Improved clinical outcomes of rhG-CSF-mobilized blood and marrow haploidentical transplantation compared to propensity score-matched rhG-CSF-primed peripheral blood stem cell haploidentical transplantation: a multicenter study

The effects of haploidentical rhG-CSF-mobilized blood and marrow transplantation(HBMT) on hematological malignances are well established. Previous prospective single-center studies have demonstrated better survival after HBMT versus haploidentical rhG-CSF-mobilized peripheral blood stem cell transplantation(HPBSCT) for acute leukemia(AL) not in remission(NR) or in more than the second complete remission(CR2). To test the hypothesis that HBMT is still superior to HPBSCT for patients with AL, multiple myeloma(MM), or non-Hodgkin lymphoma(NHL) in CR1/CR2 and for patients with chronic myeloid leukemia in the first and second chronic phase lacking a matched donor, we designed a propensity score method-based multicenter study.Hematopoietic recovery, acute graft-versus-host disease(aGVHD), and chronic GVHD were comparable between the HBMT group(n=168) and the HPBSCT group(n=42). No significant differences were found in non-relapse mortality rate(20.17%±3.58%and 27.24%±7.16%, P=0.18) or relapse rate(19.96%±3.72% and 28.49%±8.25%, P=0.32) between the HBMT group and the HPBSCT group. HBMT recipients had better overall survival(65.0%±4.2% and 54.2%±8.3%, P=0.037) and disease-free survival(59.9%±4.6% and 44.3%±8.7%, P=0.051). Multivariate analysis showed that HPBSCT was associated with poorer DFS(HR(95%CI), 1.639(0.995–2.699), P=0.052). Our comparisons showed that HBMT was superior to HPBSCT as a post-remission treatment for patients lacking an identical donor.     

Centromeric and non-centromeric satellite DNA organisation differs in holocentric <Emphasis Type="Italic">Rhynchospora</Emphasis> species

Satellite DNA repeats (or satDNA) are fast-evolving sequences usually associated with condensed heterochromatin. To test whether the chromosomal organisation of centromeric and non-centromeric satDNA differs in species with holocentric chromosomes, we identified and characterised the major satDNA families in the holocentric Cyperaceae species Rhynchospora ciliata (2n = 10), R. globosa (2n = 50) and R. tenuis (2n = 2x = 4 and 2n = 4x = 8). While conserved centromeric repeats (present in R. ciliata and R. tenuis) revealed linear signals at both chromatids, non-centromeric, species-specific satDNAs formed distinct clusters along the chromosomes. Colocalisation of both repeat types resulted in a ladder-like hybridisation pattern at mitotic chromosomes. In interphase, the centromeric satDNA was dispersed while non-centromeric satDNA clustered and partly colocalised to chromocentres. Despite the banding-like hybridisation patterns of the clustered satDNA, the identification of chromosome pairs was impaired due to the irregular hybridisation patterns of the homologues in R. tenuis and R. ciliata. These differences are probably caused by restricted or impaired meiotic recombination as reported for R. tenuis, or alternatively by complex chromosome rearrangements or unequal condensation of homologous metaphase chromosomes. Thus, holocentricity influences the chromosomal organisation leading to differences in the distribution patterns and condensation dynamics of centromeric and non-centromeric satDNA.     

High-Resolution Respirometry in Diagnostics of Mitochondrial Diseases Caused by Mitochondrial Complex I Deficiency

Mitochondrial complex I deficiency (CID) is one of the most common defects in the OXPHOS system; it represents more than 30% cases of mitochondrial diseases. The group is characterized by clinical and genetic heterogeneity and comprises several nosological forms. The most prevalent phenotypes of CID are Leber hereditary optic neuropathy (LHON) and Leigh syndrome. In this study we have analyzed skin fibroblasts from 11 patients with mutations in mtDNA, which cause LHON or Leigh-like phenotypes (m.11778 G>A (n = 3), m.3460 A>G (n = 2), m.3635 G>A (n = 1), m.3308 T>G (n = 2), m.3472 T>C (n = 1)), and 2 patients with earlier unknown substitutions m.3945 C>A and m.14441 T>C. High-resolution respirometry (HRR) was performed for complex analysis of the mitochondrial respiratory function in intact and permeabilized fibroblasts of patients and healthy controls. Flux control ratios in intact cells R/E, (R-L)/E were raised compared to the control. Rates of R, E, L normalized on the citrate synthase (CS) activity were statistically different (p < 0.05) between patients and controls. In permeabilized fibroblasts we have found statistically significant differences (p < 0.05) in ratios СII/E, Rot/E, R/CII, CI/CII between groups. These data highlight dysfunctions of the OXPHOS system, particularly CI. Increased CS activity and decreased CI/CII ratio suggest a compensatory metabolic response to the respiratory chain dysfunction. Our results show applicability of HRR in revealing biochemical abnormalities of mitochondrial complex I in fibroblasts of patients with LHON and Leigh-like syndrome. We also suggest HRR to be a useful method for inspection of new mutations causing mitochondrial complex I deficiency.     

