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1.
Ecol Lett ; 27(1): e14351, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38111128

ABSTRACT

Dominance of neotropical tree communities by a few species is widely documented, but dominant trees show a variety of distributional patterns still poorly understood. Here, we used 503 forest inventory plots (93,719 individuals ≥2.5 cm diameter, 2609 species) to explore the relationships between local abundance, regional frequency and spatial aggregation of dominant species in four main habitat types in western Amazonia. Although the abundance-occupancy relationship is positive for the full dataset, we found that among dominant Amazonian tree species, there is a strong negative relationship between local abundance and regional frequency and/or spatial aggregation across habitat types. Our findings suggest an ecological trade-off whereby dominant species can be locally abundant (local dominants) or regionally widespread (widespread dominants), but rarely both (oligarchs). Given the importance of dominant species as drivers of diversity and ecosystem functioning, unravelling different dominance patterns is a research priority to direct conservation efforts in Amazonian forests.


Subject(s)
Ecosystem , Forests , Humans , Trees , Brazil , Biodiversity
2.
Nephrol Dial Transplant ; 38(3): 778-786, 2023 02 28.
Article in English | MEDLINE | ID: mdl-36083994

ABSTRACT

BACKGROUND: Post-transplant prediabetes (PreDM) and diabetes (PTDM) are common and have an impact on cardiovascular events. We sought to investigate the pathogenesis and best approach for prediction. METHODS: We prospectively studied 115 waitlisted patients from a single center without manifest diabetes. An oral glucose tolerance test (OGTT) was performed yearly until transplantation and 12 months later. Insulin secretion, insulin sensitivity (IS) and disposition index (DI) were derived from the OGTT. RESULTS: PreDM and PTDM were observed in 27% and 28.6% of patients, respectively. Pretransplant age, body mass index (BMI), 120 min glucose, IS, DI, and prediabetes or undiagnosed diabetes were significantly associated with these alterations. In multivariate analysis, pretransplant age [odds ratio (OR) 1.5; 95% confidence interval (CI) 1.04-2.1], BMI (OR 1.16; 95% CI 1.04-1.3) and cumulative steroids (OR 1.5; 95% CI 1.02-2.2) were predictors of PreDM or PTDM. Receiver operating characteristic curve analysis showed that pretransplant BMI and 120 min glucose had the highest area under the curve (0.72; 95% CI 0.62-0.8; and 0.69; 95% CI 0.59-0.79, respectively). The highest discrimination cut-off for BMI (≥28.5 kg/m2) and 120 min glucose (≥123.5 mg/dL) yielded a similar number needed to diagnose (2.5). CONCLUSIONS: PreDM or PTDM develops in waitlisted patients with an ineffective insulin secretion and BMI shows a similar diagnostic capacity to OGTT. Pretransplant interventions may reduce post-transplant glucose alterations.


Subject(s)
Diabetes Mellitus , Insulin Resistance , Kidney Transplantation , Prediabetic State , Humans , Kidney Transplantation/adverse effects , Prospective Studies , Prediabetic State/complications , Glucose , Blood Glucose/metabolism , Diabetes Mellitus/etiology
3.
Stroke ; 53(3): 976-986, 2022 03.
Article in English | MEDLINE | ID: mdl-35130716

ABSTRACT

BACKGROUND: Cavernous cerebral malformations can arise because of mutations in the CCM1, CCM2, or CCM3 genes, and lack of Cdc42 has also been reported to induce these malformations in mice. However, the role of the CCM3 (cerebral cavernous malformation 3)-associated kinases in cavernoma development is not known, and we, therefore, have investigated their role in the process. METHODS: We used a combination of an in vivo approach, using mice genetically modified to be deficient in the CCM3-associated kinases STK24 and STK25 (serine/threonine kinases 24 and 25), and the in vitro model of human endothelial cells in which expression of STK24 and STK25 was inhibited by RNA interference. RESULTS: Mice deficient for both Stk24 and Stk25, but not for either of them individually, developed aggressive vascular lesions with the characteristics of cavernomas at an early age. Stk25 deficiency also gave rise to vascular anomalies in the context of Stk24 heterozygosity. Human endothelial cells deficient for both kinases phenocopied several of the consequences of CCM3 loss, and single STK25 deficiency also induced KLF2 expression, Golgi dispersion, altered distribution of ß-catenin, and appearance of stress fibers. CONCLUSIONS: The CCM3-associated kinases STK24 and STK25 play a major role in the inhibition of cavernoma development.


