Parallel reduction in expression of the eye development gene hedgehog in separately derived cave populations of the amphipod Gammarus minus.

Caves provide excellent settings to examine evolutionary questions. Subterranean environments are characterized by similar and consistent conditions. Cave-adapted species often share characteristics such as diminished pigmentation, elongated limbs and reduced or absent eyes. Relatively little is known about the evolution and development of troglomorphic traits in invertebrates. In this study, we compare expression of the eye development genes hedgehog, pax6, sine oculis and dachshund in individuals from multiple independently derived cave populations of the amphipod Gammarus minus. hedgehog expression was significantly reduced in cave populations, compared to genetically related surface populations. Interestingly, no differences were found in pax6, sine oculis or dachshund expression. Because hedgehog-related genes are also involved in eye reduced in Astyanax mexicanus, these genes may be consistent targets of evolution during cave adaptation. These results provide support for the hypothesis of genomic 'hotspots' of evolution and allow comparison of adaptive mechanisms among diverse animals in subterranean environments.

Thymoma-associated immunodeficiency: a syndrome characterized by severe alterations in NK, T and B-cells and progressive increase in naïve CD8+ T Cells.

Thymomas are rare tumours that sustain T-lymphopoiesis and trigger a variety of autoimmune diseases and immunodeficiencies, including a fatal hypogammaglobulinemia, namely Goods Syndrome (GS). Due to its rarity, GS has been poorly investigated and immunological features, as well as pathogenetic mechanisms underlying this syndrome, are unclear. We studied 30 thymoma patients by performing an immunological assessment, including immunophenotype and analysis of T cell repertoire (TCR). Development of GS was characterized by a progressive decrease in B, CD4 T and NK lymphocytes. These alterations paired with accumulation of CD8+CD45RA+ T cells that showed a polyclonal repertoire without expansions of specific clonotypes. GS is defined as hypogammaglobulinemia with thymoma. Here, we show for the first time that this syndrome is characterized by a severe loss of CD4+, NK and B cells. Furthermore, the accumulation of CD8+CD45RA+ T lymphocytes parallels these changes; this accumulation may have a role in determining the disease and can be used to monitor clinical stages of immunodeficiency in thymoma.

Pharmacoeconomic management of patient with severe asthma in the Emergency Department: retrospective multicentric and cost of illness study.

OBJECTIVE: The aim of the study was to develop a cost-of-illness model that would investigate the costs associated with the management of patients suffering from asthma and severe asthma in the context of acute episodes managed in the emergency room. PATIENTS AND METHODS: A total of 795 records were collected between adults and paediatric patients. The data collection form reported an identification code for each patient included, gender, age, main discharge diagnosis, medical examinations carried out in the emergency room, the hospitalizations, and, if required by the patient condition, an outpatient visit performed by a pneumologist after the acute event that led the patient to the emergency room. In addition, the data collection form included information related to the pharmacological therapy taken by the patient. RESULTS: Among adult patients who had an admission with an asthma diagnosis, the average cost for the management of an adult patient in a green code in the emergency room is €330.39. As for the yellow code and the red code, the cost rises respectively to €444.04 and €808.25. The paediatric population has a slightly higher cost. As for the green code, the average cost stands at €355.87, for the yellow code €562.34 and €1,041.96 for the red code. CONCLUSIONS: Asthma and severe asthma impose a high burden on patients and society due to its chronicity, losses of productivity, and an increase in use of healthcare resources. We carried out the present observational retrospective analysis on asthma and severe asthma patients with the aim of assessing the economic impact from the Italian NHS perspective focusing also on the prescribed pharmacological therapies in the target conditions.

The RNA-binding protein Sam68 contributes to proliferation and survival of human prostate cancer cells.

