Insulin reference intervals in Brazilian adolescents by direct and indirect approaches: validation of a data mining method from laboratory data.

OBJECTIVE: To determine reference intervals (RI) for fasting blood insulin (FBI) in Brazilian adolescents, 12 to 17 years old, by direct and indirect approaches, and to validate indirectly determined RI. METHODS: Two databases were used for RI determination. Database 1 (DB1), used to obtain RI through a posteriori direct method, consisted of prospectively selected healthy individuals. Database 2 (DB2) was retrospectively mined from an outpatient laboratory information system (LIS) used for the indirect method (Bhattacharya method). RESULTS: From DB1, 29345 individuals were enrolled (57.65 % female) and seven age ranges and sex partitions were statistically determined according to mean FBI values: females: 12 and 13 years-old, 14 years-old, 15 years-old, 16 and 17 years-old; and males: 12, 13 and 14 years-old, 15 years-old, 16 and 17 years-old. From DB2, 5465 adolescents (67.5 % female) were selected and grouped according to DB1 partitions. The mean FBI level was significantly higher in DB2, on all groups. The RI upper limit (URL) determined by Bhattacharya method was slightly lower than the 90 % CI URL directly obtained on DB1, except for group female 12 and 13 years old. High agreement rates for diagnosing elevated FBI in all groups on DB1 validated indirect RI presented. CONCLUSION: The present study demonstrates that Bhattacharya indirect method to determine FBI RI in adolescents can overcome some of the difficulties and challenges of the direct approach.

Case Report: Composite pheochromocytoma with ganglioneuroma component: A report of three cases.

Composite pheochromocytoma (CP) is a very rare tumor originating from neural crest cells, predominantly composed of pheochromocytoma (PCC), a chromaffin cell tumor arising in adrenal medulla, and ganglioneuroma, a tumor derived from autonomic ganglion cells of the nervous system. Moreover, CP may be present in the hereditary syndromes of which pheochromocytoma is part. Literature offers scarce data on this subject, and particularly about its biological behavior, clinical evolution, and molecular profile. We report the phenotype and outcome of three cases of CP (PCC and ganglioneuroma components), followed up at the Endocrine Service of the Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, UFRJ, Rio de Janeiro, Brazil. Two nonsyndromic patients (cases 1 and 2) were negative to germline mutations in genes VHL, SDHB, SDHC, SDHD, SDHAF2, TMEM127, and MAX, while the third case (case 3) had clinical diagnosis of neurofibromatosis syndrome. Cases 1, 2, and 3 were diagnosed at 29, 39, and 47 years old, respectively, and were followed up for 3, 17, and 9 years without no CP recurrence. All cases had apparent symptoms of catecholaminergic excess secreted by PCC. Ganglioneuroma, the neurogenic component present in all three cases, had a percentage representation ranging from 5% to 15%. Tumors were unilateral and large, measuring 7.0 cm × 6.0 cm × 6.0 cm, 6.0 cm × 4.0 cm × 3.2 cm, and 7.5 cm × 6.0 cm × 4.5 cm, respectively. All cases underwent adrenalectomy with no recurrence, metastasis, or development of contralateral tumor during follow-up. Genetic testing has been scarcely offered to CP cases. However, a similar frequency of genetic background is found when compared with classic PCC, mainly by the overrepresentation of NF1 cases in the CP subset. By literature review, we identified a notorious increase in cases reported with CP in the last decade, especially in the last 3 years, indicating a recent improvement in the diagnosis of this rare disorder in clinical practice.

Supergroup F Wolbachia in terrestrial isopods: Horizontal transmission from termites?

Horizontal transmission between distantly related species has been used to explain how Wolbachia infect multiple species at astonishing rates despite the selection for resistance. Recently, a terrestrial isopod species was found to be infected by an unusual strain of supergroup F Wolbachia. However, only Wolbachia of supergroup B is typically found in isopods. One possibility is that these isopods acquired the infection because of their recurrent contact with termites-a group with strong evidence of infection by supergroup F Wolbachia. Thus, our goals were: (1) check if the infection was an isolated case in isopods, or if it revealed a broader pattern; (2) search for Wolbachia infection in the termites within Brazil; and (3) look for evidence consistent with horizontal transmission between isopods and termites. We collected Neotroponiscus terrestrial isopods and termites along the Brazilian coastal Atlantic forest. We sequenced and identified the Wolbachia strains found in these groups using coxA, dnaA, and fpbA genes. We constructed phylogenies for both bacteria and host taxa and tested for coevolution. We found the supergroup F Wolbachia in other species and populations of Neotroponiscus, and also in Nasutitermes and Procornitermes termites. The phylogenies showed that, despite the phylogenetic distance between isopods and termites, the Wolbachia strains clustered together. Furthermore, cophylogenetic analyses showed significant jumps of Wolbachia between terrestrial isopods and termites. Thus, our study suggests that the horizontal transmission of supergroup F Wolbachia between termites and terrestrial isopods is likely. Our study also helps understanding the success and worldwide distribution of this symbiont. SUPPLEMENTARY INFORMATION: The online version of this article (10.1007/s10682-021-10101-4) contains supplementary material, which is available to authorized users.

