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Premise: A probe set was previously designed to target 384 nuclear loci in the Melastomataceae family; however, when trying to use it, we encountered several practical and conceptual problems, such as the presence of sequences in reverse complement, intronic regions with stop codons, and other issues. This raised concerns regarding the use of this probe set for sequence recovery in Melastomataceae. Methods: In order to correct these issues, we cleaned the Melastomataceae probe set, extended it with additional sequences, and compared its performance with the original version. Results: The final probe set targets 396 putative nuclear loci represented by 6009 template sequences. The probe set has been made available, along with details on the cleaning process, for reproducibility. We show that the new probe set performs better than the original version in terms of sequence recovery. Discussion: This updated, extended, and cleaned probe set will improve the availability of phylogenomic resources across the Melastomataceae family. It is fully compatible with sequence recovery and extraction pipelines. The cleaning process can also be applied to any plant‐targeting probe set that would need to be cleaned or updated if new genomic resources for the targeted taxa become available. [ABSTRACT FROM AUTHOR]

The interrelationships of the extant crocodylians Gavialis gangeticus and Tomistoma schlegelii have been historically disputed. Whereas molecular analyses indicate a sister taxon relationship between these two gavialoid species, morphological datasets typically place Gavialis as the outgroup to all other extant crocodylians. Recent morphological‐based phylogenetic analyses have begun to resolve this discrepancy, recovering Gavialis as the closest living relative of Tomistoma; however, several stratigraphically early fossil taxa are recovered as closer to Gavialis than Tomistoma, resulting in anomalously early divergence timings. As such, additional morphological data might be required to resolve these remaining discrepancies. 'Tomistoma' dowsoni is an extinct species of gavialoid from the Miocene of North Africa. Utilising CT scans of a near‐complete, referred skull, we reconstruct the neuroanatomy and neurosensory apparatus of 'Tomistoma' dowsoni. Based on qualitative and quantitative morphometric comparisons with other crocodyliforms, the neuroanatomy of 'Tomistoma' dowsoni is characterised by an intermediate morphology between the two extant gavialoids, more closely resembling Gavialis. This mirrors the results of recent studies based on the external anatomy of these three species and other fossil gavialoids. Several neuroanatomical features of these species appear to reflect ecological and/or phylogenetic signals. For example, the 'simple' morphology of their neurosensory apparatus is broadly similar to that of other long and narrow‐snouted (longirostrine), aquatic crocodyliforms. A dorsoventrally short, anteroposteriorly long endosseous labyrinth is also associated with longirostry. These features indicate that snout and skull morphology, which are themselves partly constrained by ecology, exert an influence on neuroanatomical morphology, as has also been recognised in birds and turtles. Conversely, the presence of a pterygoid bulla in Gavialis and several extinct gavialoids, and its absence in Tomistoma schlegelii, could be interpreted as a phylogenetic signal of crocodylians more closely related to Gavialis than to Tomistoma. Evaluation of additional fossil gavialoids will be needed to further test whether these and other neuroanatomical features primarily reflect a phylogenetic or ecological signal. By incorporating such previously inaccessible information of extinct and extant gavialoids into phylogenetic and macroecological studies, we can potentially further constrain the clade's interrelationships, as well as evaluate the timing and ecological association of the evolution of these neuroanatomical features. Finally, our study supports recent phylogenetic analyses that place 'Tomistoma' dowsoni as being phylogenetically closer to Gavialis gangeticus than to Tomistoma schlegelii, indicating the necessity of a taxonomic revision of this fossil species. [ABSTRACT FROM AUTHOR]

Wildfires have increased in frequency in many ecosystems, with implications for human health and the environment, including water quality. Increased fire frequency and urbanization also raise the prospect of fires burning into urban areas, mobilizing pollutants few have considered to date. As a result, water quality managers lack information to anticipate, respond to and potentially mitigate wildfire impacts. Here, we reviewed the scientific literature to assess wildfire effects on response endpoints of a conceptual model linking fire to water quality, quantifying response directionality, magnitude and duration. Physically, water yield, sediments, and temperature all increased post‐fire. Chemically, nutrients, ions, organic chemicals, and metals increased in burned watersheds, sometimes by orders of magnitude over pre‐fire or reference conditions. In select cases, post‐fire concentrations exceeded aquatic life criteria or drinking water standards, at times even in the finished drinking water. Biological assemblages commonly declined after post‐fire runoff events. The duration of effects was less than 5 yr for most endpoints (e.g., metals) on average following fire, although effects did extend 15 yr or more in some individual cases. We found only a few studies on pollutants mobilized from wildfire impacted urban areas with benzene contamination in drinking water and high metal concentrations in ash prominent exceptions. Overall, this review provides a resource for understanding wildfire impacts on water quality endpoints, with the goal of informing the response of managers and other decision makers to this growing problem. Plain Language Summary: Wildfires are increasing in frequency due in part to climate change, and the pollutants mobilized during and after fire threaten water quality. Water quality managers should be aware of these threats so they can plan for and respond to them. We reviewed the scientific literature on wildfire effects on water quality. Streamflow typically increases following wildfire, as do sediments and temperature. Nutrients, ions, metals, and certain organic chemicals often increase as well, sometimes 10–100 times or more above reference levels. Some post‐fire chemicals can exceed regulatory limits, even in finished drinking water (e.g., arsenic). Wildfire also commonly affects biological assemblages. Most impacts last less than 5 yr, although they can be much longer. Unfortunately, only a few studies measured pollutants from urban areas impacted by wildfire. This is a major knowledge gap since these events are likely becoming more common, can mobilize pollutants from built materials and may impact many water uses. Finally, our paper describes the implications for water quality programs, such as drinking water, water quality standards, assessment, restoration and non‐point source programs. We hope water quality managers and communities can use this information to better respond to this growing problem. Key Points: Post‐fire increases in many water quality pollutants exceeded pre‐fire levels, often by multiple orders of magnitudeNitrate, some metals, benzene, and disinfection by‐products exceeded regulatory levels in treated drinking water following some wildfiresLittle is known about pollutants from fires burning infrastructure and materials (e.g., houses, cars) within the wildland urban interface [ABSTRACT FROM AUTHOR]