Subject(s)
Central Nervous System Neoplasms/genetics , Germinal Center Kinases/genetics , Hemangioma, Cavernous, Central Nervous System/genetics , Human Umbilical Vein Endothelial Cells/metabolism , Intracellular Signaling Peptides and Proteins/genetics , Protein Serine-Threonine Kinases/genetics , Animals , Central Nervous System Neoplasms/metabolism , Germinal Center Kinases/metabolism , Hemangioma, Cavernous, Central Nervous System/metabolism , Humans , Intracellular Signaling Peptides and Proteins/metabolism , Mice , Mice, Knockout , Phosphorylation , Protein Serine-Threonine Kinases/metabolism
4.
New Phytol ; 232(6): 2506-2519, 2021 12.
Article in English | MEDLINE | ID: mdl-34379801

ABSTRACT

Recent studies have demonstrated that ecological processes that shape community structure and dynamics change along environmental gradients. However, much less is known about how the emergence of the gradients themselves shape the evolution of species that underlie community assembly. In this study, we address how the creation of novel environments leads to community assembly via two nonmutually exclusive processes: immigration and ecological sorting of pre-adapted clades (ISPC), and recent adaptive diversification (RAD). We study these processes in the context of the elevational gradient created by the uplift of the Central Andes. We develop a novel approach and method based on the decomposition of species turnover into within- and among-clade components, where clades correspond to lineages that originated before mountain uplift. Effects of ISPC and RAD can be inferred from how components of turnover change with elevation. We test our approach using data from over 500 Andean forest plots. We found that species turnover between communities at different elevations is dominated by the replacement of clades that originated before the uplift of the Central Andes. Our results suggest that immigration and sorting of clades pre-adapted to montane habitats is the primary mechanism shaping tree communities across elevations.


Subject(s)
Biodiversity , Ecosystem , Phylogeny
5.
J Pathol ; 249(3): 381-394, 2019 11.
Article in English | MEDLINE | ID: mdl-31292963

ABSTRACT

Cancer progression requires cells surrounding tumors be reeducated and activated to support tumor growth. Oncogenic signals from malignant cells directly influence stromal composition and activation, but the factors mediating this communication are still not well understood. We have previously shown that the transcription factor POU class 1 homeobox 1 (POU1F1), also known as Pit-1, induces profound changes on neoplastic cell-autonomous processes favoring metastasis in human breast cancer. Here we describe for the first time Pit-1-mediated paracrine actions on macrophages in the tumor microenvironment by using cell lines in vitro, zebrafish and mouse models in vivo, and samples from human breast cancer patients. Through the release of CXCL12, Pit-1 in tumor cells was found to mediate the recruitment and polarization of macrophages into tumor-associated macrophages (TAMs). In turn, TAMs collaborated with tumor cells to increase tumor growth, angiogenesis, extravasation and metastasis to lung. Our data reveal a new mechanism of cooperation between tumor cells and macrophages favoring metastasis and poor clinical outcome in human breast cancer, which suggests that Pit-1 and CXCL12 should be further studied as potential prognostic and therapeutic indicators. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Subject(s)
Breast Neoplasms/metabolism , Cell Movement , Lung Neoplasms/metabolism , Macrophage Activation , Macrophages/metabolism , Paracrine Communication , Transcription Factor Pit-1/metabolism , Animals , Antigens, CD/metabolism , Antigens, Differentiation, Myelomonocytic/metabolism , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Cell Proliferation , Chemokine CXCL12/metabolism , Coculture Techniques , Female , Gene Expression Regulation, Neoplastic , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Lung Neoplasms/genetics , Lung Neoplasms/secondary , MCF-7 Cells , Macrophages/pathology , Mice, Inbred BALB C , Mice, Nude , Middle Aged , Neovascularization, Pathologic , Phenotype , Receptors, Cell Surface/metabolism , Signal Transduction , Transcription Factor Pit-1/genetics , Tumor Microenvironment , U937 Cells , Zebrafish/embryology
6.
Andrologia ; 52(7): e13637, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32453875

