Spatio-Temporal Changes of Extracellular Matrix (ECM) Stiffness in the Development of the Leech Hirudo verbana

The invertebrate leech Hirudo verbana represents a powerful experimental animal model for improving the knowledge about the functional interaction between the extracellular matrix (ECM) and cells within the tissue microenvironment (TME), and the key role played by ECM stiffness during development and growth. Indeed, the medicinal leech is characterized by a simple anatomical organization reproducing many aspects of the basic biological processes of vertebrates and in which a rapid spatiotemporal development is well established and easily assessed. Our results show that ECM structural organization, as well as the amount of fibrillar and non-fibrillar collagen are deeply different from hatching leeches to adult ones. In addition, the changes in ECM remodelling occurring during the different leech developmental stages, leads to a gradient of stiffness regulating both the path of migratory cells and their fates. The ability of cells to perceive and respond to changes in ECM composition and mechanics strictly depend on nuclear or cytoplasmic expression of Yes-Associated Protein 1 (YAP1), a key mediator converting mechanical signals into transcriptional outputs, expression, and activation

RNASET2 as a tumor antagonizing gene in a melanoma cancer model

The RNASET2 gene, mapped in 6q27, was previously found to exert control of tumorigenesis in an ovarian cancer system. We present here results indicating a similar control in a melanoma cancer model. Thus, this gene is most likely involved in a common general pathway of tumorigenesis. Moreover, its antitumorigenic activity is manifested in vivo but not in vitro, suggesting that this gene belongs to the growing category of tumor antagonizing/malignancy suppressor genes. A possible role of RNASET2 in the activation of a senescence program, whose responsible locus was mapped in the same chromosomal 6q27 region, seems to be inconsistent with our data

OTX genes in adult tissues

OTX homeobox genes have been extensively studied for their role in development, especially in neuroectoderm formation. Recently, their expression has also been reported in adult physiological and pathological tissues, including retina, mammary and pituitary glands, sinonasal mucosa, in several types of cancer, and in response to inflammatory, ischemic, and hypoxic stimuli. Reactivation of OTX genes in adult tissues supports the notion of the evolutionary amplification of functions of genes by varying their temporal expression, with the selection of homeobox genes from the “toolbox” to drive or contribute to different processes at different stages of life. OTX involvement in pathologies points toward these genes as potential diagnostic and/or prognostic markers as well as possible therapeutic targets

tolterodine improves quality of life in patients with an overactive bladder with or without urinary incontinence a prospective multicenter study

AIMS: In order to analyse the effect of tolterodine on the Quality of life (QoL) of patients with overactive bladder (OB) we conducted a prospective multicentre clinical study. MATERIALS AND METHODS: Subjects were questioned at entry and 4, 12 and 24 weeks later about the number of micturitions and incontinent and urgency episodes/day, using a micturition diary. The mean volume voided per micturition and the number of pads used per day was also recorded. The QoL was measured using the Kings Health Questionnaire (KHQ) and the Incontinence Impact Questionnaire (IIQ). A total of 179 patients entered the study: 59 dropped out (4 due to lack of efficacy, 10 due to adverse events, 25 because of lack of interest in the study/other reason and 20 were lost at follow up), leaving 120 patients for analysis. One hundred and eight patients (90%) were female, their mean age was 56.5 years (SD 11.2); 87 had never received treatment for OB/UI (80.6%) and their mean weight was 70.0 Kg (SD 12.7). RESULTS: The mean number of micturitions/day was 9.3 at trial entry and it decreased to 6.8 by the end of the study. The corresponding values for the number of urge episodes, incontinence episodes and number of pads used per day were 3.5, 2.7 and 1.2 and 0.8, 0.9 and 0.4 respectively. The mean volume voided per micturition increased from 146 ml. to 178 ml. All the differences between trial entry and end of study values were statistically significant (p<0.05). Considering the results of the KHQ, the values of all the different areas/domini (?) decreased markedly and in a statistically significant way between the start of treatment and the end of study evaluations. Similar findings emerged when we considered values of the IIQ. The decrease was constant and marked during the first three months and remained constant thereafter. CONCLUSIONS: This study, conducted in a population of subjects with dry and wet OB, shows that tolterodine given for six months lowers the frequency of urgency episodes and incontinence episodes without troublesome adverse effects. These clinical effects are mirrored in the QoL, KHQ and IIQ questionnaire scores, which improved by about 50% over the same period

