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Contact with nature can contribute to health and wellbeing, but knowledge gaps persist regarding the environmental characteristics that promote these benefits. Understanding and maximising these benefits is particularly important in urban areas, where opportunities for such contact is limited. At the same time, we are facing climate and ecological crises which require policy and practice to support ecosystem functioning. Policies are increasingly being oriented towards delivering benefits for people and nature simultaneously. However, different disciplinary understandings of environments and environmental quality present challenges to this agenda. This paper highlights key knowledge gaps concerning linkages between nature and health. It then describes two perspectives on environmental quality, based respectively in environmental sciences and social sciences. It argues that understanding the linkages between these perspectives is vital to enable urban environments to be planned, designed and managed for the benefit of both environmental functioning and human health. Finally, it identifies key challenges and priorities for integrating these different disciplinary perspectives., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Emergency departments are key settings for suicide prevention. Most people are deemed to be at no or low risk in final contacts before death., Aim: To micro-analyse how clinicians ask about suicidal ideation and/or self-harm in emergency department psychosocial assessments and how patients respond., Method: Forty-six psychosocial assessments between mental health clinicians and people with suicidal ideation and/or self-harm were video-recorded. Verbal and non-verbal features of 55 question-answer sequences about self-harm thoughts and/or actions were micro-analysed using conversation analysis. Fisher's exact test was used to test the hypothesis that question type was associated with patient disclosure., Results: (a) Eighty-four per cent of initial questions ( N = 46/55) were closed yes/no questions about self-harm thoughts and/or feelings, plans to self-harm, potential for future self-harm, predicting risk of future self-harm and being okay or keeping safe. Patients disclosed minimal information in response to closed questions, whereas open questions elicited ambivalent and information rich responses. (b) All closed questions were leading , with 54% inviting no and 46% inviting yes. When patients were asked no-inviting questions, the disclosure rate was 8%, compared to 65% when asked yes-inviting questions ( P < 0.05 Fisher's exact test). (c) Patients struggled to respond when asked to predict future self-harm or guarantee safety. (d) Half of closed questions had a narrow timeframe (e.g. at the moment, overnight) or were tied to possible discharge., Conclusion: Across assessments, there is a bias towards not uncovering thoughts and plans of self-harm through the cumulative effect of leading questions that invite a no response, their narrow timeframe and tying questions to possible discharge. Open questions, yes-inviting questions and asking how people feel about the future facilitate disclosure.

Background: In the United Kingdom, suicide risk is assessed in the emergency department (ED) in a face-to-face assessment with psychiatric liaison practitioners. This study aimed to explore patient experiences of psychosocial assessment after presenting with self-harm/suicidality. Method: A total of 28 patients were interviewed within 2 weeks of ED attendance for self-harm/suicidality. Interviews were transcribed and analyzed using inductive thematic analysis. Results: People described two different experiences. A therapeutic interaction was about the "person" and made people feel their life mattered and instilled hope for the future. This was characterized by: unscripted conversation; warmth promoting disclosure; psychological exploration of feelings; validation of distress; and a coproduced care plan. A formulaic assessment was about the "risk" and made people feel their life did not matter and hopeless about the future. This was characterized by: feeling judged and not worthy of help; a focus on risk and form filling; a trivial treatment plan; and loss of trust in services. Limitations: Our study comprised a single ED and used a non-diverse sample. Conclusion: Psychosocial assessment in the ED impacts on hope for people in crisis. A focus on therapeutic communication that is about the person, as well as the risk, improves patient experience, decreases distress, and instills hope that life is worth living.

Introduction: While short-term cognitive impairment following electroconvulsive therapy (ECT) is well described and acknowledged, the relationship between ECT and persistent memory impairment, particularly of autobiographical memory, has been controversial. Methods: We describe the case of a 70-year-old consultant neurophysiologist, AW, who developed prominent, selective autobiographical memory loss following two courses of ECT for treatment-resistant depression. Results: His performance on standard measures of IQ, semantic and episodic memory, executive function and mood was normal, while he performed significantly below controls on measures of episodic autobiographical memory. Conclusions: Explanations in terms of mood-related memory loss and somatoform disorder appear unlikely. We relate AW's autobiographical memory impairment, following his ECT, to reports of similar autobiographical memory impairment occurring in the context of epilepsy, and emphasise the importance of using sensitive approaches to AbM assessment.

The dawn of animals remains one of the most mysterious milestones in the evolution of life. The fossil lipids 24-isopropylcholestane and 26-methylstigmastane are considered diagnostic for demosponges-arguably the oldest group of living animals. The widespread occurrence and high relative abundance of these biomarkers in Ediacaran sediments from 635-541 million years (Myr) ago have been viewed as evidence for the rise of animals to ecological importance approximately 100 Myr before their rapid Cambrian radiation. Here we show that the biosynthesis of 24-isopropylcholestane and 26-methylstigmastane precursors is common among early-branching unicellular Rhizaria-heterotrophic protists that play an important role in trophic cycling and carbon export in the modern ocean. Negating these hydrocarbons as sponge biomarkers, our study places the oldest evidence for animals closer to the Cambrian Explosion. Cambrian silica hexactine spicules that are approximately 535 Myr old now represent the oldest diagnostic sponge remains, whereas approximately 558-Myr-old Dickinsonia and Kimberella (Ediacara biota) provide the most reliable evidence for the emergence of animals. The proliferation of predatory protists may have been responsible for much of the ecological changes during the late Neoproterozoic, including the rise of algae, the establishment of complex trophic relationships and the oxygenation of shallow-water habitats required for the subsequent ascent of macroscopic animals.

To examine the sociocultural factors that determine the eating habits of children aged less than 5 years who attend kindergarten school in Chachapoyas in Peru, we carried out a qualitative study by means of semi-structured interviews of 18 fathers and mothers. The key factors related to eating habits were as follows: availability and easiness to prepare foods, schedule and work done by parents, intake of coffee in children as a common practice, lack of resources and economic uncertainty for food planning, and the lack of nutritional knowledge. Similarly, beliefs that might explain some eating habits, such as the beneficial effects of eating food as a family, maternal breastfeeding, and others, or the role of nutrition for the appropriate intellectual and physical development of children were identified. Our results provide evidence about the ways parents tackle and understand their children's nutrition while, in turn, determining its quality.

