Detecting N-RAS Q61R Mutated Thyroid Neoplasias by Immunohistochemistry

Abstract

Recently, the immunohistochemistry (IHC) for N-RAS Q61R has been developed and commercialized for clinical practice. Here, we investigated the reliability of IHC to identify N-RAS Q61R mutated thyroid neoplasia. A series of 24 consecutive thyroid lesions undergone surgery following indeterminate cytology were enrolled. Paraffin sections were stained for IHC using the rabbit monoclonal anti-human N-RAS Q61R, clone SP174. N-RAS mutations in codon 61 were also investigated by automated sequencing. At histology, 12 cases of follicular carcinoma, cytologically defined as follicular lesions, 1 papillary cancer, 7 follicular adenomas, and 4 hyperplastic nodules were found. Of these, 4 showed a positive IHC for anti N-RAS antibody where N-RAS expression was detected mainly at cytoplasmic level with similar intensity of reaction. The remaining cases had negative IHC. A 100% concordance between IHC and molecular analysis for N-RAS Q61R was observed. In conclusion, this study shows high reliability of IHC to identify N-RAS Q61R mutated thyroid lesions with high cost-effectiveness. These data indicate the reliability of IHC to identify N-RAS Q61R mutated thyroid neoplasia and suggest to adopt this approach for a more accurate management of patients, when indicated.

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HIV Latency: Should We Shock or Lock?

Publication date: Available online 7 January 2017
Source:Trends in Immunology
Author(s): Gilles Darcis, Benoit Van Driessche, Carine Van Lint
Combinatory antiretroviral therapy (cART) increases the survival and quality of life of HIV-1-infected patients. However, interruption of therapy almost invariably leads to the re-emergence of detectable viral replication because HIV-1 persists in viral latent reservoirs. Improved understanding of the molecular mechanisms involved in HIV-1 latency has paved the way for innovative strategies that attempt to purge latent virus. In this article we discuss the results of the broadly explored 'shock and kill' strategy, and also highlight the major hurdles facing this approach. Finally, we present recent innovative works suggesting that locking out latent proviruses could be a potential alternative therapeutic strategy.



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Risque accru de cardiopathie ischémique et de mortalité cardiovasculaire chez les personnes atteintes de maladie de Verneuil (hidradénite suppurée)

Publication date: Available online 6 January 2017
Source:Annales de Dermatologie et de Vénéréologie
Author(s): A. Maruani, B. Giraudeau, I. Abdo, P. Raphaël




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Management of an inguinal hernia in patients with pseudomyxoma peritonei

Publication date: Available online 6 January 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Paul H. Sugarbaker
BackgroundPseudomyxoma peritonei is a disease that results from a perforated mucinous neoplasm of the appendix so that mucinous ascites and mucin-producing tumor cells are widely disseminated in a characteristic pattern throughout the abdomen and pelvis. The intraabdominal mucus can accumulate in the inguinal canal and by physical examination be indistinguishable from the usual inguinal hernia.MethodsA database of patients with pseudomyxoma peritonei was used to identify patients who had an inguinal hernia prior to or at the time of cytoreductive surgery (CRS) and perioperative hyperthermic chemotherapy (HIPEC). At the time of CRS, care was taken in all patients to remove the peritoneal lining of the inguinal canal. Patients who had the inguinal hernia repaired prior to definitive treatment with CRS and HIPEC had all tissue and mesh associated with prior herniorrhaphy resected.ResultsIn 178 pseudomyxoma peritonei patients, 17 had a new onset or previously repaired inguinal hernia that required extraction of mucus and mucinous tumor from the hernia site. No repair of the open inguinal canal was attempted at the time of CRS. No recurrent inguinal hernias were recorded and no patients required an inguinal incision at a later time to resect progressive disease within the inguinal canal.ConclusionsInguinal hernias caused by mucinous ascites and tumor were definitively treated by cytoreductive surgery plus HIPEC. Extraction of tumor and peritoneum from the inguinal canal facilitates fibrous closure of the hernia defect so that hernia recurrence was not observed.



