Tracking the adoption of bread wheat varieties in Afghanistan using DNA fingerprinting.

BACKGROUND: Wheat is the most important staple crop in Afghanistan and accounts for the main part of cereal production. However, wheat production has been unstable during the last decades and the country depends on seed imports. Wheat research in Afghanistan has emphasized releases of new, high-yielding and disease resistant varieties but rates of adoption of improved varieties are uncertain. We applied DNA fingerprinting to assess wheat varieties grown in farmers' fields in four Afghan provinces. RESULTS: Of 560 samples collected from farmers' fields during the 2015-16 cropping season, 74% were identified as varieties released after 2000, which was more than the number reported by farmers and indicates the general prevalence of use of improved varieties, albeit unknowingly. At the same time, we found that local varieties and landraces have been replaced and were grown by 4% fewer farmers than previously reported. In 309 cases (58.5%), farmers correctly identified the variety they were growing, while in 219 cases (41.5%) farmers did not. We also established a reference library of released varieties, elite breeding lines, and Afghan landraces, which confirms the greater genetic diversity of the landraces and their potential importance as a genetic resource. CONCLUSIONS: Our study is the first in wheat to apply DNA fingerprinting at scale for an accurate assessment of wheat varietal adoption and our findings point up the importance of DNA fingerprinting for accuracy in varietal adoption studies.

Genetic mitigation strategies to tackle agricultural GHG emissions: The case for biological nitrification inhibition technology.

Accelerated soil-nitrifier activity and rapid nitrification are the cause of declining nitrogen-use efficiency (NUE) and enhanced nitrous oxide (N2O) emissions from farming. Biological nitrification inhibition (BNI) is the ability of certain plant roots to suppress soil-nitrifier activity, through production and release of nitrification inhibitors. The power of phytochemicals with BNI-function needs to be harnessed to control soil-nitrifier activity and improve nitrogen-cycling in agricultural systems. Transformative biological technologies designed for genetic mitigation are needed, so that BNI-enabled crop-livestock and cropping systems can rein in soil-nitrifier activity, to help reduce greenhouse gas (GHG) emissions and globally make farming nitrogen efficient and less harmful to environment. This will reinforce the adaptation or mitigation impact of other climate-smart agriculture technologies.

Justifying Nonstandard Exception Requests for Pediatric Liver Transplant Candidates: An Analysis of Narratives Submitted to the United Network for Organ Sharing, 2009-2014.

Nonstandard exception requests (NSERs), for which transplant centers provide patient-specific narratives to support a higher Model for End-stage Liver Disease/Pediatric End-stage Liver Disease score, are made for >30% of pediatric liver transplant candidates. We describe the justifications used in pediatric NSER narratives 2009-2014 and identify justifications associated with NSER denial, waitlist mortality, and transplant. Using United Network for Organ Sharing data, 1272 NSER narratives from 1138 children with NSERs were coded for analysis. The most common NSER justifications were failure-to-thrive (48%) and risk of death (40%); both associated with approval. Varices, involvement of another organ, impaired quality of life, and encephalopathy were justifications used more often in denied NSERs. Of the 25 most prevalent justifications, 60% were not associated with approval or denial. Waitlist mortality risk was increased when fluid overload or "posttransplant complication outside standard criteria" were cited and decreased when liver-related infection was noted. Transplant probability was increased when the narrative mentioned liver-related infections, and fluid overload for children <2 years old; it decreased when "posttransplant complications outside standard criteria" and primary sclerosing cholangitis were cited. This analysis provides novel insight and suggests targets for future consideration in outcomes research and exception criteria. Changes in the allocation system are needed to ensure equity and optimize outcomes for all pediatric candidates.

Nonstandard Exception Requests Impact Outcomes for Pediatric Liver Transplant Candidates.

