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Πέμπτη 10 Αυγούστου 2017

Scholar : Ειδοποίηση Μελετητή - [ Myringotom

Ειδοποίηση Μελετητή:[ Myringotomy and tubes ]

ENT Surgery

DP Sarode, CR Mulholland, M Johnston, C Murray - Introduction to Surgery for …, 2017

... Grommets (also known as tympanostomy tubes or ventilation tubes) are tiny tubes designed to
prevent closure of a myringotomy incision (Fig. 15.1). ... 2. A Boyle-Davis gag is inserted to open
the mouth and control the position of the tongue and endotracheal tube. 3. ...

CT1, 2 CV CVP CVS CXR

RA Fisher - Introduction to Surgery for Students, 2017

... surgery) sub-specialties, 186 throat (see Throat surgery) Ear surgery Grommet insertion,
175–176, 176f myringotomy incision, 175 ... 250 Endoscopic retrograde cholangiopancreatography
(ERCP), 230–231 Endoscopic ultrasonography (EUS), 234, 240 Endotracheal tube, 64, 65f ...

3D Three dimensional A&E Accident and emergency department A/V Atrioventricular AAA Abdominal aortic aneurysm ABG Arterial blood gas

RA Fisher - Introduction to Surgery for Students

Αυτή η Ειδοποίηση του Μελετητή Google σας προσφέρεται από τη Google

Ακύρωση ειδοποίησης
Δημιουργία λίστας των ειδοποιήσεών μου

Scholar : Ειδοποίηση Μελετητή - [ Laryngomal

Ειδοποίηση Μελετητή:[ Laryngomalacia ]

CLINICAL CASE

CM Furse, MD McEvoy - Advanced Perioperative Crisis Management, 2017

[PDF] Recent developments in management of a child with Down Syndrome

A Verma, K Sandhya, M Verma, R Narayan

... Commonly encountered problems are tracheomalacia (59%) laryngomalacia (28%) macroglossia
(28%) subglottic stenosis (23%) congenital tracheal stenos is (5%) were found in these patients .
Multiple sites of obstruction were seen in 38% of these cases. ...

Scholar : Ειδοποίηση Μελετητή - [ ΛΟΓΟΣ

Ειδοποίηση Μελετητή:[ ΛΟΓΟΣ ]

Das Problem moralischen Wissens: Ethischer Relationalismus in Anschluss an Hegel

FH von Waldegge - 2017

[PDF] PARMÉNIDES COMO AUTOR LITERARIO: TRADICIÓN Y NOVEDAD DEL PROEMIO

A BERNABÉ - Philosophica/Semestre I-II/2016

... Por ello Mourelatos (1970: 46) tiene razón en señalar que la pregunta "why poetry"
no debe siquiera hacerse, dado que el λόγος en prosa no sería una opción viva para
alguien que se sitúa en tales coor- denadas ideológicas. ...

Scholar : Ειδοποίηση Μελετητή - [ ωτα ]

Ειδοποίηση Μελετητή:[ ωτα ]

[PDF] PARMÉNIDES COMO AUTOR LITERARIO: TRADICIÓN Y NOVEDAD DEL PROEMIO

A BERNABÉ - Philosophica/Semestre I-II/2016

... Todo ello es consistente con una visión infernal. En efecto, en el Papiro de Bolonia, que contiene
una catábasis órfica (OF 717.123), leemos: ἐς ἔ] λ̣̣εγχος [ἀεὶ γα] ν̣όωντι πρ [οσώ] πωι πά] σ̣ηισιν
ἐοικ [ότα] μ [ι] σθὸν ὀπ [η] δεῖν Δικαιοσύν] ης θυγάτη [ρ π] ο̣λ̣ύφημος Ἀμοιβή ... ...

Scholar : Scholar Alert - [ intitle:laryngeal ]

Scholar Alert: [ intitle:laryngeal ]

[PDF] Recurrent Laryngeal Nerve Injury After Thyroid Surgery

KAA Alobaidy, SM Almafragy - Int. J. Adv. Res. Biol. Sci, 2017

Abstract Back ground: Vocal cord paresis or paralysis due to injury of the recurrent laryngeal
nerve (RLNI) is one of the main complications in thyroid surgery. Many procedures have
been introduced to prevent the nerve injury; still the incidence of recurrent laryngeal nerve

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Scholar : Ειδοποίηση Μελετητή - [ intitle:Bi

Ειδοποίηση Μελετητή:[ intitle:Bioprinting ]

Bioprinting and Cellular Therapies for Type 1 Diabetes

DJ Ravnic, AN Leberfinger, IT Ozbolat - Trends in Biotechnology, 2017

Type 1 diabetes mellitus is a chronic autoimmune disease that results from the destruction of
beta (β) cells in the pancreatic islets, leading to loss of insulin production and resultant
hyperglycemia. Recent developments in stem cell biology have generated much excitement

Scholar : Ειδοποίηση Μελετητή - [ ΜΑΣΤΟ

Ειδοποίηση Μελετητή:[ ΜΑΣΤΟΕΙΔΙΤΙΣ ]

ENT Surgery

DP Sarode, CR Mulholland, M Johnston, C Murray - Introduction to Surgery for …, 2017

... 15.1 Grommet. Indications. Bilateral otitis media with effusion (OME) of longer than 3 months
duration. Recurrent acute otitis media (AOM). Complications of AOM eg mastoiditis or facial nerve
palsy. Meniere's disease: to facilitate repeated gentamicin injections. ...

[HTML] ARCHIVED-Active surveillance for influenza infection in children; Stollery Children's Hospital, 2003-2004 season

J Bank

... There were 5 cases of pneumonia, 2 bacteremias (Streptococcus pneumoniae and Pseudomonas
aeruginosa), 2 urinary tract infections, 2 episodes of cellulitis and 5 other diagnoses including
staphylococcal scalded skin syndrome and mastoiditis. Antimicrobial Utilization. ...

