The characteristics of krill swarms in relation to aggregating Antarctic blue whales.

We model the presence of rare Antarctic blue whales (Balaenoptera musculus intermedia) in relation to the swarm characteristics of their main prey species, Antarctic krill (Euphausia superba). A combination of visual observations and recent advances in passive acoustic technology were used to locate Antarctic blue whales, whilst simultaneously using active underwater acoustics to characterise the distribution, size, depth, composition and density of krill swarms. Krill swarm characteristics and blue whale presence were examined at a range of spatiotemporal scales to investigate sub meso-scale (i.e., <100 km) foraging behaviour. Results suggest that at all scales, Antarctic blue whales are more likely to be detected within the vicinity of krill swarms with a higher density of krill, those found shallower in the water column, and those of greater vertical height. These findings support hypotheses that as lunge-feeders of extreme size, Antarctic blue whales target shallow, dense krill swarms to maximise their energy intake. As both Antarctic krill and blue whales play a key role in the Southern Ocean ecosystem, the nature of their predator-prey dynamics is an important consideration, not only for the recovery of this endangered species in a changing environment, but for the future management of Antarctic krill fisheries.

Use of Gonadotropin-Releasing Hormone Analogs in Children: Update by an International Consortium.

This update, written by authors designated by multiple pediatric endocrinology societies (see List of Participating Societies) from around the globe, concisely addresses topics related to changes in GnRHa usage in children and adolescents over the last decade. Topics related to the use of GnRHa in precocious puberty include diagnostic criteria, globally available formulations, considerations of benefit of treatment, monitoring of therapy, adverse events, and long-term outcome data. Additional sections review use in transgender individuals and other pediatric endocrine related conditions. Although there have been many significant changes in GnRHa usage, there is a definite paucity of evidence-based publications to support them. Therefore, this paper is explicitly not intended to evaluate what is recommended in terms of the best use of GnRHa, based on evidence and expert opinion, but rather to describe how these drugs are used, irrespective of any qualitative evaluation. Thus, this paper should be considered a narrative review on GnRHa utilization in precocious puberty and other clinical situations. These changes are reviewed not only to point out deficiencies in the literature but also to stimulate future studies and publications in this area.

Refining the Definitions of Biochemical and Clinical Cure for Primary Aldosteronism Using the Primary Aldosteronism Surgical Outcome (PASO) Classification System.

INTRODUCTION: Determination of outcomes after adrenalectomy for primary aldosteronism (PA) is limited by the lack of standardized definitions of cure. The Primary Aldosteronism Surgical Outcomes (PASO) group recently established new consensus definitions for biochemical and clinical cure of PA. We hypothesize that utilization of PASO definitions will better stratify patient outcomes after surgery compared to original and current criteria utilized to document cure. MATERIALS AND METHODS: Patients undergoing adrenalectomy for PA from 1996 to 2016 were studied. Clinical data were reviewed. Three different sets of criteria (original, current, and PASO) were evaluated for differences in documentation of cure. Demographic data were reported as median (range). Comparisons were made using the Mann-Whitney U test; p < 0.05 is significant. RESULTS: A total of 314 patients with PA were identified. Ninety patients (60 males) elected to proceed with surgery. In Group 1 (35 patients), 30 patients had clinical follow-up and 29 (97%) were cured using original criteria. In Group 2 (55 patients), cure was recorded in 98% when original criteria for cure were applied, 89% cured applying current criteria, and 6% had complete biochemical and clinical cure by PASO criteria. Aldosterone rose 3.6 ng/dL (0.1-34.8) in five patients during extended follow-up, with two patients changing from complete to partial or missing biochemical success. CONCLUSION: Significant heterogeneity exists in outcomes criteria utilized to document cure or clinical improvement after adrenalectomy for primary aldosteronism. Aldosterone levels change over time after adrenalectomy. PASO definitions of cure appear to allow for improved stratification of short- and long-term outcomes.

Radiographic Characteristics of Adrenal Masses Preceding the Diagnosis of Adrenocortical Cancer.

