Pehr Kalmin väitöskirjat

Pehr Kalm toimi Turun akatemian luonnonhistorian ja talousopin professorina vuodesta 1747. Hänen johdollaan julkaistiin 146 väitöskirjaa, useimmat hänen itsensä kirjoittamina. Noin kaksi kolmannesta niistä on kirjoitettu ruotsiksi, muut latinaksi. Väitöksien joukossa on usieta pitäjien, kaupunkien ja maakuntien kuvauksia sekä maataloutta ja metsänhoitoa käsitteleviä töitä. Latinankielisistä väitöskirjoista monet ovat luonteeltaan teoreettisempia.

Contribuição da pesquisa científica brasileira no desenvolvimento de algumas frutíferas de clima subtropical

Quando se considera aptidão climática, as plantas frutíferas são classificadas em: tropicais, subtropicais e temperadas. Esta tradicional classificação, por muito tempo, mostrou-se bastante efetiva. Os mais atuais conhecimentos dos centros de origens de diferentes espécies, os avanços tecnológicos na condução dos pomares e na conservação dos frutos e especialmente o melhoramento genético criaram condições excepcionais para o cultivo de espécies tropicais e temperadas em clima subtropical. No presente trabalho foram selecionadas as culturas da atemoieira, do caquizeiro, da figueira e da goiabeira com base não apenas na importância nacional e regional, mas também pelas diferentes contribuições que a pesquisa científica ofereceu a estas frutíferas. Atemoieira - dentre as espécies frutíferas exploradas em larga escala, talvez seja a de mais recente introdução de cultivo no Brasil, iniciado em meados da década de 1980. Diversas técnicas de cultivo foram desenvolvidas, como porta-enxertos mais adequados para cada região, podas de formação e produção, polinização artificial, manejo de pragas e doenças, e diversas outras tecnologias que permitiram rápida expansão da cultura em diversas regiões do País. Embora o importante papel das Universidades, Institutos de Pesquisas e Extensão seja inquestionável, foi fundamental a contribuição dos produtores pioneiros que iniciaram a busca de soluções para os problemas surgidos, indicando as necessidades para intervenções da pesquisa. Caquizeiro - a produção brasileira de caqui (IBGE - 2009), de 171.555 t, é obtida em uma área de 8.770 ha e representa um valor de 146,67 milhões de reais. São Estados maiores produtores São Paulo (111.646 t), Rio Grande do Sul, Paraná e Rio de Janeiro). As principais cultivares em produção são: Rama Forte, Giombo e Fuyu, que são comercializados prioritariamente no mercado interno. Figueira - a produção brasileira de figos vem mantendo-se com pequenas variações nos anos de 2000, atingindo 24.146 t em 2009 (IBGE - IBRAF), sendo os Estados do Rio Grande do Sul e São Paulo, os maiores produtores . No Estado de São Paulo, o cultivo concentra-se quase que exclusivamente na região de Campinas, sendo a produção de 9.469 t em 2010 (IEA). Os frutos colhidos graças à tecnologia desenvolvida é, em parte, exportada como figo de mesa (1.645 t em 2008). Fonte DECEX (MICT) IBRAF - 2010. Goiabeira - o cultivo da goiabeira no Brasil permite considerá-la atualmente como uma espécie plenamente adaptada ao clima subtropical. O desenvolvimento de variedades adaptadas e técnicas especiais de cultivo propiciaram grande expansão desta cultura no Brasil. Segundo o IBGE - IBRAF, em 2009, o Brasil produziu 297.377 t em uma área de 15.048 ha. Pernambuco, São Paulo, Brasília, Rio de Janeiro e Bahia são os principais produtores. No Estado de São Paulo, é importante destacar a produção de goiabas para mesa (50.000 t) que graças à alta qualidade dos frutos é exportado com sucesso.

Pulmonary metastasectomy in colorectal cancer patients with previously resected liver metastasis: pooled analysis.