Comparing Parietal Quantity-Processing Mechanisms between Humans and Macaques

Publication date: Available online 9 August 2017
Source:Trends in Cognitive Sciences
Author(s): Ben M. Harvey, Stefania Ferri, Guy A. Orban
Quantity processing studies typically assume functional homology between regions within macaque and human intraparietal sulcus (IPS), where apparently similar locations respond to broadly similar tasks. However, macaque single cell neurophysiology is difficult to compare to human functional magnetic resonance imaging (fMRI); particularly in multivoxel pattern analysis and adaptation paradigms, or where different tasks are used. fMRI approaches incorporating neural tuning models allow closer comparison, revealing human numerosity-selective responses only outside the IPS. Extensive functional similarities support this novel homology of physical quantity processing. Human IPS instead houses a network responding to comparisons of physical quantities, symbolic numbers, and other stimulus features. This network likely reflects interactions between physical quantity processing, spatial processing, and (in humans) linguistic processing.

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New insights into non-conventional epitopes as T cell targets: The missing link for breaking immune tolerance in autoimmune disease?

Publication date: Available online 10 August 2017
Source:Journal of Autoimmunity
Author(s): James Harbige, Martin Eichmann, Mark Peakman
The mechanism by which immune tolerance is breached in autoimmune disease is poorly understood. One possibility is that post-translational modification of self-antigens leads to peripheral recognition of neo-epitopes against which central and peripheral tolerance is inadequate. Accumulating evidence points to multiple mechanisms through which non-germline encoded sequences can give rise to these non-conventional epitopes which in turn engage the immune system as T cell targets. In particular, where these modifications alter the rules of epitope engagement with MHC molecules, such non-conventional epitopes offer a persuasive explanation for associations between specific HLA alleles and autoimmune diseases. In this review article, we discuss current understanding of mechanisms through which non-conventional epitopes may be generated, focusing on several recently described pathways that can transpose germline-encoded sequences. We contextualise these discoveries around type 1 diabetes, the prototypic organ-specific autoimmune disease in which specific HLA-DQ molecules confer high risk. Non-conventional epitopes have the potential to act as tolerance breakers or disease drivers in type 1 diabetes, prompting a timely re-evaluation of models of a etiopathogenesis. Future studies are required to elucidate the disease-relevance of a range of potential non-germline epitopes and their relationship to the natural peptide repertoire.

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American Thyroid Association Announces 2017 Research Grant Awards

ATA Awards Research Grant to Marco Medici, MD, PhD, MSc, Erasmus Medical Center

ATA Awards Research Grant to Lawrence A. Shirley, MD, MS, FACS, Ohio State University Wexner Medical Center

ATA Awards Research Grant to Jason E. Coleman, PhD, University of Florida

ATA Awards ThyCa Research Grant to Vicki Emma Smith, PhD, University of Birmingham, UK

ATA Awards ThyCa Research Grant to Jens Lohr, MD, PhD, Dana Farber Cancer Institute

ATA Awards ThyCa Research Grant to Glenn J. Hanna, M.D., Dana-Farber Cancer Institute's Center for Head and Neck Oncology

ATA Awards Bite Me Cancer Research Grant to Brian P. Danysh, PhD, University of Texas MD Anderson Cancer Center

The post American Thyroid Association Announces 2017 Research Grant Awards appeared first on American Thyroid Association.

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Editorial Board

Publication date: August 2017
Source:Current Opinion in Neurobiology, Volume 45

http://ift.tt/2hO7bxj

Corrigendum to ‘The menagerie of the basal forebrain: how many (neural) species are there, what do they look like, how do they behave and who talks to whom?’ [Curr Opin Neurobiol 2017, 44:159–166]

Publication date: August 2017
Source:Current Opinion in Neurobiology, Volume 45
Author(s): Chun Yang, Stephen Thankachan, Robert W McCarley, Ritchie E Brown

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Contents page

Publication date: August 2017
Source:Current Opinion in Neurobiology, Volume 45

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A rare case of pediatric lipoma with t(9;12)(p22;q14) and evidence of HMGA2-NFIB gene fusion

Publication date: Available online 9 August 2017
Source:Cancer Genetics
Author(s): Melanie Lacaria, Dina El Demellawy, Jean McGowan-Jordan
Lipoma is a benign tumor, typically of adulthood, with characteristic cytogenetic findings, including rearrangement of 12q13-15; these rearrangements often lead to the fusion of the HMGA2 gene at this locus to the transcriptional regulatory domain of its fusion partner, resulting in neomorphic activity that presumably facilitates the neoplastic process. Herein, we report a rare case of pediatric lipoma with t(9;12)(p22;q14) and evidence of HMGA2-NFIB gene fusion in a 9 year-old boy. This case provides further evidence of the link between NFIB rearrangement and early-onset, deep-seated lipomatous tumors.

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Regulatory mechanisms of long noncoding RNAs on gene expression in cancers

Publication date: Available online 9 August 2017
Source:Cancer Genetics
Author(s): Weiliang Sun, Yunben Yang, Chunjing Xu, Junming Guo
Long non-coding RNAs (lncRNAs) are a heterogeneous class of RNAs that are non-protein coding transcripts longer than 200 nucleotides. In this review, we introduce the mechanisms by which lncRNAs regulate gene expression in four parts, epigenetic regulation (genetic imprinting and chromatin remodeling), transcriptional regulation (molecular decoy), post-transcriptional regulation (splicing and mRNA decay), and translational regulation. H19, Xist, and others are involved in genomic imprinting. HOTAIR and ANRIL function in chromatin remodeling. GAS5 is degraded through an RNA decay pathway. NEAT1 and MALAT1 function not only in the regulation of transcription but also in splicing.

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Comparison of passive sampling and biota for monitoring of tonalide in aquatic environment

Abstract

Synthetic musk compounds are extensively used in personal care and cosmetic products all over the world. Afterwards, they are discharged into the environment mainly because they are not completely removed in wastewater treatment plants. The aim of this study was to investigate if a passive sampler is applicable for the monitoring of tonalide, a polycyclic musk compound, in the aquatic environment and to compare the levels of tonalide in pesticide-polar organic chemical integrative sampler (POCIS) and biota. For this purpose, four sampling localities on the three biggest rivers in the Czech Republic were selected. Tonalide was determined in POCIS at all sampling sites in the concentration ranging from 9 ng/POCIS (Labe River, Hradec Králové) to 25 ng/POCIS (Morava River, Blatec). The locality with the most frequent occurrence of tonalide in biota samples was the Morava River which well corresponded with the highest tonalide concentration in POCIS among sampling sites. The highest number of positive tonalide detections among all studied biota samples was found in fish plasma. To the best of our knowledge, this is the first evidence that tonalide bioaccumulates in fish blood. Tonalide levels were below the limit of quantification in benthos samples at all sampling sites.