Incidentally discovered adrenal masses are common and the clinical evaluation and surveillance aims to diagnose hormone excess and malignancy. Adrenocortical cancer (ACC) is a very rare malignancy. This study aims to define the imaging characteristics of adrenal tumors preceding the diagnosis of ACC. Patients with prior (>5 months) adrenal tumors (<6 cm) subsequently diagnosed with ACC were identified in a large registry at a tertiary referral center. Retrospective chart and image review for patient characteristics and initial, interval, and diagnostic imaging characteristics (size, homogeneity, borders, density, growth rate, etc.) was conducted. Twenty patients with a diagnosis of ACC and a prior adrenal tumor were identified among 422 patients with ACC. Of these, 17 patients were initially imaged with CT and 3 with MR. Only 2 of the 20 patients had initial imaging characteristics suggestive of a benign lesion. Of initial tumors, 25% were <2 cm in size. Surveillance led to the diagnosis of ACC within 24 months in 50% of patients. The growth pattern was variable with some lesions showing long-term stability (up to 8 years) in size. In conclusion, antecedent lesions in patients with a diagnosis of ACC are often indeterminate by imaging criteria and can be small. Surveillance over 2 years detected only 50% of ACCs. Current practice and guidelines are insufficient in diagnosing ACCs. Given the rarity of ACC, the increased risk and health care costs of additional evaluation may not be warranted.

Growth patterns and the use of growth hormone in the mucopolysaccharidoses.

Short stature is characteristic of patients with mucopolysaccharidosis (MPS) diseases. For children with skeletal dysplasias, such as MPS, it is important to know the natural history of growth. An understanding of the natural growth pattern in each MPS disease provides a measurement to which treatments can be compared, as well as data which can help families and providers make individualized decisions about growth promoting treatments. Multiple advancements have been made in the treatment of MPS with both hematopoietic cell transplantation (HCT) and enzyme replacement therapy (ERT). The long term benefit of these treatments on growth is unknown. This article will review the published data on growth in children with MPS, and describe preliminary data on the use of human growth hormone (hGH) in children with MPS.

Laparoscopic resection is inappropriate in patients with known or suspected adrenocortical carcinoma.

BACKGROUND: Complete surgical resection is the mainstay of treatment for patients with adrenocortical cancer (ACC). Use of laparoscopy has been questioned in patients with ACC. This study compares the outcomes of patients undergoing laparoscopic versus open resection (OR) for ACC. METHODS: A retrospective review (2003-2008) of patients with ACC was performed. Data were collected for demographics, operative and pathologic data, adjuvant therapy, and outcome. Chi-square analysis was performed. RESULTS: Eighty-eight patients (66% women; median age, 47 (range, 18-81) years) were identified. Seventeen patients underwent laparoscopic adrenalectomy (LA). Median tumor size of those who underwent LA was 7.0 (range, 4-14) cm versus 12.3 (range, 5-27) cm for OR. Recurrent disease in the laparoscopic group occurred in 63% versus 65% in the open group. Mean time to first recurrence for those who underwent LA was 9.6 months (+/-14) versus 19.2 months (+/-37.5) in the open group (p < 0.005). Fifty percent of patients who underwent LA had positive margins or notation of intraoperative tumor spill versus 18% of those who underwent OR (p = 0.01). Local recurrence occurred in 25% of the laparoscopic group versus 20% in the open group (p = 0.23). Mean follow-up was 36.5 months (+/-43.6). CONCLUSIONS: ACC continues to be a deadly disease, and little to no progress has been made from a treatment standpoint in the past 20 years. Careful and complete surgical resection is of the utmost importance. Although feasible in many cases and tempting, laparoscopic resection should not be attempted in patients with tumors suspicious for or known to be adrenocortical carcinoma.

Short-term growth hormone treatment in children with Hurler syndrome after hematopoietic cell transplantation.

Children with Hurler syndrome experience progressive growth failure after hematopoietic cell transplantation (HCT). The goal of this study was to review the safety and efficacy of growth hormone (GH) in eight children with Hurler syndrome who were treated at our institution with GH for short stature or GH deficiency between 2005 and 2008. The age at initiation of treatment with GH was 9.6+/-2.3 years and time since HCT was 7.5+/-1.5 years. Mean GH dose was 0.32 mg/kg/week. Baseline growth velocity was 3.5+/-1.5 cm/year (-2.6+/-1.9 s.d.), and it increased to 5.2+/-3.0 cm/year (-0.1+/-3.6 s.d.) after 1 year of treatment. Of the six patients with radiographic data, there was one progression of scoliosis, one progression of kyphosis and one progression of genu valgum. No patient discontinued treatment due to progression of skeletal disease. One patient discontinued GH due to slipped capital femoral epiphysis. Preliminary data suggest that 1-year GH treatment may modestly improve growth velocity in children with Hurler syndrome.