Purpose: The primary aim of this trial was to assess the rate of pathologic complete responses (pCR) of doxorubicin/cyclophosphamide (AC) followed by bevacizumab/docetaxel (BT), as neoadjuvant therapy for breast cancer (BC). Furthermore, the association between biomarkers and the pCR was explored., Methods: Patients with HER-negative operable stage II-III BC ≥ 2 cm were enrolled. Four cycles of AC (A 60 mg/m(2) and C 600 mg/m(2), every 3 weeks) followed by 4 cycles of BT (B 15 mg/kg and T 75 mg/m(2), every 3 weeks), were planned. A core-biopsy was performed for biological markers assessment., Results: Seventy-two women were included. Forty-three (63 %) patients were hormone receptor-positive. Sixty-four (89 %) completed the planned treatment, and 66 evaluable patients underwent surgery (92 %): a pCR was achieved in 16 of them (24, 95 % CI 15-36 %). pCR was significantly higher in tumors hormone receptor-negative, and in those with Angiotensin II type 1 receptor (AGTR1) protein overexpression. The overall clinical response rate was 86 % (95 % CI 76-93 %), including 42 complete responses. No unexpected toxicities or treatment-related deaths were observed., Conclusion: This regimen showed a remarkable clinical and pathological activity: the suggested relation between pCR and AGTR1 overexpression should be confirmed in larger trials.

Background: To assess the molecular subtypes determined by hormonal receptors (HR) and human epidermal growth factor receptor 2 (HER2) status and the role of proliferation measured by the Ki-67 marker as predictive and prognostic factors in breast cancer patients treated with neoadjuvant chemotherapy., Methods: A total of 127 breast cancer patients were treated with neoadjuvant chemotherapy every 2 weeks as part of 2 studies. Study A consisted of the administration of Adriamycin (40 mg/m(2)) on day 1 plus paclitaxel (150 mg/m(2)) and gemcitabine 2000 mg/m(2)) on day 2 for 6 cycles (n = 54). Study B consisted of the administration of epirubicin (90 mg/m(2)), cyclophosphamide (600 mg/m(2)) on day 1 for 3 cycles, followed by the administration of paclitaxel (150 mg/m(2)) and gemcitabine 2500 (mg/m(2)) on day 1 with or without trastuzumab according to HER2 status (n = 73). In study A, patients did not receive trastuzumab regardless of HER2 status. The molecular subtypes of the patients with breast cancer were classified as 49% HR(+)/HER2(-), 17.5% HR(+)/HER2(+), 13.5% HR(-)/HER2(+), and 20% HR(-)/HER2(-)., Results: Pathologic complete response (pCR), defined as the absence of invasive cells in the breast and the lymph nodes, was achieved in 35 (28%) patients. The pCR rate was significantly different between the molecular subtypes of breast cancer, with 9% in HR(+)/HER2(-), 23% in HR(+)/HER2(+), 50% in HR(-)/HER2(+), and 56% in HR(-)/HER2(-) tumors (P < .001). The pCR rate was significantly higher in tumors that had high Ki-67 (≥20%) expression and were HR(-). HER2(+) was associated with a higher trend of pCR but did not reach statistical significance. The median follow-up was 81 months (r = 15-150 months). Patients who achieved a pCR had a significantly lower recurrence (P = .01) and higher overall survival (P = .02) compared with those who did not achieve pCR. A multivariate analysis revealed that pCR (hazard ratio 0.24 [95% CI, 0.07-0.7]; P = .019), the molecular subtype (hazard ratio 0.3 [95% CI, 0.1-0.8]; P = .02), and the Ki-67 index (hazard ratio 3.2 [95% CI, 1.4-7.1]; P = .004) were significant independent predictors of disease-free survival. Similar results were obtained for overall survival, in which the pCR rate (hazard ratio 0.119 [95% CI, 0.028-0.5]; P = .004), the molecular subtype (hazard ratio 0.17 [95% CI, 0.03-0.86]; P = .02), and the Ki-67 index (hazard ratio 3.6 [95% CI, 1.3-9.7]; P = .01) also displayed a significant influence on survival., Conclusions: Molecular subtypes and Ki-67 index were independent prognostic factors for disease-free survival and overall survival in breast cancer patients treated with neoadjuvant chemotherapy. A high rate of Ki-67 and HR(-) expression were predictors of pCR., (Copyright © 2013 Elsevier Inc. All rights reserved.)

New advances in the diagnosis and treatment of cancer and the increased incidence and prevalence of this disease have led to an increase in the number and duration of visits in Medical Oncology in the last few years. Based on the functions of a medical oncologist and the time recommended for each work activity established by the Spanish Society of Medical Oncology (SEOM), we carried out a pilot study on the three most frequent neoplasias in our country [breast cancer (BC), lung cancer (LC) and colorectal cancer (CRC)], in order to determine the real time each patient requires from a physician and thus establish a recommendation on the number of medical oncologists necessary. Using the actual itinerary of the first 20 patients of 2009 in each of the three neoplasias seen at the Medical Oncology Service of the Virgen de Valme University Hospital, we measured the number of visits, the antineoplastic treatments received, the number of hospital admissions and average length of stay. During the years following the study, these data were estimated based on the natural history of each neoplasia. During the first year, the average time spent by the medical oncologist was 235, 390 and 265 min on each outpatient with BC, LC and CRC, respectively. In hospitalisation, the average oncologist/patient minutes were 40, 360 and 118 for BC, LC and CRC, respectively. Finally, the time spent on each visit or day of hospitalisation was that recommended by the SEOM, achieving an ultimate ratio of 1 oncologist for every 83 first visits.