The use of molecular genetic methods for prognosis of aerobic and anaerobic performance in athletes

The distribution of genotypes and alleles of ACE (I/D polymorphism), ACTN3 (R577X), NOS3 (5/4), UCP2 (Ala55Val), and UCP3 (-55C/T) genes, as well as the correlation between the genotype and physiological parameters, was studied in rowers (n = 230) and in a control group (n = 855). The genotypes were determined by analyzing restriction fragment length polymorphism. Physiological parameters were determined with a PM 3 rowing ergometer and a MetaMax 3B gas analyzer. The frequency of the ACE II genotype was significantly higher in elite rowers (n = 107) than in the control subjects. The frequency of the ACTN3 XX genotype, unfavorable for development of speed and strength qualities, was twofold lower in all rowers than in the control subjects. The frequencies of the ACE I, ACTN3 R, UCP2 Val, and UCP3 T alleles increased in the athletes along with an increase in skill, which suggested natural sports selection. In addition, ACE I, NOS3 5, UCP2 Val, and UCP3 T alleles correlated with a high aerobic performance. Thus, the ACE I, NOS3 5, UCP2 Val, and UCP3 T alleles may be regarded as genetic markers associated with enhanced aerobic performance and may be included in a diagnostic system for prognosis of human physical performance.     

Application of discrete choice experiments to enhance stakeholder engagement as a strategy for advancing implementation: a systematic review

Background

One of the key strategies to successful implementation of effective health-related interventions is targeting improvements in stakeholder engagement. The discrete choice experiment (DCE) is a stated preference technique for eliciting individual preferences over hypothetical alternative scenarios that is increasingly being used in health-related applications. DCEs are a dynamic approach to systematically measure health preferences which can be applied in enhancing stakeholder engagement. However, a knowledge gap exists in characterizing the extent to which DCEs are used in implementation science.

Methods

We conducted a systematic literature search (up to December 2016) of the English literature to identify and describe the use of DCEs in engaging stakeholders as an implementation strategy. We searched the following electronic databases: MEDLINE, Econlit, PsychINFO, and the CINAHL using mesh terms. Studies were categorized according to application type, stakeholder(s), healthcare setting, and implementation outcome.

Results

Seventy-five publications were selected for analysis in this systematic review. Studies were categorized by application type: (1) characterizing demand for therapies and treatment technologies (n?=?32), (2) comparing implementation strategies (n?=?22), (3) incentivizing workforce participation (n?=?11), and (4) prioritizing interventions (n?=?10). Stakeholders included providers (n?=?27), patients (n?=?25), caregivers (n?=?5), and administrators (n?=?2). The remaining studies (n?=?16) engaged multiple stakeholders (i.e., combination of patients, caregivers, providers, and/or administrators). The following implementation outcomes were discussed: acceptability (n?=?75), appropriateness (n?=?34), adoption (n?=?19), feasibility (n?=?16), and fidelity (n?=?3).

Conclusions

The number of DCE studies engaging stakeholders as an implementation strategy has been increasing over the past decade. As DCEs are more widely used as a healthcare assessment tool, there is a wide range of applications for them in stakeholder engagement. The DCE approach could serve as a tool for engaging stakeholders in implementation science.

