Pariwisata saat ini mengalami pergeseran dari pariwisata massal ke wisata minat khusus berfokus pada alam dan budaya. Dalam konteks pelestarian, pariwisata mengalami pro kontra yang cukup tajam ...sebagai pendukung pelestarian atau sebaliknya penghambat pelestarian. Penelitian ini menggunakan salah satu instrumen evaluasi pelestarian lingkungan dengan model perhitungan jejak ekologi yang menganalisis secara kuantitatif dari aspek transportasi, penggunaan air, penggunaan pakaian, rekreasi, makanan, sampah dan tempat tinggal. Mengingat keterbatasan model kalkulator jejak ekologi untuk diterapkan di desa Wisata, maka penerapan model perlu dilakukan modifikasi dengan menggunakan pendekatan antropologi. Metode penelitian yang dipergunakan adalah partisipasi riset aksi dengan mengukur dampak aktifitas wisata di perdesaan menggunakan indikator sederhana dari perhitungan jejak ekologi serta dilengkapi wawancara mendalam untuk mengeksplorasi aspek perilaku kolektif sebagai focus pendekatan antropologi yang diteliti. Studi kasus meliputi tiga desa di wilayah Yogyakarta yaitu Pentingsari di kabupaten Sleman, Lopati di kabupaten Bantul dan Kalibiru di kabupaten Kulonprogo. Hasil yang diperoleh adalah rekomendasi pendekatan antropologi untuk mengevaluasi hasil jejak ekologi agar lebih tepat jika digunakan sebagai rencana aksi pelestarian lingkungan di desa wisata dengan tekanan pada pembentukan kesadaran hidup bersama alam.
Target therapies in pancreatic carcinoma Silvestris, Nicola; Gnoni, Antonio; Brunetti, Anna Elisabetta ...
Current medicinal chemistry,
2014, Letnik:
21, Številka:
8
Journal Article
Recenzirano
Pancreatic ductal adenocarcinoma (PDAC) occurs in the majority of cases with early locoregional spread and distant metastases at diagnosis, leading to dismal prognosis and limited treatment options. ...Traditional cytotoxic chemotherapy provides only modest benefit to patients with PDAC. Identification of different molecular pathways, overexpressed in pancreatic cancer cells, has provided the opportunity to develop targeted therapies (monoclonal antibodies and small-molecule inhibitors) and peculiar new class of taxanes with a crucial therapeutic role in this cancer setting. A phase III trial has shown that erlotinib in combination with gemcitabine was clinically irrelevant and skin toxicity can be a positive prognostic factor. Moreover, the combination of cetuximab or erlotinib with radiotherapy in advanced pancreatic cancer has shown to be synergistic and a reversal of radio-resistance has been suggested by inhibition of VEGF/EGFR pathway. To overcome EGFR-inhibition therapy resistance several alternative pathways targets are under investigation (IGF- 1R, MMPs, Hedgehog proteins, m-TOR, MEK, COX-2) and provide the rationale for clinical use in phase II/III studies. Also nab-paclitaxel, a new taxanes class, uses high pancreatic albumin-binding protein SPARC levels to act in cancer cells with a less toxic and more effective dose with respect to classic taxanes. Understanding of molecular pathogenesis of pancreatic adenocarcinoma continues to expand. However, many promising data in preclinic and phase I/II trials did not yield promise in phase III trials, suggesting that identification of predictive biomarkers for these new agents is mandatory. The knowledge of biologic and molecular aspects of pancreatic cancer can be the basis for future therapeutic developments.
Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce ...bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection.
In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants.
Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18–45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference −1·4%, 95% CI −7·0 to 4·3; hazard ratio 0·96, 0·68–1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3–4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005).
Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia.
UK National Institute for Health Research Health Technology Assessment.
•BRCA1-2 mutations (gBRCA1-2) are responsible for PDAC in 15–20% of familiar cases.•gBRCA1-2 and DDR genes mutations (gDDR) emerged as therapeutic targets for PDAC.•Rigorous studies on gBRCA1-2/DDR ...geographic distribution are lacking in PDAC.•Improving the gBRCA1-2/DDR epidemiology may lead to pharmacoethnicity-based trials.