The tyrosine kinase Src is frequently activated in advanced human prostate carcinomas and its activation correlates with tyrosine phosphorylation of the RNA-binding protein Sam68. Herein, we have investigated the expression and function of Sam68 in human prostate cancer cells. Analysis of specimens obtained from 20 patients revealed that Sam68 is upregulated at the protein level in 35% of the samples. Real-time polymerase chain reaction confirmed the results at the mRNA level in most patients. Downregulation of Sam68 by RNAi in LNCaP prostate cancer cells delayed cell cycle progression and reduced the proliferation rate. Moreover, depletion of Sam68 sensitized cells to apoptosis induced by DNA-damaging agents. Similarly, stable cell lines expressing a truncated GFP-Sam68(GSG) protein displayed reduced growth rates and higher sensitivity to cisplatin-induced apoptosis. Microarray analyses revealed that a subset of genes involved in proliferation and apoptosis were altered when Sam68 was knocked down in LNCaP cells. Our results indicate that Sam68 expression supports prostate cancer cells proliferation and survival to cytotoxic agents.

Risk of developing chronic myeloid neoplasms in well-differentiated thyroid cancer patients treated with radioactive iodine.

Exposure to ionizing radiation increases the risk of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN), but such risks are not known in well-differentiated thyroid cancer (WDTC) patients treated with radioactive iodine (RAI). A total of 148 215 WDTC patients were identified from Surveillance, Epidemiology and End Results registries between 1973 and 2014, of whom 54% underwent definitive thyroidectomy and 46% received adjuvant RAI. With a median follow-up of 6.6 years, 77 and 66 WDTC patients developed MDS and MPN, respectively. Excess absolute risks for MDS and MPN from RAI treatment when compared to background rates in the US population were 6.6 and 8.1 cases per 100 000 person-years, respectively. Compared to background population rates, relative risks of developing MDS (3.85 (95% confidence interval, 1.7-7.6); P=0.0005) and MPN (3.13 (1.1-6.8); P=0.012) were significantly elevated in the second and third year following adjuvant RAI therapy, but not after thyroidectomy alone. The increased risk was significantly associated with WDTC size ⩾2 cm or regional disease. Development of MDS was associated with shorter median overall survival in WDTC survivors (10.3 vs 22.5 years; P<0.001). These data suggest that RAI treatment for WDTC is associated with increased risk of MDS with short latency and poor survival.

Apoptosome inactivation rescues proneural and neural cells from neurodegeneration.

Deficiency of the apoptosome component Apaf1 leads to accumulation of supernumerary brain cells in mouse embryos. We observed that neural precursor cells (NPCs) in Apaf1(-/-) embryos escape programmed cell death, proliferate and retain their potential to differentiate. To evaluate the circumstances of Apaf1(-/-) NPC survival and investigate their fate under neurodegenerative conditions, we established cell lines of embryonic origin (ETNA). We found that Apaf1(-/-) NPCs resist common apoptotic stimuli and neurodegenerative inducers such as amyloid-beta peptide (typical of Alzheimer's disease) and mutant G93A superoxide dismutase 1 (typical of familial amyotrophic lateral sclerosis). Similar results were obtained in Apaf1(-/-) primary cells. When death is prevented by Apaf1 deficiency, cytochrome c is released from mitochondria and rapidly degraded by the proteasome, but mitochondria remain intact. Under these conditions, neither activation by cleavage of initiator caspases nor release of alternative apoptotic inducers from mitochondria takes place. In addition, NPCs can still differentiate, as revealed by neurite outgrowth and expression of differentiation markers. Our findings imply that the mitochondrion/apoptosome pathway is the main route of proneural and neural cells to death and that its inhibition prevents them from dismantling in neurodegenerative conditions. Indeed, the ETNA cell model is ideally suited for exploring the potential of novel cell therapies for the treatment of human neurodegenerations.

Nurse-midwifery in a large teaching hospital.