Nonstandard exceptions requests (NSERs), in which transplant centers appeal on a case-by-case basis for Pediatric End-Stage Liver Disease/Mayo End-Stage Liver Disease points, have been highly utilized for pediatric liver transplant candidates. We evaluated whether NSE outcomes are associated with waitlist and posttransplant mortality. United Network for Organ Sharing (UNOS) Scientific Registry of Transplant Recipients data on pediatric liver transplant candidates listed in 2009-2014 were analyzed after excluding those granted automatic UNOS exceptions. Of 2581 pediatric waitlist candidates, 44% had an NSE request. Of the 1134 children with NSERs, 93% were approved and 7% were denied. For children 2-18 years at listing, NSER denial increased the risk of waitlist mortality or removal for being too sick (subhazard ratio 2.99, 95% confidence interval [CI] 1.26-7.07, p = 0.01 in multivariate analysis). For children younger than 2 years, NSER denial did not impact waitlist mortality/removal. Children with NSER approved had reduced risk of graft loss 3 years posttransplant in univariate but not multivariable analysis (odds ratio 0.73, 95% CI 0.53-1.01, p = 06). Those with NSER denial had a higher risk of posttransplant death than those with no NSER (hazard ratio 2.43, 95% CI 0.99-5.95, p = 0.05, multivariable analysis), but NSER approval did not impact posttransplant death. Further research on NSER utilization in pediatric liver transplant is needed to optimize organ allocation and outcomes for children.

The effect of resveratrol on normal and osteoarthritic chondrocyte metabolism.

BACKGROUND: Resveratrol is a polyphenolic compound commonly found in the skins of red grapes. Sirtuin 1 (SIRT1) is a human gene that is activated by resveratrol and has been shown to promote longevity and boost mitochondrial metabolism. We examined the effect of resveratrol on normal and osteoarthritic (OA) human chondrocytes. METHODS: Normal and OA chondrocytes were incubated with various concentrations of resveratrol (1 µM, 10 µM, 25 µM and 50 µM) and cultured for 24, 48 or 72 hours or for six weeks. Cell proliferation, gene expression, and senescence were evaluated. RESULTS: SIRT1 was significantly upregulated in normal chondrocytes with resveratrol concentrations of 25 µM and 50 µM on both two- (2D) (both p = 0.001) and three-dimensional (3D) cultures (p = 0.008 and 0.001, respectively). It was significantly upregulated in OA chondrocytes treated with 10 µM, 25 µM and 50 µM resveratrol on 2D cultures (p = 0.036, 0.002 and 0.001, respectively) and at 50 µM concentration on 3D cultures (p = 0.001). At 72 hours, the expression of collagen (COL)-10, aggrecan (AGG), and runt-related transcription factor 2 (RUNX2) was significantly greater in both 25 µM (p = 0.011, 0.006 and 0.015, respectively) and 50 µM (p = 0.019, 0.004 and 0.002, respectively) resveratrol-treated normal chondrocyte cultures. In OA chondrocytes, expression of COL10 and RUNX2 was significantly greater in 25 µM (p = 0.004 and 0.024) and 50 µM (p = 0.004 and 0.019) cultures at 72 hours on 3D cultures. CONCLUSIONS: At concentrations of 25 µM and/or 50 µM, resveratrol treatment significantly upregulates SIRT1 gene expression in normal and osteoarthritic chondrocytes. Resveratrol induces chondrocytes into a hypertrophic state through upregulation of COL1, COL10, and RUNX2. Cite this article: Bone Joint Res 2014;3:51-9.

Phytosiderophore release in Aegilops tauschii and Triticum species under zinc and iron deficiencies.