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Interaction of niobium with iron-oxide colloids and the role of humic acid

Publication date: November 2017
Source:Journal of Environmental Radioactivity, Volumes 178–179
Author(s): Madhusudan Ghosh, K.K. Swain, Rakesh Verma
In this work, we report the sorption of Nb on iron oxides and the effect of humic acid. Iron oxides viz. goethite, hematite and magnetite were chemically synthesised and characterised by X-ray diffraction, particle size, surface area and zeta potential measurement. The sorption of Nb on all the three iron oxides was low (∼40%) at pH 1, increased to ∼ 90% at pH 8 and decreased marginally above pH 8. The effect of humic acid on the sorption was very small. Thermodynamic parameters viz. activation energy, enthalpy, entropy, free energy and sticking probability were calculated to understand the mechanism of the sorption process. Although the enthalpy was positive, the free energy change was negative i.e. the sorption was entropy driven process. The sorption followed pseudo-second-order kinetics and sticking probability model indicated that the process was chemisorption. This study is important to understand the probable migration of ⁹⁴Nb (half life 20300 y) during underground storage of radioactive waste.

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Telomere Length and Risk of Cancer and Non-Neoplastic Diseases

To the Editor In a recent publication, Haycock et al focused on the association between telomere length and risk of cancer and non-neoplastic diseases. Findings in this Mendelian randomization study showed that genetically longer telomeres were linked to higher odds ratio for 9 of 22 primary cancers tested but to reduced odds of disease for 6 of 32 primary non-neoplastic diseases, including cardiovascular diseases. From their results, the authors concluded that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.

http://ift.tt/2wM9zrj

Individualized Adaptive Stereotactic Body Radiotherapy for Liver Tumors

This phase 2 clinical trial evaluated the safety and efficacy of individualized adaptive stereotactic body radiotherapy for liver tumors in patients who have preexisting liver dysfunction.

http://ift.tt/2vSFZ6M

Out-of-Pocket Costs, Financial Distress, and Underinsurance in Cancer Care

This cross-sectional survey study examines financial distress and cost expectations among patients with cancer presenting for anticancer therapy.

http://ift.tt/2wLUhmh

Telomere Length and Risk of Cancer and Non-Neoplastic Diseases—Reply

In Reply We thank Dr Mormile for her letter, which proposes that survivin, encoded by BIRC5 and a regulator of apoptosis and cellular lifespan, may display conflicting directions of association with risk of cancer and some non-neoplastic diseases, similar to the findings reported for telomere length by the Telomeres Mendelian Randomization Collaboration (TMRC). Mormile further proposes that upregulation of hTERT, the reverse transcriptase that lengthens telomeres, may mediate associations between survivin and disease. We tested the former hypothesis using MR-Base (http://www.mrbase.org, which includes summary data from the GTEx, CARDIoGRAMplusC4D, and ILCCO consortia). Although we found some evidence to suggest that each unit increase in survivin gene expression in lung tissue is associated with higher risk of lung adenocarcinoma (odds ratio, 1.35; 95% CI, 1.13-1.61), there was little evidence in MR-Base to support associations with other cancers or cardiovascular disease (false-discovery rate, ≥0.20; further details available at http://ift.tt/2wM33Rh). Notably, the TMRC used leukocyte telomere length as an index of telomere length in other normal somatic tissues, whose telomerase activity is typically repressed during extrauterine life. In contrast, the proposal by Mormile is based on studies conducted in cells or tissues that display telomerase activity (eg, cancer cells, human placenta, and mouse somatic tissues). What's more, atherosclerotic cardiovascular disease principally affects arteries and is not strictly a process related to cardiomyocyte proliferation. Although the role of survivin may be in doubt, we agree that more research is required to resolve the role of apoptosis and cellular lifespan in the cancer–vascular disease trade-off reported by the TMRC.

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Systemic Inflammation, Sarcopenia, and Survival in Colorectal Cancer

This cohort study of patients with early-stage colorectal cancer examines whether prediagnostic systemic inflammation is associated with at-diagnosis sarcopenia and explores whether these factors interact to predict cancer survival.

http://ift.tt/2vSFyK2

New Painful Nodules in a Patient With Multiple Myeloma

A woman in her 60s presented with multiple painful cutaneous nodules and a history of IgGκ multiple myeloma. What is your diagnosis?

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The different effects of lithium and tamoxifen on memory formation and the levels of neurotrophic factors in the brain of male and female rats

Publication date: Available online 9 August 2017
Source:Brain Research Bulletin
Author(s): Samira S. Valvassori, Cenita Borges, Roger B. Varela, Daniela V. Bavaresco, Guilherme Bianchini, Edemilson Mariot, Camila O. Arent, Wilson R. Resende, Josiane Budni, João Quevedo
Lithium (Li) is a mood-stabilizing drug used in the treatment of bipolar disorder (BD). Recently, preclinical studies have demonstrated the potential of tamoxifen (TMX) in the treatment of acute episodes of BD. However, the prolonged use of TMX for mood disorders treatment is controversial. In this study, we evaluated the effects of TMX or Li on cognitive behavior, as well as the levels of neurotrophic factors in the brain of male and female rats. Male and female Wistar rats received administrations of water (control group), TMX or Li via gavage for a period of 28 days; the rats were then subjected to the open-field test (to evaluate spontaneous locomotion), and the novel object recognition and step-down inhibitory avoidance tests (to evaluate cognition). The levels of NGF, BDNF and GDNF were evaluated in the hippocampus and frontal cortex of the subject rats. No significant differences were observed in the open-field and inhibitory avoidance tests after drug administration in either the male or female rats. The administration of TMX, but not Li, decreased the recognition index of both the male and female rats in the object recognition test. The chronic administration of TMX decreased, whereas Li increased the levels of BDNF in the hippocampus of both the male and female rats. Tamoxifen decreased the levels of NGF in the hippocampus of female rats. In conclusion, it can be suggested that long-term treatments with TMX can lead to significant cognitive impairments by reducing the levels of neurotrophic factors in the brain of rats.