Incidence of pancreatic ductal adenocarcinoma (PDAC) is increasing over the last years, while patients prognosis remains grim. Recently germline BRCA1 and 2 pathogenic variants (gBRCA1-2) have emerged as risk factors for PDAC development, as well as new predictors of response to specific therapeutic interventions. However, data on gBRCA1-2 incidence in PDAC are currently sparse and limited to selected categories of patients, as for positive cancer history cases, for patients affected only by early or late stages of disease and mainly from the North-American population, thus generating incomplete information about the gBRCA1/2 epidemiology.
In Western Countries gBRCA1-2 incidence ranges between 4.5% and 8% in unselected PDAC patients, raising up to 26% in cohorts with positive family cancer history. To date a limited number of studies from Asian countries are available, reporting a 10% as highest incidence of gBRCA1-2 in familiar PDAC, claiming at least in part a role of ethnicity in the gBRCA1-2 incidence and in other genes potentially implicated in the therapeutic decisions.
Drawing a better defined map for the incidence of gBRCA1-2 and other germline pathogenic variants of DNA Damage Response genes (gDDR) might help assessing the therapeutic strategies for mutated patients according to the geographic areas. These informations may enhance the chance to predict efficacy and toxicity of selected chemotherapy regimens, fostering the development and implementation of the pharmaco-ethnicity knowledge in the routine-clinical practice, and increasing the awareness of the potential incorrect generalization of trials results outside of the geographic area where they are conducted.
Indonesian rural youth face challenges accessing farmland and sustaining an agricultural livelihood while their labour is not necessarily absorbed by other sectors. In that context, the Omnibus Law ...on Job Creation (Law 11/2020) promises to liberalise trade and investment across multiple sectors, including agriculture and food security. Combining legal research and political economy approaches to youth and agrarian challenges, we identify amendments to legislation that reduce safeguards for the environment, workers' and farmers' rights and their livelihoods. If fully implemented, the legislative amendments could further narrow youth's options both for secure formal work and futures in farming by accelerating the expansion of infrastructure, industrial plantations and extractive industries that utilise low‐wage labour and huge areas of land. This exposes inconsistencies in the government's approach to increase future food security by promoting intensification of agriculture and attracting youth to farming, while enabling agro‐ and resource extraction that absorbs land yet offers limited and precarious employment prospects.
An application of a specific analysis on recordings obtained from urinary bladder (UB) preparations influenced with Angiotensin II (AngII) and AngII receptor (ATR) blockers was performed.
UB ...preparations were divided as follows: group 1 stimulated with AngII only; group 2:PD123319 (ATR type-2 blocker)+AngII; group 3:Losartan (ATR type-1 blocker)+AngII. The averaged time and force parameters of the contractions were processed by a spline interpolation and graphic images of the different patterns of the contractile activity were obtained.
The speed of AngII-induced UB contraction, when PD123319 was administered, was significantly higher than those, registered by the application of AngII alone and Losartan + AngII. The presence of Losartan markedly delayed the speed of the overall AngII-induced contraction.
The study indicates the contribution of both ATR subtypes for the development of AngII-induced UB contraction. Our results showed that probably ATR mediate a reciprocal dynamic response to AngII in the bladder.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Acquired brain injury (ABI) may result in lifelong impairment of physical, cognitive, and psychosocial functions. Several rehabilitative treatments are often needed to support walking recovery, thus ...participants' engagement becomes a crucial aspect, especially when patients are children. In the last few years, traditional physiotherapy (PT) has been flanked by innovative technologies for rehabilitation in the fields of robotics and Virtual Reality (VR). Preliminary results have shown interesting perspectives in the use of a VR system, the GRAIL (Gait Real-time Analysis Interactive Lab), in improving walking abilities in a small group of children with ABI, although further insights are needed about its use as rehabilitative tool in the pediatric population.