Introduction: The identification and validation of biomarkers of chemotherapy sensitivity is critical in order to individualise therapy in breast cancer. We evaluated pathological complete response (pCR) to GAT, and its correlation with tumour biomarkers before and after neoadjuvant chemotherapy., Materials and Methods: Stage III (and stage II with T≥5 cm) breast cancer patients were included. Treatment consisted of adriamycin (40 mg/m(2)) day 1, and paclitaxel (150 mg/ m(2)) followed by gemcitabine (2000 mg/m(2)) day 2, every 14 days for six cycles. Tissue from pre-treatment biopsy and surgery was evaluated for biologic markers by immunohistochemistry. Two XPD single nucleotide polymorphisms (SNP) were also analysed., Results: Forty-six patients entered the trial. Median age was 49.5 years (range 31-72); 25 patients (54%) were pre-menopausal; 12 (26%) were ER-PgR-negative; pCR was observed in 17% (95% CI: 6.4-28.4) of patients. Significant differences in marker expression (mean±SD) in correlation to pathological response were only found in Ki- 67. After treatment, tumours showed lower Ki-67-, surviving- and pERK-positive cells. No correlation between XPD polymorphisms and pCR was found. The overall response rate was 89% (95% CI: 80.1-98.1). Fifteen patients (33%) underwent breast-conserving surgery. The most frequent grade 3 or 4 toxicities were neutropenia (with one febrile neutropenia) and asthenia., Conclusion: These results show an effective regimen with acceptable tolerability. Our data suggest that not only classical markers (ER, Ki-67), but also survivin and pERK could be involved in the response to GAT, which may contribute to therapy individualisation in future study designs.

The functions and workload of medical oncologists are becoming increasingly relevant as cancer is a priority health issue in our country. Taking into account the specific characteristics and complexity of caring for cancer patients, the time of physicians attached to Medical Oncology could be distributed as follows: 70% for consultation (including participation in tumour committees and multidisciplinary units), 15% for research and 15% for training, teaching and clinical sessions. The time distribution for Heads of Services or Heads of Units is different, since it must also include their clinical management tasks, team coordination, and relations with other services and institutions. The average time, calculated in minutes, spent on each activity per patient is as follows: first visit and "second visit or results visit" 60-90 min; successive visits at the day hospital 15 min; successive visits of patients for follow-up or checkups 20 min; visits with family members 15-20 min; telephone or e-mail consultations 5-10 min; hospitalisation 20 min; and interconsultation 30-60 min. Also, participation in multidisciplinary committees takes up 60-120 min of an oncologist's time each week. When new technologies such as electronic medical records, e-mail and other software are used, these times increase with a correction factor that is still to be defined and which could vary according to the centre. Finally, the ratio recommended by SEOM is one medical oncologist for every 83 new patients a year.

Background and Objectives: Early age of onset is a marker of a possible hereditary component in colorectal cancer (CRC). We evaluated whether early age of onset is a good marker to identify Lynch syndrome, especially retrospectively, and if there is any other feature that could improve this identification., Methods: We selected patients with CRC aged 45 years or younger from the pathological reports of three different institutions and different periods of time. Clinical information, family history, and tumor samples were obtained. Cases were classified according to mismatch repair (MMR) proficiency., Results: Of 133 tumors, 22 showed microsatellite instability (MSI). In 15 MSI cases, a germline mutation in 1 of the MMR genes was identified, 7 of which were not identified before. The positive predictive value (PPV) of right colon CRC for a positive genetic MMR test is 30.6%, whereas "signet ring" cells and fulfillment Amsterdam II criteria have PPVs of 42.9% and 47.8%, respectively. Combining right-sided CRC with mucin production, with fulfilling Amsterdam II criteria, or with "signet ring" cells, PPVs are 54.5, 64.3, and 100%. The probability of the absence of a mutation when CRC is located in the left colon is 94.7%, whereas absence of aggregation for Lynch-related neoplasm has a 100% probability., Conclusions: Early age of onset is an effective method to identify retrospectively Lynch syndrome. Taking into account the location and histology features of the tumor, and the familial history of the cases, we notably increase the a priori probability of detecting a germline MMR mutation.

Background: Expressed short hairpin RNAs (shRNA) used in mammalian RNA interference (RNAi) are often designed around a specific short interfering RNA (siRNA) core. Whilst there are algorithms to aid siRNA design, hairpin-specific characteristics such as stem-length and siRNA core placement within the stem are not well defined., Results: Using more than 91 hairpins designed against HIV-1 Tat and Vpu, we investigated the influence of both of these factors on suppressive activity, and found that stem length does not correspond with predictable changes in suppressive activity. We also detected multiple processed products for all stem lengths tested. However, the entire length of the hairpin stem was not equally processed into active products. As such, the placement of the siRNA core at the base terminus was critical for activity., Conclusion: We conclude that there is no fixed correlation between stem length and suppressive activity. Instead, core selection and placement likely have a greater influence on the effectiveness of shRNA-based silencing.

Introduction: To assess the efficacy and safety profile of biweekly vinorelbine and tegafur/uracil (UFT) as treatment in patients with metastatic breast cancer previously treated with anthracyclines and taxanes., Patients and Methods: Patients with histologically confirmed breast cancer, measurable disease, no more than one prior chemotherapy regimen for metastatic disease, an Eastern Cooperative Oncology Group (ECOG) performance status ≤2, and adequate bone marrow, renal and liver function were eligible. Patients received vinorelbine (30 mg/m(2) on day 1) and UFT (250 mg/m(2) daily) every two weeks for 12 cycles unless progression or unacceptable toxicity was observed., Results: Thirty-seven patients were included and received 311 cycles of chemotherapy. Efficacy and toxicity analyses were carried out on an intention-to-treat basis. The overall response rate was 35% (95% CI: 20-53). With a median follow-up of 18.6 months (95% CI: 1.0-74.3), the median time to progression was 7.0 months (96% CI: 5.2-8.9) and the median overall survival was 19.4 months (95% CI: 11.1-27.8). The most common severe toxicities were neutropenia (38% of patients) and asthenia (11% of patients)., Conclusion: The combination of biweekly vinorelbine and UFT in patients with metastatic breast cancer pretreated with anthracyclines and taxanes is a well tolerated and effective regimen. AEMPS Trial Registration No.: 00-0534.

Colorectal cancer (CRC) has become a highly relevant condition nowadays. In this respect, advances in the understanding of its molecular basis are key for an adequate management. From the time when the adenoma-carcinoma sequence was formulated as a carcinogenesis model to this day, when -among other things- three major carcinogenic pathways have been identified, the CRC concept has evolved from that of a single disease to the notion that each CRC is a differentiated condition in itself. The suppressor or chromosome instability pathway, the mutator or microsatellite instability pathway, and the methylator or CpG island methylation pathway allow various phenotypes to be identified within CRC. Similarly, the presence of different changes in certain genes confers several behaviors on CRC from both the prognostic and responsive standpoints to specific therapies. However, this apparent complexity does help develop the clinical management of this disease through the identification of novel, more specific therapy targets, and also markers for various behaviors within the condition, which will most likely lead us to an individualized management for these patients.