ABSTRACT

The objective was to explore presence/detection of microorganisms in the male reproductive tract (PMMRT) in asymptomatic patients undergoing infertility treatment and their effects on semen quality in our region. This study enrolled 205 men (mean age, 35.9 years) in a single-centre, tertiary university hospital from December 2015 to December 2016. We used the modified Meares-Stamey test, real-time polymerase chain reaction (rt-PCR) and the National Institutes of Health Chronic Prostatitis Sympton Index (NHI-CPSI) questionnaire to address this issue. No patient met the prostatitis criteria by the modified Meares-Stamey 4-sample test, 33 (16.1%) were positive for rt-PCR in the first-voided urine for any of the Mycoplasma (Ureaplasma urealyticum/parvum, Mycoplasma hominis/genitalium) and C. trachomatis was detected in two cases (1%), and three for rt-PCR in semen for HPV high-risk genotypes non-16/18 (1.5%). Significant statistical differences were reported among patients with and without PMMRT in terms of lower rate of progressive spermatozoa (PR) (p < .034), total motile sperm count (p < .028), normal morphologic forms, especially in the sperm head (p < .001) and highest viscosity (p < .012). It was concluded that PMMRT, specially Mycoplasmas, in asymptomatic infertility men, affects semen quality. The NIH-CPSI questionnaire was not a valid initial screening to subsequently evaluate the presence of prostatitis/PMMRT.


Subject(s)
Infertility, Male , Mycoplasma Infections , Mycoplasma genitalium , Adult , Humans , Male , Semen , Semen Analysis , Ureaplasma urealyticum
7.
Kidney Int ; 96(4): 995-1004, 2019 10.
Article in English | MEDLINE | ID: mdl-31420192

ABSTRACT

Malignant hypertension is listed among the causes of secondary thrombotic microangiopathy, but pathogenic mutations in complement genes have been reported in patients with hypertension-induced thrombotic microangiopathy. Here we investigated the frequency and severity of hypertension in 55 patients with primary atypical hemolytic uremic syndrome (aHUS). A genetic analysis was performed in all patients, and funduscopic examination was performed in all the patients with Grades 2 and 3 hypertension. A cohort of 110 patients with malignant hypertension caused by diseases other than aHUS served as control. Thirty-six patients with aHUS presented Grade 2 or Grade 3 hypertension and funduscopic examination showed malignant hypertension in 19. Genetic abnormalities in complement were found in 19 patients (37% among patients with malignant hypertension). Plasmapheresis was performed in 46 patients and 26 received eculizumab. Renal and hematological responses were significantly lower after plasmapheresis (24%) than after eculizumab (81%). Renal survival was significantly higher in patients treated with eculizumab (85% at one, three and five years) compared to patients who did not receive this treatment (54%, 46% and 41%), respectively. Response to eculizumab was independent of hypertension severity and the presence of complement genetic abnormalities. Among patients with malignant hypertension caused by other diseases the prevalence of thrombotic microangiopathy was very low (5%). Thus, severe and malignant hypertension are common among patients with aHUS and eculizumab treatment leads to a higher renal survival when compared to plasmapheresis. However, thrombotic microangiopathy is uncommon among patients presenting with malignant hypertension caused by diseases other than aHUS.


Subject(s)
Atypical Hemolytic Uremic Syndrome/complications , Complement System Proteins/genetics , Hypertension, Malignant/epidemiology , Severity of Illness Index , Adult , Antibodies, Monoclonal, Humanized/therapeutic use , Atypical Hemolytic Uremic Syndrome/genetics , Atypical Hemolytic Uremic Syndrome/therapy , Complement Inactivating Agents/therapeutic use , Female , Humans , Hypertension, Malignant/diagnosis , Hypertension, Malignant/genetics , Hypertension, Malignant/therapy , Incidence , Male , Middle Aged , Plasmapheresis , Retrospective Studies , Young Adult
8.
Nephrol Dial Transplant ; 32(3): 466-474, 2017 03 01.
Article in English | MEDLINE | ID: mdl-28339660