Growth and endocrine function in patients with Hurler syndrome after hematopoietic stem cell transplantation.

Short stature is characteristic of Hurler syndrome, or mucopolysaccharidosis type IH (MPS IH). Hematopoietic stem cell transplantation (HSCT) is used to treat children with MPS IH. While HSCT corrects some of the metabolic features of MPS IH, its effects on growth are not well delineated. We investigated growth in patients with MPS IH after HSCT and described accompanying endocrine abnormalities. A cohort of 48 patients with MPS IH who had received HSCT between 1983 and 2005 were included. The prevalence of short stature (height <-2 s.d. score, SDS) before HSCT was 9%, and increased to 71% at last follow-up (6.9+/-5.1 years after HSCT). Short stature was positively associated with increased age at HSCT (P=0.002) and TBI (P=0.009). In total, 23% had growth hormone deficiency and/or low insulin-like growth factor-1, one female patient had premature adrenarche, one precocious puberty and 27% had clinical or subclinical hypothyroidism. Growth failure is highly prevalent in children with MPS IH after HSCT. Children who had no TBI exposure and were younger at the time of HSCT had a better height outcome.

Complete reconstitution of human IkappaB kinase (IKK) complex in yeast. Assessment of its stoichiometry and the role of IKKgamma on the complex activity in the absence of stimulation.

The IkappaB kinase (IKK) complex, composed of two catalytic subunits (IKKalpha and IKKbeta) and a regulatory subunit (IKKgamma), is the key enzyme in activation of nuclear factor kappaB (NF-kappaB). To study the mechanism and structure of the complex, we wanted to recombinantly express IKK in a model organism that lacks IKK. For this purpose, we have recombinantly reconstituted all three subunits together in yeast and have found that it is biochemically similar to IKK isolated from human cells. We show that there is one regulatory subunit per kinase subunit. Thus, the core subunit composition of IKKalpha.beta.gamma complex is alpha(1)beta(1)gamma(2), and the core subunit composition of IKKbeta.gamma is beta(2)gamma(2). The activity of the IKK complex (alpha+beta+gamma or beta+gamma) expressed in yeast (which lack NF-kappaB and IKK) is 4-5-fold higher than an equivalent amount of IKK from nonstimulated HeLa cells. In the absence of IKKgamma, IKKbeta shows a level of activity similar to that of IKK from nonstimulated HeLa cells. Thus, IKKgamma activates IKK complex in the absence of upstream stimuli. Deleting the gamma binding domain of IKKbeta or IKKalpha prevented IKKgamma induced activation of IKK complex in yeast, but it did not prevent the incorporation of IKKgamma into IKK and large complex formation. The possibility of IKK complex being under negative control in mammalian cells is discussed.

Alfalfa rapidly remediates excess inorganic nitrogen at a fertilizer spill site.

By 19%, standard remediation techniques had significantly reduced the concentration of nitrate nitrogen (NO3- -N) in local ground water at the site of a 1989 anhydrous ammonia spill, but NO3- -N concentrations in portions of the site still exceeded the public drinking water standard. Our objective was to determine whether local soil and ground water quality could be improved with alfalfa (Medicago sativa L.). A 3-yr study was conducted in replicated plots (24 by 30 m) located hydrologically upgradient of the ground water under the spill site. Three alfalfa entries ['Agate', Ineffective Agate (a non-N2-fixing elite germplasm similar to Agate), and MWNC-4 (an experimental germplasm)] were seeded in the spring of 1996. Corn (Zea mays L.) or wheat (Triticum aestivum L.) was seeded adjacent to the alfalfa each year. Crops were irrigated with N-containing ground water to meet water demand. During the 3-yr period, about 540 kg of inorganic N was removed from the aquifer through irrigation of 4.9 million L water. Cumulative N removal from the site over 3 yr was 972 kg N ha(-1) in Ineffective Agate alfalfa hay, compared with 287 kg N ha(-1) for the annual cereal grain. Soil solution NO3- concentrations were reduced to low and stable levels by alfalfa, but were more variable under the annual crops. Ground water quality improved, as evidenced by irrigation water N concentration. We do not know how much N was removed by the N2-fixing alfalfas, but it appears that either fixing or non-N2-fixing alfalfa will effectively remove inorganic N from N-affected sites.