Colorectal cancer is the third most common malignant neoplasm and the second cause of death by cancer in western countries. In this manuscript, the clinical guidelines of the Spanish Society of Medical Oncology (SEOM) for diagnosis and adjuvant treatment of colon cancer and rectal cancer are reported.

Colorectal cancer is the first cause of cancer diagnosis in Spain. Over half of the patients are diagnosed with or will eventually develop distant metastasis. The current manuscript aims to provide synthetic practical guidelines for the therapeutic approaches in advanced disease. Available systemic therapeutic options, and integration and sequencing of chemotherapy with surgical procedures are discussed. Extent of disease, treatment objective, tumor kras mutation status, as well as patient's functional and comorbid conditions shall be considered to properly design the most adequate therapeutic strategy.

Terrestrial gross primary production (GPP) is the largest global CO(2) flux driving several ecosystem functions. We provide an observation-based estimate of this flux at 123 +/- 8 petagrams of carbon per year (Pg C year(-1)) using eddy covariance flux data and various diagnostic models. Tropical forests and savannahs account for 60%. GPP over 40% of the vegetated land is associated with precipitation. State-of-the-art process-oriented biosphere models used for climate predictions exhibit a large between-model variation of GPP's latitudinal patterns and show higher spatial correlations between GPP and precipitation, suggesting the existence of missing processes or feedback mechanisms which attenuate the vegetation response to climate. Our estimates of spatially distributed GPP and its covariation with climate can help improve coupled climate-carbon cycle process models.

The importance of colorectal cancer (CRC) is increasing. A proportion show a hereditary component, as in Lynch syndrome and Familial Adenomatous Polyposis, and a recently defined entity as well, namely, Familial Colorectal Cancer type X. The high probability to develop CRC in these groups may, at the time of recognition, change surgical management, including its timing or even the surgical technique. In some cases prophylactic surgery can play an important role. The possibility of using tools that allow recognition of the aforementioned syndromes, including microsatellite instability, immunohistochemistry for DNA mismatch repair system proteins, and especially their mutations, is on the basis of therapeutic strategies that differ from those employed in sporadic CRC cases.

Background: We performed an adaptation of the system of evaluation of metatarsal protrusion described by Oller in 1994 to study the metatarsal parabola group., Methods: The system of measurement was applied to the five metatarsals of 169 normal feet (72 feet of women and 97 feet of men) according to the inclusion criteria established., Results: The mean +/- SD metatarsal protrusion angle with respect to the second ray in women was 87.49 degrees +/- 5.48 degrees for metatarsal I, 70.00 degrees +/- 5.74 degrees for metatarsal III, 63.47 degrees +/- 4.17 degrees for metatarsal IV, and 56.38 degrees +/- 3.27 degrees for metatarsal V. In men, the values were 85.30 degrees +/- 6.75 degrees for metatarsal I, 68.00 degrees +/- 6.72 degrees for metatarsal III, 60.56 degrees +/- 4.61 degrees for metatarsal IV, and 54.13 degrees +/- 3.75 degrees for metatarsal V. The comparative analysis between women and men showed significant differences (P < .05) for all of the values of metatarsal protrusion., Conclusions: The comparative analysis between women and men indicates a possible difference between the anthropometric values of these variables in humans, suggesting a possible repercussion on the biomechanical patterns by sex.

Introduction: Treatment of HER-2-negative metastatic breast cancer (MBC) patients after anthracycline exposure is controversial. Docetaxel/capecitabine is a promising regimen, but the administration schedule is not well established., Materials and Methods: Treatment included 3 cycles of docetaxel 100 mg/m2 day 1 every 21 days followed by 3 cycles of capecitabine 1250 mg/m2/12 h days 1-14. Patients not progressing were maintained with capecitabine 900 mg/m2/12 h on days 1-14 every 21 days until progression or unacceptable toxicity., Results: Fifty-three anthracycline-pretreated patients were enrolled: median age 54 years, ECOG grade 0-1 86.7%. Most of the women received adjuvant chemotherapy (81%) and 5 patients (9%) had had prior metastatic chemotherapy treatment. Median time from anthracycline exposure was 29 months. ORR (intent-to-treatment analysis) after the sequential therapy was 51% (CI 95% 37-65) with 15% (CI 95% 7-28) of patients reaching complete responses. Median time to progression was 8.2 (CI 95% 7.1-10.7) months, with 61.9% (CI 95% 45.6-76.4) of the patients free of disease after 6 months. Median overall survival was not reached after a median follow-up of 10.4 months, and 75% of the patients were alive after 14.3 months. Survival rate after 12 months was 81.1% (CI 95% 68.0-90.6). The most frequent NCI grade 3-4 toxicities were hair loss (28.3%), asthenia (15.1%), stomatitis (11.32%) and nausea (11.32%). Severe hand-foot syndrome rate was 7.5%., Conclusions: Sequential docetaxel-capecitabine is feasible, effective and well tolerated in first-line MBC treatment. Evaluation of this schedule in randomised studies is warranted.