Using three diploid (Triticum monococcum, AA), three tetraploid (Triticum turgidum, BBAA), two hexaploid (Triticum aestivum and Triticum compactum, BBAADD) wheats and two Aegilops tauschii (DD) genotypes, experiments were carried out under controlled environmental conditions in nutrient solution (i) to study the relationships between the rates of phytosiderophore (PS) release from the roots and the tolerance of diploid, tetraploid, and hexaploid wheats and AE: tauschii to zinc (Zn) and iron (Fe) deficiencies, and (ii) to assess the role of different genomes in PS release from roots under different regimes of Zn and Fe supply. Phytosiderophores released from roots were determined both by measurement of Cu mobilized from a Cu-loaded resin and identification by using HPLC analysis. Compared to tetraploid wheats, diploid and hexaploid wheats were less affected by Zn deficiency as judged from the severity of leaf symptoms. Aegilops tauschii showed very slight Zn deficiency symptoms possibly due to its slower growth rate. Under Fe-deficient conditions, all wheat genotypes used were similarly chlorotic; however, development of chlorosis was first observed in tetraploid wheats. Correlation between PS release rate determined by Cu-mobilization test and HPLC analysis was highly significant. According to HPLC analysis, all genotypes of Triticum and AE: tauschii species released only one PS, 2'-deoxymugineic acid, both under Fe and Zn deficiency. Under Zn deficiency, rates of PS release in tetraploid wheats averaged 1 micromol x (30 plants)(-1) x (3 h)(-1), while in hexaploid wheats rate of PS release was around 14 micromol x (30 plants)(-1) x (3 h)(-1). Diploid wheats and AE: tauschii accessions behaved similarly in their capacity to release PS and intermediate between tetraploid and hexaploid wheats regarding the PS release capacity. All Triticum and Aegilops species released more PS under Fe than Zn deficiency, particularly when the rate of PS release was expressed per unit dry weight of roots. On average, the rates of PS release under Fe deficiency were 3.0, 5.7, 8.4, and 16 micromol x (30 plants)(-1) x (3 h)(-1) for AE: tauschii, diploid, tetraploid and hexaploid wheats, respectively. The results of the present study show that the PS release mechanism in wheat is expressed effectively when three genomes, A, B and D, come together, indicating complementary action of the corresponding genes from A, B and D genomes to activate biosynthesis and release of PS.

Measurements of blood pressure with various techniques in daily practice: uncertainty in diagnosing office hypertension with short-term in-hospital registration of blood pressure.

OBJECTIVE: To predict blood pressure outside the clinic from a short-term in-hospital registration for patients referred for ambulatory blood pressure monitoring (ABPM) with special attention to office hypertension. PATIENTS AND METHODS: A series of measurements of blood pressure was performed by the same technician for 187 patients, 82% of whom were being administered antihypertensive therapy. She performed three mercury measurements of blood pressure (Hg stress 1) and then three manually started measurements with a semi-automatic device (Dinamap 1846SX; Dinamap stress) alternated with three manually started readings with a SpaceLabs 90207 monitor (SpaceLabs stress) on the contralateral non-dominant arm. The in-hospital session was continued with 15 automatic Dinamap registrations at 2 min intervals without the technician being present (Dinamap unstressed, five periods of three measurements averaged) before the patient left the hospital for 24h ABPM. RESULTS: The percentages of patients with hypertension in the office (systolic blood pressure >/= 140 mmHg or diastolic blood pressure >/= 90 mmHg, or both) were 80% with Hg stress 1, 76% with Dinamap stress and 85.0% with SpaceLabs stress. Average diastolic SpaceLabs stress was 6.0+/-5.6 mmHg (significantly) higher than diastolic Dinamap stress, whereas the difference between systolic blood pressures was 0.2+/-10.0 mmHg. No further change in blood pressure occurred after the fourth period of Dinamap unstressed measurements. Office hypertension defined as SpaceLabs stress systolic blood pressure >/= 140 mmHg or diastolic blood pressure >/= 90 mmHg, or both, and SpaceLabs daytime systolic blood pressure < 135 mmHg and diastolic blood pressure < 85 mmHg was found in 21 individuals. Office hypertension defined with similar cut-off points in the comparison of Dinamap stress versus Dinamap unstressed period 5 was found in 29 cases, 10 of which overlapped with the definition SpaceLabs stress versus SpaceLabs daytime. The differences between Dinamap stress and Dinamap unstressed period 5 were significantly correlated to the changes of SpaceLabs stress and SpaceLabs daytime both for systolic (r =0.41) and for diastolic (r =0.32) blood pressures. CONCLUSIONS: Measurements of blood pressure in the office with various techniques (mercury, Dinamap and SpaceLabs) are not equivalent. Office hypertension cannot be reliably predicted from a short-term semi-automatic in-hospital registration of blood pressure with a Dinamap device.