     

Comparison of the Effect of Cognitive Rehabilitation and Neurofeedback on Sustained Attention Among Elementary School Students with Specific Learning Disorder: A Preliminary Randomized Controlled Clinical Trial

Specific learning disorder (SLD) can occur along with the problems of attention performance and be complicated by them. Recent studies have reported the positive effects of cognitive rehabilitation (CR) and neurofeedback (NFB) on sustained attention (SA) in SLD. Nevertheless, it has not yet been determinedwhat kind of treatment may be the most appropriate option for this disorder in terms of the different functions of cognitive status, especially SA. This preliminary study aimed to compare CR and NFB effects on SA among elementary school students with SLD using a randomized controlled clinical trial (RCT). Fifty- three eligible students with a DSM-5 SLD diagnosis, aged 7–10, were randomly allocated in NFB (n?=?18), CR (n?=?18), and control groups (n?=?17). All the participants were evaluated for SA by performing the continuous performance test (CPT) on the studied groups at the time of their inclusion in the study and 7 weeks after it. The intervention groups took part in 20 sessions of CR and 20 sessions of NFB. Conversely, the untreated group were evaluated without any intervention.15 boys and 30 girls in 3 groups completed the study (n?=?15 per group). The mean and standard deviation of participants’ age were (8.66?±?1.48) years, (8.40?±?1.73) years and (8.53?±?1.63) years in CR, NFB and untreated groups, respectively. The results showed significant differences between the groups based on the variables of the CPT test (p?<?0.05). Also, the significant effects of the variables represented the higher scores of the CR compared to the NFB group (p?<?0.001). This study provides einitial evidence that CR is more effective than NFB on SA improvement among students with SLD.     

Anomalous pinch in the T-11M tokamak in an enhanced-collisionality regime

The formation of a peaked bell-shaped profile of the electron density n _e (r) in the T-11M tokamak (B _t=1 T, R/a = 0.7/0.2 m, I _p = 100 kA, t _shot ≤ 300 ms, Li and C limiters) was observed in Li experiments carried out in the near-plateau collisionality regime (the collisionality parameter at one-half of the minor radius was v* ≥ 0.5) under the conditions of low hydrogen recycling and intense hydrogen influx from the plasma edge. It is well known that peaked n _e (r) profiles are observed in collisionless regimes at v* values as low as 10^?1–10^?2 or in impurity-contaminated discharges, in which this effect can be attributed to the impurity accumulation on the plasma column axis. Moreover, a bell-shaped n _e (r) profile in discharges with low n _e can result from the ionization of hydrogen atoms at the column axis, where they arrive from the plasma edge due to cascade charge-exchange. In quasi-steady lithium discharges in T-11M, however, peaked n _e (r) profiles were observed at a relatively high central electron density n _e (0) and relatively high collision frequency, such that the influence of impurities on the n _e (r) profile could be ignored (Z _eff = 1.1±0.1). To explain this effect, one has to assume that the pinching of hydrogen ions in T-11M is anomalous. The lower estimate of the observed pinch velocity is 4 ± 1 m/s, which is three to five times higher than the velocity of the neoclassical (Ware) pinch, characteristic of these conditions. The work is devoted to the experimental study of this effect.     

Effect of high-intensity interval training on muscle remodeling in rheumatoid arthritis compared to prediabetes

Background

Sarcopenic obesity, associated with greater risk of cardiovascular disease (CVD) and mortality in rheumatoid arthritis (RA), may be related to dysregulated muscle remodeling. To determine whether exercise training could improve remodeling, we measured changes in inter-relationships of plasma galectin-3, skeletal muscle cytokines, and muscle myostatin in patients with RA and prediabetes before and after a high-intensity interval training (HIIT) program.

Methods

Previously sedentary persons with either RA (n = 12) or prediabetes (n = 9) completed a 10-week supervised HIIT program. At baseline and after training, participants underwent body composition (Bod Pod^®) and cardiopulmonary exercise testing, plasma collection, and vastus lateralis biopsies. Plasma galectin-3, muscle cytokines, muscle interleukin-1 beta (mIL-1β), mIL-6, mIL-8, muscle tumor necrosis factor-alpha (mTNF-α), mIL-10, and muscle myostatin were measured via enzyme-linked immunosorbent assays. An independent cohort of patients with RA (n = 47) and age-, gender-, and body mass index (BMI)-matched non-RA controls (n = 23) were used for additional analyses of galectin-3 inter-relationships.