http://ift.tt/2uKd4Nv

Effect of vertical sleeve gastrectomy on alcohol consumption and preferences in dietary obese rats and mice: A plausible role for altered ghrelin signaling

Publication date: Available online 9 August 2017
Source:Brain Research Bulletin
Author(s): Elise R. Orellana, Catherine Jamis, Nelli Horvath, Andras Hajnal
Vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) are the most common surgical options for the treatment of obesity and metabolic disorder. Whereas RYGB may result in greater and more durable weight loss, recent clinical and pre-clinical studies in rats have raised concerns that RYGB surgery may increase risk for alcohol use disorder (AUD). In contrast, recent clinical reports suggest a lesser risk for AUD following VSG, although no preclinical studies have been done to confirm that. Therefore, the present study sought to determine the effects of VSG on ethanol intake and preferences in rodent models using protocols similar to those previously used in animal studies for RYGB. Male Sprague Dawley rats and male C57B6 mice were made obese on a high fat diet (60%kcal from fat) and received VSG or no surgery (controls). All animals then were given access to increasing concentrations of ethanol (2%, 4%, 6%, and 8%), presented for few days each. Compared to controls, VSG rats consumed significantly less of 2, 6 and 8% ethanol and showed significantly reduced preferences to 6 and 8% ethanol over water. VSG mice also displayed reduced intake and preference for 6 and 8% ethanol solutions. After a two-week period of forced abstinence, 8% ethanol was reintroduced and the VSG rats and mice continued to exhibit reduced consumption and less preference for ethanol. Regarding the underlying mechanism, we hypothesized that the removal of the ghrelin producing part of the stomach in the VSG surgery is a possible contributor to the observed reduced ethanol preference. To test for functional changes at the ghrelin receptors, the VSG and control rats were given IP injections of acyl-ghrelin (2.5nmol and 5nmol) prior to ethanol access. Neither concentration of ghrelin resulted in a significant increase in 8% ethanol consumption of VSG or control subjects. Next, the rats were given IP injections of the ghrelin receptor antagonist, JMV (2.5mg/kg body weight). This dose induced a significant reduction in 8% ethanol consumption in the VSG group, but no effect on ethanol intake in the controls. While ghrelin injection was uninformative, increased sensitivity to subthreshold doses of the ghrelin receptor antagonist may indicate reduced ghrelin signaling following VSG. Overall, these findings suggest that bariatric patients with increased susceptibility to AUD may benefit from receiving VSG instead of RYGB surgery, and that changes in ghrelin signaling, at least in part, may play a role in the differential AUD risks between the two most commonly performed bariatric surgical procedures.

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Adolescent chronic variable social stress influences exploratory behavior and nicotine responses in male, but not female, BALB/cJ mice

Publication date: Available online 9 August 2017
Source:Brain Research Bulletin
Author(s): M.J. Caruso, D.E. Reiss, J.I. Caulfield, J.L. Thomas, A.N. Baker, S.A. Cavigelli, H.M. Kamens
Anxiety disorders and nicotine use are significant contributors to global morbidity and mortality as independent and comorbid diseases. Early-life stress, potentially via stress-induced hypothalamic-pituitary-adrenal axis (HPA) dysregulation, can exacerbate both. However, little is known about the factors that predispose individuals to the development of both anxiety disorders and nicotine use. Here, we examined the relationship between anxiety-like behaviors and nicotine responses following adolescent stress. Adolescent male and female BALB/cJ mice were exposed to either chronic variable social stress (CVSS) or control conditions. CVSS consisted of repeated cycles of social isolation and social reorganization. In adulthood, anxiety-like behavior and social avoidance were measured using the elevated plus-maze (EPM) and social approach-avoidance test, respectively. Nicotine responses were assessed with acute effects on body temperature, corticosterone production, locomotor activity, and voluntary oral nicotine consumption. Adolescent stress had sex-dependent effects on nicotine responses and exploratory behavior, but did not affect anxiety-like behavior or social avoidance in males or females. Adult CVSS males exhibited less exploratory behavior, as indicated by reduced exploratory locomotion in the EPM and social approach-avoidance test, compared to controls. Adolescent stress did not affect nicotine-induced hypothermia in either sex, but CVSS males exhibited augmented nicotine-induced locomotion during late adolescence and voluntarily consumed less nicotine during adulthood. Stress effects on male nicotine-induced locomotion were associated with individual differences in exploratory locomotion in the EPM and social approach-avoidance test. Relative to controls, adult CVSS males and females also exhibited reduced corticosterone levels at baseline and adult male CVSS mice exhibited increased corticosterone levels following an acute nicotine injection. Results suggest that the altered nicotine responses observed in CVSS males may be associated with HPA dysregulation. Taken together, adolescent social stress influences later-life nicotine responses and exploratory behavior. However, there is little evidence of an association between nicotine responses and prototypical anxiety-like behavior or social avoidance in BALB/cJ mice.