BACKGROUND: Data addressing the outcomes and patterns of recurrence after pulmonary metastasectomy (PM) in patients with colorectal cancer (CRC) and previously resected liver metastasis are limited. METHODS: We searched the PubMed database for studies assessing PM in CRC and gathered individual data for patients who had PM and a previous curative liver resection. The influence of potential factors on overall survival (OS) was analyzed through univariate and multivariate analysis. RESULTS: Between 1983 and 2009, 146 patients from five studies underwent PM and had previous liver resection. The median interval from resection of liver metastasis until detection of lung metastasis and the median follow-up from PM were 23 and 48 months, respectively. Five-year OS and recurrence-free survival rates calculated from the date of PM were 54.4 and 29.3 %, respectively. Factors predicting inferior OS in univariate analysis included thoracic lymph node (LN) involvement and size of largest lung nodule ≥2 cm. Adjuvant chemotherapy and whether lung metastasis was detected synchronous or metachronous to liver metastasis had no influence on survival. In multivariate analysis, thoracic LN involvement emerged as the only independent factor (hazard ratio 4.86, 95 % confidence interval 1.56-15.14, p = 0.006). CONCLUSIONS: PM offers a chance for long-term survival in selected patients with CRC and previously resected liver metastasis. Thoracic LN involvement predicted poor prognosis; therefore, significant efforts should be undertaken for adequate staging of the mediastinum before PM. In addition, adequate intraoperative LN sampling allows proper prognostic stratification and enrollment in novel adjuvant therapy trials.

Subclinical thyroid dysfunction and fracture risk: a meta-analysis.

IMPORTANCE: Associations between subclinical thyroid dysfunction and fractures are unclear and clinical trials are lacking. OBJECTIVE: To assess the association of subclinical thyroid dysfunction with hip, nonspine, spine, or any fractures. DATA SOURCES AND STUDY SELECTION: The databases of MEDLINE and EMBASE (inception to March 26, 2015) were searched without language restrictions for prospective cohort studies with thyroid function data and subsequent fractures. DATA EXTRACTION: Individual participant data were obtained from 13 prospective cohorts in the United States, Europe, Australia, and Japan. Levels of thyroid function were defined as euthyroidism (thyroid-stimulating hormone [TSH], 0.45-4.49 mIU/L), subclinical hyperthyroidism (TSH <0.45 mIU/L), and subclinical hypothyroidism (TSH ≥4.50-19.99 mIU/L) with normal thyroxine concentrations. MAIN OUTCOME AND MEASURES: The primary outcome was hip fracture. Any fractures, nonspine fractures, and clinical spine fractures were secondary outcomes. RESULTS: Among 70,298 participants, 4092 (5.8%) had subclinical hypothyroidism and 2219 (3.2%) had subclinical hyperthyroidism. During 762,401 person-years of follow-up, hip fracture occurred in 2975 participants (4.6%; 12 studies), any fracture in 2528 participants (9.0%; 8 studies), nonspine fracture in 2018 participants (8.4%; 8 studies), and spine fracture in 296 participants (1.3%; 6 studies). In age- and sex-adjusted analyses, the hazard ratio (HR) for subclinical hyperthyroidism vs euthyroidism was 1.36 for hip fracture (95% CI, 1.13-1.64; 146 events in 2082 participants vs 2534 in 56,471); for any fracture, HR was 1.28 (95% CI, 1.06-1.53; 121 events in 888 participants vs 2203 in 25,901); for nonspine fracture, HR was 1.16 (95% CI, 0.95-1.41; 107 events in 946 participants vs 1745 in 21,722); and for spine fracture, HR was 1.51 (95% CI, 0.93-2.45; 17 events in 732 participants vs 255 in 20,328). Lower TSH was associated with higher fracture rates: for TSH of less than 0.10 mIU/L, HR was 1.61 for hip fracture (95% CI, 1.21-2.15; 47 events in 510 participants); for any fracture, HR was 1.98 (95% CI, 1.41-2.78; 44 events in 212 participants); for nonspine fracture, HR was 1.61 (95% CI, 0.96-2.71; 32 events in 185 participants); and for spine fracture, HR was 3.57 (95% CI, 1.88-6.78; 8 events in 162 participants). Risks were similar after adjustment for other fracture risk factors. Endogenous subclinical hyperthyroidism (excluding thyroid medication users) was associated with HRs of 1.52 (95% CI, 1.19-1.93) for hip fracture, 1.42 (95% CI, 1.16-1.74) for any fracture, and 1.74 (95% CI, 1.01-2.99) for spine fracture. No association was found between subclinical hypothyroidism and fracture risk. CONCLUSIONS AND RELEVANCE: Subclinical hyperthyroidism was associated with an increased risk of hip and other fractures, particularly among those with TSH levels of less than 0.10 mIU/L and those with endogenous subclinical hyperthyroidism. Further study is needed to determine whether treating subclinical hyperthyroidism can prevent fractures.