Results

Exercise training did not reduce mean concentration of galectin-3, muscle cytokines, or muscle myostatin in persons with either RA or prediabetes. However, training-induced alterations varied among individuals and were associated with cardiorespiratory fitness and body composition changes. Improved cardiorespiratory fitness (increased absolute peak maximal oxygen consumption, or VO₂) correlated with reductions in galectin-3 (r = ?0.57, P = 0.05 in RA; r = ?0.48, P = 0.23 in prediabetes). Training-induced improvements in body composition were related to reductions in muscle IL-6 and TNF-α (r < ?0.60 and P <0.05 for all). However, the association between increased lean mass and decreased muscle IL-6 association was stronger in prediabetes compared with RA (Fisher r-to-z P = 0.0004); in prediabetes but not RA, lean mass increases occurred in conjunction with reductions in muscle myostatin (r = ?0.92; P <0.05; Fisher r-to-z P = 0.026). Subjects who received TNF inhibitors (n = 4) or hydroxychloroquine (n = 4) did not improve body composition with exercise training.

Conclusion

Exercise responses in muscle myostatin, cytokines, and body composition were significantly greater in prediabetes than in RA, consistent with impaired muscle remodeling in RA. To maximize physiologic improvements with exercise training in RA, a better understanding is needed of skeletal muscle and physiologic responses to exercise training and their modulation by RA disease–specific features or pharmacologic agents or both.

Trial registration

ClinicalTrials.gov Identifier: NCT02528344. Registered on August 19, 2015.

     

Carriage of 2R allele at VNTR polymorphous site of <Emphasis Type="Italic">XRCC5</Emphasis> gene increases risk of multiple sclerosis in an Iranian population

The DNA damage has considerably raised in active MS lesions compared to normal brains, indicating the possible role of DNA repairing genes in MS. In the current study, we sought to highlight the association between genetic polymorphisms of XRCC5 and XRCC6 genes, involved in Double Strand Breaks (DSBs) repair, and MS susceptibility. A total of 235 Iranian individuals; including 113 MS patients and 122 healthy controls were participated in this study. They were genotyped for the XRCC5 VNTR polymorphism by polymerase chain reaction (PCR). The genotype analysis of the XRCC6–61C>G polymorphism was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The genotypic frequency of 2R/2R in the XRCC5 VNTR polymorphism was significantly higher in MS patients than controls (p = 0.048). The frequency of individuals with 2R allele was statistically significant in MS patients compared to controls (p = 0.041). Moreover, the frequency of 2R allele of the XRCC5 VNTR polymorphism was found to be significantly difference between MS patients and healthy groups (p = 0.003). The present study suggests that the presence of 2R allele in XRCC5 VNTR gene polymorphism may be a genetic risk factor for MS susceptibility in Iranian population.     

Implementation of the Tobacco Tactics intervention versus usual care in Trinity Health community hospitals

Background

Guided by the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) implementation framework, a National Institutes of Health-sponsored study compared the nurse-administered Tobacco Tactics intervention to usual care. A prior paper describes the effectiveness of the Tobacco Tactics intervention. This subsequent paper provides data describing the remaining constructs of the RE-AIM framework.

Methods

This pragmatic study used a mixed methods, quasi-experimental design in five Michigan community hospitals of which three received the nurse-administered Tobacco Tactics intervention and two received usual care. Nurses and patients were surveyed pre- and post-intervention.Measures included reach (patient participation rates, characteristics, and receipt of services), adoption (nurse participation rates and characteristics), implementation (pre-to post-training changes in nurses' attitudes, delivery of services, barriers to implementation, opinions about training, documentation of services, and numbers of volunteer follow-up phone calls), and maintenance (continuation of the intervention once the study ended).

Results

Reach: Patient participation rates were 71.5 %. Compared to no change in the control sites, there were significant pre- to post-intervention increases in self-reported receipt of print materials in the intervention hospitals (n?=?1370, p?<?0.001). Adoption: In the intervention hospitals, all targeted units and several non-targeted units participated; 76.0 % (n?=?1028) of targeted nurses and 317 additional staff participated in the training, and 92.4 % were extremely or somewhat satisfied with the training. Implementation: Nurses in the intervention hospitals reported increases in providing advice to quit, counseling, medications, handouts, and DVD (all p?<?0.05) and reported decreased barriers to implementing smoking cessation services (p?<?0.001). Qualitative comments were very positive (“user friendly,” “streamlined,” or “saves time”), although problems with showing patients the DVD and charting in the electronic medical record were noted. Maintenance: Nurses continued to provide the intervention after the study ended.