To evaluate the efficacy of a rehabilitation treatment on a GRAIL system for the improvement of walking abilities, in a group of children suffering from ABI.
12 children with ABI (study group - SG; mean age = 12.1 ± 3.8 years old) underwent a 10-session treatment with the GRAIL, an instrumented multi-sensor platform based on immersive VR for gait training and rehabilitation in engaging VR environments. Before (T0) and at the end of the treatment (T1), the participants were assessed by means of functional scales (Gross Motor Function Measure (GMFM), Functional Assessment Questionnaire (FAQ), 6-Minute Walk Test (6minWT) and the 3D-Gait Analysis, over ground (OGA) and on GRAIL (GGA).
All the participants completed the rehabilitative treatment. The functional evaluations showed an improvement in Gross Motor abilities (GMFM-88, p = 0.008), especially in standing (GMFM-D, p = 0.007) and walking (GMFM-E, p = 0.005), an increase of the endurance (6minWT, p = 0.002), and enhanced autonomy in daily life activities (FAQ, p = 0.025). OGA identified a significant decrease of the Gillette Gait Index for the impaired side and a general increase of symmetry. GGA showed improvements in spatiotemporal parameters and joints range of motion that moved towards normality and symmetry recovery.
A 10-session treatment with GRAIL on children with ABI led to improvements in their walking abilities and enhanced their engagement during the training. This is desirable when long life impairments are faced and children's motor functions have to be regained and it supports the leading role that VR might have in the rehabilitation field.
The serotonin transporter promoter region polymorphism (5-HTTLPR) has been implicated in stress regulation, with increased stress reactivity often being found in carriers of the low-expressing short ...(S) allele. Nevertheless, the role of the 5-HTTLPR in influencing parasympathetic stress reactivity, as indexed by Respiratory Sinus Arrhythmia (RSA), is still unknown. This study examined, for the first time, whether the 5-HTTLPR was associated with variations in RSA response to maternal separation in a sample of 69 healthy 5-year-old children. Preschoolers’ RSA was measured during an age-adapted version of the Strange Situation Procedure (SSP). The 5-HTTLPR polymorphism was tested as a predictor of RSA dynamic response to the SSP through multilevel models. A significant interaction between 5-HTTLPR and SSP episodes was found. In particular, whereas a significant decrease in RSA levels was observed during the stranger episode in the whole sample, S allele carriers showed a significant decrease in RSA levels from the stranger episode to the first separation episode, followed by an increase for the rest of the procedure. Albeit preliminary, data support the view that the 5-HTTLPR may contribute to individual differences in RSA stress reactivity from preschool age.
ObjectiveThe prognosis of either pituitary carcinoma or aggressive pituitary adenoma resistant to standard therapies is poor. We assessed the efficacy of treatment with temozolomide, an oral ...second-generation alkylating agent, in a consecutive series of six patients with aggressive pituitary adenomas.DesignThis was a 1-year prospective study of temozolomide therapy in six consecutive patients with pituitary carcinoma (one case) or atypical pituitary adenoma (five cases) resistant to standard therapies. There were three males and three females. Age at enrollment ranged between 52 and 64 years. Temozolomide was given orally at a dose of 150–200 mg/m2 per day for 5 days every 4 weeks for a maximum of 12 cycles.MethodsResponse assessment was based on measurable change in tumor size, as assessed on magnetic resonance imaging, and hormone levels. Response was defined as reduction of at least 50% of tumor size and hormone levels.ResultsFour patients completed the 12 cycles of temozolomide treatment, as planned. Two patients stopped the drug after 3 and 6 months respectively because of the progression of disease. Two patients responded to temozolomide, while the remaining two patients had stable disease. Immunohistochemistry for O6-methylguanine-DNA methyltransferase (MGMT) in tumor sample showed a partial association with treatment response.ConclusionsTemozolomide treatment has a wide range of efficacy in patients with pituitary carcinoma or locally aggressive pituitary adenoma. Positive staining for MGMT seems likely to predict a lower chance of response.
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