The role of the nurse-midwife in a busy obstetric hospital is explored. This report reviews the role and development of this service and teaching program in a high volume obstetric service. The relationship among the nurse-midwives, residents, and faculty demonstrates the ability of these services to work effectively with a high-risk population. The occasional complication in the obstetric patient as seen in this study dictates a close working relationship within the hospital environment. With the ever increasing demands being placed on obstetric care, a strong working relationship among health care professionals is essential.

Verapamil versus amlodipine in proteinuric non-diabetic nephropathies treated with trandolapril (VVANNTT study): design of a prospective randomized multicenter trial.

Angiotensin converting enzyme inhibitors (ACEI) are the most effective antiproteinuric agents and should be used as first-line drugs in both diabetic and non-diabetic proteinuric nephropathies. The role of calcium channel blockers (CCB) is much more controversial. In diabetic patients verapamil and diltiazem seem more effective than dihydropyridines in reducing urinary protein excretion, and have additive effects with ACEI, but little is available on chronic treatment of non-diabetic nephropathies for non-dihydropyridine CCBs. To test whether the combination of verapamil 180 mg or amlodipine 5 mg with trandolapril 2 mg reduces urinary protein excretion more than trandolapril 2 mg alone, we planned a prospective, randomized, double-blind, multicenter trial. The secondary aims are to evaluate the effects of both treatments on the selectivity of proteinuria and check their safety. Consecutive patients aged between 18 and 70 years with non-diabetic proteinuria > or =2 g/24 h and plasma creatinine < 3 mg/dl or creatinine clearance > or = 20 ml/min are asked to participate. After a four-week run-in during which previous antihypertensive therapy is withdrawn, a single dose of trandolapril 2 mg is given once a day in open conditions for four weeks. At the end of this period patients are randomly assigned to receive once a day, in a double blind fashion, either trandolapril 2 mg and verapamil 180 mg [plus a placebo], or trandolapril 2 mg plus amlodipine 5 mg. They are monitored after one, two, five and eight months.

Immunologic disturbances and levels of parathyroid hormone in uremic patients in replacement dialysis therapy.

We studied the changes in cellular immunity in patients in replacement dialysis therapy (RDT) and examined the relationship between T-lymphocyte function and plasma levels of parathyroid hormone (PTH). In a preliminary study we found that increased plasma levels of PTH were associated with a decrease of T-lymphocytes and CD4, an increase in CD8 and a reduction in the ratio of CD4 to CD8. In the present study we examined the relationship between plasma levels of PTH, interleukin 2 receptors (IL-2R) and soluble human CD8 (S-CD8). We studied 54 patients divided into two groups: 26 patients with normal levels of PTH and 28 patients with increased levels of PTH. We found a significant reduction in total T-lymphocytes in both groups as compared to controls, with an inverse correlation between total T-lymphocytes and plasma PTH in the second group (R = -0.52). There was an increase in IL-2R in the group II as compared to the controls and also in the total population of uremic patients with a linear correlation between levels of IL-2R and PTH (R = 0.6). The levels of S-CD8 showed a significant increase in both groups with a linear correlation between levels of SC-D8 and PTH (R = 0.63). No specific differences were seen between patients treated with and without 1,25-dihydroxyvitamin D3. The elevated levels of PTH affect the lymphocyte function and are associated with change in cellular immunity with reduction in total number of T cells, and increases in levels of CD8, S-CD8 and IL-2R.

Mentoring in the career development of hospital staff nurses: models and strategies.

Mentoring in the career development of hospital staff nurses was explored using a qualitative, grounded-theory method in a descriptive study design. Verbatim audiotaped interviews of hospital staff nurses and their nurse managers from four hospitals in the northeast were used. Document analysis of key hospital and nursing organizational policy statements was included. Two models were identified from the study regarding the mentoring of hospital staff nurses, ie, a structural and a process model. Within the structural model, mentoring influentials were noted to be people, events, and environments. Peers and nurse managers proved to be the primary people influential in providing key mentoring strategies. Within the process model, four phases were identified leading to three separate career development outcomes toward which hospital staff nurses strive: the development of career-building relationships, facilitation of career transition points, and positive interaction within the organizational climate.