Osteochondromas of the distal aspect of the tibia or fibula. Natural history and treatment.

BACKGROUND: There is little information on the natural history or treatment of osteochondromas arising from the distal aspect of either the tibia or the fibula. It is believed that there is a risk of deformation of the ankle if these exostoses are left untreated or if the physis or neurovascular structures are injured during operative intervention. METHODS: We reviewed the records of twenty-three patients who had been treated for osteochondroma of the distal aspect of the tibia or fibula between 1980 and 1996. Four of the patients had hereditary multiple cartilaginous exostoses. There were seventeen male and six female patients, and the average age at the time of presentation was sixteen years (range, eight to forty-eight years). RESULTS: Preoperative radiographs showed evidence of plastic deformation of the fibula in eleven patients who had a large osteochondroma. Four patients elected not to have an operation. The tumor was excised in nineteen patients. Postoperatively, all nineteen patients had a Musculoskeletal Tumor Society score of 100 percent for function of the lower extremity with pain-free symmetrical and unrestricted motion of the ankle at the latest follow-up examination. Partial remodeling of the tibia and fibula gradually diminished the asymmetry of the ankles in all nineteen operatively managed patients; however, the remodeling was most complete in the younger patients. Pronation deformities of the ankle did not change after excision of the tumor. Complications of operative treatment included four recurrences (only three of which were symptomatic), one sural neuroma, one superficial wound infection, and one instance of growth arrest of the distal aspects of the tibia and fibula. CONCLUSIONS: Osteochondromas of the distal and lateral aspects of the tibia were more often symptomatic than those of the distal aspect of the fibula; they most commonly occurred in the second decade of life with ankle pain, a palpable mass, and unrestricted ankle motion. Untreated or partially excised lesions in skeletally immature patients may become larger and cause plastic deformation of the tibia and fibula and a pronation deformity of the ankle. Ideally, operative intervention should be delayed until skeletal maturity, but, in symptomatic patients, partial excision preserving the physis may be necessary for the relief of symptoms and the prevention of progressive ankle deformity. However, partial excision is associated with a high rate of recurrence, so a close follow-up is required. Skeletally mature patients who are symptomatic may require excision of the tumor.

A new mechanism of action of fluoride on streptococci.

Addition of fluoride to the growth medium of Streptococcus sobrinus resulted in a loss of glucan-binding lectin activity. Upon removal of fluoride, the bacteria regained their ability to bind glucan in about one generation. Chloramphenicol prevented recovery of ability to produce the lectin, showing the requirement for protein synthesis. Fluoride also caused a significant reduction in the tendency of the streptococci to form chains of cells, although the spent medium from fluoride-containing growth media did not dechain control cells. The fluoride thus does not activate autolytic enzymes. Importantly, 2-D electrophoresis and SDS-PAGE revealed several proteins were synthesized in the presence of fluoride that were not synthesized in its absence. It seems possible that fluoride places a stress on the bacteria, causing the synthesis of proteins that may play a role in protecting the cells against the stress. Numerous stress proteins are known for bacteria, including those resulting from heat, enzymes and osmotic shocks. The ability of fluoride to cause loss of glucan-binding may be related to its reported beneficial effects on oral health.

Bradykinin induces tubulin phosphorylation and nuclear translocation of MAP kinase in mesangial cells.