Background: We aim to analyze the clinicopathological profile and outcomes of management for children with papillary thyroid carcinoma (PTC). Methods: Relevant clinical data of children ≤ 18 years of age managed for PTC between January 2006 and July 2018 as well as details of their follow-up till December 2019 were retrospectively collected and analyzed. Results: There were 82 children with PTC that were managed during the study period. At presentation, 39 (47.6%) had cervical lymphadenopathy, while 9 (11%) had systemic metastasis. Majority of patients 39 (47.6%) underwent total thyroidectomy with a selective neck dissection, while total thyroidectomy alone was performed in 26 (31.7%). Following surgery, hypocalcemia was seen in 39 (47.6%): 28 (34.1%) were temporary, while 11 (13.4%) were permanent. Twenty-eight (34%) developed persistent disease after surgery and 131I therapy. Significant risk factors for persistence and metastatic disease were metastatic cervical lymph node at presentation (p = 0.002) and tumor size (p = 0.014), respectively. The mean duration of follow-up was 60.3 (range 12–150) months with a mean overall disease-free survival of 60 months (95% CI 57.11, 77.95). Conclusion: Children with papillary thyroid cancers present with aggressive disease, 47.6% with cervical nodal metastasis and 11% with distant metastasis in this cohort. The rate of post-thyroidectomy hypocalcemia in this study is substantial, and efforts to reduce it are actively being pursued. The presence of metastatic cervical lymph node at presentation (p = 0.002) and tumor size (p = 0.014) were the only significant risk factors for persistent and metastatic disease, respectively, in this study. [ABSTRACT FROM AUTHOR]

Summary: Determining where species diversify (cradles) and persist (museums) over evolutionary time is fundamental to understanding the distribution of biodiversity and for conservation prioritization. Here, we identify cradles and museums of angiosperm generic diversity across tropical Africa, one of the most biodiverse regions on Earth.Regions containing nonrandom concentrations of young (neo‐) and old (paleo‐) endemic taxa were identified using distribution data of 1719 genera combined with a newly generated time‐calibrated mega‐phylogenetic tree. We then compared the identified regions with the current network of African protected areas (PAs).At the generic level, phylogenetic diversity and endemism are mainly concentrated in the biogeographically complex region of Eastern Africa. We show that mountainous areas are centres of both neo‐ and paleo‐endemism. By contrast, the Guineo‐Congolian lowland rain forest region is characterized by widespread and old lineages. We found that the overlap between centres of phylogenetic endemism and PAs is high (> 85%).We show the vital role played by mountains acting simultaneously as cradles and museums of tropical African plant biodiversity. By contrast, lowland rainforests act mainly as museums for generic diversity. Our study shows that incorporating large‐scale taxonomically verified distribution datasets and mega‐phylogenies lead to an improved understanding of tropical plant biodiversity evolution. [ABSTRACT FROM AUTHOR]

Frozen section analysis ( FS) during cancer surgery is widely used to assess resection margins. However, in hilar cholangiocarcinoma ( HCCA), FS may be less reliable because of the specific growth characteristics of the tumor. The aim of this study was to determine the accuracy and consequences of intraoperative FS of the proximal bile duct margins in HCCA. Between 1990 and 2014, 67 patients underwent combined extrahepatic bile duct resection and partial liver resection for HCCA with the use of FS. Sensitivity and specificity of FS was 68% and 97%, respectively. Seventeen of 67 patients (25%) displayed a positive bile duct margin at FS. The false-negative rate was 16% (eight patients). Ten patients (15%) with a positive bile duct margin underwent an additional resection in an attempt to achieve negative margins, which succeeded in three patients (4%). However, only one of these three patients did not have concomitant lymph node metastases, which are associated with a poor prognosis by itself. The use of FS of the proximal bile duct is of limited clinical value because of the relatively low sensitivity, high risk of false-negative results, and the low rate of secondary obtained tumor-free resection margins. Supported by the literature, a new approach to the use of FS in HCCA should be adopted, reserving the technique only for cases in which a substantial additional resection is possible. [ABSTRACT FROM AUTHOR]

Little is known about the achievement of developmental milestones (i.e., COL) after pediatric liver transplantation. The aim of this study was to examine the COL of young adults who underwent a liver transplantation during childhood and to compare it to healthy peers. Furthermore, we studied factors possibly related to their COL. COL was assessed using the CLQ, which assesses the achievement of developmental milestones (autonomy, psychosexual, social, and antisocial development) and risk behavior (substance abuse and gambling). Sociodemographic characteristics and clinical data were collected using the prospective institutional liver transplantation database. A total of 39 young adults who underwent a liver transplantation at the UMCG in their childhood completed the CLQ. They achieved fewer milestones with regard to autonomy, psychosexual, and social development compared to healthy peers, and they reported less risk behavior. Neither age at the time of study nor age at the time of transplantation was significantly correlated with any of the COL subscales. Young adults show delay in reaching developmental milestones in every dimension after a liver transplantation during their childhood. [ABSTRACT FROM AUTHOR]

Significant recent interest has focussed on improving outcomes after emergency laparotomy. This retrospective database analysis estimated the annual incidence and associated inpatient costs of emergency laparotomy in England. Demographic, process and outcome data were collected for all patients undergoing emergency laparotomy in Brighton for two calendar years (2009-2010). Cost analysis assumed £16 per minute theatre time, and £282 per day ward bed and £1382 per day critical care bed costs. National incidence was confirmed from Hospital Episode Statistics and Office of National Statistics mid-year population data. In total, 768 patients underwent 850 emergency laparotomies. The incidence of emergency laparotomy was estimated as ∼1:1100 population. Thirty-six percent (276 patients) were admitted for a median (IQR [range]) of 5 (3-11 [1-76]) days of critical care. Postoperative median (IQR [range]) length of stay was 13 (8-24 [1-176]) days. Our estimated annual inpatient cost of emergency laparotomy for Brighton was ∼£5 million, equivalent to ∼£13 000 per patient, and for England, an annual estimated cost of ∼£650 million. However, 'Payment by Results' reimbursement amounted to a mean (SD) hospital income of just £6905 (2639) per patient, a net financial loss of ∼£6100 per patient, equivalent to a reimbursement shortfall nationally of ∼£300 million. We also found that patients > 70 years (46%) had significantly higher 30-day postoperative mortality (18% vs 6%, p < 0.0001), significantly prolonged median (IQR [range]) length of stay (15 (10-26 [1-123]) days vs 12 (7-22 [1-176]) days, p < 0.001) and incurred higher costs (median (IQR [range]) £9667 (6620-15 732 [1920-103 624]) vs £7467 (4975-14 251 [1178-118 060]), p < 0.001). Emergency laparotomy is a common procedure associated with considerable cost, particularly among elderly patients. A National Emergency Laparotomy Database will help provide an evidence base on which to improve clinical outcome and cost efficiency. [ABSTRACT FROM AUTHOR]