Background: Addition of carboplatin (C) to trastuzumab (T) and paclitaxel (P) improves the efficacy in HER2+ metastatic breast cancer (MBC). The aim of this phase-II study was to evaluate the efficacy and safety of this combination given weekly (3x) followed by a week off. The primary endpoint was: objective response rate (ORR), and secondary endpoints were: time to progression (TTP), overall survival (OS), and toxicity profile., Methods: HER2+ MBC patients were included in the study. Treatment was as follows: T (loading dose:4 mg/kg per week and 2 mg/kg per day thereafter), P (80 mg/m(2)) and C (AUC 2) given weekly 3x, followed by 1 week off until disease progression or unacceptable toxicity., Results: Forty-one patients (pts) were enrolled-median age: 54.5 years (range 29-75); 87.8% PS 0 or 1; 39 (97.5%) had received prior adjuvant or neoadjuvant treatment; 11 (27%) had received one prior CT line for metastatic disease; disease sites: liver (40%), bone (32.5%), lymph nodes (32.5%) and lung (20%); 19 (47.5%) had > or =2 lesions and 97.5% had measurable disease. A total of 37 pts were evaluated for response: 11(26.8%) CR; 12 (29.3%) PR; 9 (22%) SD; 5 (12.2%) PD and 4 NE, resulting in an ORR of 56.1% (95% CI 39.7-71.5%) and tumor growth control rate (RR + SD) of 78% (95% CI 62.4-89.4%). With a median follow up of 39.4 months, 26 (70.3%) patients have progressed. The median time to progression was 12.3 months (95% CI 8.2-15.5). At the time of this report, ten patients have died. Forty patients received 202 cycles (median five cycles). Grades 3-4 toxicities/pts: 3 (7.5%) anemia, 2 (5%) leucopenia, 10 (25%) neutropenia, 1 (2.5%) febrile neutropenia,1 (2.5%) thrombopenia, 2 (5%) asthenia, 2 (5%) diarrhea, 3 (7.5%) nausea, 2 (5%) vomiting, and 3 (7.5%) mucositis., Conclusions: The schedule showed an interesting activity, taking into account that 27% of patients had received previous treatment for MBC. One week of rest may benefit not only the patient but may also improve tolerability and efficacy of the combination.

Objective: To identify serotypes and susceptibility of S. pneumoniae strains from 48 children with invasive infections and 50 carriers., Material and Methods: Typing was performed by the Quellung reaction and susceptibility by Kirby-Bauer and Etest according to CLSI standards., Results: Of 31 meningeal strains, serotypes 19F, 3, 6B, 14 and 23F were predominant. Resistance to penicillin and STX was 16 and 58%, respectively; of 17 invasive non-meningeal strains, serotypes 19F and 3 were predominant and resistance to penicillin and SXT was 0 and 82%, respectively; of carrier strains, serotypes 6A, 6B, 19F and 23F were predominant., Conclusions: A 10-valent conjugate vaccine could offer a better coverage for meningeal strains.

Objectives: To describe the incidence of germ cell testicular tumors in our Center, their characteristics and therapy results., Methods: Retrospective study of 66 cases of germ cell testicular tumors diagnosed in the Health Area of Badajoz between 1993 and 2005., Results: Mean age of the time of diagnosis was 32 years (range 16-80 years), presenting a younger age patients with non seminomatous germ cell tumors (NSGCT) (mean age 30 years). 86.5% of the patients did not have risk factors associated with the diagnosis of germ cell testicular tumor. Testicular mass was the most frequent symptom, and a higher proportion of tumors were located in the left testicle (51.5%). Non seminomatous germ cell tumors were the most frequent histological type (64.8%). Stage I (72%) was the most frequent stage in the group of seminomatous tumors, in comparison with 68.5% of non seminomatous tumors. Stages II-III appeared in 34.4% of the NSGCT and 28% of seminomatous, having worse prognosis. 92% of the patients received adjuvant treatment with chemotherapy and/or radiotherapy, and curative surgery was the only treatment in the remainder 8%. Residual mass surgery was undertaken in five patients (stages IIa, IIc and IIIa). Eight of the 66 cases were lost for follow-up. Fifty-three of the 58 patients with follow-up are disease-free, 18 of them with more than five years of follow-up., Conclusions: An increased incidence of germ cell testicular tumors have been verified over last years, mainly NSGCT Nevertheless, the diagnosis of advanced stages of the disease has diminished in favour of initial stages, which have a better prognosis for the patient. Oncologycal treatment protocols have high cure rates, although a long-term follow-up is needed due to the natural history of these tumors.

Introduction: Many surgical techniques -both through the perineal and abdominal routes- have been described for the treatment of rectal prolapse. The aim of this work is to evaluate the clinical and functional outcome with Delorme's perineal procedure., Patients and Methods: Twenty-one patients with complete rectal prolapse were studied from July 2000 to October 2005. Age, gender, anesthetic risk, and accompanying symptoms were all assessed. Diagnostic tests performed included: colonoscopy, anorectal manometry before and after surgery, and 360 masculine endoanal ultrasonography. Delorme's procedures were carried out by only one surgical team., Results: No mortality occurred, and morbidity was minimal. Prolapse relapse rate was 9.52% with a mean follow-up of 34 months. Anal continence improved in 87.5% of patients, and no surgery-associated constipation ensued. Mean hospital stay was 2 (range 1-4) days. During the postoperative period no pain developed in 17 patients, and 4 patients had mild pain. Satisfaction with surgery was high in 16 cases (76.19%), moderate in 3 (14.28%), and low in 2 (9.52%)., Conclusions: Delorme's procedure for the management of complete rectal prolapse is associated with low morbidity, improves anal continence, gives rise to no postsurgical constipation, and has an acceptable relapse rate. Patient satisfaction with this procedure is high because of its high comfortability (intradural anesthesia, short hospital stay, and little postoperative pain) and optimal results.

Purpose: To evaluate the feasibility, toxicity and efficacy of the combination of docetaxel and mitomycin C as second-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC)., Patients and Methods: Thirty-eight patients with histologically confirmed, locally advanced or metastatic NSCLC were included in this phase II trial. All patients had been previously treated with a platinum-based regimen. Treatment consisted of docetaxel (75 mg/m2) followed by mitomycin C (8 mg/m2) on day 1, every 21 days. Patients received a minimum of three courses unless progressive disease was detected., Results: A total of 190 courses of docetaxel-mitomycin C were administered (median five courses per patient). This combination was well tolerated with grade 3-4 toxicity experienced with the following frequency: neutropenia in five patients (13%), fatigue in four (11%), anaemia, thrombocytopenia, nausea/vomiting and peripheral neuropathy in one each (3%). Three of 38 patients had a partial response (8%, 95% confidence interval 2.6-21.6%), 14 patients (37%) experienced stabilization of disease and 21 (55%) had disease progression. Median time to progression was 3.6 months. Overall median survival was 10.4 months, with the 1-year actuarial survival rate being 35%., Conclusions: The addition of mitomycin C to docetaxel as second-line therapy in NSCLC is well tolerated but does not seem to improve the response rate.