ABSTRACT

Background: Complement dysregulation occurs in thrombotic microangiopathies (TMAs) other than primary atypical haemolytic uraemic syndrome (aHUS). A few of these patients have been reported previously to be successfully treated with eculizumab. Methods: We identified 29 patients with so-called secondary aHUS who had received eculizumab at 11 Spanish nephrology centres. Primary outcome was TMA resolution, defined by a normalization of platelet count (>150 × 10 9 /L) and haemoglobin, disappearance of all the markers of microangiopathic haemolytic anaemia (MAHA), and improvement of renal function, with a ≥25% reduction of serum creatinine from the onset of eculizumab administration. Results: Twenty-nine patients with secondary aHUS (15 drug-induced, 8 associated with systemic diseases, 2 with postpartum, 2 with cancer-related, 1 associated with acute humoral rejection and 1 with intestinal lymphangiectasia) were included in this study. The reason to initiate eculizumab treatment was worsening of renal function and persistence of TMA despite treatment of the TMA cause and plasmapheresis. All patients showed severe MAHA and renal function impairment (14 requiring dialysis) prior to eculizumab treatment and 11 presented severe extrarenal manifestations. A rapid resolution of the TMA was observed in 20 patients (68%), 15 of them showing a ≥50% serum creatinine reduction at the last follow-up. Comprehensive genetic and molecular studies in 22 patients identified complement pathogenic variants in only 2 patients. With these two exceptions, eculizumab was discontinued, after a median of 8 weeks of treatment, without the occurrence of aHUS relapses. Conclusion: Short treatment with eculizumab can result in a rapid improvement of patients with secondary aHUS in whom TMA has persisted and renal function worsened despite treatment of the TMA-inducing condition.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Atypical Hemolytic Uremic Syndrome/drug therapy , Complement Inactivating Agents/therapeutic use , Adult , Atypical Hemolytic Uremic Syndrome/etiology , Atypical Hemolytic Uremic Syndrome/metabolism , Churg-Strauss Syndrome/complications , Creatinine/metabolism , Female , Humans , Immunosuppressive Agents/adverse effects , Kidney Function Tests , Lupus Erythematosus, Systemic/complications , Male , Middle Aged , Plasmapheresis , Platelet Count , Recurrence , Renal Insufficiency/etiology , Renal Insufficiency/metabolism , Scleroderma, Systemic/complications , Thrombotic Microangiopathies/drug therapy , Thrombotic Microangiopathies/metabolism
9.
BMC Nephrol ; 18(1): 324, 2017 Oct 28.
Article in English | MEDLINE | ID: mdl-29080561

ABSTRACT

BACKGROUND: The differential diagnosis of thrombotic microangiopathy (TMA) is complex however the rapid diagnosis of the underlying condition is vital to inform urgent treatment decisions. A survey was devised with the objective of understanding current practices across Europe and the Middle East, and of challenges when diagnosing the cause of TMA. METHODS: Over 450 clinicians, from 16 countries were invited to complete an online survey. RESULTS: Of 254 respondents, the majority were nephrologists, had >10 years' experience in their specialty, and had diagnosed a patient with TMA. The triad of thrombocytopenia, haemolytic anaemia and acute kidney injury are the main diagnostic criteria used. Responses indicate that a differential diagnosis of TMA is usually made within 1-2 (53%) or 3-4 days (26%) of presentation. Similarly, therapy is usually initiated within the first 4 days (74%), however 13% report treatment initiation >1-week post-presentation. Extrarenal symptoms and a panoply of other conditions are considered when assessing the differential diagnosis of TMA. While 70 and 78% of respondents stated they always request complement protein levels and ADAMTS13 activity, respectively. Diagnostic considerations of paediatric and adult nephrologists varied. A greater proportion of paediatric than adult nephrologists consider extrarenal manifestations clinically related to a diagnosis of TMA; pulmonary (45% vs. 18%), gastrointestinal (67% vs. 50%), CNS (96% vs. 84%) and cardiovascular (54% vs. 42%), respectively. Variability in the availability of guidelines and extent of family history taken was also evident. CONCLUSIONS: This survey reveals the variability of current practices and the need for increased urgency among physicians in the differential diagnosis of TMA, despite their experience. Above all, the survey highlights the need for international clinical guidelines to provide systematically developed recommendations for understanding the relevance of complement protein levels, complement abnormalities and ADAMTS13 testing, in making a differential diagnosis of TMA. Such clinical guidelines would enable physicians to make a more rapid and informed diagnosis of TMA, therefore initiate effective treatment earlier, with a consequent improvement in patient outcomes.