This article presents a model-based control approach for optimal operation of a seeded fed-batch evaporative crystallizer. Various direct optimization strategies, namely, single shooting, multiple shooting, and simultaneous strategies, are used to examine real-time implementation of the control approach on a semi-industrial crystallizer. The dynamic optimizer utilizes a nonlinear moment model for on-line computation of the optimal operating policy. An extended Luenberger-type observer is designed to enable closed-loop implementation of the dynamic optimizer. In addition, the observer estimates the unmeasured process variable, namely, the solute concentration, which is essential for the intended control application. The model-based control approach aims to maximize the batch productivity, as satisfying the product quality requirements. Optimal control of crystal growth rate is the key to fulfill this objective. This is due to the close relation of the crystal growth rate to product attributes and batch productivity. The experimental results suggest that real-time application of the control approach leads to a substantial increase, i.e., up to 30%, in the batch productivity. The reproducibility of batch runs with respect to the product crystal size distribution is achieved by thorough seeding. The simulation and experimental results indicate that the direct optimization strategies perform similarly in terms of optimal process operation. However, the single shooting strategy is computationally more expensive. © 2010 American Institute of Chemical Engineers AIChE J, 57: 1557-1569, 2011 [ABSTRACT FROM AUTHOR]

de Vries W, de Langen ZJ, Aronson DC, Hulscher JBF, Peeters PMJG, Jansen-Kalma P, Verkade HJ also on behalf of NeSBAR. Mortality of biliary atresia in children not undergoing liver transplantation in the Netherlands. Pediatr Transplantation 2011: 15:176-183. © 2010 John Wiley & Sons A/S. In order to further improve the outcome of BA, we characterized the mortality of BA patients who did not undergo OLT in the Netherlands, and compared our results with international data. For this purpose, we analyzed the causes of mortality of non-transplanted BA patients before the age of five yr, using the NeSBAR database. To evaluate trends in mortality, we compared the cohort 1987-1996 (n = 99) with 1997-2008 (n = 111). We compared clinical condition at OLT assessment with available international data, using the PELD-score. Mortality of non-transplanted BA children was 26% (26/99) in 1987-1996 and 16% (18/111) in 1997-2008 (p = 0.09). Sepsis was the prevailing direct cause of death (30%; 13/44). PELD-scores at the time of assessment were higher in non-transplanted BA patients (median 20.5; range 13-40) compared with international data (mean/median between 11.7 and 13.3). Based on our national data, we conclude that pretransplant mortality of BA patients is still considerable, and that sepsis is a predominant contributor. Our results strongly indicate that the prognosis of patients with BA in the Netherlands can be improved by earlier listing of patients for OLT and by improving pretransplant care. [ABSTRACT FROM AUTHOR]

Hox transcription factors play an essential role in patterning the anteroposterior axis during embryogenesis and exhibit a complex array of spatial and temporal patterns of expression. Their earliest onset of expression in vertebrates is during gastrulation in a temporally collinear sequence in the presomitic/ventrolateral mesoderm, and it is not clear which upstream signal transduction events initiate this expression. Using Xenopus, we present evidence that Xwnt8 is necessary for initiation of this collinear sequence by activating Hox-1 expression in three Hox clusters: hoxd, hoxa, and hoxb. All three labial genes appear to be direct targets of canonical Wnt signaling through Tcf/Lef. In addition, Xwnt8 loss- and gain-of-function leads to indirect regulation of other Hox genes: Hoxb4, Hoxd4, Hoxa7, Hoxc6, and Hoxc8. These findings shed new light on the early role of Wnt8 as well as of a proposed WNT gradient in patterning the Xenopus central nervous system (Kiecker and Niehrs [] Development 128:4189-4201). Developmental Dynamics 239:126-139, 2010. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Seasonally breeding animals use a combination of photic (i.e. day length) and nonphotic (e.g. food availability, temperature) cues to regulate their reproduction. How these environmental cues are integrated is not understood. To assess the potential role of two candidate neuropeptides, kisspeptin and RFamide-related peptide-3 (RFRP), we monitored regional changes in their gene expression in a seasonally breeding mammal exposed to moderate changes in photoperiod and food availability. Adult male Siberian hamsters ( Phodopus sungorus) were housed under a long (16 h light/day; 16 L) or intermediate (13.5 L) photoperiod and fed ad lib. or a progressive food restriction schedule (FR; reduced to 80% of ad lib.) for 11 weeks. Gonadal regression occurred only in FR hamsters housed under 13.5 L. Immunohistochemistry was used to identify diencephalic populations of kisspeptin- and RFRP-immunoreactive cells, and quantitative PCR was used to measure gene expression in adjacent coronal brain sections. Photoperiod, but not food availability, altered RFRP mRNA expression in the dorsomedial sections, whereas food availability but not photoperiod altered Kiss1 expression in the arcuate sections; intermediate photoperiods elevated RFRP expression, and food restriction suppressed Kiss1 expression. Regional- and neuropeptide-specific activity of RFamides may provide a mechanism for integration of multi-modal environmental information in the seasonal control of reproduction. [ABSTRACT FROM AUTHOR]