Conclusions

Given that nurses represent the largest group of front-line providers, this intervention, which meets Joint Commission guidelines for treating inpatient smokers, has the potential to have a wide reach and to decrease smoking, morbidity, and mortality among inpatient smokers. As we move toward more population-based interventions, the RE-AIM framework is a valuable guide for implementation.

Trial registration

ClinicalTrials.gov, NCT01309217

     

The Effect of Citrulline/Malate on Blood Lactate Levels in Intensive Exercise

The purpose of this study was to examine the effects of Citrulline/Malate supplementation with intensive training on blood lactate level in active handball players. The athletes were subjected to intense training for 4 weeks, 4 days a week, mainly pre-season strength and technique training. In this training period, stimol group (n = 11) athletes were given stimol 3 times a day as 1 g for breakfast, 1 g for lunch, and 1 g for dinner while the placebo group (n = 11) athletes were given only placebo in the same dosage and the same color at the same time. Blood lactate levels in athletes were measured 4 times, prior to and after a 1-month program as follows: rest (R), end effort (EE), recuperation 5 min (R5 m), and recuperation 20 min (R20 m). Blood lactate levels were compared both as intra-group and between the groups. In intra-group comparison, no change was observed in blood lactate levels in placebo group while a significant difference was found in the levels of stimol group as p < 0.05 with a 49.8% decrease in blood lactate level. In the measurements between groups, in the post-test measurements made after the training period, significant differences as p < 0.05 were found with a 60.7% decrease in blood lactate level EE. Considerable decline was seen especially immediately after exercise in blood lactate levels of the athletes being given stimol supplement. In this case, we can say that Citrulline/Malate supplementation may contribute positively to the performance of athletes and may help postpone fatigue at excessive or prolonged activity.     

On the cause of variability of the cosmic ray spectrum in the knee region

Cosmic ray (CR) energy spectra for H, He, Si, and Fe nuclei with energy-to-charge number ratios ?/Z in the range from 10 to 5 × 10⁷ GeV are studied using observational data obtained at different times in different energy ranges: AMS-02, CREAM, Tibet ASγ, Tibet (hybrid), GRAPES-3, KASCADE, and KASCADE-Grande. Comparison of the H and He CR fluxes according to the KASCADE and KASCADE-Grande data (for different models of deconvolving CR spectra) with the Tibet ASγ and Tibet (hybrid) data obtained at another time in the range of ?/Z ～ 3 × 10⁶ GeV demonstrates space weather-caused variability of the CR flux. This feature of CR energy spectra in the Tibet ASγ data is most clearly observed in the spectra of heavier nuclei (Si and Fe) according to the KASCADE-Grande and GRAPES-3 data. The variability in the energy spectra of all CRs in the vicinity of the “knee” is shown in the data of Yakutsk EAS, CASA-BLANCA, and Tibet-III experiments. The variability of the CR flux on a time scale on the order of several years exists only if the source corresponding to the peak in the energy spectrum is situated at a distance of no more than 1 pc from the Sun. Rapid surfatron acceleration of CRs may result from colliding interstellar clouds nearest to the Sun (LIC and G). This acceleration mechanism allows one to explain the variability of the CR spectrum in the range 10³ GeV < ?/Z < 10⁸ GeV. Conditions for the trapping of strongly relativistic Fe nuclei by an electromagnetic wave, the dynamics of the components of the particle velocity and momentum, and the dependence of the particle acceleration rate on the initial parameters of the problem are analyzed using numerical calculations. The structure of the phase plane of the accelerated Fe nuclei is examined. Optimal conditions for the implementation of ultrarelativistic surfatron acceleration of Fe nuclei by an electromagnetic wave are formulated.     