Características morfofisiológicas de plantas clonais de Passiflora alata crescidas em diferentes doses de nitrogênio e níveis de sombreamento

Plantas clonais de Passiflora alata foram submetidas a quatro níveis de sombreamento (0; 25; 50 e 75%) aos 75 dias após o estaqueamento (DAE). Dez dias após, aplicou-se nitrogênio (N) nas dosagens de 0; 25;50; 100 e 200 mg N kg-1 de solo. Verificou-se, aos 175 DAE, interação significativa (p<0,05) entre níveis de sombreamento (NS) e doses de N, para todos os parâmetros fotossintéticos avaliados. Observou-se um aumento na taxa fotossintética líquida com a elevação de NS e de N até a dose de 146 mg N kg-1. A taxa transpiratória apresentou efeito quadrático tanto para NS quanto para N, tendendo a aumentar com o incremento de NS e N até 50% de sombreamento e 137 mg N kg-1, respectivamente. A espessura dos tecidos do mesofilo foliar foi reduzida com a intensificação de NS. Os teores de clorofila a, b e total aumentaram com a elevação de NS e N. Todos os parâmetros de crescimento analisados não apresentaram diferenças significativas (p<0,05) para a interação NSxN. O maior acúmulo de biomassa seca total foi obtido em 69% de sombreamento e na dose de 113 mg N kg-1, ocorrendo um declínio nos NS nas e doses de N subsequentes. Em suma, os resultados demonstraram que o sombreamento moderado (50%), associado a um suprimento moderado de N, promoveu maior eficiência fotossintética e, consequentemente, incremento na biomassa seca, na planta toda.

LC-MS/MS based assay and reference intervals in children and adolescents for oxysterols elevated in Niemann-Pick diseases.

BACKGROUND: Niemann-Pick type C (NP-C) is a rare progressive neurodegenerative lipid storage disorder with heterogeneous clinical presentation and challenging diagnostic procedures. Recently oxysterols have been reported to be specific biomarkers for NP-C but knowledge on the intra-individual variation and on reference intervals in children and adolescents are lacking. METHODS: We established a LC-MS/MS assay to measure Cholestane-3β, 5α, 6β-triol (C-triol) and 7-Ketocholesterol (7-KC) following Steglich esterification. To assess reference intervals and intra-individual variation we determined oxysterols in 148 children and adolescents from 0 to 18 years and repeat measurements in 19 of them. RESULTS: The reported method is linear (r>0.99), sensitive (detection limit of 0.03 ng/mL [0.07 nM] for C-triol, and 0.54 ng/mL [1.35 nM] for 7-KC) and precise, with an intra-day imprecision of 4.8% and 4.1%, and an inter-day imprecision of 7.0% and 11.0% for C-triol (28 ng/ml, 67 nM) and 7-KC (32 ng/ml, 80 nM), respectively. Recoveries for 7-KC and C-triol range between 93% and 107%. The upper reference limit obtained for C-triol is 40.4 ng/mL (95% CI: 26.4-61.7 ng/mL, 96.0 nM, 95% CI: 62.8-146.7 nM) and 75.0 ng/mL for 7-KC (95% CI: 55.5-102.5 ng/mL, 187.2 nM, 95% CI: 138.53-255.8 nM), with no age or gender dependency. Both oxysterols have a broad intra-individual variation of 46%±23% for C-triol and 52%±29% for 7-KC. Nevertheless, all Niemann-Pick patients showed increased C-triol levels including Niemann-Pick type A and B patients. CONCLUSIONS: The LC-MS/MS assay is a robust assay to quantify C-triol and 7-KC in plasma with well documented reference intervals in children and adolescents to screen for NP-C in the pediatric population. In addition our results suggest that especially the C-triol is a biomarker for all three Niemann-Pick diseases.