A retrospective analysis of scientific publications on the deep sea from 1987 to 2016.

The deep sea remains the least known biome. Despite this fact, anthropic activities have affected these regions in various ways. The objective of this study was to outline the scientific production scenario based on deep sea research and to analyze trends present in the literature. For this, the bibliographical resources available from the Web of Science (WoS) were surveyed. Between 1987 and 2016, 11,079 articles on the deep sea were published. Growth was over 100% from the first to second decade and 75% from the second to third. The most productive countries were the USA, Germany, France, England and Japan. Of the 404 journals that published articles on the deep sea, 10% accounted for approximately 60% of the total published articles. The keyword with the highest occurrence was "diversity". In the first two decades, the keywords with the greatest "strength" were related to research on mining, especially for hydrocarbons. The description of new species and the analysis of the effects of climate change appear to be emerging trends in deep sea research. Mining continues to be primarily responsible for driving the development of deep sea research.

Woodlice and their parasitoid flies: revision of Isopoda (Crustacea, Oniscidea) - Rhinophoridae (Insecta, Diptera) interaction and first record of a parasitized Neotropical woodlouse species.

Terrestrial isopods are soil macroarthropods that have few known parasites and parasitoids. All known parasitoids are from the family Rhinophoridae (Insecta: Diptera). The present article reviews the known biology of Rhinophoridae flies and presents the first record of Rhinophoridae larvae on a Neotropical woodlouse species. We also compile and update all published interaction records. The Neotropical woodlouse Balloniscusglaber was parasitized by two different larval morphotypes of Rhinophoridae. Including this new record, there are 18 Isopoda species known to be parasitized and 13 Rhinophoridae species with known hosts, resulting in 35 interactions. There are a total of 53 interaction records from Holarctic and Neotropical countries. Of the 18 known isopod hosts, only five species have more than one parasitoid, including the new Neotropical host record presented in this work.

Wolbachia in Neotropical terrestrial isopods.

Despite Wolbachia being widespread among terrestrial isopods, studies on this symbiotic relationship are still incipient in the Neotropical region. The aims of the present study were to investigate the presence and prevalence of Wolbachia in natural populations of terrestrial isopod species in South America, and to analyze the diversity and phylogenetic relationships of Wolbachia strains. A total of 1172 individuals representing 11 families and 35 species were analyzed. We observed distinct evolutionary scenarios according to the geographical origins of the species: strains harbored by most of the introduced species belong to the Oniclade in supergroup B and are identical to those found in their original ecozone (i.e. Palearctic). On the other hand, the strains found in native Neotropical terrestrial isopods showed low prevalence, high diversity and none of them belonged to the Oniclade, although most belonged to supergroup B. The dynamics of infection in Neotropical species seems to be the result of several events of loss and acquisition of the bacteria, which refutes the hypothesis of an ancestral acquisition of Wolbachia in Oniscidea. The presence of strains from supergroups A and F was also detected for the first time in terrestrial isopods, revealing a Wolbachia diversity previously unknown for this group of host.

Metabolic glucose status and pituitary pathology portend therapeutic outcomes in acromegaly.

INTRODUCTION: Acromegaly is frequently associated with impaired glucose tolerance and/or diabetes. To evaluate the relationship between glucose metabolism and acromegaly disease, we evaluated 269 consecutive patients from two referral centres. METHODS: Clinical presentation, pituitary tumor size and invasiveness, and pituitary pathology were captured in a dedicated database. RESULTS: 131 women and 138 men with a mean age of 53.8 years were included. Of these, 201 (74.7%) presented with a macroadenoma and 18 (6.7%) with a microadenoma. Radiographic invasion was present in 91 cases (33.8%). Mean tumor diameter was 1.86 cm (0.2-4.6). Pituitary histopathologic findings revealed pure GH-producing somatotroph adenomas (SA) in 147 patients, prolactin-production by mixed lactotroph (LA) and SA or mammosomatotroph adenoma (MSA) in 46 [22.4%], acidophil stem cell adenoma in 6 [2.9%], and other diagnoses in 6 [2.9%]. Medical treatment included octreotide in 96 [36.9%] and in combination with pegvisomant or dopamine agonists in 63 [24.2%]. Nearly 80% of patients achieved IGF-1 normalization. Importantly, patients with pure somatotroph adenomas were significantly more likely to present with abnormal glucose metabolism [48.7%] than those with mixed adenomas [9.7%] [p<0.001] independent of GH/IGF-1 levels or tumor invasiveness. Abnormal glucose metabolism and pituitary pathology also remained linked following IGF-1 normalization. Moreover patients with pure SA and abnormal glucose metabolism were significantly (p<0.001) less likely to achieve disease remission despite the same therapeutic strategies. Conversely, patients with mixed adenomas were more likely (OR: 2.766 (95% CI: 1.490-5.136) to achieve disease remission. CONCLUSIONS: Patients with pure somatotroph adenomas are more likely than those with mixed adenomas to exhibit abnormal glucose metabolism.