The spectrum of mutations in genes associated with resistance to rifampicin,isoniazid, and fluoroquinolones in the clinical strains of <Emphasis Type="Italic">M. tuberculosis</Emphasis> reflects the transmissibility of mutant clones

To study the transmissibility of drug resistant mutant clones, M. tuberculosis samples were isolated from the patients of the clinical department and the polyclinic of the Central TB Research Institute (n = 1455) for 2011–2014. A number of clones were phenotypically resistant to rifampicin (n = 829), isoniazid (n = 968), and fluoroquinolones (n = 220). We have detected 21 resistance-associated variants in eight codons of rpoB, six variants in three codons of katG, three variants in two positions of inhA, four variants in four positions of ahpC, and nine variants in five codons of gyrA, which were represented in the analyzed samples with varied frequencies. Most common mutations were rpoB 531 Ser→Leu (77.93%), katG 315 (Ser→Thr) (94.11%), and gyrA 94 (Asp→Gly) (45.45%). We found that the mutations at position 15 of inhA (C→T) (frequency of 25.72%) are commonly associated with katG 315 (Ser→Thr). This association of two DNA variants may arise due to the double selection by coexposure of M. tuberculosis to isoniazid and ethionamide. The high transmissibility of mutated strains was observed, which may be explained by the minimal influence of the resistance determinants on strain viability. The high transmissibility of resistant variants may also explain the large populational prevalence of drug-resistant TB strains.     

Predictors of relapse or maintenance of response in pediatric and adult patients with attention-deficit/hyperactivity disorder following discontinuation of long-term treatment with atomoxetine

We identified relapse/maintenance-of-response (MOR) predictors following discontinuation of long-term atomoxetine treatment in pediatric and adult patients with attention-deficit/hyperactivity disorder (ADHD) and assessed correlations between ADHD symptoms and quality of life (QoL). Post hoc analyses of data from two randomized, double-blind, placebo-controlled, phase 3 withdrawal studies in patients with ADHD meeting predefined response criteria before randomization. Study 1: patients (N = 163; 6–15 years) received atomoxetine (1.2–1.8 mg/kg/day) for 1 year, followed by randomization to atomoxetine (n = 81) or placebo (n = 82) for 6 months. Study 2: patients (N = 524; 18–50 years) received atomoxetine (80–100 mg/day) for ~6 months, followed by randomization to atomoxetine (n = 266) or placebo (n = 258) for ~6 months. Placebo patients were used for the analyses. Relapse: ≥50% worsening of prerandomization improvement in ADHD symptoms and ≥2 level severity increase on the Clinical Global Impression-Severity (CGI-S) scale at 2 consecutive visits; MOR: retaining ≥75% of prerandomization symptom improvement and CGI-S ≤ 2 at all visits (study 1); retaining ≥70% of prerandomization symptom improvement and CGI-S ≤ 3 at all visits (study 2). In adults, statistically significantly (P ≤ .05) increased likelihood of relapse was associated with prerandomization presence of Conners’ Adult Attention-Deficit/Hyperactivity Disorder Rating Scale-Investigator-Rated:Screening Version (CAARS-Inv:SV) items “difficulty awaiting turn” and “careless mistakes.” In pediatric patients, less MOR was associated with prerandomization presence of ADHD Rating Scale-IV-Parent Version Investigator-Rated item “does not listen”; in adults, less MOR was associated with prerandomization presence of CAARS-Inv:SV items “loses things” and “difficulty awaiting turn.” Changes in patients’ QoL after withdrawal from atomoxetine moderately correlated with changes in ADHD symptoms in pediatric patients and mildly in adults.     

Evaluation of the new TNM-staging system for thymic malignancies: impact on indication and survival

Background

The objective of this study is the evaluation of the Masaoka-Koga and the International Association for the Study of Lung Cancer (IASLC)/International Thymic Malignancy Interest Group (ITMIG) proposal for the new TNM-staging system on clinical implementation and prognosis of thymic malignancies.

Methods

A retrospective study of 76 patients who underwent surgery between January 2005 and December 2015 for thymoma. Kaplan–Meier survival analysis was used to determine overall and recurrence-free survival rates.

Results

Indication for surgery was primary mediastinal tumor (n =?55), pleural manifestation (n =?17), or mediastinal recurrence (n =?4) after surgery for thymoma. Early Masaoka-Koga stages I (n =?9) and II (n =?14) shifted to the new stage I (n =?23). Advanced stages III (Masaoka-Koga: n =?20; ITMIG/IASLC: n =?17) and IV (Masaoka-Koga: n =?33; ITMIG/IASLC: n =?35) remained nearly similar and were associated with higher levels of WHO stages. Within each staging system, the survival curves differed significantly with the best 5-year survival in early stages I and II (91%). Survival for stage IV (70 to 77%) was significantly better compared to stage III (49 to 54%). Early stages had a significant longer recurrence-free survival (86 to 90%) than advanced stages III and IV (55 to 56%).