Exosomes for Intramyocardial Intercellular Communication.

Cross-talk between different cell types plays central roles both in cardiac homeostasis and in adaptive responses of the heart to stress. Cardiomyocytes (CMs) send biological messages to the other cell types present in the heart including endothelial cells (ECs) and fibroblasts. In turn, CMs receive messages from these cells. Recent evidence has now established that exosomes, nanosized secreted extracellular vesicles, are crucial mediators of such messages. CMs, ECs, cardiac fibroblasts, and cardiac progenitor cells (CPCs) release exosomes carrying nonrandom subsets of proteins, lipids, and nucleic acids present in their cells of origin. Exosomes secreted from CMs are internalized by fibroblasts and regulate gene expression in these cells as well as in ECs. CPC-derived exosomes protect CMs against apoptosis while also stimulating angiogenesis. They are rich in cardioprotective and proangiogenic microRNAs such as miR-146, miR-210, and miR-132. When injected into infracted hearts in vivo, CPC-derived exosomes reduce infarct size and improve cardiac function. Thus, exosomes are emerging both as key mediators of intercellular communication in the heart and as therapeutic candidates for heart disease.

Parasitismo de Meloidogyne enterolobii em espécies de myrtaceae

A meloidoginose da goiabeira, causada por M. enterolobii (= M. mayaguensis), é hoje considerado o principal problema fitossanitário desta cultura em todo o País, pois sua incidência resulta em acentuada queda de produtividade e, na maioria das vezes, a morte das plantas em médio prazo. Visando a seu controle, objetivou-se neste trabalho identificar fontes de resistência em goiabeira Psidium guajava L e araçazeiro Psidium sp.. Foram avaliados onze genótipos oriundos do Câmpus da Universidade Federal de Lavras (UFLA) e de regiões próximas ao município de Lavras (MG). As sementes foram coletadas de frutos fisiologicamente maduros e germinadas em piscinas hidropônicas. Ao atingirem 12 cm de altura, foram transferidas para casa de vegetação, em vasos individuais, e mantidas a temperatura entre 18-38°C. Após quinze dias, foram inoculados individualmente com suspensão de 10.000 ovos e juvenis de segundo estádio (J2) de M. enterolobii e avaliadas após 120 dias. As reações dos hospedeiros foram enquadradas nos parâmetros estabelecidos pelo fator de reprodução FR, estimado pelo quociente Pf/Pi, em que Pf representa a população final e Pi a população inicial. O delineamento utilizado foi o inteiramente casualizado, com 11 genótipos, uma espécie de nematoide e seis repetições, sendo duas plantas em cada genótipo adicionadas como controle. Quatro meses depois, foram avaliados os teores foliares de macro e micronutrientes e o grau de infecção de cada genótipo. A produção média de ovos e J2 de M. enterolobii variou de 200 a 428.146,1, e os fatores de reprodução (FR) médios variaram de 0,02(ALU1) a 42,81(A-PASTO). Os genótipos de araçazeiro (Psidium spp.) AUFLA1, AUFLA4, AUFLA5 e APASTO e os genótipos de goiabeira (P. guajava) G-ROXA e G-AMAR foram considerados suscetíveis. Os genótipos de araçazeiro ALU1, ALU2, ALU3, AROXO-C e AROXO-U mostraram-se resistentes, reforçando a necessidade de trabalhos complementares com essas espécies para uso como porta-enxerto em cultivares comerciais de goiabeira. A absorção de macro e micronutrientes é alterada quando os genótipos de Psidium spp. são inoculados com o fitonematoide M. enterolobii.

