophotometric turbidity measurements, we showed that ceramide-loaded M6P-liposomes significantly increased apoptosis in MCF7 with respect to HDF cells.     

Nonredundant roles of antibody,cytokines, and perforin in the eradication of established Her-2/neu carcinomas

Since the mechanisms by which specific immunity destroys Her-2/neu carcinoma cells are highly undetermined, these were assessed in BALB/c mice vaccinated with plasmids encoding extracellular and transmembrane domains of the protein product (p185(neu)) of the rat Her-2/neu oncogene shot into the skin by gene gun. Vaccinated mice rejected a lethal challenge of TUBO carcinoma cells expressing p185(neu). Depletion of CD4 T cells during immunization abolished the protection, while depletion of CD8 cells during the effector phase halved it, and depletion of polymorphonuclear granulocytes abolished all protection. By contrast, Ig mu-chain gene KO mice, as well as Fcgamma receptor I/III, beta-2 microglobulin, CD1, monocyte chemoattractant protein 1 (MCP1), IFN-gamma, and perforin gene KO mice were protected. Only mice with both IFN-gamma and perforin gene KOs were not protected. Although immunization also cured all BALB/c mice bearing established TUBO carcinomas, it did not cure any of the perforin KO or perforin and IFN-gamma KO mice. Few mice were cured that had knockouts of the gene for Ig mu-chain, Fcgamma receptor I/III, IFN-gamma, or beta-2 microglobulin. Moreover, vaccination cured half of the CD1 and the majority of the MCP1 KO mice. The eradication of established p185(neu) carcinomas involves distinct mechanisms, each endowed with a different curative potential.     

Cutaneous adverse reactions linked to targeted anticancer therapies bortezomib and lenalidomide for multiple myeloma: new drugs,old side effects

Context: Cutaneous toxicity is a frequent side effect of new anticancer targeted therapies. Skin reactions can severely impact the patient’s physical, psychological and social well-being and may sometimes lead to discontinuations either treatment dose reductions.

Objective: This study evaluates the impact of cutaneous adverse drug reactions (cADR) of the new therapies bortezomib and lenalidomide and presents a review of their skin side effects.

Materials and method: Type, frequency, severity, time of onset and management of cADR were collected and the medical records of all multiple myeloma patients receiving bortezomib or lenalidomide in the Hematology and Medical Oncology Institute of the University of Bologna, were analyzed.

Results: A total of 17 cADR occurred in 10 patients of 17 (58.8% of patients) treated with bortezomib: 5 rashes, 3 events of pruriginous rash, 1 purpuric rash, 2 records of mouth swelling, 1 stomatitis-mucositis, 3 cases of edema in the lower limbs, 1 patient referred pruritus and another telogen effluvium. Eight skin manifestations were due to lenalidomide in 7 patients of 25 treated (28%): 2 pruriginous rashes, 3 cases of edema, 2 records of pruritus, 1 case of stomatitis-mucositis. Three adverse events linked to bortezomib and 4 to lenalidomide forced to a complete withdrawal of the drug, while 3 reactions due to bortezomib mandated a dose reduction. Dermatological evaluation was performed only in 2 patients treated with bortezomib and 1 with lenalidomide.

Discussion: Evaluations of cADR due to bortezomib and lenalidomide were performed. There are no other reports focused on skin events in patients treated with the triple regimen velcade (bortezomib)-thalidomide-dexamethasone (VTD) up to date. Our study suggests that cutaneous toxicities, when researched by Dermatologists, are a side effect even more frequent than the reported data.

Limitations: As it is a single institute and retrospective study, ongoing cADR were rarely evaluated by dermatologists; thus, it is possible that cutaneous reactions (especially mild) may have been under reported by Hematologists and Oncologists in clinical records.

Conclusions: Even with the development of new drugs for cancer treatment, “old” cutaneous side effects may still be present, compromising patients’ quality of life. Physicians prescribing bortezomib and lenalidomide should monitor their patients for the spectrum of cADR, and they should involve dermatologists in consultations and management of these events. A multidisciplinar approach is necessary to oncologic patient in order to provide a tailored supportive clinical care.