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Very Early Onset Sporadic Alzheimer’s disease with a De Nove Mutation in the PSEN1 gene

Publication date: Available online 6 January 2017
Source:Neurobiology of Aging
Author(s): Fan Lou, Xiaoguang Luo, Ming Li, Yan Ren, Zhiyi He
We report a 22 year-onset age man diagnosed with rapidly progressing early-onset Alzheimer's disease (EOAD) with predominant extrapyramidal symptoms as the initial presenting symptoms and V391G mutation in presenilin 1 gene (PSEN1) was founded. The unaffected parents of the proband are not carriers of the mutation but have histories of extrapyramidal diseases, suggesting de novo origin of V391G mutation. The novel Val391Gly variation widens the number of PSEN1 mutations responsible for EOAD with extrapyramidal phenotype and would help to establish a functional map of presenilin 1 protein architecture.

Graphical abstract

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Distinct patterns of increased translocator protein in posterior cortical atrophy and amnestic Alzheimer's disease

Publication date: March 2017
Source:Neurobiology of Aging, Volume 51
Author(s): William C. Kreisl, Chul Hyoung Lyoo, Jeih-San Liow, Joseph Snow, Emily Page, Kimberly J. Jenko, Cheryl L. Morse, Sami S. Zoghbi, Victor W. Pike, R. Scott Turner, Robert B. Innis
We sought to determine whether patients with posterior cortical atrophy (PCA) demonstrate a pattern of binding to translocator protein 18 kDa, a marker of microglial activation, that is distinct from that in patients with amnestic presentation of Alzheimer's disease (AD). Eleven PCA patients, 11 amnestic AD patients, and 15 age-matched controls underwent positron emission tomography with ¹¹C-PBR28 to measure translocator protein 18 kDa. PCA patients showed greater ¹¹C-PBR28 binding than controls in occipital, posterior parietal, and temporal regions. In contrast, amnestic AD patients showed greater ¹¹C-PBR28 binding in inferior and medial temporal cortex. Increased ¹¹C-PBR28 binding overlapped with reduced cortical volume for both PCA and amnestic AD patients, and with areas of reduced glucose metabolism in PCA patients. While both patient groups showed diffuse amyloid binding, PCA patients showed greater binding than amnestic AD patients in bilateral occipital cortex. These results suggest that microglial activation is closely associated with neurodegeneration across different subtypes of AD.



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Retinal thinning is uniquely associated with medial temporal lobe atrophy in neurologically normal older adults

Publication date: March 2017
Source:Neurobiology of Aging, Volume 51
Author(s): Kaitlin B. Casaletto, Michael E. Ward, Nicholas S. Baker, Brianne M. Bettcher, Jeffrey M. Gelfand, Yaqiao Li, Robert Chen, Shubir Dutt, Bruce Miller, Joel H. Kramer, Ari J. Green
Given the converging pathologic and epidemiologic data indicating a relationship between retinal integrity and neurodegeneration, including Alzheimer's disease (AD), we aimed to determine if retinal structure correlates with medial temporal lobe (MTL) structure and function in neurologically normal older adults. Spectral-domain optical coherence tomography, verbal and visual memory testing, and 3T-magnetic resonance imaging of the brain were performed in 79 neurologically normal adults enrolled in a healthy aging cohort study. Retinal nerve fiber thinning and reduced total macular and macular ganglion cell volumes were each associated with smaller MTL volumes (ps < 0.04). Notably, these markers of retinal structure were not associated with primary motor cortex or basal ganglia volumes (regions relatively unaffected in AD) (ps > 0.70), or frontal, precuneus, or temporoparietal volumes (regions affected in later AD Braak staging ps > 0.20). Retinal structure was not significantly associated with verbal or visual memory consolidation performances (ps > 0.14). Retinal structure was associated with MTL volumes, but not memory performances, in otherwise neurologically normal older adults. Given that MTL atrophy is a neuropathological hallmark of AD, retinal integrity may be an early marker of ongoing AD-related brain health.