Currently, liver transplantation (LT) is an accepted method of treatment of end-stage liver disease, metabolic diseases with their primary defect in the liver and unresectable primary liver tumors. Surgical techniques in LT have evolved considerably over the past 40 yr. The developments have led to a safer procedure for the recipient reflected by continuously improving survival figures after LT. Also the new techniques offer the possibility of tailoring the operation to the needs and condition of the recipient as in partial grafting or in different revascularization techniques, or in techniques of biliary reconstructions. In addition, the new techniques such as split LT, domino transplantation and living donor LT have brought about an increase in the available grafts. In this review the evolution of surgical techniques in LT over the past 40 yr and their contribution to the current results are discussed. [ABSTRACT FROM AUTHOR]

The aim of this study was to describe the localization and management of patients with pancreatic insulinomas and determine the most effective localization and surgical techniques in the presence of significant financial constraints in the patient population. We retrospectively reviewed the case records of 18 patients with insulinomas treated at our institution over a period of 10 years. The medical records were reviewed for demographic data, clinical presentation, biochemistry, details of localization studies, intraoperative findings, postoperative outcome, and long-term follow-up. The sensitivities of the various localization procedures were calculated using the intraoperative findings as the gold standard. There were 10 men and 8 women in the study, with a median age of 43 years. All patients underwent a supervised 72-hour fast and developed symptomatic hypoglycemia within 48 hours. An average of 1.9 localization procedures was performed per patient. Computed tomography (CT) had a sensitivity of 62% and specificity of 100%. Magnetic resonance imaging and digital subtraction angiography had specificities of 85% and 100%, respectively, with a specificity of 66% and 50%, respectively. Fourteen patients underwent surgery. Intraoperatively the excised tumor was palpable in nine patients, and all patients had postoperative euglycemia. In five patients the tumor was not palpable during the time of surgery; three of these patients underwent blind distal pancreactomy, with two patients having persistent hypoglycemia during the postoperative period. Two patients had a negative exploratory laparotomy. Patients with a surgical cure were followed up for a mean period of 24 months. On the background of financial constraints in connection with patient care, CT scanning is a cost-effective option with good specificity. Intraoperative palpation of the tumor and enucleation is the most effective technique for surgical cure. Blind distal pancreactomy is not advocated for tumors that are not localized intraoperatively. [ABSTRACT FROM AUTHOR]

Between November 1982 and March 2006, 67 children with body weight ≤10 kg had a primary liver transplantation from deceased donors in our unit. The aim of this study was to analyze the outcome in terms of patient and graft survival and to search for factors affecting this outcome. Overall, one-, three-, five-, and 10-yr primary patient and graft survival rates were 73%, 71%, 66%, 63% and 59%, 56%, 53%, 48%, respectively. Twenty-four of 67 (36%) children died and in the remaining 22 (33%), the first grafts failed and they were retransplanted. Cox regression analysis revealed that a need for retransplantation and urgent transplantation were important predictors for patient survival (p = 0.04 and p = 0.001, respectively). To assess whether the need for retransplantation can be influenced, all study variables were compared between surviving grafts and failed grafts. Cox regression analysis showed that only donor/recipient (D/R) weight ratio proved to be independent predictor for graft survival (p = 0.004). After comparison of graft survival with the long rank test according to different D/R weight ratios (3.0–7.0), the cut-off point for significantly different graft survival approached 4.0. The one-, three-, five-, and 10-yr graft survival for technical variant grafts with a D/R weight ratio <4.0 was 85%, 68%, 68%, and 68% compared with a D/R weight ratio >4.0 was 44%, 38%, 38%, and 30%, respectively (p = 0.02). In summary, patient survival in children with body weight ≤10 kg is determined by urgent transplantation and the need for retransplantation. Graft loss and retransplantation in small children can be prevented by adequate size matching of donor and recipient whereby a D/R weight ratio <4.0 seems to offer the favorable outcome. [ABSTRACT FROM AUTHOR]

No consensus exists regarding the optimal reconstruction of the cavo-caval anastomosis in piggyback orthotopic liver transplantation (PB-LT). The aim of this study was to analyze our experience with end-to-side (ES) cavo-cavostomy. Outcome parameters were patient and graft survival and surgical complications. During the period 1995–2002 146 full-size PB-LT in 137 adult patients were performed with ES cavo-cavostomy without the routine use of temporary portocaval shunt (TPCS). In 12 patients (8%) this technique was used for implantation of second or third grafts. Veno-venous bypass was not used in any case and TPCS was performed only in eight patients (6%). One-, three- and five-yr patient and graft survival were 84%, 79% and 75%, and 81%, 74% and 69%, respectively. The median number of intraoperative transfusion of packed red blood cells (RBC) was 2.0 (range 0–33) and 30% of the patients (n = 43) did not require any RBC transfusion. Surgical complications of various types were observed after 49 LT (34%) and none of the complications was specifically related to the technique of ES cavo-cavostomy. Our experience indicates that PB-LT with ES cavo-cavostomy is a safe procedure, can safely be performed without the routine use of a TPCS, has a very low risk of venous outflow obstruction and can also be used effectively during retransplantations. [ABSTRACT FROM AUTHOR]

Eukaryotic translation initiation factor 5A (eIF5A) is the only cellular protein that contains the unusual amino acid hypusine [ Nε-(4-amino-2-hydroxybutyl)lysine]. Vertebrates carry two genes that encode two eIF5A isoforms, eIF5A-1 and eIF5A-2, which, in humans, are 84% identical. eIF5A-1 mRNA (1.3 kb) and protein (18 kDa) are constitutively expressed in human cells. In contrast, expression of eIF5A-2 mRNA (0.7–5.6 kb) and eIF5A-2 protein (20 kDa) varies widely. Whereas eIF5A-2 mRNA was demonstrable in most cells, eIF5A-2 protein was detectable only in the colorectal and ovarian cancer-derived cell lines SW-480 and UACC-1598, which showed high overexpression of eIF5A-2 mRNA. Multiple forms of eIF5A-2 mRNA (5.6, 3.8, 1.6 and 0.7 kb) were identified as the products of one gene with various lengths of 3′-UTR, resulting from the use of different polyadenylation (AAUAAA) signals. The eIF5A-1 and eIF5A-2 precursor proteins were modified comparably in UACC-1598 cells and both were similarly stable. When eIF5A-1 and eIF5A-2 coding sequences were expressed from mammalian vectors in 293T cells, eIF5A-2 precursor was synthesized at a level comparable to that of eIF5A-1 precursor, indicating that the elements causing inefficient translation of eIF5A-2 mRNA reside outside of the open reading frame. On sucrose gradient separation of cytoplasmic RNA, only a small portion of total eIF5A-2 mRNA was associated with the polysomal fraction, compared with a much larger portion of eIF5A-1 mRNA in the polysomes. These findings suggest that the failure to detect eIF5A-2 protein even in eIF5A-2 mRNA positive cells is, at least in part, due to inefficient translation. [ABSTRACT FROM AUTHOR]