Quest for Orthologs Entails Quest for Tree of Life: In Search of the Gene Stream.

Quest for Orthologs (QfO) is a community effort with the goal to improve and benchmark orthology predictions. As quality assessment assumes prior knowledge on species phylogenies, we investigated the congruency between existing species trees by comparing the relationships of 147 QfO reference organisms from six Tree of Life (ToL)/species tree projects: The National Center for Biotechnology Information (NCBI) taxonomy, Opentree of Life, the sequenced species/species ToL, the 16S ribosomal RNA (rRNA) database, and trees published by Ciccarelli et al. (Ciccarelli FD, et al. 2006. Toward automatic reconstruction of a highly resolved tree of life. Science 311:1283-1287) and by Huerta-Cepas et al. (Huerta-Cepas J, Marcet-Houben M, Gabaldon T. 2014. A nested phylogenetic reconstruction approach provides scalable resolution in the eukaryotic Tree Of Life. PeerJ PrePrints 2:223) Our study reveals that each species tree suggests a different phylogeny: 87 of the 146 (60%) possible splits of a dichotomous and rooted tree are congruent, while all other splits are incongruent in at least one of the species trees. Topological differences are observed not only at deep speciation events, but also within younger clades, such as Hominidae, Rodentia, Laurasiatheria, or rosids. The evolutionary relationships of 27 archaea and bacteria are highly inconsistent. By assessing 458,108 gene trees from 65 genomes, we show that consistent species topologies are more often supported by gene phylogenies than contradicting ones. The largest concordant species tree includes 77 of the QfO reference organisms at the most. Results are summarized in the form of a consensus ToL (http://swisstree.vital-it.ch/species_tree) that can serve different benchmarking purposes.

Assessing positive mental health in people with chronic physical health problems: correlations with socio-demographic variables and physical health status

Background: A holistic perspective on health implies giving careful consideration to the relationship between physical and mental health. In this regard the present study sought to determine the level of Positive Mental Health (PMH) among people with chronic physical health problems, and to examine the relationship between the observed levels of PMH and both physical health status and socio-demographic variables. Methods: The study was based on the Multifactor Model of Positive Mental Health (Lluch, 1999), which comprises six factors: Personal Satisfaction (F1), Prosocial Attitude (F2), Self-control (F3), Autonomy (F4), Problem-solving and Self-actualization (F5), and Interpersonal Relationship Skills (F6). The sample comprised 259 adults with chronic physical health problems who were recruited through a primary care center in the province of Barcelona (Spain). Positive mental health was assessed by means of the Positive Mental Health Questionnaire (Lluch, 1999). Results: Levels of PMH differed, either on the global scale or on specific factors, in relation to the following variables: age: global PMH scores decreased with age (r=-0.129; p=0.038); b) gender: men scored higher on F1 (t=2.203; p=0.028) and F4 (t=3.182; p=0.002), while women scored higher on F2 (t -3.086; p=0.002) and F6 (t=-2.744; p=0.007); c) number of health conditions: the fewer the number of health problems the higher the PMH score on F5 (r=-0.146; p=0.019); d) daily medication: polymedication patients had lower PMH scores, both globally and on various factors; e) use of analgesics: occasional use of painkillers was associated with higher PMH scores on F1 (t=-2.811; p=0.006). There were no significant differences in global PMH scores according to the type of chronic health condition. The only significant difference in the analysis by factors was that patients with hypertension obtained lower PMH scores on the factor Autonomy (t=2.165; p=0.032). Conclusions: Most people with chronic physical health problems have medium or high levels of PMH. The variables that adversely affect PMH are old age, polypharmacy and frequent consumption of analgesics. The type of health problem does not influence the levels of PMH. Much more extensive studies with samples without chronic pathology are now required in order to be able to draw more robust conclusions.