Subject(s)
Nephrologists , Nephrology/methods , Surveys and Questionnaires , Thrombotic Microangiopathies/blood , Thrombotic Microangiopathies/diagnosis , Biomarkers/blood , Diagnosis, Differential , Europe/epidemiology , Female , Humans , Male , Middle East/epidemiology , Nephrologists/standards , Nephrology/standards , Surveys and Questionnaires/standards , Thrombotic Microangiopathies/epidemiology
10.
Nephrol Dial Transplant ; 31(3): 495-505, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26538615

ABSTRACT

BACKGROUND: The long-term clinical evolution of prediabetes and post-transplant diabetes mellitus (PTDM) is unknown. METHODS: We analysed, in this cohort study, the reversibility, stability and progression of PTDM and prediabetes in 672 patients using repeated oral glucose tolerance tests (OGTTs) for ≤5 years. RESULTS: Most patients were on tacrolimus, steroids and mycophenolate. About half developed either PTDM or prediabetes. The incidence of PTDM was 32% and bimodal: early PTDM (≤3 months) and late PTDM. Early PTDM reverted in 31%; late PTDM developed in patients with post-transplant prediabetes. The use of OGTTs was necessary to detect around half of PTDM. Pretransplant obesity was a major risk factor for early PTDM, for its persistence and for late PTDM {odds ratio [OR] 1.18 [95% confidence interval (CI) 1.09-1.28]}. At 3 months, higher HbA1c promoted [OR 2.37 (95% CI 1.38-4.06)], while insulin sensitivity protected against [OR 0.64 (95% CI 0.48-0.86)] late PTDM. At 3 months, 28% had prediabetes; of these, 36% remained stable, 43% normalized and 21% developed late PTDM. Pretransplant obesity [OR 1.20 (95% CI 1.04-1.39)] and higher HbA1c [OR 3.80 (95% CI 1.45-9.94)] at 3 months promoted while insulin sensitivity protected against [OR 0.57 (95% CI 0.34-0.95)] evolution from prediabetes to late PTDM. Immunosuppressive levels or acute rejection did not influence PTDM. Most (84%) of the patients with normal tests at 3 months remained stable without evolving into PTDM; 14% developed prediabetes. CONCLUSIONS: PTDM and prediabetes are very common in renal transplantation. Classic metabolic factors like obesity, prediabetes and insulin resistance promote the evolution of PTDM and prediabetes. Patients with normal glucose metabolism rarely develop PTDM. OGTT is necessary to detect PTDM and prediabetes and thus should be included in clinical practice.


Subject(s)
Diabetes Mellitus/etiology , Insulin Resistance , Kidney Transplantation/adverse effects , Postoperative Complications/etiology , Adult , Diabetes Mellitus/blood , Diabetes Mellitus/epidemiology , Female , Glucose Tolerance Test , Humans , Incidence , Male , Middle Aged , Odds Ratio , Postoperative Complications/epidemiology , Prospective Studies , Risk Factors , Spain/epidemiology
12.
BMC Womens Health ; 16: 48, 2016 07 30.
Article in English | MEDLINE | ID: mdl-27475909

ABSTRACT

BACKGROUND: By focusing upon formal sex education programmes, the Mozambican government has significantly enhanced the general health of adolescents and young adults. However, when it comes to contraception, little is known about how adolescents and young adults actually behave. METHODS: Based upon a qualitative study in two settings in Maputo province - Ndlavela and Boane - this paper explores the knowledge and practices of contraception among adolescents and young adults. A total of four focus group discussions, 16 in-depth interviews, four informal conversations, and observations were equally divided between both study sites. RESULTS: Discrepancies between what adolescents and young adults know and what they do quickly became evident. Ambivalent and contradictory practices concerning contraceptive use was the result. As well, young people had numerous interpretations of risk-taking when not using contraceptives. These inconsistencies are influenced by social and medical barriers such as restricted dialogue on sexuality among adolescents and young adults and their parents and peers. Additionally, ideas about indigenous contraceptives, notions of masculinity and femininity, misconceptions and fear of the side effects of contraceptives, make people of all ages wary of modern birth control. Other barriers include imposed contraceptive choice - meaning no choice, overly technical medical language used at clinics and the absence of healthcare workers more attuned to the needs of adolescents and young adults. CONCLUSIONS: Adolescents and young adults have numerous - often erroneous - opinions about contraception, leading to inconsistent use as well as vague perceptions of risk-taking. Moreover, social norms and cultural gender roles often contradict and hinder risk-avoiding behaviour. Therefore, in order to improve young people's health, policymakers must address the reasons behind this ambivalence and inconsistency.