Tacrolimus is an important drug for immunosuppression after liver transplantation. Bioavailability of enterally administered tacrolimus is poor, and further reduced by gastric residuals or by enteral nutrition. Buccal administration might be an alternative route especially in children. Tacrolimus trough levels (TTLs) obtained after buccal administration of tacrolimus after liver transplantation have not been reported. The aim of this study was to determine whether buccal administration of tacrolimus is feasible and to compare TTLs after nasogastric tube (NGT) administration with buccal administration. TTLs after NGT or buccal administration during the first week after pediatric liver transplantation were analyzed from 28 cadaveric liver transplants in 23 pediatric recipients between June 2002 and March 2004. Each level was scored within, under or above the target range. Buccal administration was well tolerated in all patients. A total of 149 TTLs were obtained of which nine were excluded because of incomplete information on target levels. Overall 27% of TTLs was adequate. The percentage of levels under, within and above the target range were comparable in both groups (chi-square test; p = 0.64). Both groups had a decrease in percentages within the target range on day 3 and 4 after liver transplantation with a subsequent rise. Buccal tacrolimus administration is feasible. Similar TTLs are achieved compared with NGT tacrolimus administration during the first week after pediatric liver transplantation. [ABSTRACT FROM AUTHOR]

Assessment of tumour vascularity may characterize malignancy as well as predict responsiveness to anti-angiogenic therapy. Non-invasive measurement of tumour perfusion and blood vessel permeability assessed as the transfer constant, Ktrans, can be provided by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Using the orthotopic murine tumour model B16/BL6 melanoma, the small contrast agent GdDOTA (DOTAREM®; Guerbet, Paris) was applied to assess the vascular transfer constant, Ktrans, and interstitial leakage space, whereas intravascular iron oxide nanoparticles (Endorem®; Guerbet, Paris) were used to detect relative tumour blood volume (rTBV), and in one experiment blood flow index (BFI). No correlations were observed between these four parameters ( r2 always <0.05). The B16/BL6 primary tumour and lymph-node cervical (neck) metastases produced high levels of the permeability/growth factor, VEGF. To probe the model, the novel VEGF receptor (VEGF-R) tyrosine kinase inhibitor, PTK787/ZK222584 (PTK/ZK) was tested for anti-tumour efficacy and its effects on DCE-MRI measured parameters of tumour vascularity. Data from the non-invasive measure of tumour vascularity were compared with a histological measurement of vasculature using the DNA-staining dye H33342. PTK/ZK inhibited growth of the primary and, particularly, cervical tumour metastases following chronic treatment for 2 weeks (50 or 100 mg/kg daily) of 1-week-old tumours, or with 1 week of treatment against more established (2-week-old) tumours. After chronic treatment with PTK/ZK, DCE-MRI detected significant decreases in Ktrans and interstitial leakage space, but not rTBV of both primary tumours and cervical metastases. Histological data at this time-point showed a significant decrease in blood vessel density of the cervical metastases but not the primary tumours. However, in the cervical metastases, the mean blood vessel width was increased by 38%, suggesting overall no marked change in blood volume. After acute (2-4 day) treatment, DCE-MRI of the cervical metastases demonstrated a significant decrease in Ktrans and interstitial leakage space and also in the initial area under the enhancement curve for GdDOTA (IAUC), but no change in the rTBV or BFI. Thus, significant changes could be detected in the DCE-MRI measurement of tumour uptake of a small contrast agent prior to changes in tumour size, which suggests that DCE-MRI could be applied in the clinic as a rapid and sensitive biomarker for the effects of VEGF-R inhibition on tumour blood vessel permeability and thus may provide an early marker for eventual tumour response. Copyright © 2005 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Miyamoto S, Polak WG, Geuken E, Peeters PMJG, de Jong KP, Porte RJ, van den Berg AP, Hendriks HG, Slooff MJH. Liver transplantation with preservation of the inferior vena cava. A comparison of conventional and piggyback techniques in adults.Clin Transplant 2004 DOI: 10.1111/j.1399-0012.2004.00278.x© Blackwell Munksgaard, 2004The aim of this study is to analyse a single centre's experience with two techniques of liver transplantation (OLT), conventional (CON-OLT) and piggyback (PB-ES), and to compare outcome in terms of survival, morbidity, mortality and post-operative liver function as well as operative characteristics. A consecutive series (1994–2000) of 167 adult primary OLT were analysed. Ninety-six patients had CON-OLT and 71 patients had PB-ES. In PB-ES group two revascularization protocols were used. In the first protocol reperfusion of the graft was performed first via the portal vein followed by the arterial anastomosis (PB-seq). In the second protocol the graft was reperfused simultaneously via portal vein and hepatic artery (PB-sim). One-, 3- and 5-yr patient survival in the CON-OLT and PB-ES groups were 90, 83 and 80%, and 83, 78 and 78%, respectively (p = ns). Graft survival at the same time points was 81, 73 and 69%, and 78, 69 and 65%, respectively (p = ns). Apart from the higher number of patients with cholangitis and sepsis in CON-OLT group, morbidity, retransplantation rate and post-operative liver and kidney function were not different between the two groups. The total operation time was not different between both groups (9.4 h in PB-ES vs. 10.0 h in CON-OLT), but in PB-ES group cold and warm ischaemia time (CIT and WIT), revascularization time (REVT), functional and anatomic anhepatic phases (FAHP and AAHP) were significantly shorter (8.9 h vs. 10.7 h, 54 min vs. 63 min, 82 min vs. 114 min, 118 min vs. 160 min and 87 min vs. 114 min, respectively, p < 0.05). RBC use in the PB-ES group was lower compared to the CON-OLT group (4.0 min vs. 10.0 units, p < 0.05). Except for WIT and REVT there were no differences in operative characteristics between PB-Sim and PB-Seq groups. The WIT was significantly longer in PB-Sim group compared with PB-Seq group (64 min vs. 50 min, p < 0.05); however REVT was significantly shorter in PB-Sim group (64 min vs. 97 min, p < 0.05). Results of this study show that both techniques are comparable in survival and morbidity; however PB-ES results in shorter AAHP, FAHP, REVT and WIT as well as less RBC use. In the PB-ES group there seems to be no adavantage for any of the revascularization protocols. [ABSTRACT FROM AUTHOR]