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Neurochemical evidence that Cocaine- and Amphetamine-Regulated Transcript (CART) 55-102 peptide modulates the dopaminergic reward system by decreasing the dopamine release in the mouse nucleus accumbens

Publication date: Available online 9 August 2017
Source:Brain Research Bulletin
Author(s): Angelina Rakovska, Maria Baranyi, Katalin Windish, Polina Petkova-Kirova, Hristo Gagov, Reni Kalfin
CART (Cocaine- and Amphetamine-Regulated Transcript) peptide is a neurotransmitter naturally occurring in the CNS and found mostly in nucleus accumbens, ventrotegmental area, ventral pallidum, amygdalae and striatum, brain regions associated with drug addiction. In the nucleus accumbens, known for its significant role in motivation, pleasure, reward and reinforcement learning, CART peptide inhibits cocaine and amphetamine-induced dopamine-mediated increases in locomotor activity and behavior, suggesting a CART peptide interaction with the dopaminergic system. Thus in the present study, we examined the effect of CART (55-102) peptide on the basal, electrical field stimulation-evoked (EFS-evoked) (30V, 2Hz, 120 shocks) and returning basal dopamine (DA) release and on the release of the DA metabolites 3,4-dihydroxyphenyl acetaldehyde (DOPAL), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3,4-dihydroxyphenylethanol (DOPET), 3-methoxytyramine (3-MT) as well as on norepinephrine (NE) and dopamine-o-quinone (Daq) in isolated mouse nucleus accumbens, in a preparation, in which any CART peptide effects on the dendrites or soma of ventral tegmental projection neurons have been excluded. We further extended our study to assess the effect of CART (55-102) peptide on basal cocaine-induced release of dopamine and its metabolites DOPAL, DOPAC, HVA, DOPET and 3-MT as well as on NE and Daq. To analyze the amount of [³H]dopamine, dopamine metabolites, Daq and NE in the nucleus accumbens superfusate, a high-pressure liquid chromatography (HPLC), coupled with electrochemical, UV and radiochemical detections was used. CART (55-102) peptide, 0.1μM, added alone, exerted: (i) a significant decrease in the basal and EFS-evoked levels of extracellular dopamine (ii) a significant increase in the EFS-evoked and returning basal levels of the dopamine metabolites DOPAC and HVA, major products of dopamine degradation and (iii) a significant decrease in the returning basal levels of DOPET. At the same concentration, 0.1μM, CART (55-102) peptide did not have any effect on the release of noradrenaline. In the presence of CART (55-102) peptide, 0.1μM, the effect of cocaine, 30μM, on the basal dopamine release was inhibited and the effect on the basal DOPAC release substantially increased.To our knowledge, our findings are the first to show direct neurochemical evidence that CART (55-102) peptide plays a neuromodulatory role on the dopaminergic reward system by decreasing dopaminein the mouse nucleus accumbens and by attenuating cocaine-induced effects on dopamine release.

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A species dependent response to the pro-epileptic drug pentylentetrazole in birds

Publication date: Available online 9 August 2017
Source:Brain Research Bulletin
Author(s): Faiq Amin, Asim H. Dar, Khan Osama, Faezah Khan, Rida Mitha, Arsal Tharwani, Ghulam Haider, Prem Chand, Fazal M. Arain
Epilepsy is common disorder that affects over 50 million people worldwide. Birds remain a promising yet largely under-explored model of epilepsy. This study reports the comparison of the response of two species of birds, Australian Parrots (APs) and Sparrows (SPs), to a pro-epileptic drug, Pentylenetetrazole (PTZ). PTZ injections caused myoclonic jerks (MCJs) and tonic clonic seizures (TCSs) in both species. The frequency of MCJs in APs was greater at the dose of 75mg/kg compared to both 50mg/kg and 25mg/kg while it was not significantly different in SPs. The comparison of APs and SPs showed that the frequency of MCJs was greater in APs compared to SPs at 25mg/kg and 75mg/kg while its latency was reduced at 25mg/kg and 50mg/kg. Interestingly SPs had a reduced latency of TCSs compared to APs at 75mg/kg. Glutamatergic and Gabaergic cell count was conducted to determine an association with the epileptic response to PTZ. The Glutamatergic cell counts for SPs was significantly greater than APs and conversely the Gabaergic cell counts in APs was higher compared to SPs. The reason for this difference in findings needs to be further investigated. This study shows that birds, and APs and SPs in particular, are a valid, interesting and under-explored model of epilepsy that should be further explored in order to understand the mysteries of epilepsy.

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Daily bathing strategies and cross-transmission of multidrug-resistant organisms: Impact of chlorhexidine-impregnated wipes in a multidrug-resistant gram-negative bacteria endemic intensive care unit

Publication date: Available online 10 August 2017
Source:American Journal of Infection Control
Author(s): Jesus Ruiz, Paula Ramirez, Esther Villarreal, Monica Gordon, Inmaculada Saez, Alfonso Rodríguez, María Jesús Castañeda, Álvaro Castellanos-Ortega
BackgroundHealth–care associated infections are a major cause of morbidity and mortality in critical care units. The aim of this study is to evaluate the effectiveness of chlorhexidine gluconate (CHG)–impregnated wipes in the daily bathing of patients in an intensive care unit (ICU) to prevent cross-transmission and colonization by multidrug-resistant organisms (MDROs)MethodsProspective cohort study with an intervention of 11 months. The intervention consisted of using CHG-impregnated wipes for the daily bathing of patients on mechanical ventilation or colonized by MDROs. Monthly trends in the number of patients colonized by MDROs and the incidence of nosocomial infections were evaluated.ResultsA total of 1,675 patients were admitted to the unit during the intervention period, and 430 (25.7%) were bathed with chlorhexidine wipes. A significant decrease was observed in the incidence of colonization by MDROs over the months (β = −0.209; r² = 0.549; P = .027), and in the number of patients colonized compared with the equivalent period of the previous year (22.0% vs 18.4%; P = .01). No significant decrease was observed in the incidence of nosocomial infection between the two periods (4.11% vs 4.57%; P = .355). No dermatologic problems were observed in the treated patients.ConclusionsThe use of CHG-impregnated wipes reduces cross-transmission and colonization by MDROs in the ICUs in an endemic situation because of multidrug-resistant Enterobacteriaceae.