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Mitochondrial genes are altered in blood early in Alzheimer's disease

Publication date: Available online 7 January 2017
Source:Neurobiology of Aging
Author(s): Katie Lunnon, Aoife Keohane, Ruth Pidsley, Stephen Newhouse, Joanna Riddoch-Contreras, Elisabeth B. Thubron, Matthew Devall, Hikka Soininen, Iwona Kłoszewska, Patrizia Mecocci, Magda Tsolaki, Bruno Vellas, Leonard Schalkwyk, Richard Dobson, Afshan N. Malik, John Powell, Simon Lovestone, Angela Hodges
Although mitochondrial dysfunction is a consistent feature of Alzheimer's disease (AD) in the brain and blood, the molecular mechanisms behind these phenomena are unknown. Here we have replicated our previous findings demonstrating reduced expression of nuclear-encoded oxidative phosphorylation (OXPHOS) subunits and subunits required for the translation of mitochondrial-encoded OXPHOS genes in blood from people with AD and mild cognitive impairment (MCI). Interestingly this was accompanied by increased expression of some mitochondrial-encoded OXPHOS genes, namely those residing closest to the transcription start site of the polycistronic heavy chain mitochondrial transcript (MT-ND1, MT-ND2, MT-ATP6, MT-CO1, MT-CO2, MT-C03) and MT-ND6 transcribed from the light chain. Further we show that mitochondrial DNA copy number was unchanged suggesting no change in steady-state numbers of mitochondria. We suggest an imbalance in nuclear and mitochondrial genome-encoded OXPHOS transcripts may drive a negative feedback loop reducing mitochondrial translation and compromising OXPHOS efficiency, which is likely to generate damaging reactive oxygen species (ROS).



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Retraction notice to “Management of liver hydatid cysts – Current perspectives” [Medical Journal Armed forces India 68 (2012) 304–309]

Publication date: January 2017
Source:Medical Journal Armed Forces India, Volume 73, Issue 1
Author(s): S. Anand, S. Rajagopalan, Raj Mohan
This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://ift.tt/1poHqya).This article has been retracted at the request of the Editor-in-Chief.The authors have plagiarized part of a paper that had already appeared in Am J Trop Med Hyg, 79 (2008) 301–311. http://ift.tt/2jnvAKn. One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. Re-use of any data should be appropriately cited. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.



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Letter to the Editor

Publication date: January 2017
Source:Medical Journal Armed Forces India, Volume 73, Issue 1
Author(s): Amit Dua, Mathangi Krishnakumar




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Governing Council Page

Publication date: January 2017
Source:Medical Journal Armed Forces India, Volume 73, Issue 1





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Ending AIDS: The 90–90–90 strategy

Publication date: January 2017
Source:Medical Journal Armed Forces India, Volume 73, Issue 1
Author(s): R.R. Gangakhedkar




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Antitubercular therapy induced liver function tests abnormalities in human immunodeficiency virus infected individuals

Publication date: January 2017
Source:Medical Journal Armed Forces India, Volume 73, Issue 1
Author(s): Pankaj Puri, Navjyot Kaur, Sunny Pathania, Sandeep Kumar, P.K. Sharma, V.K. Sashindran
BackgroundBoth antitubercular therapy (ATT) and antiretroviral therapy (ART) can cause drug induced liver injury (DILI) in tuberculosis (TB) and human immunodeficiency virus (HIV) coinfection. The aim of this research was to study ATT-induced liver function test (LFT) abnormalities in HIV-infected patients.MethodsHIV-infected patients diagnosed with TB were evaluated with baseline LFT and CD4 counts. ATT regimen was modified if baseline LFT was significantly abnormal. Patients on protease inhibitors were given rifabutin instead of rifampicin. In patients on nevirapine-based ART, efavirenz was substituted for nevirapine. In ART-naive patients, the timing of introduction of ART was according to CD4 cell counts. LFT were repeated fortnightly or as clinically indicated for 10 weeks.ResultsWe studied 100 patients with HIV ([M – 67, F – 23], mean age: 40.05±10.75 years, mean CD4 cell count: 239.157±228.49cells/dL). Sixty-one patients were on ART prior to diagnosis of TB. Baseline LFT abnormalities (n=40) were similar in ART and non-ART group (28/61 vs 12/39, p=0.13). After starting ATT, derangement of LFT was observed in majority of patients (99/100). However, liver sparing ATT was required only in 15 patients. Bilirubin >2.5mg/dL was seen only in 9 patients. Significant rise in transaminases was commoner in patients on concurrent ART and ATT (p=0.044) and with baseline LFT abnormalities (p=0.00016). There was no case of acute liver failure or mortality.ConclusionMild LFT abnormalities are common in HIV-infected individuals on ATT. Concomitant use of ATT and ART and baseline LFT abnormalities increase the risk of significant DILI. However, with closer follow-up, serious liver injury can be prevented.