Glomerular hypertension and glomerular hypertrophy act early and synergistically to promote glomerular injury in diabetes. We have previously shown that increased renal kinin production contributes to the glomerular hemodynamic abnormalities associated with diabetes. Glomerulosclerosis, characterized by mesangial cell proliferation and matrix expansion, is the final pathway leading to renal failure. The signal(s) initiating mesangial cell proliferation is ill defined. In the present study, we utilized immunofluorescence, immunoprecipitation, and immunoblotting techniques to identify substrates that are tyrosine phosphorylated in response to bradykinin action in mesangial cells. Immunofluorescence microscopy of mesangial cells stained with anti-phosphotyrosine (anti-PY) antibodies following bradykinin treatment (10(-9)-10(-6) M) revealed a dose-dependent increase in the labeling of cytoplasmic and nuclear proteins. Immunoprecipitation with anti-PY, followed by immunoblot revealed bradykinin-induced tyrosyl phosphorylation of tubulin and mitogen-activated protein kinase (MAPK). Confocal microscopy of mesangial cells stained for MAPK indicated that bradykinin stimulation resulted in translocation of MAPK from the cytoplasm to the nucleus by 2 h. These data demonstrate that bradykinin action results in the tyrosine phosphorylation of cellular proteins in mesangial cells and suggest a role for tubulin and MAPK in the signaling cascade of bradykinin leading to altered mesangial function.

Activation of C-jun N-terminal kinase/stress-activated protein kinase in primary glial cultures.

Glial cells in the mammalian CNS are subject to environmental stress resulting from a variety of neuro-pathological conditions. In this study, we have examined the activation of a stress signal responsive kinase, i.e., stress-activated protein kinase (SAPK) or c-Jun N-terminal kinase (JNK), in primary cultures of rat brain glial cells (i.e., astrocytes and oligodendrocytes) and an oligodendrocyte progenitor cell line, CG4, in response to cytokines and other stress inducers. JNK/SAPK activity was measured by an immune complex kinase assay using polyclonal anti-JNK antibodies along with GST c-Jun (1-79) as the substrate. Among the cytokines tested, TNF-alpha had the strongest effect on JNK activation followed by TNF-beta in both the glial cell types while a substantial level of kinase activation was observed in response to IL-1 in astrocytes. JNK activation by TNF-alpha in astrocytes, but not in oligodendrocytes, showed a biphasic response. An in-gel kinase assay of cell extracts and immunoprecipitated JNK confirmed the activation of JNK1 in cells treated with TNF-alpha. JNK was also activated by several other stress-inducing factors including. UV light, heat shock, inhibitors of protein synthesis, and mechanical injury. Incubation of cells with bacterial sphingomyelinase and a cell-permeable ceramide stimulated JNK activity, suggesting that the ceramide pathway may play a role in JNK activation, although the time course of activation did not correspond to that of TNF-alpha. The results are discussed in terms of possible roles of JNK activation in signaling for gliosis in astrocytes and as a protective/toxic response in oligodendrocytes.

Activation of cJun NH2-terminal kinase/stress-activated protein kinase by insulin.

One of insulin's many biological effects is the increased transcription of AP-1-regulated genes. cJun is the principal component of the AP-1 transcription complex, which is regulated by the newly discovered members of the MAPK superfamily referred to as cJun NH2-terminal kinases (JNKs) or stress-activated protein kinases (SAPKs). We show that insulin stimulates a dose- and time-dependent increase in JNK activity in Rat 1 fibroblasts overexpressing human insulin receptors (Rat 1 HIR cells). Using two different polyclonal anti-JNK antibodies, JNK activity was measured after immunoprecipitation from whole cell extracts by phosphorylation of GSTcJun(1-79). Peak activation occurred 15 min after insulin addition, resulting in a 2.5-fold increase in GSTcJun(1-79) phosphorylation over unstimulated controls. Maximal JNK activation correlated with the onset of AP-1 DNA binding activity. Both insulin-stimulated JNK activity and insulin-induced AP-1 transcriptional activity were found to be Ras-dependent. These data suggest that in Rat 1 cells, JNK activation may play a role in insulin-regulated AP-1 transcriptional activity leading to a mitogenic response.

Anxiety disorders of childhood, Implications for adult psychopathology.

Although the exact path of acquisition remains incompletely understood, research supports the association between anxiety disorders in children and psychopathologic conditions in adults. This article addresses this relationship; reviews findings on the temperamental profile and behavioral inhibition, which may be an early identifiable childhood predictor of later anxiety disorders; and discusses the importance of early intervention.