Subject(s)
Contraception Behavior/psychology , Contraception/psychology , Health Knowledge, Attitudes, Practice , Sexual Behavior/psychology , Adolescent , Adolescent Behavior/psychology , Contraception/methods , Contraception Behavior/trends , Female , Focus Groups , Humans , Male , Mozambique , Perception , Qualitative Research , Risk-Taking , Sexual Behavior/statistics & numerical data , Young Adult
13.
J Am Soc Nephrol ; 26(1): 220-9, 2015 Jan.
Article in English | MEDLINE | ID: mdl-24970885

ABSTRACT

Diabetic kidney disease (DKD) is the leading cause of ESRD. We conducted an open-label, prospective, randomized trial to determine whether pentoxifylline (PTF), which reduces albuminuria, in addition to renin-angiotensin system (RAS) blockade, can slow progression of renal disease in patients with type 2 diabetes and stages 3-4 CKD. Participants were assigned to receive PTF (1200 mg/d) (n=82) or to a control group (n=87) for 2 years. All patients received similar doses of RAS inhibitors. At study end, eGFR had decreased by a mean±SEM of 2.1±0.4 ml/min per 1.73 m(2) in the PTF group compared with 6.5±0.4 ml/min per 1.73 m(2) in the control group, with a between-group difference of 4.3 ml/min per 1.73 m(2) (95% confidence interval [95% CI], 3.1 to 5.5 ml/min per 1.73 m(2); P<0.001) in favor of PTF. The proportion of patients with a rate of eGFR decline greater than the median rate of decline (0.16 ml/min per 1.73 m(2) per month) was lower in the PTF group than in the control group (33.3% versus 68.2%; P<0.001). Percentage change in urinary albumin excretion was 5.7% (95% CI, -0.3% to 11.1%) in the control group and -14.9% (95% CI, -20.4% to -9.4%) in the PTF group (P=0.001). Urine TNF-α decreased from a median 16 ng/g (interquartile range, 11-20.1 ng/g) to 14.3 ng/g (interquartile range, 9.2-18.4 ng/g) in the PTF group (P<0.01), with no changes in the control group. In this population, addition of PTF to RAS inhibitors resulted in a smaller decrease in eGFR and a greater reduction of residual albuminuria.


Subject(s)
Albumins/analysis , Diabetic Nephropathies/drug therapy , Diabetic Nephropathies/urine , Kidney/drug effects , Pentoxifylline/therapeutic use , Aged , Diabetes Mellitus, Type 2/complications , Disease Progression , Female , Glomerular Filtration Rate , Humans , Inflammation , Male , Middle Aged , Prospective Studies , Research Design , Treatment Outcome
14.
Biol Conserv ; 186: 251-259, 2015 Jun 01.
Article in English | MEDLINE | ID: mdl-26097240

ABSTRACT

Understanding how indigenous peoples' management practices relate to biological diversity requires addressing contemporary changes in indigenous peoples' way of life. This study explores the association between cultural change among a Bolivian Amazonian indigenous group, the Tsimane', and tree diversity in forests surrounding their villages. We interviewed 86 informants in six villages about their level of attachment to traditional Tsimane' values, our proxy for cultural change. We estimated tree diversity (Fisher's Alpha index) by inventorying trees in 48 0.1-ha plots in old-growth forests distributed in the territory of the same villages. We used multivariate models to assess the relation between cultural change and alpha tree diversity. Cultural change was associated with alpha tree diversity and the relation showed an inverted U-shape, thus suggesting that tree alpha diversity peaked in villages undergoing intermediate cultural change. Although the results do not allow for testing the direction of the relation, we propose that cultural change relates to tree diversity through the changes in practices and behaviors that affect the traditional ecological knowledge of Tsimane' communities; further research is needed to determine the causality. Our results also find support in the intermediate disturbance hypothesis, and suggest that indigenous management can be seen as an intermediate form of anthropogenic disturbance affecting forest communities in a subtle, non-destructive way.

