Clinical and biological aspects of sentinel node biopsy in malignant melanoma — an update

The diagnostic usefulness of sentinel lymph node biopsy (SLNB) has been well established, but its therapeutic value remains unproven. First introduced by Morton and colleagues, the SLNB procedure is now widely available, and markedly enhances our ability to pathologically stage the regional nodes. Although the SLN status is acknowledged as the most powerful indicator of prognosis in melanoma, there is no evidence to-date, of survival advantage for complete lymphadenectomy in SLN-positive patients. Also, there is no effective adjuvant therapy that could benefit these sentinel node-positive patients, as yet. Additionally, new data have emerged indicating a possible increase in local/in-transit recurrence following complete lymphadenectomy in sentinel node-positive patients. To understand fully and to evaluate these observations we need information from randomized controlled trials. Major changes have occurred following the latest revision of melanoma staging system (AJCC, 6th edition). Concerning N category, these include the incorporation of the number of metastatic lymph nodes, the tumour burden of nodal metastases, and the ulceration of the primary tumour. The data obtained from the new staging system will reflect differences in prognosis that were not previously emphasized and which, we hope, will serve as a guide to more accurate analysis of metastatic pathways in cutaneous melanoma as well as a rationale for new forms of treatment.     

A Novice Teacher as Facilitator of Learning During a Hybrid Sport Education/Step-Game Approach Volleyball Season

This study aimed to examine how a novice Physical Education teacher unfolded her pedagogical practice as a facilitator of learning during a hybrid Sport Education/Step-Game-Approach volleyball season; and to investigate students’ perceptions about their lived learning experiences and active involvement in building their own learning process. For this purpose, an insider action-research design was implemented throughout one school term (20 lessons of 45 minutes each in total). Twenty-five students (aged between16 and17 years old), enrolled in the 12^th grade at a Portuguese high school took part in this investigation. The novice teacher, who held two years of professional experience, assumed the dual role of teacher-researcher, facilitating an in-depth understanding of the complexity featuring of the teaching-learning process. Qualitative data were collected using multiple data sources (i.e., teacher’s lesson plans and field diary, and student’s focus-group interviews), and analyzed using a hybrid approach of inductive and deductive thematic analysis. The results revealed that the use of this hybrid season helped the teacher to act as facilitator of learning, namely by: (i) using two student-centered models with unique internal structures and functionalities, (ii) increasing the level of responsibility taken by students for their own learning experiences, (iii) adapting the lesson plans to students’ individual needs, and (iv) combining a more supportive intervention with the use of more indirect teaching strategies. Together, these strategies seemed to prompt students’ autonomy and sense of active control of the class activities, the development of students’ abilities and volleyball-based knowledge, leading them to be more interested and engaged in Physical Education. In conclusion, the alliance between the student-centered environment (Sport Education) and the specificity of the content subject-knowledge (Step-Game Approach for non-invasion games) seems to have allow the novice teacher to adjust her pedagogical intervention as facilitator of learning to students’ individual learning needs. Key points

• The alliance between the Sport Education and the Step-Game Approach allows the novice teacher to adjust her pedagogical intervention as facilitator of learning to students’ individual learning needs.
• Students perceived that they developed their autonomy and sense of active control of the class activities, their abilities and volleyball-based knowledge, which made them more interested and engaged in PE.
• Future studies should consider longitudinal AR designs and video-audio as a complementary data source data.
• PETE and professional development programs should be more focused on developing teacher’s ability to game design, to use effective questioning and gradually to empower students to assume an active role over their learning experiences. Also, offer school placement training and postgraduate professional practice based on student-centered approaches.

