Clinical and pathological prognostic factors in squamous cell carcinoma of the vulva

OBJECTIVE: The objective of this study was the prognostic analysis of clinicopathologic variables related to primary tumor and to lymph node metastases. METHODS: We retrospectively analyzed 389 cases of squamous cell carcinoma of the vulva. The following variables were studied: patients' age, diameter and location of the tumor, clinical tumor characteristics, depth of invasion, grade, lymphovascular space involvement (LVSI) and lymph node status. In the subset of 110 node positive patients, we evaluated number of positive nodes, laterality, extension of node dissection, lymph node chains involved, presence of extracapsular spread and rate of lymph node replacement. All variables with P value < 0.2 by the univariate analysis were successively subjected to multivariate analysis (Cox proportional hazard model). RESULTS: Among all the tumor-related variables age, clinical tumor characteristics, LVSI and lymph node status were found to be statistically significant predictors of survival for the log-rank test. On the basis of multivariate analysis, the nodal status was the most significant independent prognostic factor (hazard rate [HR]: 2.06; confidence interval [CI] 95%: 1.57-12.07) followed by LVSI (HR: 3.47; CI95%: 1.85-7.85). The independent prognostic factors among the variables relative to positive nodes were the percentage of nodal replacement (HR: 6.99; CI95%: 3.51-16.14) and the extracapsular spread (HR: 4.88; CI95%: 2.96-10.14). CONCLUSIONS: Lymph node status and nodal features, such as extracapsular spread and nodal replacement rate, were shown to be independent factors. These factors should be considered to identify high risk patients and in planning further adjuvant therapy.     

Staphylococcus aureus genotyping using novel real-time PCR formats

One approach to microbial genotyping is to make use of sets of single-nucleotide polymorphisms (SNPs) in combination with binary markers. Here we report the modification and automation of a SNP-plus-binary-marker-based approach to the genotyping of Staphylococcus aureus and its application to 391 S. aureus isolates from southeast Queensland, Australia. The SNPs used were arcC210, tpi243, arcC162, gmk318, pta294, tpi36, tpi241, and pta383. These provide a Simpson's index of diversity (D) of 0.95 with respect to the S. aureus multilocus sequence typing database and define 61 genotypes and the major clonal complexes. The binary markers used were pvl, cna, sdrE, pT181, and pUB110. Two novel real-time PCR formats for interrogating these markers were compared. One of these makes use of "light upon extension" (LUX) primers and biplexed reactions, while the other is a streamlined modification of kinetic PCR using SYBR green. The latter format proved to be more robust. In addition, automated methods for DNA template preparation, reaction setup, and data analysis were developed. A single SNP-based method for ST-93 (Queensland clone) identification was also devised. The genotyping revealed the numerical importance of the "South West Pacific" and "Queensland" community-acquired methicillin-resistant S. aureus (MRSA) clones and the clonal complex 239 "Aus-1/Aus-2" hospital-associated MRSA. There was a strong association between the community-acquired clones and pvl.     

Special Time in a crèche

The paper describes Special Time carried out in a crèche with a boy with developmental delay and autistic features. Special Time is a form of therapeutic intervention that consists of weekly sessions during which a child is given individual attention by a teacher, an educator or a specific professional. A key aspect of the methodology is that there is a Work Discussion seminar where the professional can be helped to develop the specific stance required by the work and give meaning to the child’s communication. In this case, the Work Discussion seminar was tailor-made and included the Special Time professional and the head of the crèche who presented her work with the child's parents and with the educators, which took place in parallel with the Special Time sessions. The developments achieved by the child in the area of language, his capacity to relate to people, the symbolic use of toys and play, and the reduction of autistic states of mind and behaviour is illustrated through excerpts from the sessions.     

Psychopathological features in Noonan syndrome

Introduction

Noonan syndrome (NS) is an autosomal dominant disorder characterized by short stature, skeletal and haematological/lymphatic defects, distinctive facies, cryptorchidism, and a wide spectrum of congenital heart defects. Recurrent features also include variable cognitive deficits and behavioural problems. Recent research has been focused on the assessment of prevalence, age of onset and characterization of psychiatric features in this disorder. Herein, we evaluated the prevalence of attention deficit and hyperactivity disorder (ADHD), anxiety and depressive symptoms and syndromes in a cohort of individuals with clinical and molecular diagnosis of NS.