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Discovery of Novel Inhibitors of Multidrug-resistant Acinetobacter baumannii

Publication date: Available online 9 August 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Iswarduth Soojhawon, Nagarajan Pattabiraman, Arthur Tsang, Amanda L. Roth, Ellen Kang, Schroeder M. Noble
The recent emergence of multidrug-resistant Acinetobacter baumannii strains and the non-efficacy of currently available antibiotics against such infections have led to an urgent need for the development of novel antibacterials. In an effort to address this problem, we have identified three novel inhibitors, namely, D5, D12 and D6 using in silico screening with a homology model of the outer membrane protein W2 (OmpW2) from A. baumannii, as the proposed new drug target. OmpW is an eight-stranded β-barrel protein involved in the transport of hydrophobic molecules across the outer membrane and maintenance of homeostasis under cellular stress. The antimicrobial activities of compounds D5, D12 and D6 were evaluated against a panel of clinical isolates of A. baumannii strains. These compounds inhibited the growth of the strains with minimum inhibition concentration (MIC) ranges of 1 to 32 μg/ml. Time-kill kinetic studies with the highly virulent and drug resistant strain, A. baumannii 5075, indicated that D6 exhibited the highest bactericidal activity as a ≥ 3 log10 CFU/mL (99.9%) reduction in colony count from the initial inoculum was observed after 30 minutes incubation. D5 and D12 reduced at least 1log10 CFU/mL (90%) of the initial inoculum after 24 hours. In conclusion, these three lead inhibitors have provided two distinct chemical scaffolds for further analog design and optimizations, using chemical synthesis, to develop more potent inhibitors of the pathogen.

Graphical abstract

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Synthesis of Amide Isosteres of Schweinfurthin-based Stilbenes

Publication date: Available online 9 August 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): David P. Stockdale, John A. Beutler, David F. Wiemer
The schweinfurthins are plant-derived stilbenes with an intriguing profile of anti-cancer activity. To obtain analogues of the schweinfurthins that might preserve the biological activity but have greater water solubility, a formal replacement of the central olefin with an amide has been explored. Two pairs of amides have been prepared, each containing the same hexahydroxanthene "left half" joined through an amide linkage to two different "right halves." In each series, the amide has been inserted in both possible orientations, placing the carbonyl group on the tricyclic ABC ring system and the amine on the D-ring, or placing the amine on the hexahydroxanthene and the carbonyl group on the D-ring. The four new schweinfurthin analogues have been tested in the NCI 60 cell line screen, and in both cases the more active isomer carried the carbonyl group on the C-ring.

Graphical abstract

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Synthesis of novel 1,2,5-oxadiazoles and evaluation of action against Acinetobacter baumannii

Publication date: Available online 10 August 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Rebecca M. Christoff, Gerald L. Murray, Xenia P. Kostoulias, Anton Y. Peleg, Belinda M. Abbott
With multidrug resistant bacteria on the rise, novel antibiotics are becoming highly sought after. In 2008, eleven compounds were identified by high throughput screening as inhibitors of BasE, a key enzyme of the non-ribosomal peptide synthetase pathway found in Acinetobacter baumannii. Herein, we describe the preparation of four structurally similar heterocyclic lead compounds from that study, including one 1,2,5-oxadiazole. A further library of 30 analogues containing the oxadiazole moiety was then generated. All compounds were screened against Acinetobacter baumannii and their minimum inhibitory concentration data is reported, with (E)-3-(2-hydroxyphenyl)-N-(4-methyl-1,2,5-oxadiazol-3-yl)acrylamide 32 found to have an MIC of 0.5 mM. This work provides the foundation for further investigation of 1,2,5-oxadizoles as novel inhibitors of A. baumannii.

Graphical abstract

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Discovery of non-zwitterionic aryl sulfonamides as Nav1.7 inhibitors with efficacy in preclinical behavioral models and translational measures of nociceptive neuron activation

Publication date: Available online 9 August 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Yong-Jin Wu, Jason Guernon, Andrea McClure, Guanglin Luo, Ramkumar Rajamani, Alicia Ng, Amy Easton, Amy Newton, Clotilde Bourin, Dawn Parker, Kathleen Mosure, Omar Barnaby, Matthew G. Soars, Ronald J. Knox, Michele Matchett, Rick Pieschl, James Herrington, Ping Chen, D.V. Sivarao, Linda J. Bristow, Nicholas A. Meanwell, Joanne Bronson, Richard Olson, Lorin A. Thompson, Carolyn Dzierba
Since zwitterionic benzenesulfonamide Nav1.7 inhibitors suffer from poor membrane permeability, we sought to eliminate this characteristic by replacing the basic moiety with non-basic bicyclic acetals and monocyclic ethers. These efforts led to the discovery of the non-zwitterionic aryl sulfonamide 49 as a selective Nav1.7 inhibitor with improved membrane permeability. Despite its moderate cellular activity, 49 exhibited robust efficacy in mouse models of neuropathic and inflammatory pain and modulated translational electromyogram measures associated with activation of nociceptive neurons

Graphical abstract

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The design and synthesis of a novel compound of berberine and baicalein that inhibits the efficacy of lipid accumulation in 3T3-L1 adipocytes

Publication date: Available online 9 August 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Mengjiao Hao, Zhuoji Guan, Yan Li, Lixian Liu, Xiao Yuan, Ying Gao, Weimin Li
The combination of berberine and baicalein may have a better therapeutic effect against disease. To explore the combined effect of baicalein and berberine in the treatment of obesity, we designed and synthesized a hybrid compound, and its biological activities were evaluated in 3T3-L1 adipocytes. The structures of the berberine-baicalein (BBS) compounds were confirmed by ¹H NMR, ¹³C NMR, ultraviolet spectroscopy and high resolution mass sectrometry (HRMS). The present study showed that the IC50 values of the inhibitory effects of baicalein, berberine and BBS against 3T3-L1 cells were 29.81±0.90, 21.84±1.67 and 9.42±0.60 µM, respectively. The expression of mRNAs related to lipolysis and lipogenesis were examined by quantitative real-time PCR. The results showed that BBS could up-regulate the expression of the Atgl gene and down-regulate the mRNA expression of Srebp-1c, Fasn, Scd1, and Acc in 3T3-L1 adipocytes. These results indicate that BBS may have a stronger effect than baicalein and berberine on the viability of 3T3-L1 preadipocytes. In addition, BBS may have therapeutic effects and pharmacological activities against obesity. This "medicine couple" may be beneficial for studies of traditional Chinese medicine.