Feasibility, endocrine and anti-tumour effects of a triple endocrine therapy with tamoxifen, a somatostatin analogue and an antiprolactin in post-menopausal metastatic breast cancer: a randomized study with long-term follow-up.

Suppression of the secretion of prolactin, growth hormone and insulin-like growth factor 1 (IGF-1) might be important in the growth regulation and treatment of breast cancer. Because oestrogens may counteract the anti-tumour effects of such treatment, the combination of an anti-oestrogen (tamoxifen), a somatostatin analogue (octreotide) and a potent anti-prolactin (CV 205-502) might be attractive. In this respect, we performed a first exploratory long-term study on the feasibility of combined treatment and possible clear differences in endocrine and anti-tumour effects during such combined treatment vs standard treatment with tamoxifen alone. Twenty-two post-menopausal patients with metastatic breast cancer (ER and/or PR positive or unknown) were randomized to receive either 40 mg of tamoxifen per day or the combination of 40 mg of tamoxifen plus 75 microg of CV 205-502 orally plus 3 x 0.2 mg of octreotide s.c. as first-line endocrine therapy. An objective response was found in 36% of the patients treated with tamoxifen alone and in 55% of the patients treated with combination therapy. Median time to progression was 33 weeks for patients treated with tamoxifen and 84 weeks for patients treated with combination therapy, but the numbers are too small for hard conclusions. There was no difference in overall post-relapse survival between the two treatment arms. With respect to the endocrine parameters, there was a significant decrease of plasma IGF-1 levels in both treatment arms, whereas during combined treatment plasma growth hormone tended to decrease and plasma prolactin levels were strongly suppressed; in some patients insulin and transforming growth factor alpha (TGF-alpha) decreased during the triple therapy. Although there was no significant difference in mean decrease of plasma IGF-1 levels between the two treatment arms, combined treatment resulted in a more uniform suppression of IGF-1. Therefore, the addition of a somatostatin analogue and an anti-prolactin may potentially enhance the efficacy of anti-oestrogens in the treatment of breast cancer owing to favourable endocrine and possible direct anti-tumour effects. Large phase III trials using depot formulations (to increase the feasibility) of somatostatin analogues are warranted to demonstrate the potential extra beneficial anti-tumour effects of such combination therapy.

Pyridinium cross-links in multiple myeloma: correlation with clinical parameters and use for monitoring of intravenous clodronate therapy--a pilot study of the German Myeloma Treatment Group (GMTG).

The relevance of quantitative determinations of urinary deoxypyridinolines (DPY) and pyridinolines (PY), and of serum type I collagen carboxyterminal cross-linked telopeptides (ICTP), has been evaluated for patient monitoring in multiple myeloma (MM). In 178 untreated MM patients, a clear correlation was found between ICTP concentrations, bone destructions and serum calcium levels. Furthermore, serum ICTP, urinary DPY and PY concentrations were estimated before and during treatment in a further 33 MM patients randomly allocated to four groups receiving intravenous melphalan/prednisone (MivP) chemotherapy alone, or MivP in combination with three different doses of i.v. clodronate. 1800 mg of i.v. clodronate combined monthly with MivP induced a rapid and sustained reduction in bone resorption parameters to the normal range, a result not obtained with either MivP alone, or with a lower clodronate dose. While confirming the relevance of determining pyridinium cross-links for estimating bone resorption in MM, our data indicate that measurements of these parameters could be useful for dose finding and monitoring of bisphosphonate therapy.

A comparison of polychemotherapy and melphalan/prednisone for primary remission induction, and interferon-alpha for maintenance treatment, in multiple myeloma. A prospective trial of the German Myeloma Treatment Group.