Background: Gemcitabine is currently considered the standard treatment for advanced pancreatic cancer (APC). Cisplatin and a fluoropyrimidine have some activity in the treatment of this cancer. The aim of this trial is to evaluate the efficacy and toxicity of a fixed dose-rate infusion of gemcitabine associated with cisplatin and UFT in patients with APC., Patients and Methods: Forty-six chemotherapy-naïve patients with APC that was either unresectable or metastatic were included in this phase II study. All of them had Karnofsky performance status > or =50 and unidimensionally measurable disease. Treatment consisted of gemcitabine 1,200 mg/m2 given as a 120-min infusion weekly for three consecutive weeks, cisplatin 50 mg/m2 on day 1 and oral UFT 400 mg/m2/day (in two to three daily doses) on days 1 to 21; cycles of treatment were given every 28 days., Results: A total of 208 cycles of chemotherapy were given with a median of 4 per patient. Fourteen patients (30%) achieved partial responses (95% CI 19-48%) and 17 (37%) had stable disease. The median time to progression was 5 months, and the median overall survival 9 months. Nineteen patients (49%; 95% CI 32-64%) had a clinical benefit response. Grade 3-4 WHO toxicities were as follows: neutropaenia in 26 patients (57%), with 5 cases of febrile neutropaenia (11%), thrombocytopaenia in 15 (33%), anaemia in six (13%), diarrhoea in 5 (11%), asthenia in 2 (4%) and mucositis in 1 (2%). Seven patients required hospitalisation for treatment-related complications., Conclusion: A fixed dose-rate infusion of gemcitabine associated with cisplatin and UFT is active in patients with APC, though at the cost of considerable toxicity.

Overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN or CD147), a member of the immunoglobulin family and a glycoprotein enriched on the surface of tumor cells, promotes invasion, metastasis, and growth and survival of malignant cells and confers resistance to some chemotherapeutic drugs. However, the molecular mechanisms underlying the actions of EMMPRIN are not fully understood. In this study we sought to determine whether EMMPRIN contributes to the malignant phenotype of breast cancer by inhibiting anoikis, a form of apoptosis induced by loss or alteration of cell-cell or cell-matrix anchorage, and to explore the signaling pathways involved. We found that in the absence of attachment, human breast carcinoma cells expressing high levels of EMMPRIN formed less compact aggregates with larger surface area and less fibronectin matrix assembly, had higher viability, and were resistant to anoikis. Knockdown of EMMPRIN expression by RNA interference (small interfering RNA or short hairpin RNA) sensitized cancer cells to anoikis, as demonstrated by activation of caspase-3, increased DNA fragmentation, and decreased cellular viability. Furthermore, we observed that the accumulation of Bim, a proapoptotic BH3-only protein, was reduced in EMMPRIN-expressing cells and that silencing of EMMPRIN expression elevated Bim protein levels and enhanced cellular sensitivity to anoikis. Treatment of cells with a MEK inhibitor (U0126) or proteasome inhibitor (epoxomicin) also up-regulated Bim accumulation and rendered cells more sensitive to anoikis. These results indicated that expression of EMMPRIN protects cancer cells from anoikis and that this effect is mediated at least in part by a MAP kinase-dependent reduction of Bim. Because anoikis deficiency is a key feature of neoplastic transformation and invasive growth of epithelial cancer cells, our study on the role of EMMPRIN in anoikis resistance and the mechanism involved underscores the potential of EMMPRIN expression as a prognostic marker and novel target for cancer therapy.

We present our experience in subcutaneous venous reservoir (SVR) implanting, laying emphasis on the surgical technique, the protocol followed for assessing difficulty, implant care and per- and post-implant complications and their management. Between March 1996 and December 2002 we installed 1200 SVRs on an outpatient basis, with subsequent result follow-up. The reservoir was successfully installed by the standard procedure in 99.33% of cases (1194), while in the remaining six patients (0.67%) the participation of the Intervention Radiology Department was required for correct implantation. Results were excellent with a morbidity of 3.3% and we had to single out two cases of immediate infection (0.16%), nine of tardive infection (over three months); twelve cases of pneumothorax (1%); seven episodes of venous thrombosis (0.58%) and four cases of catheter migration (0.3%). SVR implanting is possible on an outpatient basis but requires strict measures of asepsis and an experienced team and personnel responsible for its handling and maintenance, although there are a small number of complications inherent in the patient's general state.

Presentation of a case of small intestine primary angiosarcoma in a 70-year-old male. There is question of an extremely rare tumor in the gastrointestinal tract. Its symptomatology is similar to that of other tumors in the small intestine. An immunohistochemical study is usually essential for its anatomopathological diagnosis. The diagnosis is generally arrived at in its advanced stages, and that makes for a bad prognosis. The bibliography has been revised from this case on.

The purpose of this study was to evaluate the efficacy, assessed as response rate, and toxicity of UFT (Tegafur-Uracil) in combination with oxaliplatin as first-line treatment of advanced colorectal cancer (CRC). In all, 84 patients with recurrent or metastatic CRC with measurable disease were included. Treatment consisted of oxaliplatin 85 mg m(-2) in 120-min intravenous (i.v.) infusion on days 1 and 15; i.v. l,leucovorin (l,LV) 250 mg m(-2) given in 2 h on day 1, followed by oral UFT 390 mg m(-2) on days 1-14, and oral l,LV 7.5 mg/12 h on days 2-14. Cycles were repeated every 28 days. A total of 492 cycles of chemotherapy were delivered with a median of six per patient (range 1-12). There was one complete response (1%) and 28 partial responses (34%) for an overall response rate of 35% (95% confidence interval (CI): 24-46%). A total of 36 patients (44%) had stable disease, whereas 17 (21%) had a progression. The median time to progression was 7.3 months and the median overall survival was 16.8 months. A prescheduled preliminary analysis was performed after inclusion of 16 patients who detected a high gastrointestinal toxicity, which led to a reduction of the UFT dose to 300 mg m(-2). With this new dosage, grade 3-4 diarrhoea and grade 3-4 nausea/vomiting dropped to 21 and 14% of patients, respectively. Other grade 3-4 toxicities were stomatitis in one (1%), anaemia in three (5%), neutropenia in two (3%), thrombocytopenia in one(1%), fatigue in six (9%), peripheral sensory neuropathy in nine (14%) and laryngopharyngeal dysesthesia in two patients (2%). The combination of oxaliplatin and UFT-l,LV is an active, easy-to-administer regimen with moderate toxicity. Hence, this regimen is worthy of further investigation.