The partitioning of resources between different plant organs and compounds is an important determinant of crop quality. We are attempting to change resource partitioning in crop plants by manipulating the cellular mechanisms involved in metabolite sensing and signalling. One of the proteins involved is SnRK1 (sucrose nonfermenting-1-related protein kinase 1), so-called because of its homology and functional similarity with sucrose non-fermenting 1 (SNF1) of yeast. SnRK1 is a protein kinase that plays a key role in the global control of plant carbon metabolism. Here we review studies on the characterisation of SnRK1 gene families, SnRK1 regulation and function, and the identification of SnRK1-interacting proteins. We also describe some potential applications of manipulating SnRK1 activity, including controlling sprouting in stored potato tubers, inducing male sterility in barley and increasing sterol levels in oilseeds. [ABSTRACT FROM AUTHOR]

SUMMARY 1. The effects of catchment urbanisation on water quality were examined for 30 streams (stratified into 15, 50 and 100 km2 ± 25% catchments) in the Etowah River basin, Georgia, U.S.A. We examined relationships between land cover (implying cover and use) in these catchments (e.g. urban, forest and agriculture) and macroinvertebrate assemblage attributes using several previously published indices to summarise macroinvertebrate response. Based on a priori predictions as to mechanisms of biotic impairment under changing land cover, additional measurements were made to assess geomorphology, hydrology and chemistry in each stream. 2. We found strong relationships between catchment land cover and stream biota. Taxon richness and other biotic indices that reflected good water quality were negatively related to urban land cover and positively related to forest land cover. Urban land cover alone explained 29–38% of the variation in some macroinvertebrate indices. Reduced water quality was detectable at c . >15% urban land cover. 3. Urban land cover correlated with a number of geomorphic variables such as stream bed sediment size (–) and total suspended solids (+) as well as a number of water chemistry variables including nitrogen and phosphorus concentrations (+), specific conductance (+) and turbidity (+). Biotic indices were better predicted by these reach scale variables than single, catchment scale land cover variables. Multiple regression models explained 69% of variation in total taxon richness and 78% of the variation in the Invertebrate Community Index (ICI) using phi variability, specific conductance and depth, and riffle phi , specific conductance and phi variability, respectively. 4. Indirect ordination analysis was used to describe assemblage and functional group changes among sites and corroborate which environmental variables were most important in driving differences in macroinvertebrate assemblages. The first axis in a... [ABSTRACT FROM AUTHOR]

1. We studied whole-ecosystem metabolism in eight streams from several biomes in North America to identify controls on the rate of stream metabolism over a large geographic range. The streams studied had climates ranging from tropical to cool-temperate and from humid to arid and were all relatively uninfluenced by human disturbances. 2. Rates of gross primary production (GPP), ecosystem respiration (R) and net ecosystem production (NEP) were determined using the open-system, two-station diurnal oxygen change method. 3. Three general patterns in metabolism were evident among streams: (1) relatively high GPP with positive NEP (i.e. net oxygen production) in early afternoon, (2) moderate primary production with a distinct peak in GPP during daylight but negative NEP at all times and (3) little or no evidence of GPP during daylight and a relatively constant and negative NEP over the entire day. 4. Gross primary production was most strongly correlated with photosynthetically active radiation (PAR). A multiple regression model that included log PAR and stream water soluble reactive phosphorus (SRP) concentration explained 90% of the variation in log GPP. 5. Ecosystem respiration was significantly correlated with SRP concentration and size of the transient storage zone and, together, these factors explained 73% of the variation in R. The rate of R was poorly correlated with the rate of GPP. 6. Net ecosystem production was significantly correlated only with PAR, with 53% of the variation in log NEP explained by log PAR. Only Sycamore Creek, a desert stream in Arizona, had positive NEP (GPP: R > 1), supporting the idea that streams are generally net sinks rather than net sources of organic matter. 7. Our results suggest that light, phosphorus concentration and channel hydraulics are important controls on the rate of ecosystem metabolism in streams over very extensive geographic areas. [ABSTRACT FROM AUTHOR]

Plants of Mesembryanthemum crystallinum L. were grown from seed in phosphate-sufficient and phosphate-deficient conditions. Separate plants were subjected to nitrate deficiency by removing nitrate from the rooting medium of previously nitrate-sufficient plants. Subsequently, they were also irrigated with 400 mM NaCl to induce CAM. Plants of M. crystallinum with induced CAM that had been grown in complete nutrient medium were deinduced by rehydration. Nitrate and phosphate deficiencies caused enhanced CAM activity prior to salt treatments. After salinisation, phosphate deficiency also caused higher background levels of malate. Prolonged nitrate deficiency reduced CAM activity. Endogenous P1 levels in phosphate-sufficient plants correlated with CAM activity. However in phosphate-deficient plants CAM occurred without a significant rise in P1 content. Levels of endogenous P1 appeared more related to nitrate deficiency than to CAM or salt treatment. Nitrate and phosphate deficiencies and salt treatment could all cause a nitrate deficiency within the leaf, causing high endogenous P1 when available in the rooting medium. It is speculated that a change in nitrogen status could play a role in the initiation of CAM induction in M. crystallinum. A further possibility is that CAM could be induced by reduced water potential due to dehydration and increased ion content in saline conditions, and by an inhibition of growth and concomitant accumulation of solutes in phosphate- and nitrate-deficient conditions. [ABSTRACT FROM AUTHOR]