[Laparoscopic surgical treatment in abdominal emergencies: personal experience]. / Trattamento chirurgico laparoscopico delle urgenze addominali: esperienza personale.

In recent years laparoscopic surgery has reached a crucial role in the surgical approach of both abdominal and thoracic pathologies. A diffused as elective surgery, its utilization has become necessary even in emergency surgery, both as diagnostic approach as curative aim. In this work the purpose of the Authors is to show their own experience in a six years period in the laparoscopic treatment of abdominal emergencies.

[Duodenal villous adenoma: a case report]. / Adenoma villoso del duodeno: un caso clinico.

Small bowel tumours are rare neoplasms representing just 1% of all the gastrointestal tract lesions. Adenomas are the benign forms which, developing in the duodenum, tend to localize in periampullary region, with high incidence of malignant degeneration. The authors report a case of a fifty-five-years old woman with a periampullary villous adenoma.

[Cystadenocarcinoma in situ of the urachus: a clinical case]. / Cistoadenocarcinoma in situ dell'uraco: caso clinico.

Urachal carcinoma is a rare neoplasm which represents 0.01% cancers in adults. If this neoplasm is unusual, the development of cystadenocarcinoma on a urachal cyst is still more rare. The surgical treatment of choice is en-bloc excision of umbilicus and median umbilical ligament with partial cystectomy. As the urachal cystadenocarcinoma of Authors' patient was in situ and without bladder-invasion, they performed a more conservative treatment without partial cystectomy. They believe that this treatment may be indicated in association with a close follow-up after surgery.

[Synchronous multiple gastric adenocarcinoma: a clinical case]. / Adenocarcinomi gastrici multipli sincroni: un caso clinico.

The Authors present a case of synchronous double gastric carcinoma in a 75-year-old man. Synchronous multiple gastric carcinoma (SMGC) constitutes 4% to 10% of all gastric cancers. It exhibits several clinicopathological characteristics that differ from those of solitary cancers: SMGC occurs in older people (men more than women); early carcinoma is observed more frequently in SMGC than in solitary cancers; the rate of intestinal type lesions is higher in multiple than in single gastric carcinoma. With regard to the pathogenesis of multiple gastric cancer, the theory proposing a multicentric or independent origin rather than the local or distant spread of one cancer (multifocality) has been favored.

[Single asymptomatic splenic metastasis of breast carcinoma: report of a clinical case]. / Metastasi splenica unica asintomatica da carcinoma della mammella: descrizione di un caso clinico.

The spleen is rarely involved from metastatic disease. Metastases from breast cancer are extremely rare although described in the Literature. The Authors report a case of a woman who had undergone to radical mastectomy for breast cancer nine years previously and admitted to the hospital because of a single splenic lesion shown by U.S. scan during the follow up.

[An appendiceal-vesical fistula in a patient with cystic fibrosis]. / Fistola appendico-vescicale in un malato di fibrosi cistica.

Cystic fibrosis is an hereditary disease in which abnormally viscous secretion of exocrine glands causes chronic pulmonary infections and gastrointestinal disorders. The authors report the case of a patient with cystic fibrosis and appendicitis complicated by appendico-vesical fistula. The appendico-vesical fistula has been described during appendicitis; its association with the cystic fibrosis however has never been reported in the literature.

The utilization of nurse-midwives as providers of obstetric triage services. Results of a national survey.

Obstetric triage services are rapidly advancing, and the concept is becoming a popular practice pattern. As more pregnant women are evaluated in ambulatory settings, especially in high volume obstetric tertiary centers, it is now realized more and more that labor and other complaints cannot be addressed solely in labor and delivery units, nor are most of these complaints solely labor related. This article presents the results of a national survey designed to discover what contributions nurse-midwives are making to obstetric triage services. In addition, the results provide initial benchmark data on obstetric triage components against which other midwifery services can address practice issues.