High-dose epirubicin plus cisplatin was compared with the reference regimen of etoposide/cisplatin in small-cell lung cancer (SCLC). Four hundred two previously untreated patients with SCLC were randomized to receive etoposide 100 mg/m(2) on days 1-3 and cisplatin 100 mg/m(2) on day 1 or epirubicin 100 mg/m(2) and cisplatin 100 mg/m(2) on day 1 every 21 days for a total of 6 cycles. Patients were stratified according to treatment center and extent of disease (limited disease, n = 207; extensive disease, n = 195). Patients with limited disease were treated with thoracic radiation therapy after completion of chemotherapy, and those who exhibited a complete response were advised to receive prophylactic cranial irradiation. The primary endpoint was survival, and secondary endpoints were time to progression (TTP), response, toxicity, and costs. Patient characteristics were generally well balanced in the 2 arms, even though more patients in the epirubicin/cisplatin arm had > 5% weight loss and poor Karnofsky performance index compared with the etoposide/cisplatin arm. One hundred thirty-four patients (66.3%) in the etoposide/cisplatin arm and 126 (63.0%) in the epirubicin/cisplatin arm received all 6 planned cycles of chemotherapy. Response rate, TTP, and survival did not differ significantly between the 2 arms. Grade 3/4 neutropenia and toxic deaths occurred more frequently in the etoposide/cisplatin arm. Epirubicin/cisplatin showed a similar activity with a slightly lower toxicity profile than the reference regimen of etoposide/cisplatin. The epirubicin/cisplatin regimen may be recommended in the treatment of SCLC.

Background: The purpose of this study was to induce immunity to p53 by using an idiotypic vaccine, composed of a pool of eight peptides derived from the complimentarity determining regions (CDRs) of human anti-p53 antibodies., Patients and Methods: Subjects with advanced malignancy received up to four, monthly intradermal injections of pooled peptides (500 microg of each) admixed with granulocyte-macrophage colony-stimulating factor (GM-CSF; 100 microg). In addition, two sheep and two rabbits were also vaccinated with the pooled peptides., Results: Fourteen subjects were enrolled into the study and six of these completed the vaccination schedule. The vaccine was well tolerated by all subjects and no major adverse events were attributable to the vaccine. All subjects mounted in vivo delayed type hypersensitivity (DTH) responses to two or more of the individual vaccine peptides. Vaccine-induced antibodies specific for peptides 2, 5 or 8 were detected in four of six subjects, and two of these had vaccine-specific, cell-mediated responses. Increasing titers of p53-specific antibodies were found in one patient. No T-cell response to p53 was observed in any of the subjects. All animals developed humoral immunity to the peptides and one of the sheep developed rising serum titers of anti-p53 antibodies., Conclusions: Vaccination with human antibody CDR regions represents a novel method for inducing human antibodies, which may in turn serve as immunological mimics of p53.

This phase II study was designed to evaluate the response rate (RR) and toxicity of gemcitabine/vinorelbine in patients with metastatic breast cancer. All patients had previously received anthracyclines. Treatment consisted of gemcitabine 1200 mg/m2 and vinorelbine 30 mg/m2 on days 1 and 8, every 3 weeks. Twenty-five patients were enrolled. Median age was 59 years (range, 33-73 years). Ten patients had received only adjuvant therapy with anthracyclines. The remaining 15 patients had received chemotherapy for metastatic disease, including taxanes in 11 cases. Four patients could not be evaluated for response. By intent-to-treat analysis, the overall RR was 44% (95% CI, 24.4%-65%). Median duration of response and median time to treatment failure were 21 and 17 weeks, respectively. The main toxicity was hematologic, with grade 3/4 neutropenia occurring in 13 patients and 1 patient developing febrile neutropenia. Two deaths from pneumonia occurred. These results reveal an encouraging activity with a reasonable toxicity profile in a patient population with an unfavorable prognosis. Our group is conducting a randomized study to compare this combination with vinorelbine alone in patients with metastatic breast cancer after failure to respond to anthracyclines and taxanes

Tax, the trans-activator of human T-lymphotropic virus type I (HTLV-I), is the dominant target antigen for cytotoxic T lymphocytes (CTLs) in the majority of infected individuals, although the reason for this immunodominance is not clear. Tax has been shown to associate physically with the proteasome, a protease that is responsible for the generation of the majority of major histocompatibility complex (MHC) class I ligands recognized by CTLs. This association could lead to the preferential targeting of Tax to the MHC class I pathway and account for its high immunogenicity. Here, the CTL response to Tax was investigated in mice by priming with a Tax expression vector and boosting with a Tax recombinant vaccinia virus (modified vaccinia virus Ankara strain). This approach led to the identification of a new H-2D(k)-restricted epitope in Tax, amino acid residues 38-46, sequence ARLHRHALL. Surprisingly, presentation of this epitope was found to be enhanced by the proteasome inhibitor lactacystin, although Tax was shown to associate with proteasomes in murine cells. The difficulties encountered in generating Tax-specific CTL responses and the results of enzyme-linked immunospot (ELISpot) analysis suggested that Tax is only poorly immunogenic for CTLs in mice. Therefore, the immunodominance of Tax in human CTL responses to HTLV-I is probably not due to an intrinsic property of the protein itself, such as an association with the proteasome, but instead may result from the fact that Tax is the predominant protein synthesized early after infection.