406 untreated multiple myeloma patients of stage I (n = 54), II (n = 148) and III (n = 204) were enrolled in the trial. 51/54 stage I and 60/148 stage II patients were asymptomatic and followed without treatment until disease progression (progression free survival: 60% after 4 years for stage I versus 50% after 1 year for stage II). Symptomatic patients of stage I (n = 3/54) and II (n = 88/148) presenting with tumour progression, received melphalan 15 mg/m2 intravenously (i.v.) and prednisone 60 mg/m2 oral days 1-4 (MP). Stage II disease remission rate was 59%, and 50% tumour related survival (TRS) was 59 months. Stage III patients were randomised to receive MP or VBAMDex (vincristine/BCNU/doxorubicin/melphalan/dexamethasone) treatment. 43% of MP treated patients responded compared with 64% of the VBAMDex group. 50% TRS was 36 months in both groups without a detectable difference. 117 responders of stage II and III with stable disease were randomised to receive either IFN-alpha (5 x 10(6) IU, subcutaneous (S.C.) 3 times per week) or no maintenance treatment. The relapse rate in both groups was 50% after 13 months. No survival benefit for IFN alpha treated patients was observed (50% TRS: 45 months).

Melphalan and prednisone (MP) versus vincristine, BCNU, adriamycin, melphalan and dexamethasone (VBAM Dex) induction chemotherapy and interferon maintenance treatment in multiple myeloma. Current results of a multicenter trial. The German Myeloma Treatment Group.

277 untreated multiple myeloma patients of stage 1 (n = 33), II (n = 106) and III (n = 138) entered the study. Patients of stage II presenting a progressive tumor (n = 64) initially or during observation (n = 14) were treated with MivP (remissions: 61%). 138 patients of stage III were randomized to receive MivP or VBAMDex treatment. 51% of MivP treated patients responded versus 70% of the VBAMDex group. 71 responders of stage II and III with stable disease were randomized on Ifn-alpha maintenance versus no maintenance treatment. The relapse rate in both groups was 50% after 7 months. 75% survival was greater than 36 months in stage II and 11 months in stage III patients.

Presynaptic alpha-2 adrenoceptor activation and coupling of the receptor-presynaptic effector system in the perfused rat heart: affinity and efficacy of phenethylamines and imidazoline derivatives.

The right sympathetic nerves of perfused rat hearts were stimulated in the presence of inhibitors of neuronal and extraneuronal uptake and propranolol. The inhibition by alpha adrenoceptor agonists of stimulation-evoked (10 pulses, 0.1 Hz) [3H]norepinephrine (NE) overflow into the perfusate was taken as a parameter of presynaptic adrenoceptor activation. Under the present conditions, autoinhibition of NE release is not activated by endogenous NE as evident from ineffectiveness of adrenoceptor antagonists in facilitating evoked [3H]NE overflow. The potency (EC50, -log10), affinity (agonist-presynaptic receptor dissociation constant KA, -log10) and relative efficacies (RE) were determined for phenethylamines (NE or alpha-methylepinephrine) and for imidazoline derivatives. NE (-log EC50, 7.76) was 0.88 log units more potent than alpha-methylepinephrine (-log EC50, 6.88) and about the same difference was observed for the -log KA values (5.92 vs. 4.75). RE were similar (NE, 100%; alpha methylepinephrine, 98%) and 22- to 50-fold higher than efficacies of imidazoline derivatives. Hydroxylations in positions 3 and 4 of the phenyl moiety of phenylaminoimidazoline (-log EC50, less than 5; -log KA, less than 5; RE, less than 1%) resulted in a marked increase in potency (-log EC50, 8.32) of the resulting dihydroxyphenylaminoimidazoline due to a high affinity (-log KA, 8.22) at a low efficacy (2% of NE). In contrast, hydroxylation in positions 3 and 4 of the phenyl ring of tolazoline (no agonist activity under the present conditions; antagonist affinity constant from the literature, 6.4-6.6) produced dihydroxytolazoline, a moderately potent agonist (-log EC50, 7.25) with an efficacy of 3.5% at an affinity (-log KA, 6.92) not much different from that of tolazine.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium and glucose uptake in rat small intestinal brush-border membrane vesicles. Modulation by exogenous hypercortisolism and 1,25-dihydroxyvitamin D-3.