15.
Breast Cancer Res ; 16(6): 505, 2014 Dec 20.
Article in English | MEDLINE | ID: mdl-25527274

ABSTRACT

INTRODUCTION: The POU class 1 homeobox 1 transcription factor (POU1F1, also known as Pit-1) is expressed in the mammary gland and its overexpression induces profound phenotypic changes in proteins involved in cell proliferation, apoptosis, and invasion. Patients with breast cancer and elevated expression of Pit-1 show a positive correlation with the occurrence of distant metastasis. In this study we evaluate the relationship between Pit-1 and two collagenases: matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-13 (MMP-13), which have been related to metastasis in breast cancer. METHODS: We began by transfecting the MCF-7 and MDA-MB-231 human breast adenocarcinoma cell lines with the Pit-1 overexpression vector (pRSV-hPit-1). Afterward, the mRNA, protein, and transcriptional regulation of both MMP-1 and MMP-13 were evaluated by real-time PCR, Western blot, chromatin immunoprecipitation (ChIP), and luciferase reporter assays. We also evaluated Pit-1 overexpression with MMP-1 and MMP-13 knockdown in a severe combined immunodeficiency (SCID) mouse tumor xenograft model. Finally, by immunohistochemistry we correlated Pit-1 with MMP-1 and MMP-13 protein expression in 110 human breast tumors samples. RESULTS: Our data show that Pit-1 increases mRNA and protein of both MMP-1 and MMP-13 through direct transcriptional regulation. In SCID mice, knockdown of MMP-13 completely blocked lung metastasis in Pit-1-overexpressing MCF-7 cells injected into the mammary fat pad. In breast cancer patients, expression of Pit-1 was found to be positively correlated with the presence of both MMP-1 and MMP-13. CONCLUSIONS: Our data indicates that Pit-1 regulates MMP-1 and MMP-13, and that inhibition of MMP-13 blocked invasiveness to lung in Pit-1-overexpressed breast cancer cells.


Subject(s)
Adenocarcinoma/genetics , Breast Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Matrix Metalloproteinase 13/genetics , Matrix Metalloproteinase 1/genetics , RNA, Messenger/metabolism , Transcription Factor Pit-1/genetics , Adenocarcinoma/metabolism , Adenocarcinoma/secondary , Animals , Apoptosis , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Line, Tumor , Cell Proliferation , Female , Humans , Lung Neoplasms/secondary , MCF-7 Cells , Matrix Metalloproteinase 1/metabolism , Matrix Metalloproteinase 13/metabolism , Mice , Neoplasm Invasiveness , Neoplasm Metastasis , Neoplasm Transplantation
16.
Hum Organ ; 73(2): 162-173, 2014.
Article in English | MEDLINE | ID: mdl-27642188

ABSTRACT

Among the different factors associated to change in traditional ecological knowledge, the study of the relations between cultural change and traditional ecological knowledge has received scan and inadequate scholarly attention. Using data from indigenous peoples of an Amazonian society facing increasing exposure to the mainstream Bolivian society, we analyzed the relation between traditional ecological knowledge, proxied with individual plant use knowledge (n=484), and cultural change, proxied with individual- and village-level (n=47) measures of attachment to traditional beliefs and values. We found that both the individual level of detachment to traditional values and the village level of agreement in detachment to traditional values were associated with individual levels of plant use knowledge, irrespective of other proxy measures for cultural change. Because both the individual- and the village-level variables bear statistically significant associations with plant use knowledge, our results suggest that both the individual- and the supra-individual level processes of cultural change are related to the erosion of plant use knowledge. Results from our work highlight the importance of analyzing processes that happen at intermediary social units -the village in our case study- to explain changes in traditional ecological knowledge.

17.
Econ Bot ; 68(1): 1-15, 2014 Mar 01.
Article in English | MEDLINE | ID: mdl-26097243

ABSTRACT

Researchers have argued that indigenous peoples preferably use the most apparent plant species, particularly for medicinal uses. However, the association between the ecological importance of a species and its usefulness remains unclear. In this paper we quantify such association for six use categories (firewood, construction, materials, food, medicines and other uses). We collected data on the uses of 58 tree species, as reported by 93 informants in 22 villages in the Tsimane' territory (Bolivian Amazon). We calculated the ecological importance of the same species by deriving their importance value index (IVI) in 48 0.1-ha old-growth forest plots. Matching both data sets, we found a positive relation between the IVI of a species and its overall use value (UV) as well as with its UV for construction and materials. We found a negative relation between IVI and UV for species that were reportedly used for medicine and food uses, and no clear pattern for the other categories. We hypothesize that species used for construction or crafting purposes because of their physical properties are more easily substitutable than species used for medicinal or edible purposes because of their chemical properties.