Introduction: Information on the relative cost-effectiveness of treatments for cancer is being increasingly sought as pressure on health care resources increases. The objective of this study was to assess the cost-effectiveness of gemcitabine/cisplatin (GC) versus cisplatin/etoposide (CE) in patients with advanced non-small cell lung cancer (NSCLC), using resource utilization data collected in conjunction with the first randomized clinical trial comparing both combinations., Methods: Efficacy and medical care resource utilization data were collected prospectively in an open-label, multicenter, randomized, comparative, phase III trial conducted in Spain which compared gemcitabine/cisplatin and cisplatin/etoposide in 135 chemonaive patients with Stage IIIB or IV NSCLC. There were no differences between both regimens when survival was used as primary end-point, so a cost-minimization analysis was used to compare them. In addition, cost-effectiveness analyses were conducted when percentage of responses and time to progression were used as secondary end-points., Results: There were no differences between both regimens when survival was selected as the efficacy end-point. Despite the higher chemotherapy cost of GC when compared to CE, there were no differences in total direct costs (584523 pts for GC and 589630 pts for CE; P=NS) between both regimens. Potential savings with GC were mainly associated with a decrease in hospitalization rate. There were differences in favor of GC when response rate (40.6% for GC and 21.9% for CE; P<0.05) and time to disease progression (8.7 months for GC and 7.2 months for CE; P<0. 05) were used as clinical end-points. GC presented a favorable cost-effectiveness profile when compared to CE., Conclusions: This prospective economic evaluation conducted alongside a clinical trial offers valuable preliminary information on the potential efficiency of the combination gemcitabine-cisplatin in NSCLC. Future assessments based on larger clinical trials focused on survival and naturalistic economic studies conducted in real clinical practice settings are necessary to confirm these findings.

Purpose: We conducted a randomized trial to compare gemcitabine-cisplatin with etoposide-cisplatin in the treatment of patients with advanced non-small-cell lung cancer (NSCLC). The primary end point of the comparison was response rate., Patients and Methods: A total of 135 chemotherapy-naive patients with advanced NSCLC were randomized to receive either gemcitabine 1,250 mg/m2 intravenously (IV) days 1 and 8 or etoposide 100 mg/m2 IV days 1 to 3 along with cisplatin 100 mg/m2 IV day 1. Both treatments were administered in 21-day cycles. One hundred thirty-three patients were included in the intent-to-treat analysis of response., Results: The response rate (externally validated) for patients given gemcitabine-cisplatin was superior to that for patients given etoposide-cisplatin (40.6% v 21.9%; P = .02). This superior response rate was associated with a significant delay in time to disease progression (6.9 months v 4.3 months; P = .01) without an impairment in quality of life (QOL). There was no statistically significant difference in survival time between both arms (8.7 months for gemcitabine-cisplatin v 7.2 months for etoposide-cisplatin; P = .18). The overall toxicity profile for both combinations of drugs was similar. Nausea and vomiting were reported more frequently in the gemcitabine arm than in the etoposide arm. However, the difference was not significant. Gemcitabine-cisplatin produced less grade 3 alopecia (13% v 51%) and less grade 4 neutropenia (28% v 56% ) but more grade 3 and 4 thrombocytopenia (56% v 13%) than did etoposide-cisplatin. However, there were no thrombocytopenia-related complications in the gemcitabine arm., Conclusion: Compared with etoposide-cisplatin, gemcitabine-cisplatin provides a significantly higher response rate and a delay in disease progression without impairing QOL in patients with advanced NSCLC.

Gastric cancer is the most chemosensitive adenocarcinoma among digestive neoplasms. A few years ago, we performed a phase II trial with the FLEP regimen, in which fluorouracil (5-FU) and leucovorin are combined with etoposide and cisplatin (Platinol). This regimen resulted in a 39% response rate and high toxicity. Then we used the combination UFT (tegafur and uracil)/leucovorin/etoposide: UFT 390 mg/m2/day orally on days 1 to 14; leucovorin 500 mg/m2 i.v. day 1, and 15 mg/12 h orally on days 2 to 14; and etoposide 100 mg/m2 i.v. on day 1 and then 200 mg/m2/day orally on days 2 and 3. Forty-six patients received a median of five courses. Five patients (11%) achieved a complete response and 12 (26%) a partial response, for an overall response rate of 37%. The response rate was 50% in patients with an Eastern Cooperative Oncology Group performance status of 0 to 1. Grades 3 to 4 toxicities appeared as follow: 17% of patients had diarrhea, 11% had nausea/vomiting, and 13% of patients had anemia. One patient died of neutropenia and sepsis. The median survival time was 9 months. In summary, UFT/leucovorin/etoposide is effective and moderately toxic in patients with advanced gastric cancer. A new trial with UFT/leucovorin/epirubicin is ongoing.

The treatment of the burns is successful in situation when there is a separate department for burns with well-educated and highly skilled surgeons. The adequate reanimation during the first 48 hours is essential for the patients with burns to survive. Burns patients with circumferential burns of the body or the bower extremities should have at least three longitudinal incisions (escharotomy) prior to the development of the arterial ischaemia. The early tangential necrectomy should be performed between third and fifth day. The early grafting of the necrotic surfaces reduces the possibility of septicemic complications with deep burns and thus decreases the mortality rate.

The eukaryotic green alga Dunaliella tertiolecta acclimates to decreased growth irradiance by increasing cellular levels of light-harvesting chlorophyll protein complex apoproteins associated with photosystem II (LHCIIs), whereas increased growth irradiance elicits the opposite response. Nuclear run-on transcription assays and measurements of cab mRNA stability established that light intensity-dependent changes in LHCII are controlled at the level of transcription. cab gene transcription in high-intensity light was partially enhanced by reducing plastoquinone with 3-(3,4-dichlorophenyl)-1,1-dimethyl urea (DCMU), whereas it was repressed in low-intensity light by partially inhibiting the oxidation of plastoquinol with 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone (DBMIB). Uncouplers of photosynthetic electron transport and inhibition of water splitting had no effect on LHCII levels. These results strongly implicate the redox state of the plastoquinone pool in the chloroplast as a photon-sensing system that is coupled to the light-intensity regulation of nuclear-encoded cab gene transcription. The accumulation of cellular chlorophyll at low-intensity light can be blocked with cytoplasmically directed phosphatase inhibitors, such as okadaic acid, microcystin L-R, and tautomycin. Gel mobility-shift assays revealed that cells grown in high-intensity light contained proteins that bind to the promoter region of a cab gene carrying sequences homologous to higher plant light-responsive elements. On the basis of these experimental results, we propose a model for a light intensity signaling system where cab gene expression is reversibly repressed by a phosphorylated factor coupled to the redox status of plastoquinone through a chloroplast protein kinase.