Key words: Student-centered models, volleyball, physical education, high school, action-research, qualitative analysis     

New Compounds Hybrids 1H‐1,2,3‐Triazole‐Quinoline Against Plasmodium falciparum

Malaria is one of the most prevalent parasitic diseases in the world. The global importance of this disease, current vector control limitations, and the absence of an effective vaccine make the use of therapeutic antimalarial drugs the main strategy to control malaria. Chloroquine is a cost‐effective antimalarial drug with a relatively robust safety profile, or therapeutic index. However, chloroquine is no longer used alone to treat patients with Plasmodium falciparum due to the emergence and spread of chloroquine‐resistant strains, which have also been reported for Plasmodium vivax. However, the activity of 1,2,3‐triazole derivatives against chloroquine‐sensitive and chloroquine‐resistant strains of P. falciparum has been reported in the literature. To enhance the anti‐P. falciparum activity of quinoline derivatives, we synthesized 11 new quinoline‐1H‐1,2,3‐triazole hybrids with different substituents in the 4‐positions of the 1H‐1,2,3‐triazole ring, which were assayed against the W2‐chloroquine‐resistant P. falciparum clone. Six compounds exhibited activity against the P. falciparum W2 clone, chloroquine‐resistant, with IC₅₀ values ranging from 1.4 to 46 μm . None of these compounds was toxic to a normal monkey kidney cell line, thus exhibiting good selectivity indexes, as high 351 for one compound ( 11 ).     

Chinikomycins A and B: isolation, structure elucidation, and biological activity of novel antibiotics from a marine Streptomyces sp. isolate M045

In our screening of marine Streptomycetes for bioactive principles, two novel antitumor antibiotics designated as chinikomycins A (2a) and B (2b) were isolated together with manumycin A (1), and their structures were elucidated by a detailed interpretation of their spectra. Chinikomycins A (2a) and B (2b) are chlorine-containing aromatized manumycin derivatives of the type 64-pABA-2 with an unusual para orientation of the side chains. They exhibited antitumor activity against different human cancer cell lines, but were inactive in antiviral, antimicrobial, and phytotoxicity tests.     

Vitamin D Treatment Prevents Uremia-Induced Reductions in Aortic microRNA-145 Attenuating Osteogenic Differentiation despite Hyperphosphatemia

In chronic kidney disease, systemic inflammation and high serum phosphate (P) promote the de-differentiation of vascular smooth muscle cells (VSMC) to osteoblast-like cells, increasing the propensity for medial calcification and cardiovascular mortality. Vascular microRNA-145 (miR-145) content is essential to maintain VSMC contractile phenotype. Because vitamin D induces aortic miR-145, uremia and high serum P reduce it and miR-145 directly targets osteogenic osterix in osteoblasts, this study evaluated a potential causal link between vascular miR-145 reductions and osterix-driven osteogenic differentiation and its counter-regulation by vitamin D. Studies in aortic rings from normal rats and in the rat aortic VSMC line A7r5 exposed to calcifying conditions corroborated that miR-145 reductions were associated with decreases in contractile markers and increases in osteogenic differentiation and calcium (Ca) deposition. Furthermore, miR-145 silencing enhanced Ca deposition in A7r5 cells exposed to calcifying conditions, while miR-145 overexpression attenuated it, partly through increasing α-actin levels and reducing osterix-driven osteogenic differentiation. In mice, 14 weeks after the induction of renal mass reduction, both aortic miR-145 and α-actin mRNA decreased by 80% without significant elevations in osterix or Ca deposition. Vitamin D treatment from week 8 to 14 fully prevented the reductions in aortic miR-145 and attenuated by 50% the decreases in α-actin, despite uremia-induced hyperphosphatemia. In conclusion, vitamin D was able to prevent the reductions in aortic miR-145 and α-actin content induced by uremia, reducing the alterations in vascular contractility and osteogenic differentiation despite hyperphosphatemia.     

Phase I/II study of gefitinib and capecitabine in patients with colorectal cancer