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Emotional and behavioral disturbances in school going HIV positive children attending HIV clinic

Publication date: January 2017
Source:Medical Journal Armed Forces India, Volume 73, Issue 1
Author(s): Deepak Joshi, Mithilesh K. Tiwari, Venkatnarayan Kannan, S.S. Dalal, S.S. Mathai
BackgroundTo study the emotional and behavioral disturbances (EBD) in school going HIV positive children attending HIV center in a tertiary care hospital.MethodThis cross-sectional study was conducted on 258 HIV infected children between 6 and 16 years of age, 200 were on Anti-retroviral therapy (ART) and 58 were not on ART. They were evaluated for EBD by using Pictorial Pediatric Symptom Checklist (PPSC) screening tool. A cut-off score of 28 was taken as significant for detecting early EBD.ResultsThe prevalence of EBD in our study is 11.2%. Demographic and disease related profile were assessed for correlation with EBD. Type of family (p=0.023), school attendance (p=0.034), school performance (p=0.045), and CD4 count (p=0.015) were detected to have significant association with early manifestation of EBD in the study group.ConclusionsHIV positive children who have low CD4 count, poor school attendance, and performance are at a higher risk of being detected with EBD. Screening with PPSC to identify EBD in HIV positive children attending HIV clinic in a hospital setting could help in early diagnosis and management.



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A cross-sectional study of liver function tests in HIV-infected persons in Western India

Publication date: January 2017
Source:Medical Journal Armed Forces India, Volume 73, Issue 1
Author(s): Sunny Pathania, Navjyot Kaur, Sandeep Kumar, V.K. Sashindran, Pankaj Puri
BackgroundDerangement of liver function tests (LFTs) is common in people living with human immunodeficiency virus/acquired immune deficiency syndrome (PLHA). The cause is multifactorial. Drug-induced liver injury (DILI) is the commonest cause and others being alcohol abuse and concomitant viral hepatitis. The aim of the research was to study the prevalence of LFT abnormalities in PLHA.MethodsThe study was carried out in a tertiary care hospital. Evaluation included a detailed history, thorough clinical examination and investigations including a haemogram, serum biochemistry, serology for hepatitis, and CD4 cell count.ResultsA total of 247 patients were evaluated. Of these, 212 (85.82%) were on antiretroviral therapy (ART), 111 (44.93%) were on anti-tubercular therapy (ATT), and 94 (38.05%) were on concurrent ATT–ART.Abnormal LFTs were seen in 128/247 (51.82%) PLHA. In the majority (88.28%), the LFT abnormalities were mild. LFT abnormalities were seen in 109/212 (51.4%) patients on ART, in 56/111 (50.5%) patients on ATT, 46/94 (48.93%) patients on concurrent ART–ATT. There was no difference in LFT abnormalities among the three groups nor was there any significant association with alcohol consumption. There was a statistically significant co-relation between albumin/globulin ratio and CD4 count (p=0.0002). Counter-intuitively, LFT abnormalities were commoner in patients not receiving nevirapine (p=0.043), but severe abnormalities (grade III/grade IV) were commoner in those receiving nevirapine (p=0.005) and in those on concurrent ART–ATT (p=0.008).ConclusionLFT abnormalities in PLHA are common; but usually mild. There is a strong association between severe abnormalities and nevirapine-based therapy (p=0.02) and concurrent ATT–ART (p=0.008).



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Overweight and obesity management guidelines 2016

Publication date: January 2017
Source:Medical Journal Armed Forces India, Volume 73, Issue 1
Author(s): Tukaram Gadekar, M.P. Cariappa




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Metabolic syndrome and BPH: What do we know?