18.
Expert Rev Pharmacoecon Outcomes Res ; 24(2): 227-235, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38126738

ABSTRACT

BACKGROUND: Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) are rare autoimmune diseases characterized by inflammation of blood vessels. This study aimed to assess the cost-utility of avacopan in combination with rituximab (RTX) or cyclophosphamide (CYC) compared with glucocorticoids (GC) for the treatment of severe, active AAV in Spain. METHODS: A 9-state Markov model was designed to reflect the induction of remission and sustained remission of AAV over a lifetime horizon. Clinical data and utility values were mainly obtained from the ADVOCATE trial, and costs (€ 2022) were sourced from national databases. Quality-adjusted life years (QALYs), and incremental cost-utility ratio (ICUR) were evaluated. An annual discount rate of 3% was applied. Sensitivity analyses were performed to examine the robustness of the results. RESULTS: Avacopan yielded an increase in effectiveness (6.52 vs. 6.17 QALYs) and costs (€16,009) compared to GC, resulting in an ICUR of €45,638 per additional QALY gained. Avacopan was associated with a lower incidence of end-stage renal disease (ESRD), relapse and hospitalization-related adverse events. Sensitivity analyses suggested that the model outputs were robust and that the progression to ESRD was a driver of ICUR. CONCLUSIONS: Avacopan is a cost-effective option for patients with severe, active AAV compared to GC in Spain.


Subject(s)
Aniline Compounds , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Kidney Failure, Chronic , Nipecotic Acids , Humans , Antibodies, Antineutrophil Cytoplasmic/therapeutic use , Cost-Benefit Analysis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/chemically induced , Spain , Remission Induction , Rituximab , Glucocorticoids/adverse effects
19.
Evol Hum Behav ; 34(4)2013 Jul 01.
Article in English | MEDLINE | ID: mdl-24277979

ABSTRACT

As biological and linguistic diversity, the world's cultural diversity is on decline. However, to date there are no estimates of the rate at which the specific cultural traits of a group disappear, mainly because we lack empirical data to assess how the cultural traits of a given population change over time. Here we estimate changes in cultural traits associated to the traditional knowledge of wild plant uses among an Amazonian indigenous society. We collected data among 1151 Tsimane' Amerindians at two periods of time. Results show that between 2000 and 2009, Tsimane' adults experienced a net decrease in the report of plant uses ranging from 9% (for the female subsample) to 26% (for the subsample of people living close to towns), equivalent to a 1 to 3 % per year. Results from a Monte Carlo simulation show that the observed changes were not the result of randomness. Changes were more acute for men than for women and for informants living in villages close to market towns than for informants settled in remote villages. The Tsimane' could be abandoning their traditional knowledge as they perceive that this form of knowledge do not equip them well to deal with the new socio-economic and cultural conditions they face nowadays.

20.
Learn Individ Differ ; 27: 206-212, 2013 Oct 01.
Article in English | MEDLINE | ID: mdl-24518817

ABSTRACT

Empirical research provides contradictory evidence of the loss of traditional ecological knowledge across societies. Researchers have argued that culture, methodological differences, and site-specific conditions are responsible for such contradictory evidences. We advance and test a third explanation: the adaptive nature of traditional ecological knowledge systems. Specifically, we test whether different domains of traditional ecological knowledge experience different secular changes and analyze trends in the context of other changes in livelihoods. We use data collected among 651 Tsimane' men (Bolivian Amazon). Our findings indicate that different domains of knowledge follow different secular trends. Among the domains of knowledge analyzed, medicinal and wild edible knowledge appear as the most vulnerable; canoe building and firewood knowledge seem to remain constant across generations; whereas house building knowledge seems to experience a slight secular increase. Our analysis reflects on the adaptive nature of traditional ecological knowledge, highlighting how changes in this knowledge system respond to the particular needs of a society in a given point of time.

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