Differences in carbohydrate metabolism between the C3 and CAM forms of Mesembryanthemum crystallinum L. were demonstrated and studied. The CAM form accumulated less starch (defined as boiling water-insoluble polyglucan) than the C3 form at high irradiances, but at limiting light diverted a greater proportion of photosynthate to starch. Starch accumulation was more sensitive to the effects of exogenous inorganic phosphate in the C3 form than in the CAM form. Following induction of CAM by salt treatment, the CAM form ceased to accumulate glucose and fructose and commenced accumulating pinitol. Pinitol is not involved directly in CAM but may act as a compatible osmoregulatory solute. Concentrations of fructose 2,6-bisphosphate in the C3 and CAM forms were similar, but the cytosolic fructose 1,6-bisphophatase extracted from the two forms was markedly different in sensitivity to this effector. The two enzymes also differed both in their sensitivity to inorganic phosphate and in their affinity for fructose 1,6-bisphosphate. The concentrations of key intermediates of carbohydrate metabolism, fructose and glucose 6-phosphate and fructose 1,6-bisphosphate were measured in the C3 and CAM forms. Concentrations of fructose 1,6-bisphosphate were higher in the CAM form, whereas those of glucose and fructose 6-phosphate were higher in the C3 form. The differences observed are discussed in relation to the regulation of storage carbohydrate metabolism in the two forms. A partial explanation is offered for the differences in the characteristics of starch accumulation between the C3 and CAM forms through the influence of the effector fructose 2,6-bisphosphate on the enzyme fructose 1,6-bisphosphatase. [ABSTRACT FROM AUTHOR]

The aim of this work was to examine whether carbohydrates are involved in signalling N deficiency through source:sink imbalance. Photosynthetic metabolism in tobacco was studied over 8 d during the withdrawal of N from previously N-sufficient plants in which the source:sink ratio was manipulated by shading leaves on some of the plants. In N-sufficient plants over this timescale, there was a small decline in photosynthetic rate, Rubisco protein and amino acid content, with a larger decrease in carbohydrate content. Withdrawal of N from the growing medium induced a large decrease in the rate of photosynthesis (35% reduction after 8 d under the growing conditions, with a reduction also apparent at high and low measuring CO2), which was caused by a large decrease in the amount of Rubisco protein (62% after 8 d) and Rubisco activity. Higher amounts of hexoses preceded the loss of photosynthetic activity and sucrose and starch accumulation. Reduction of the source:sink ratio by shading prevented the loss of photosynthetic activity and the increase in hexoses and other carbohydrates. These data indicate that the reduction of photosynthesis that accompanies N deficiency in intact plants has the characteristics of sugar repression of photosynthesis observed in model systems, but that the accumulation of hexose prior to the decline in photosynthesis is small. The possibility that sugar repression of photosynthesis under physiological conditions depends more crucially on the C:N status of leaves than the carbohydrate status alone is discussed. [ABSTRACT FROM AUTHOR]

A simple method of growing plants in agar was exploited to investigate the effect of long-term nitrogen (N) and phosphorus (P) deficiencies on respiratory metabolism and growth in shoots and roots of Nicotiana tabacum seedlings, and their interaction with exogenously supplied sucrose. Levels of hexose phosphates and 3-phosphoglyceric acid (3-PGA) were low in P-deficient shoots and roots and high in N-deficient shoots and roots. The ratio of hexose phosphates to 3-PGA and levels of fructose-2,6-bisphosphate were high in P-deficient plants and low in N-deficient plants. These data reflect differences in the way metabolism was perturbed, yet both deficiencies were associated with increased root growth relative to shoot growth, starch accumulation in the shoots, and soluble carbohydrate accumulation, especially hexoses, in the roots. Enzymes for sucrose degradation (sucrose synthase, acid and alkaline invertase) and glycolysis (phosphofructokinase, pyrophosphate-dependent phospho-fructokinase and pyruvate kinase) remained unaltered or declined in the shoots and roots. The accumulation of hexoses in roots of N- and P-deficient plants may result from maintenance of high invertase activities relative to sucrose synthase and glycolytic enzymes in the roots. The possibility that hexose accumulation may drive preferential root growth osmotically in N and P deficiencies is discussed. The addition of sucrose to roots to further investigate the interaction of carbohydrates with growth and allocation in low N and low P produced clear effects even though endogenous levels of soluble carbohydrate were already high in the nutrient-deficient plants. In complete nutrition, growth was stimulated, protein content particularly of the roots was increased and there was a preferential increase in activity of sucrose synthase in roots. At low P, enzyme activities in roots were increased, including sucrose synthase, and protein content increased, particularly in the roots, but there was no increase in growth. In N-deficient plants, exogenous sucrose led to decreased protein, Rubisco and chlorophyll content in shoots, in contrast to the other conditions, and a higher protein content and a general increase of catabolic enzyme activities and growth in the roots, [ABSTRACT FROM AUTHOR]

Mesembryanthemum crystallinum plants were irrigated with 400 mol m-3 NaCl to induce CAM and levels of leaf starch, and activities of starch-degrading enzymes were measured. During Crassulacean acid metabolism (CAM) induction, daily starch turnover gradually became more pronounced and was three- to four-fold greater than in leaves of C3 plants alter 3 weeks. Activities of α- and β- amylase, D-enzyme and starch phosphorylase all increased 10- to 20-fold within 3 weeks of the start of salt treatment. Activities of α- and β-amylase increased more than fourfold within the first 24 h of salt treatment, which is the fastest increase in enzyme activities so far measured during the induction of CAM with salt solution in intact plants of this species. Most enzyme activities were partially chloroplastic; however, the principal starch-degrading activity was constituted by an extra-chloroplastic β-amylase. CAM starch-phosphorylase activity, which was mainly chloroplastic, exhibited a two- to three-fold diurnal change in parallel with starch content. CAM induction in M. crystallinum is clearly associated with greater starch turnover and enhanced starch-degrading enzyme activities, which as catalysts of the initial reaction to release carbon for synthesis of phosphoenolpyruvate (PEP) appear highly significant for the functioning of the CAM pathway. The diurnal rhythm of phosphorylase activity may be of particular significance. [ABSTRACT FROM AUTHOR]