Children’s and parent’s psychological profiles in selective mutism and generalized anxiety disorder: a clinical study

Selective mutism (SM) is classified in DSM-5 as an anxiety disorder. The aim of the study was to investigate the psychological features of children with SM and their parental psychological profiles, compared to generalized anxiety disorder (GAD) children and their parents. The parents of 26 preschool children with SM and 32 with children with GAD filled out the child behavior check list for 1½–5 years (CBCL1½–5) and the symptom checklist-90-revised (SCL-90-R). Information about the children and their parents’ histories was collected through clinical interviews. Children with SM scored higher than children with GAD on the CBCL1½–5 withdrawn scale and lower on the attention problems, aggressive behavior, and externalizing problems scales. Mothers of children with SM scored higher on the SCL-90-R obsessive–compulsive subscale and Global Severity Index than mothers of children with GAD, while fathers of children with SM scored higher on the SCL-90-R Phobic Anxiety subscale and on the Global Severity Index than fathers of children with GAD. Parents of children with SM displayed a greater presence of stressful life events than parents of children with GAD. Data appeared to confirm that SM and GAD share a common anxious core, though some differences in the children’s psychological profiles and the parents’ history and personality emerged. Future research should focus on the role of external factors, such as parent–child relationship, in the development of SM.     

Iatrogenesis in intensive care units: dramatization of contemporary bio/ethical problems

This qualitative investigation, based in Foucauldian analysis with approximations to the post-structuralism theoretical framework, explores iatrogenesis as one of the tensions in the nursing to do/to know which can be discursively articulated to bioethics and to technobiomedicine. The documentary sources and intensive interviews with nurses, permitted the activation of a reflection on the act of the nurse in a context permeated by the ever-present possibility of failure in both the procedure and in the conduct and, from this possibility, they should meet their obligation to correct this failure not so much or not only in knowledge, not so much or not only in law but in practice itself.     

Expression profiling in progressive stages of fumarate-hydratase deficiency: the contribution of metabolic changes to tumorigenesis

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is caused by mutations in the Krebs cycle enzyme fumarate hydratase (FH). It has been proposed that "pseudohypoxic" stabilization of hypoxia-inducible factor-α (HIF-α) by fumarate accumulation contributes to tumorigenesis in HLRCC. We hypothesized that an additional direct consequence of FH deficiency is the establishment of a biosynthetic milieu. To investigate this hypothesis, we isolated primary mouse embryonic fibroblast (MEF) lines from Fh1-deficient mice. As predicted, these MEFs upregulated Hif-1α and HIF target genes directly as a result of FH deficiency. In addition, detailed metabolic assessment of these MEFs confirmed their dependence on glycolysis, and an elevated rate of lactate efflux, associated with the upregulation of glycolytic enzymes known to be associated with tumorigenesis. Correspondingly, Fh1-deficient benign murine renal cysts and an advanced human HLRCC-related renal cell carcinoma manifested a prominent and progressive increase in the expression of HIF-α target genes and in genes known to be relevant to tumorigenesis and metastasis. In accord with our hypothesis, in a variety of different FH-deficient tissues, including a novel murine model of Fh1-deficient smooth muscle, we show a striking and progressive upregulation of a tumorigenic metabolic profile, as manifested by increased PKM2 and LDHA protein. Based on the models assessed herein, we infer that that FH deficiency compels cells to adopt an early, reversible, and progressive protumorigenic metabolic milieu that is reminiscent of that driving the Warburg effect. Targets identified in these novel and diverse FH-deficient models represent excellent potential candidates for further mechanistic investigation and therapeutic metabolic manipulation in tumors.     

High abdominal adiposity and low phase angle in overweight renal transplant recipients

Obesity is associated with increased risk of cardiovascular disease (CVD). Body mass index (BMI) is the most used parameter for obesity screening. However, the evaluation of CVD risk in overweight individuals should include the assessment of body fat distribution and body composition. Renal transplant recipients (RTR) have a high CVD risk and frequently present weight gain and loss of lean mass. The aim of this study was to evaluate body fat distribution and body composition in overweight RTR. This cross‐sectional study was conducted with 86 RTR and 86 hypertensive individuals (comparison group, CG) presenting BMI 25‐35 Kg/m² and 45‐70 years. Anthropometric evaluation included BMI, waist circumference, waist‐to‐height ratio, and a body shape index. Body composition was evaluated with bioelectrical impedance analysis (BIA). Glomerular filtration rate was estimated (eGFR) by CKD‐EPI equation. RTR group (RTRG) and CG presented similar age and BMI. RTRG when compared to CG presented lower percentage of women and eGFR; higher central adiposity; and lower values of reactance, intracellular water, body cell mass and phase angle, more consistently observed in women. This study suggests that overweight RTR present higher abdominal adiposity and impairment in BIA parameters that are sensitive indicators of impaired membrane integrity, water distribution, and body cell mass.