Graphical abstract

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Editorial board

Publication date: September 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 172

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Gamma Knife Radiosurgery for Cavernous Sinus Meningiomas: Analysis of Outcome in 166 Patients

Objectives: The outcomes of Gamma Knife radiosurgery (GKRS) for cavernous sinus meningioma (CSM) are presented, and factors possibly affecting outcome are investigated. Methods: The medical records and imaging and procedural reports of 166 patients with CSM were retrospectively reviewed. Demographic data, procedural data, symptomatic improvement, radiological regression, and progression-free survival (PFS) rates were evaluated. Results: There were 124 women and 42 men; including 44 postoperative and 122 primary GKRS cases. Mean follow-up was 32.4 months. Mean marginal dose was 13 Gy. Symptomatic improvement was seen in 40.4%, while neurologic deterioration occurred in 9.6%; 50% remained symptomatically stable. Radiological regression was noted in 57.2%; the tumor remained stable in 35.5%, and 7.2% of the patients experienced tumor progression. The actuarial 5- and 10-year PFS rates were 90.1% (±3.3) and 75.8% (±8.8), respectively. History of previous surgery or radiotherapy were associated with lower symptomatic improvement. Higher tumor coverage and isodose lines were accompanied with better radiological prognosis. However, a history of conventional radiotherapy, presence of facial sensory deficits at presentation, a higher tumor volume, and tumor extension to the suprasellar compartment affected the radiologic outcome negatively. Conclusion: This study revealed a high efficacy and safety for GKRS in both postoperative and primary GKRS patients. Achievability of a good profile of tumor coverage and isodose lines at radiosurgical planning predict a better outcome.
Stereotact Funct Neurosurg 2017;95:259-267

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Changing Diagnostic Paradigms for Microbiology: Report on an American Academy of Microbiology Colloquium held in Washington, DC, from 17 to 18 October 2016.

Near-patient and point-of-care (POC) testing for infectious disease diagnostics is rapidly evolving. The American Academy of Microbiology convened a colloquium in October 2016 to explore the impact of near-patient and POC tests on patient outcomes, healthcare delivery models, public health, and healthcare costs. This report reviews characteristics and applications of near-patient and POC tests for infectious diseases, provides an overview of considerations pertaining to their implementation, oversight, and evaluation, and provides recommendations. As near-patient and POC testing is increasingly implemented in new settings and by non-laboratorians, clinical microbiology laboratory expertise is needed to ensure proper oversight. Utilization of trained personnel and evaluation of tests will ensure that the best-quality tests are ordered and interpreted correctly to benefit patient care.

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Parkinsonian rest tremor can be detected accurately based on neuronal oscillations recorded from the subthalamic nucleus

Publication date: Available online 9 August 2017
Source:Clinical Neurophysiology
Author(s): J. Hirschmann, J.M. Schoffelen, A. Schnitzler, M.A.J. van Gerven
ObjectiveTo investigate the possibility of tremor detection based on deep brain activity.MethodsWe re-analyzed recordings of local field potentials (LFPs) from the subthalamic nucleus in 10 PD patients (12 body sides) with spontaneously fluctuating rest tremor. Power in several frequency bands was estimated and used as input to Hidden Markov Models (HMMs) which classified short data segments as either tremor-free rest or rest tremor. HMMs were compared to direct threshold application to individual power features.ResultsApplying a threshold directly to band-limited power was insufficient for tremor detection (mean area under the curve [AUC] of receiver operating characteristic: 0.64, STD:0.19). Multi-feature HMMs, in contrast, allowed for accurate detection (mean AUC: 0.82, STD: 0.15), using four power features obtained from a single contact pair. Within-patient training yielded better accuracy than across-patient training (0.84 vs. 0.78, p = 0.03), yet tremor could often be detected accurately with either approach. High frequency oscillations (>200 Hz) were the best performing individual feature.ConclusionsLFP-based markers of tremor are robust enough to allow for accurate tremor detection in short data segments, provided that appropriate statistical models are used.SignificanceLFP-based markers of tremor could be useful control signals for closed-loop deep brain stimulation.

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Standardized Computer-based Organized Reporting of EEG: SCORE – second version

Publication date: Available online 9 August 2017
Source:Clinical Neurophysiology
Author(s): Sándor Beniczky, Harald Aurlien, Jan C. Brøgger, Lawrence J. Hirsch, Donald L. Schomer, Eugen Trinka, Ronit M Pressler, Richard Wennberg, Gerhard H. Visser, Monika Eisermann, Beate Diehl, Ronald P Lesser, Peter W. Kaplan, Sylvie Nguyen The Tich, Jong Woo Lee, Antonio Martins-da-Silva, Hermann Stefan, Miri Neufeld, Guido Rubboli, Martin Fabricius, Elena Gardella, Daniella Terney, Pirgit Meritam, Tom Eichele, Eishi Asano, Fieke Cox, Walter van Emde Boas, Ruta Mameniskiene, Petr Marusic, Jana Zárubová, Friedhelm C. Schmitt, Ingmar Rosén, Anders Fuglsang-Frederiksen, Akio Ikeda, David B. MacDonald, Kiyohito Terada, Yoshikazu Ugawa, Dong Zhou, Susan T. Herman
Standardized terminology for computer-based assessment and reporting of EEG has been previously developed in Europe. The International Federation of Clinical Neurophysiology established a taskforce in 2013 to develop this further, and to reach international consensus. This work resulted in the second, revised version of SCORE (Standardized Computer-based Organized Reporting of EEG), which is presented in this paper. The revised terminology was implemented in a software package (SCORE EEG), which was tested in clinical practice on 12,160 EEG recordings. Standardized terms implemented in SCORE are used to report the features of clinical relevance, extracted while assessing the EEGs. Selection of the terms is context sensitive: initial choices determine the subsequently presented sets of additional choices. This process automatically generates a report and feeds these features into a database. In the end, the diagnostic significance is scored, using a standardized list of terms. SCORE has specific modules for scoring seizures (including seizure semiology and ictal EEG patterns), neonatal recordings (including features specific for this age group), and for Critical Care EEG Terminology. SCORE is a useful clinical tool, with potential impact on clinical care, quality assurance, data-sharing, research and education.