Conclusions

The proportion of patients with IASLC/ITMIG stage I increased remarkably, whereas the distribution in advanced stages III and IV was nearly similar. The new TNM-staging system presents a clinically useful and applicable system, which can be used for indication, stage-adapted therapy, and prediction of prognosis for overall and recurrence-free survival.

     

Use of foreign genetic variability to improve the quality of wheat grain

Foreign genetic variability, which is represented by different wild-growing relatives of wheat such as Ae. umbellulata (UU, 2n = 14), Ae. cylindrica (CCDD, 2n = 28), Ae. tauschii (DD, 2n = 14), Ae. ventricosa (DDUnUn, 2n = 28), Ae. variabilis (UUSS, 2n = 28), and T. palmovae (AADD, 2n = 28) is used in interspecies crossings with the wheat cultivar T. aestivum for the purpose of transferring exotic Gli/Glu alleles into the genome of the crop. As a result, a series of new exotic Gli/Glu alleles is introgressed into the genome of wheat cultivar. An essential negative as well as positive influence of the wild exotic alleles on the baking quality indicators of the flour and the consistency of the wheat endosperm is discovered in the course of the study. The new genetic material with the improved grain quality indicators is recommended for use in wheat selection.     

The maize <Emphasis Type="Italic">brevis plant1</Emphasis> is a type II inositol polyphosphate 5-phosphatase

The genes associated with the dwarf phenotype have been utilized in crop breeding to prevent lodging and stem breakage. Brevis plant1 (Bv1), encoding a putative inositol polyphosphate 5-phosphatase (5PTase), has been associated with stem elongation in maize (Zea mays L.); however, the enzymatic activity of BV1 has not been experimentally characterized. In this study, the phosphatase activity of BV1 was verified with biochemical assays. BV1 demonstrated type II 5PTase activity capable of hydrolyzing both inositol polyphosphates and phosphoinositides. Similar to other type II 5PTases that share similar sequences and common domain architecture with BV1, the enzymatic activity of BV1 is sensitive to changes in Mg²⁺ and pH. 367G-R and 565S-L are two mutations in Bv1 that have been associated with the dwarfing phenotype in maize. To characterize the dwarfing mechanism, mutant BV1 proteins were expressed in vitro and assayed for phosphatase activity. The results showed that both mutations significantly reduced the enzymatic activity of BV1, but neither altered its substrate specificity and dependence on Mg²⁺ and pH. This biochemical verification of BV1 as a type II 5PTase is important as it sheds light on the molecular basis of deficient BV1-mediated dwarfing phenotype.     

Comparative cytomolecular analyses reveal karyotype variability related to biogeographic and species richness patterns in Bombacoideae (Malvaceae)

Bombacoideae is one out of nine subfamilies of Malvaceae and encompasses 160 tree species. The subfamily is karyotypically characterized by small and numerous chromosomes and is traditionally known by a remarkable inter- and intraspecific chromosome number variation. We conducted a comparative cytogenetic analysis to investigate karyotype diversity and chromosome evolution within Bombacoideae. To achieve this, we performed new chromosome counts, CMA/DAPI double staining, genome size estimations, and localization of 5S and 45S rDNA by fluorescence in situ hybridization for 21 species distributed across the Bombacoideae phylogeny. We performed ancestral states reconstruction analyses to elucidate chromosome evolution and provide insights into the systematics and evolution of Bombacoideae in comparison with other Malvaceae species. Newly generated data on chromosome number on Bombacoideae revealed diploids (Ochroma (2n = 84), Cavanillesia, Pochota, Pseudobombax (2n = 88), and Pachira (2n = 92)) and polyploids (Adansonia digitata (2n = 160) and Eriotheca species (2n = ca. 194 and 2n = 276)). For most species, in situ hybridization revealed karyotype, with two pairs of 45S rDNA sites co-located with CMA⁺ bands, and 5S rDNA sites in only one chromosome pair. Taken together, our results provide support to the hypothesis of karyotypic stability in Bombacoideae. Only the Pachira s.l. clade displayed some variability in ploidy level, number of CMA⁺ bands and 45S rDNA sites, and genome size compared to other Bombacoideae clades. The Striated bark clade was characterized by comparatively small genomes and low cytomolecular variability. Karyotypic data were related to biogeographic and species richness patterns of Bombacoideae.