2-carboxy-D-ambinitol-1-phosphate (CA1P) bound to Rubisco either in leaf extracts or after purification can be displaced by SO42- ions. Thus, treatment of leaf extracts with a buffer containing 200 mol m-3 SO42- displaces any bound CA1P and enables measurement of maximum carboxylation potential. In tobacco leaves, the activity following treatment with SO42- ions ('maximal activity') is greater than the total Rubisco activity. The ratio of the two activities altered in a dynamic way with fluctuations in irradiance. Even in species which do not produce significant amounts of CA1P, the maximal activity greatly exceeded the total activity. Anion exchange separation of components in acid extracts confirmed the absence of CA1P in tobacco leaves harvested above an irradiance of 300 μmol quanta m-2s-1, but the presence of another inhibitor of Rubisco. These results are consistent with the regulation of Rubisco activity by inhibitors other than CA1P which, like CA1P, can be displaced by SO42- ions. [ABSTRACT FROM AUTHOR]

Here we report on the molecular defect that leads to a deficiency of lipoprotein lipase (LPL) activity in a proband of Dutch descent. Southern-blot analysis of the LPL gene from the patient did not reveal any major DNA rearrangements. Sequencing of polymerase-chain-reaction-amplified DNA revealed that the proband is a homozygote for G725C, resulting in a substitution of Pro157 for Arg. This substitution alters a restriction site for PvuII, which allowed rapid identification of the mutant allele in family members. Site-directed mutagenesis and transient expression of the mutant LPL in COS cells produced an enzymaticany inactive protein, establishing the functional significance of this mutation. This naturally occurring mutation which alters the Pro157 adjacent to Asp156 of the proposed catalytic triad, indicates that this region of the protein is indeed crucial for LPL catalytic activity. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses the mutational analysis of RET proto-oncogene in medullary thyroid carcinoma patients and carriers who are at risk in India.

A letter to the editor is presented in response to the article "Radioactive iodine ablation does not prevent recurrences in patients with papillary thyroid microcarcinoma," by H. J. Kim and colleagues in the 2012 issue.

Objectives: To assess the incidence, risk factors and clinical relevance of inadvertent parathyroidectomy during thyroidectomy. Design: Retrospective study. Setting: Tertiary care hospital and post-graduate teaching institute. Subjects & Methods: Patients who underwent total thyroidectomy between 2004 and 2006 (three years) in a general surgical unit with a special interest in endocrine surgery were included in the study. Medical records were accessed for patient demographic data, diagnosis, operative details, histopathology reports, postoperative hypocalcaemia and the total duration of hospital stay. Results: Inadvertent removal of parathyroid glands occurred in 12.9% of cases. Removed parathyroids were intra-capsular / intra-thyroidal in 44.6% of cases. Female sex, malignancy and central neck dissection were found to be risk factors. These patients had an increased incidence of temporary and permanent biochemical hypocalcaemia but the hospital stay was not prolonged. Conclusion: In our study, inadvertent parathyroid excision accounted for increased morbidity. Steps should be taken to preserve more parathyroid glands by improving surgical technique (magnification) and auto-transplantation of parathyroid gland if necessary. [ABSTRACT FROM AUTHOR]

Background Pheochromocytomas are diagnosed in <1% of patient evaluated for hypertension. Methodology A retrospective analysis of case records of those patients with histopathologically confirmed pheochromocytoma in our hospital from 1976–2006 [30 YEARS] was conducted. Result A total of 123 patients were diagnosed during this period. The median age at presentation was 31 years (range 9–71) with a male to female sex distribution of 75% and 36%. 80% were hypertensive at the time of diagnosis. Headache(84%), palpitations(64%) and sweating(60%) are the most common presenting complaints.Tachycardia [>100 per minute]were seen in 31%. Hypertensive changes in eyes were seen in 87%. In ECG, QTc prolongation in 26%, left ventricular hypertrophy in 30%. Diabetes mellitus/IGT was seen in 35%. Elevated urinary VMA (24 hrs) was seen in 93% when done on 3 consecutive days. MIBG was positive in 85%. Malignant pheochromocytoma was diagnosed by tumour invasion/metastasis seen 10.44%. Extra adrenal pheochromocytoma 18%, followed by bilateral pheochromocytoma in 11%. Hereditary pheochromocytoma in 13% which include 5 with Von Hippel Lindau and 6 with MEN. A median follow-up was 12 months (range 1–204) in which persistent hypertension was seen in 16%. Cholelithiasis in 7%. Conclusion In our case series the mean age (31 yrs) of presentation seems to be younger compared to other case series. 16% of our patients were asymptomatic at the time of presentation. Urinary VMA was elevated in 93% of patients when done in 3 consecutive samples. Extra adrenal pheo was common in our patients (18%). MIBG was false negative in 15% of those patients with pheochromocytoma. [ABSTRACT FROM AUTHOR]

Introduction Parathyroid carcinoma is a challenging problem to a surgeon and adjuvant radiotherapy is important to reduce the recurrence. Methods A retrospective review was conducted of all cases of parathyroid carcinoma from 1990–2006. 6 patients were identified. Results There was a male preponderance. Mean age of presentation was 49 years. The clinical presentation was similar to benign primary hyperparathyroidism except for the presence of palpable nodule in 80% of patients with carcinoma compared to 11% among patients with benign primary hyperparathyroidism. One patient had chronic pancreatits propably secondary to hyperparathyroidism. All patients had hypercalcaemia with elevated serum PTH levels and no significant difference compared to benign hyperparathyroidism. Surgery was done in all. Local metastasis to the cervical lymph nodes was seen in 33% off patients. The tumors showed a high predilection to the inferior parathyroid glands.. All subjects underwent radiotherapy with cobalt at mean dose of 50 cGy. The mean duration of recurrence was about 2 years. 50% had local recurrence, 2 had recurrent tumor excision including one from vocal cord. Bony metastasis was found in one as evidenced by hot spots in sestamibi scan. 2 of the 6 died, both of them had unrelated disease as cause of death. 1 lost to follow up. Conclusion Parathyroid carcinoma constitutes around 2–3% of patients. In the presence of a palpable nodule, chance of being malignant should be kept in mind. Recurrence rate can be reduced by post operative external radiotherapy. [ABSTRACT FROM AUTHOR]