Evaluation of the WHO 2010 grading and AJCC/UICC staging systems in prognostic behavior of intestinal neuroendocrine tumors.

BACKGROUND: The increasing incidence and heterogeneous behavior of intestinal neuroendocrine tumors (iNETs) pose a clinicopathological challenge. Our goal was to decribe the prognostic value of the new WHO 2010 grading and the AJCC/UICC TNM staging systems for iNETs. Moreover, outcomes of patients treated with somatostatin analogs were assessed. METHODS: We collected epidemiological and clinicopathological data from 93 patients with histologically proven iNETs including progression and survival outcomes. The WHO 2010 grading and the AJCC/UICC TNM staging systems were applied for all cases. RECIST criteria were used to define progression. Kaplan-Meier analyses for progression free survival (PFS) and overall survival (OS) were performed. RESULTS: Mean follow-up was 58.6 months (4-213 months). WHO 2010 grading yielded PFS and disease-specific OS of 125.0 and 165.8 months for grade 1 (G1), 100.0 and 144.2 months for G2 and 15.0 and 15.8 months for G3 tumors (p = 0.004 and p = 0.001). Using AJCC staging, patients with stage I and II tumors had no progression and no deaths. Stage III and IV patients demonstrated PFS of 138.4 and 84.7 months (p = 0.003) and disease-specific OS of 210.0 and 112.8 months (p = 0.017). AJCC staging also provided informative PFS (91.2 vs. 50.0 months, p = 0.004) and OS (112.3 vs. 80.0 months, p = 0.005) measures with somatostatin analog use in stage IV patients. CONCLUSION: Our findings underscore the complementarity of WHO 2010 and AJCC classifications in providing better estimates of iNETS disease outcomes and extend the evidence for somatostatin analog benefit in patients with metastatic disease.

Hormone profiling, WHO 2010 grading, and AJCC/UICC staging in pancreatic neuroendocrine tumor behavior.

Pancreatic neuroendocrine tumors (pNETs) are the second most common pancreatic neoplasms, exhibiting a complex spectrum of clinical behaviors. To examine the clinico-pathological characteristics associated with long-term prognosis we reviewed 119 patients with pNETs treated in a tertiary referral center using the WHO 2010 grading and the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) staging systems, with a median follow-up of 38 months. Tumor size, immunohistochemistry (IHC) profiling and patient characteristics-determining stage were analyzed. Primary clinical outcomes were disease progression or death. The mean age at presentation was 52 years; 55% were female patients, 11% were associated with MEN1 (multiple endocrine neoplasia 1) or VHL (Von Hippel-Lindau); mean tumor diameter was 3.3 cm (standard deviation, SD) (2.92). The clinical presentation was incidental in 39% with endocrine hypersecretion syndromes in only 24% of cases. Nevertheless, endocrine hormone tissue immunoreactivity was identified in 67 (56.3%) cases. According to WHO 2010 grading, 50 (42%), 38 (31.9%), and 3 (2.5%) of tumors were low grade (G1), intermediate grade (G2), and high grade (G3), respectively. Disease progression occurred more frequently in higher WHO grades (G1: 6%, G2: 10.5%, G3: 67%, P = 0.026) and in more advanced AJCC stages (I: 2%, IV: 63%, P = 0.033). Shorter progression free survival (PFS) was noted in higher grades (G3 vs. G2; 21 vs. 144 months; P = 0.015) and in more advanced AJCC stages (stage I: 218 months, IV: 24 months, P < 0.001). Liver involvement (20 vs. 173 months, P < 0.001) or histologically positive lymph nodes (33 vs. 208 months, P < 0.001) were independently associated with shorter PFS. Conversely, tissue endocrine hormone immunoreactivity, independent of circulating levels was significantly associated with less aggressive disease. Age, gender, number of primary tumors, and heredity were not significantly associated with prognosis. Although the AJCC staging and WHO 2010 grading systems are useful in predicting disease progression, tissue endocrine hormone profiling provides additional information of potentially important prognostic value.

Low triglyceride levels are associated with a better metabolic control in patients with type 1 diabetes.

BACKGROUND: Although it is well known in the literature that high triglyceride serum (TG) levels can jeopardize the metabolic control, little is known about the influence of low TG on type 1 diabetes patients (T1D). The aim of this study is to investigate the distribution of TG serum levels in individuals with T1D and its relationship with metabolic control. FINDINGS: We reviewed the medical charts of 180 patients with T1D, who were classified in groups according to TG levels: 1) low (below 50 mg/dL); 2) normal (50-150 mg/dL); 3) high (above 150 mg/dL). TG were low in 21.1% (n = 38; group 1), normal in 68.6% (n = 123; group 2) and high in 10.6% (n = 19; group 3). High TG was associated with a poor metabolic control (p < 0.001). Patients with TG lower than 50 mg/dL had a lower HbA1c than those with TG between 50 and 150 mg/dL (7.41+/-1.50% vs 8.56%+/-1.94%; p = 0.002). CONCLUSION: TG lower than 50 mg/dL was common and might be associated with a better metabolic control in patients with T1D, although it is not clear whether the former is the cause or consequence for the latter.