Publication date: January 2017
Source:Medical Journal Armed Forces India, Volume 73, Issue 1
Author(s): Amit Agrawal




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Anxiety and risk assessment-related traits in a rat model of Spinocerebellar ataxia type 17

Publication date: 15 March 2017
Source:Behavioural Brain Research, Volume 321
Author(s): Elisavet I. Kyriakou, Giuseppe Manfré, Jesús A. Spadaro, Huu Phuc Nguyen, Johanneke E.Van der Harst, Judith R. Homberg
Anxiety as a common feature of several neurodegenerative/polyglutamine diseases is an important aspect for the face validity of an animal model for Spinocerebellar Ataxia type 17 (SCA17). Risk assessment and anxiety-like traits were characterised in 3–6–9 months old rats of a transgenic model for SCA17 using the standard behavioural test elevated plus maze. In addition, c-Fos immunostainings in the basolateral amygdala evaluated neuronal activation in correlation to the behavioural responses. The most prominent behavioural effect was a higher level of risk assessment in the transgenic rats. In addition, an increase in anxiety-related behaviour in these rats was found. Although the EPM caused no overall effect on c-Fos expression, a negative correlation with the anxiety-like behavioural response was observed. Our results suggest that the SCA17 rat model displays an anxious phenotype already at 3 months of age resembling the generalized anxiety in early symptomatic SCA17 patients, thus confirming the validity of this rat model.



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Testing the correlation between experimentally-induced hypothyroidism during pregnancy and autistic-like symptoms in the rat offspring

Publication date: 15 March 2017
Source:Behavioural Brain Research, Volume 321
Author(s): Francesca Melancia, Michela Servadio, Sara Schiavi, Patrizia Campolongo, Alexandre Giusti-Paiva, Viviana Trezza
Thyroid hormones are important for the development of the central nervous system. Since the fetal thyroid gland is not functioning until mid-gestation, transport of maternal thyroid hormones across the placenta is essential during the early phases of gestation. Maternal thyroid deficiency has been associated with a higher incidence of neurodevelopmental disorders in the newborns. The relationship between maternal hypothyroidism and the onset of autism spectrum disorders (ASD) in the offspring, however, is still debated. To address this issue, we used a validated animal model of prenatal hypothyroidism based on the administration of the thyroid peroxidase inhibitor methimazole (MMI, 0.02g/100ml in tap water) to rat dams from gestational day 9 up to delivery. The offspring was tested in behavioral tasks during infancy (PNDs 5, 9, 13) and adolescence (PND 35-40) to capture some of the core and associated symptoms of ASD. MMI-exposed pups were able to vocalize as controls when separated from the nest, and showed intact social discrimination abilities in the homing behavior test. At adolescence, the offspring from both sexes did not show an anxious-phenotype in the elevated plus maze and showed intact object recognition. However, MMI-exposed male rats showed increased novelty-directed exploratory behaviors: they solicited their partner to play more and showed more interest for novel rather than familiar objects compared to control rats. Our results show that prenatal MMI-induced hypothyroidism does not cause in the rat offspring behaviors that resemble core and associated ASD symptoms, like deficits in communication and social interaction and anxiety.



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Overshadowing depends on cue and reinforcement sensitivity but not schizotypy

Publication date: 15 March 2017
Source:Behavioural Brain Research, Volume 321
Author(s): Clare Pickett, Helen J. Cassaday, Peter A. Bibby
There is evidence for impaired selective learning mechanisms in individuals high in schizotypy. Overshadowing provides a direct test of selective learning based on cue salience and has previously been reported to be impaired in relation to schizotypy scores. The present study tested for overshadowing using food allergy and Lego construction task variants. Both variants used the same number of conditioned stimulus (CS) cues and the same number of learning trials. CS cues were trained in compound pairs or in isolation and overshadowing was subsequently tested on trials followed by negative versus positive outcomes. Participants also completed the O-LIFE to measure schizotypy and BIS-BAS scales to measure reinforcement sensitivity. Learning was demonstrated for both cue variants; however overshadowing emerged only in the Lego variant and only on the trials followed by the negative outcome. Contrary to expectations, there was no evidence for any relationship between overshadowing and O-LIFE scores. However, there was evidence of a positive relationship between overshadowing and BAS-Drive as well as a negative relationship with BIS-Anxiety, for the trials followed by the positive outcome in the food allergy variant. These results suggest that the development of overshadowing depends on cue and reinforcement sensitivity, but not necessarily on schizotypy.



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