The effect of exogenous hypercortisolism and 1,25-dihydroxyvitamin D-3 on small-intestinal calcium and glucose transport in the rat was studied at the level of brush-border membrane vesicles generated from isolated villous cells by a freeze-thaw procedure. At 5 X 10(-5) M extravesicular calcium, initial uptake rates in vesicles prepared from triamcinolone-treated adult rats were decreased by 30% after 5 days. Since calcium ionophore A23187 virtually abolished the difference in calcium uptake, triamcinolone appeared to affect calcium channel density or activity rather than intravesicular binding capacity. Kinetic analysis showed that a decrease in Vmax of a saturable calcium transport system could entirely account for the diminished rate of vesicular calcium uptake. Calcium transport rates could be partially restored by in vivo administration of 1,25-dihydroxyvitamin D-3 at a dosage which did not affect vesicular calcium uptake in control animals. Conversely, sodium-driven glucose accumulation in brush-border vesicles from triamcinolone-treated rats was stimulated by 50-70% after 36 h and appeared insensitive to vitamin D. A specific triamcinolone action on the glucose carrier itself rather than on the driving force of the sodium gradient was indicated by (i) a similar stimulation of glucose transport under equilibrium exchange conditions and (ii) an opposite effect of triamcinolone on sodium-driven alanine transport. The triamcinolone-induced changes in calcium and glucose uptake were not accompanied by a gross alteration of membrane integrity in vitro or by major alterations in vesicular protein composition, intravesicular glucose space and sucrase or alkaline phosphatase activity. The modification of vesicular transport properties is discussed in relation to the vitamin D-antagonized inhibition of intestinal calcium uptake and the stimulation of glucose absorption in response to supraphysiologic amounts of glucocorticoids observed in intact epithelium.

[Primary amyloidosis presenting as intrahepatic cholestasis (author's transl)]. / Intrahepatische Cholestase als Leitsymptom einer primären Amyloidose

In a 37-year-old female patient with marked signs of cholestasis and excessive hyperbilirubinaemia without any recognisable cause, the unexpected diagnosis of massive amyloidosis of the peri-collagenous and perireticular type was made after hepatic needle biopsy. There were also amyloid deposits in the rectal mucosa and in the bone marrow. Fifteen months after the onset of disease symptoms the patient died from the consequences of spontaneous intrahepatic haemorrhage. At the post-mortem investigation generalised amyloidosis with massive involvement of nearly all organs was found. Primary amyloidosis should be considered in the differential diagnosis of any aetiologically unexplained cholestasis.

[Hairy cell leukaemia. I. Clinical features, cytochemistry, phagocytosis, establishment of permanent growing cell lines (author's transl)]. / Haarzell-Leukämie. I. Klinik, Zytochemie, Phagozytosefähigkeit von Haarzellen, Etablierung permanent wachsender Zellinien

In seven patients the diagnosis of hair cell leukaemia (leukaemic reticuloendotheliosis) was confirmed cytochemically and histologically. Splenectomy, in six patients, apparently favourably influenced the course. Isoenzyme 5 of the acid phosphatase was demonstrated in the hairy cells of all patients. Reaction of alpha-naphthylacetate esterase was moderately positive in the hairy cells. Phagocytosis of latex and India-ink particles was demonstrated especially in tartrate-resistant cells of one patient. In two patients eight permanently growing cell lines were demonstrated from leucocytes and defined cytochemically. Capacity for phagocytosis of hairy cells and positive reaction of alpha-naphthylacetate esterase in the hairy cells suggest properties of monocytes. But it is not possible definitively to classify the hairy cells among B-cells or monocytes.