Donor cell acute myeloid leukemia after hematopoietic stem cell transplantation for chronic granulomatous disease: a case report and literature review

The patient reported here underwent hematopoietic stem cell transplantation (HSCT) due to chronic granulomatous disease (CGD) caused by biallelic mutations of the NCF1 gene. Two years later, he developed AML, which was unexpected and was recognized via sex-mismatched chromosomes as deriving from the donor cells; the patient was male, and the donor was his sister. Donor cell leukemia (DCL) is very rare, and it had never been reported in patients with CGD after HSCT. In the subsequent ten years, the AML relapsed three times and the patient underwent chemotherapy and three further HSCTs; donors were the same sister from the first HSCT, an unrelated donor, and his mother. The patient died during the third relapse. The DCL was characterized since onset by an acquired translocation between chromosomes 9 and 11, with a molecular rearrangement between the MLL and MLLT3 genes-a quite frequent cause of AML. In all of the relapses, the malignant clone had XX sex chromosomes and this rearrangement, thus indicating that it was always the original clone derived from the transplanted sister's cells. It exhibited the ability to remain quiescent in the BM during repeated chemotherapy courses, remission periods and HSCT. The leukemic clone then acquired different additional anomalies during the ten years of follow-up, with cytogenetic results characterized both by anomalies frequent in AML and by different, non-recurrent changes. This type of cytogenetic course is uncommon in AML

Dyadic Profiles of Couples Coping with Body Image Concerns after Breast Cancer: Preliminary Results of a Cluster Analysis.

Breast cancer treatments have multiple adverse effects, including concerns about body appearance and function that are experienced by most patients. Altered body image negatively affects mental health, social, and relationship functioning. While the relationship with a partner is critical for patients’ psychological wellbeing and partners can promote positive body image, limited research has investigated individual and relational factors affecting the experience of both. This cross-sectional study aimed at (1) exploring rates of body image concerns among breast cancer patients, and (2) identifying dyadic profiles among participating dyads. Couples composed by patients who had undergone surgery and their romantic partners (n = 32) were recruited from the Breast Unit of a hospital in northern Italy. Both partners completed measures of personality characteristics (BFQ-2), psychological distress (HADS), coping flexibility (PACT), dyadic coping (DCQ), and closeness (IOS). Body image (BIS) and adjustment to cancer (Mini-MAC) measures were completed by patients only. K-mean cluster analyses identified 2-cluster solution among patients and partners, respectively. “Active patients” (cluster-1) reported low rates of body image concerns (p < 0.001), anxious preoccupation, negative dyadic coping, and self-oriented stress communication (p < 0.05), compared to “worried patients” (cluster-2). “Comfortable partners” (cluster-1) reported lower anxiety and depression (p < 0.001), self-oriented negative dyadic coping and closeness (p < 0.05) than “uncomfortable partners” (cluster-2). Three different dyadic profiles emerged: functional, dysfunctional, and ambivalent. Significant variations (p < 0.05) by anxiety, depression, and delegating dyadic coping existed. Results indicate there are groups of couples at greater risk for impaired psychological distress and body image concerns, which should be addressed in the context of dyadic psychosocial interventions

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

RNASET2 (ribonucleaseT2)

This gene represents the first human member of the Rh/T2/S-glycoprotein family of extracellular ribonucleases. It belongs to the recently defined class of tumor-antagonizing genes, based on its ability to suppress tumor growth in vivo, but not in vitro. It is likely involved in the pathogenesis of several human neoplasias (both solid and haematological) such as ovarian cancer, melanoma and non-Hodgkin lymphoma. Mutations in this gene have also been recently described in children affected by a rare congenital neurological defect. Moreover, GWAS studies have recently reported the association of gene variants mapping close to the RNASET2 gene with susceptibilty to a few autoimmune disorders