Synthesis and thermodynamic studies of two new polymers carrying amido and amino groups in the side chains

Two linear vinyl polymers carrying amido and primary amino groups in the side chains were synthesized and characterized. Their behaviour in aqueous solution was investigated by potentiometric, viscometric and calorimetric techniques. In both cases, the basicity constants show a linear dependence on the degree of protonation α, while the enthalpy values of protonation do not. The thermodynamic results demonstrate the important role of hydrophobic interactions on the protonation process.     

Expansions and contractions of the FMR1 CGG repeat in 5,508 transmissions of normal,intermediate, and premutation alleles

Instability of the FMR1 repeat, commonly observed in transmissions of premutation alleles (55–200 repeats), is influenced by the size of the repeat, its internal structure and the sex of the transmitting parent. We assessed these three factors in unstable transmissions of 14/3,335 normal (~5 to 44 repeats), 54/293 intermediate (45–54 repeats), and 1561/1,880 premutation alleles. While most unstable transmissions led to expansions, contractions to smaller repeats were observed in all size classes. For normal alleles, instability was more frequent in paternal transmissions and in alleles with long 3′ uninterrupted repeat lengths. For premutation alleles, contractions also occurred more often in paternal than maternal transmissions and the frequency of paternal contractions increased linearly with repeat size. All paternal premutation allele contractions were transmitted as premutation alleles, but maternal premutation allele contractions were transmitted as premutation, intermediate, or normal alleles. The eight losses of AGG interruptions in the FMR1 repeat occurred exclusively in contractions of maternal premutation alleles. We propose a refined model of FMR1 repeat progression from normal to premutation size and suggest that most normal alleles without AGG interruptions are derived from contractions of maternal premutation alleles.     

Primary Immunodeficiency Syndrome in Spain: First Report of the National Registry in Children and Adults

The Spanish Registry for Primary Immunodeficiency Diseases (REDIP) was organized in 1993. One thousand sixty-nine cases of primary immunodeficiency diseases (PID) were registered in patients diagnosed between January 1980 and December 1995. PID diagnosis was made according to the World Health Organization criteria. The most frequent disorders were IgA deficiency (n = 394) and common variable immunodeficiency (n = 213), followed by severe combined immunodeficiency (n = 61), C1 inhibitor deficiency (n = 52), X-Iinked agammaglobulinemia (n = 49), IgG subclass deficiency (n = 48), and chronic granulomatous disease (n = 32). A comparative study between REDIP and data recently obtained from the European registry (ESID Report, 1995) revealed important differences between phagocytic disorders and complement deficiencies reported in both registries, 4.9 vs 8.7 and 6.0 vs 3.6, while percentages of predominantly antibody deficiencies and T cell and combined deficiencies concurred with those reported in the European registry, 69.3 vs 64.7 and 14.7 vs 20.2, respectively. The heterogeneous nature of the geographical distribution of cases submitted may indicate underdiagnosis of PID in some country areas; surprisingly, the interval between the onset of clinical symptoms and diagnosis was significant, even in immunodeficiency diseases, such as IgA deficiency, which are easy to diagnose.     

Management of advanced pelvic cancer by exenteration.

AIM: To describe our results in managing locally advanced primary or recurrent pelvic malignancies. METHOD: Investigations included: clinical, laboratory, endoscopic (rectoscopy and colonoscopy) examinations, ultrasound scan, and CT scan or MRI of the abdomen and pelvis, to determine the extent of the pelvic malignancy. A careful explorative laparatomy of abdomen and pelvis was performed, followed by anterior, posterior or total pelvic exenteration. RESULTS: In the period June 1995-Jan 2002, 7 anterior, 2 posterior and 51 total pelvic exenterations were performed in 60 patients, distributed as follows: 28 for rectal cancer (12 primary, 16 recurrent), 20 for cervical cancer (9 primary, 11 recurrent) and 12 for other pelvic malignancies. The median survival time and overall 5-year survival rates were as follows: primary rectal cancer--50 months and 32%; recurrent rectal cancer--31 months and 17%; primary cervical cancer--46.4 months and 41% and recurrent cervical cancer--23.4 months and 16%. During the same period, 559 of our patients were treated for primary or recurrent rectal cancer by different types of straightforward resection. CONCLUSION: Pelvic exenteration is justifiable in cases of locally advanced primary and recurrent malignancies of rectum, cervical cancer and possibly in cases of other pelvic malignancies.     