Comparative effectiveness of gemcitabine plus cisplatin versus methotrexate, vinblastine, doxorubicin, plus cisplatin as neoadjuvant therapy for muscle-invasive bladder cancer.

BACKGROUND: Gemcitabine plus cisplatin (GC) has been adopted as a neoadjuvant regimen for muscle-invasive bladder cancer despite the lack of Level I evidence in this setting. METHODS: Data were collected using an electronic data-capture platform from 28 international centers. Eligible patients had clinical T-classification 2 (cT2) through cT4aN0M0 urothelial cancer of the bladder and received neoadjuvant GC or methotrexate, vinblastine, doxorubicin, plus cisplatin (MVAC) before undergoing cystectomy. Logistic regression was used to compute propensity scores as the predicted probabilities of patients being assigned to MVAC versus GC given their baseline characteristics. These propensity scores were then included in a new logistic regression model to estimate an adjusted odds ratio comparing the odds of attaining a pathologic complete response (pCR) between patients who received MVAC and those who received GC. RESULTS: In total, 212 patients (146 patients in the GC cohort and 66 patients in the MVAC cohort) met criteria for inclusion in the analysis. The majority of patients in the MVAC cohort (77%) received dose-dense MVAC. The median age of patients was 63 years, they were predominantly men (74%), and they received a median of 3 cycles of neoadjuvant chemotherapy. The pCR rate was 29% in the MVAC cohort and 31% in the GC cohort. There was no significant difference in the pCR rate when adjusted for propensity scores between the 2 regimens (odds ratio, 0.91; 95% confidence interval, 0.48-1.72; P = .77). In an exploratory analysis evaluating survival, the hazard ratio comparing hazard rates for MVAC versus GC adjusted for propensity scores was not statistically significant (hazard ratio, 0.78; 95% confidence interval, 0.40-1.54; P = .48). CONCLUSIONS: Patients who received neoadjuvant GC and MVAC achieved comparable pCR rates in the current analysis, providing evidence to support what has become routine practice. Cancer 2015;121:2586-2593. © 2015 American Cancer Society.

A novel set of DIP-STR markers for improved analysis of challenging DNA mixtures.

Currently available molecular biology tools allow forensic scientists to characterize DNA evidence found at crime scenes for a large variety of samples, including those of limited quantity and quality, and achieve high levels of individualization. Yet, standard forensic markers provide limited or no results when applied to mixed DNA samples where the contributors are present in very different proportions (unbalanced DNA mixtures). This becomes an issue mostly for the analysis of trace samples collected on the victim or from touched objects. To this end, we recently proposed an innovative type of genetic marker, named DIP-STR that relies on pairing deletion/insertion polymorphisms (DIP) with standard short tandem repeats (STR). This novel compound marker allows detection of the minor DNA contributor in a DNA mixture of any gender and cellular origin with unprecedented resolution (beyond a DNA ratio of 1:1000). To provide a novel analytical tool useful in practice to common forensic laboratories, this article describes the first set of 10 DIP-STR markers selected according to forensic technical standards. The novel DIP-STR regions are short (between 146 and 271 bp), include only highly polymorphic tri-, tetra- and pentanucleotide tandem repeats and are located on different chromosomes or chromosomal arms to provide statistically independent results. This novel set of DIP-STR can target the amplification of 0.03-0.1 ng of DNA when mixed with a 1000-fold excess of major DNA. DIP-STR relative allele frequencies are estimated based on a survey of 103 Swiss individuals. Finally, this study provides an estimate of the occurrence of informative alleles and a calculation of the corresponding random match probability of the detected minor DIP-STR genotype assessed across 10,506 pairwise conceptual mixtures.