Objective The objectives of this phase I/II study were to determine the maximum tolerated dose (MTD), characterise the principal toxicities in the phase I part and assess the efficacy in the phase II part of gefitinib, an oral selective inhibitor of the epidermal growth factor receptor, in combination with capecitabine in patients with advanced colorectal cancer (CRC). Methods and patients Patients with advanced CRC were treated with gefitinib administered daily for 21 days and capecitabine administered twice daily for 14 days of a 21-day cycle. The dose levels of gefitinib (mg) and capecitabine (mg/m² bid) assessed were 250/1000 and 250/ 1250. An expanded cohort was enrolled at the MTD to better characterise toxicity and efficacy. A total of 32 previously treated patients were accrued. In the phase I part 10 subjects were treated, with one dose-limiting toxicity. Overall 26 patients were treated at the MTD of the combination, which was gefitinib 250 mg/day and capecitabine 1250 mg/m² twice daily. Results The most frequent treatment-related adverse events included asthenia, diarrhoea, nausea, rash and anorexia. The incidence profile was very similar in phases I and II. No objective responses were documented but 53% of the patients achieved stable disease as best response to therapy. Conclusions Capecitabine 1250 mg/m² twice daily 14 of 21 days and gefitinib at 250 mg/day can be safely administered in combination. The combination is relatively well tolerated. There were no objective responses, although an interesting stabilisation rate was documented, in previously treated advanced CRC patients.     

The opposing effects of the flavonoids isoquercitrin and sissotrin, isolated from Pterospartum tridentatum, on oral glucose tolerance in rats

The effect of an aqueous extract of Pterospartum tridentatum on the blood glucose levels of normal Wistar rats was investigated in a situation of oral glucose challenge. The extract at 300 mg/kg showed an antihyperglycaemic effect in the first 30 min after glucose challenge but then the blood glucose levels rose above those of the control group, indicating the presence of compounds with different effects on glucose tolerance. Nine compounds of isoflavone and flavonol skeletons were identified in the extract by HPLC-ESI-MS(n), four of them being identified for the first time in this species. The isoflavone sissotrin and the flavonol derivative, isoquercitrin, were selected for the oral glucose tolerance test. Isoquercitrin (100 mg/kg) showed time-dependent antihyperglycaemic activity by delaying the post-oral glucose load glycaemic peak at 30 min, as did the sodium-dependent glucose transporter inhibitor phloridzin (100 mg/kg). In contrast, sissotrin (100 mg/kg) showed an opposite effect, impairing glucose tolerance. In conclusion, these preliminary results indicate that the effect of the extract on blood glucose may be either antihyperglycaemic or hyperglycaemic. Additionally, as far as is known, these are the first in vivo results on the acute antihyperglycaemic potential of isoquercitrin.     

Pronóstico perinatal y materno de la gestación múltiple en función del protocolo intraparto

Objectives

To evaluate maternal and fetal outcomes of multiple pregnancy according to route of delivery.

Material and methods

We performed a retrospective study of all twin deliveries in the previous 5 years and evaluated the route of delivery, especially in the final year. The information was recorded with Microsoft EXCEL and was analyzed with the statistical program SPSS 12.0 for Windows.

Results

The mean gestational age was 35.3 weeks. Route of delivery was through cesarean section in 59.8%. The mean interval between twins was 7.82 minutes when the first twin was delivered vaginally. Neonatal morbidity was found in 49%, and was higher in the second twin and in preterm deliveries.

Conclusions

Multiple pregnancies are associated with a large number of maternal and perinatal complications, as well as with a greater number of cesarean sections. Consequently, correct intrapartum management is required to reduce neonatal morbility as far as possible.     

Extraosseous vulvar chondroma: a case report

BACKGROUND: Extraosseous chondromas are cartilaginous tissue tumors with a nodular appearance on the hands and feet. There are reports of these tumors occurring on the knee, neck, back, liver and testis and in the oral cavity. Occurrence in the pelvis is generally rare. The origin is metaplastic and may be mesenchymal or subcelomic. Treatment is by surgery and requires removing the tumor with a safety margin. Recurrences are infrequent, and distant metastasis has never been reported. CASE: An 11-year-old girl was referred for a painless solid tumor located on the mons pubis. Surgical removal of the tumor with a safety margin was performed. Macroscopically, the tumor was shiny when cut open and yellowish. Microscopic examination revealed a very distinct cartilage-forming tumor compatible with extraosseous chondroma. Two years after the operation, the patient had no recurrence. CONCLUSION: Extraosseous chondroma is a rare benign tumor. Finding it in children is even less frequent, and localization in the vulvar region has never before been reported. This appears to be the first such report of this type of tumor in this region and age range.