Cytoreductive surgery for ovarian cancer.

AIM: The aim of this study is to describe the technique of managing peritoneal dissemination in patients with ovarian cancer, based on radical surgical excision and, later, perioperative chemotherapy. METHOD:Treatments included complete surgical resection of the peritoneal disease, and intraperitoneal intraoperative and postoperative chemotherapy, using Adriamycin intraoperatively, and Cis-platinol next 1-5 postoperative days. RESULTS: Eleven cytoreductive procedures were performed between 1996 and 2002. Eight patients with primary ovarian cancer underwent total hysterectomy with bilateral adnexectomy, omentectomy and peritonectomy of the pelvic cavity. In 3 cases with recurrent ovarian cancer, peritonectomy alone was performed. Bowel resection was performed in all patients. The median operation time was 279 min (range 190-500min). Median total blood loss was 919 mL (range 450-1330 mL). The median survival time was 22 months. CONCLUSION: Cytoreductive procedure offers satisfactory results in peritoneal carcinomatosis in patients with advanced primary ovarian cancer.     

Targeting cancer by binding iron: Dissecting cellular signaling pathways

Newer and more potent therapies are urgently needed to effectively treat advanced cancers that have developed resistance and metastasized. One such strategy is to target cancer cell iron metabolism, which is altered compared to normal cells and may facilitate their rapid proliferation. This is supported by studies reporting the anti-neoplastic activities of the clinically available iron chelators, desferrioxamine and deferasirox. More recently, ligands of the di-2-pyridylketone thiosemicarbazone (DpT) class have demonstrated potent and selective anti-proliferative activity across multiple cancer-types in vivo, fueling studies aimed at dissecting their molecular mechanisms of action. In the past five years alone, significant advances have been made in understanding how chelators not only modulate cellular iron metabolism, but also multiple signaling pathways implicated in tumor progression and metastasis. Herein, we discuss recent research on the targeting of iron in cancer cells, with a focus on the novel and potent DpT ligands. Several key studies have revealed that iron chelation can target the AKT, ERK, JNK, p38, STAT3, TGF-β, Wnt and autophagic pathways to subsequently inhibit cellular proliferation, the epithelial-mesenchymal transition (EMT) and metastasis. These developments emphasize that these novel therapies could be utilized clinically to effectively target cancer.     

Hybrid EANN-EA System for the Primary Estimation of Cardiometabolic Risk

The most important part of the early prevention of atherosclerosis and cardiovascular diseases is the estimation of the cardiometabolic risk (CMR). The CMR estimation can be divided into two phases. The first phase is called primary estimation of CMR (PE-CMR) and includes solely diagnostic methods that are non-invasive, easily-obtained, and low-cost. Since cardiovascular diseases are among the main causes of death in the world, it would be significant for regional health strategies to develop an intelligent software system for PE-CMR that would save time and money by extracting the persons with potentially higher CMR and conducting complete tests only on them. The development of such a software system has few limitations - dataset can be very large, data can not be collected at the same time and the same place (eg. data can be collected at different health institutions) and data of some other region are not applicable since every population has own features. This paper presents a MATLAB solution for PE-CMR based on the ensemble of well-learned artificial neural networks guided by evolutionary algorithm or shortly EANN-EA system. Our solution is suitable for research of CMR in population of some region and its accuracy is above 90 %.     

Thirty-Day Readmission Following Total Hip and Knee Arthroplasty – A Preliminary Single Institution Predictive Model

We sought to identify demographic or care process variables associated with increased 30-day readmission within the total hip and knee arthroplasty patient population. Using this information, we generated a model to predict 30-day readmission risk following total hip and knee arthroplasty procedures. Longer index length of stay, discharge disposition to a nursing facility, blood transfusion, general anesthesia, anemia, anticoagulation status prior to index admission, and Charlson Comorbidity Index greater than 2 were identified as independent risk factors for readmission. Care process factors during the hospital stay appear to have a large predictive value for 30-day readmission. Specific comorbidities and patient demographic factors showed less significance. The predictive nomogram constructed for primary total joint readmission had a bootstrap-corrected concordance statistic of 0.76.