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Comparison of Visual Evoked Potential Monitoring During Spine Surgeries under Total Intravenous Anesthesia versus Balanced General Anesthesia

Publication date: Available online 9 August 2017
Source:Clinical Neurophysiology
Author(s): Alberto A. Uribe, Ehud Mendel, Zoe A. Peters, Bassel F. Shneker, Mahmoud Abdel-Rasoul, Sergio D. Bergese
ObjectiveTo determine the comparison of its clinical utility and safety profile for visual evoked potential (VEP) monitoring during prone spine surgeries under total intravenous anesthesia (TIVA) versus balanced general anesthesia using the SightSaver™ visual stimulator.MethodsThe protocol was designed as a pilot, single center, prospective, randomized and double-arm study. Subjects were randomized to receive either TIVA or balanced general anesthesia. Following induction and intubation, 8 electrodes were placed subcutaneously to collect VEP recordings. The SightSaver™ visual stimulator was placed on the subject's scalp before prone positioning. VEP waveforms were recorded every 30 minutes and assessed by a neurophysiologist throughout the length of surgery.ResultsA total of 19 subjects were evaluated and VEP waveforms were successfully collected. TIVA group showed higher amplitude and lower latency than balanced anesthesia.ConclusionsOur data suggested that TIVA is associated with higher VEP amplitude and shorter latencies than balanced general anesthesia; therefore, TIVA could be the most efficient anesthesia regimen for VEP monitoring.SignificanceThe findings help better understand the effect of different anesthesia regimens on intra-operative visual evoked potential monitoring.

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Review of the current medical literature and assessment of current utilization patterns regarding human papillomavirus in situ hybridization and immunohistochemistry in dermatopathology

Abstract

Human papillomaviruses have been implicated in many cutaneous diseases. Practicing dermatopathologists often consider using immunohistochemistry and in situ hybridization to help clarify the histologic diagnosis, particularly in cases with borderline or non-diagnostic features. We reviewed the current evidence behind the use of these two techniques in dermatopathology. We identified only two studies utilizing the currently available immunohistochemical antibodies. We found more evidence regarding the use of in situ hybridization; however, the majority of this evidence focuses on diagnosing condylomas and other lesions of the genital skin. We also assessed current utilization patterns of attendees of the American Society of Dermatopathology annual meeting (Chicago, 2016) which revealed a wide spectrum of current utilization ranging from no use to regular use more than once per month. Two-thirds of respondents utilized these tests primarily when requested by the submitting clinician and one-third of the respondents utilize these tests reflexively in specific clinical scenarios.

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Development of RET mutant cutaneous angiosarcoma during BRAF inhibitor therapy

Abstract

Treatment with BRAF inhibitors may lead to paradoxical mitogen-activated protein kinase (MAPK) pathway activation and accelerated tumorigenesis in cells with preexisting oncogenic hits. This phenomenon manifests clinically in the development of squamous cell carcinomas (SCCs) and keratoacanthomas (KAs) in patients treated with BRAF inhibitors. Cases of extracutaneous malignancies associated with BRAF inhibitors have also been reported. We present a case of a patient who developed a cutaneous angiosarcoma six months after initiation of vemurafenib therapy. Next generation sequencing (NGS) revealed a mutation in RET, which lies upstream of the MAPK pathway. This case highlights that treatment with BRAF inhibitors may promote the accelerated growth of secondary malignancies. Physician awareness of the spectrum of secondary malignancies associated with BRAF inhibitor treatment will support their early detection and treatment.

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Benign and malignant hybrid adnexal tumors in a patient with epidermodysplasia verruciformis

Abstract

Epidermodysplasia verruciformis (EV) is a genodermatosis characterized by overgrowth of flat warts, pityriasis versicolor-like lesions and an increased propensity for developing cutaneous squamous cell carcinomas due to abnormal susceptibility to infection with beta-human papilloma viruses. Adnexal tumors are not typically associated with EV. Here we report a spectrum of hybrid adnexal tumors with divergent eccrine and folliculosebaceous differentiation, and cytologic features ranging from benign to frankly atypical, in a patient with inherited EV.

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Tisotumab Vedotin Continued Treatment in Patients With Solid Tumors.

Conditions: Ovary Cancer; Cervix Cancer; Endometrium Cancer; Bladder Cancer; Prostate Cancer; Esophagus Cancer; Lung Cancer, Nonsmall Cell; Squamous Cell Carcinoma of the Head and Neck
Intervention: Drug: Tisotumab Vedotin
Sponsor: Genmab
Recruiting - verified August 2017

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Pembrolizumab in Combination With Anti-platelet Therapy for Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

Condition: Head and Neck Cancer
Interventions: Drug: Pembrolizumab; Drug: Clopidogrel; Drug: acetylsalicylic acid
Sponsor: Medical University of South Carolina
Not yet recruiting - verified July 2017

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Effectiveness of Lay Navigators in Meeting Cancer Patients' Non-Clinical Needs: A Pilot Study

Conditions: Breast Cancer; Gynecologic Cancer; Neck Cancer; Head Cancer; Gastrointestinal Cancer; Thoracic Cancer; Cutaneous Tumor
Intervention: Other: Lay Navigation
Sponsor: Stanford University
Recruiting - verified August 2017

http://ift.tt/2vSdBC0

Stroke in a child with dengue encephalopathy

Sangeetha Yoganathan, Sniya Valsa Sudhakar, Leena Priyambada, Maya Thomas

Annals of Indian Academy of Neurology 2017 20(3):329-331

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Post bariatric surgery acute axonal polyneuropathy: Doing your best is not always enough

Zakia Mohammad Yasawy, Ali Hassan

Annals of Indian Academy of Neurology 2017 20(3):309-312

Neurological complications are frequently recognized with weight reduction surgeries for morbid obesity. The spectrum of peripheral neuropathies complicating the weight loss surgery is wide, and among them, the acute axonal peripheral neuropathy resembling Guillain-Barre syndrome is rare and only less than a dozen cases are reported. We present three cases, which after bariatric surgery developed acute polyneuropathy that rapidly progressed over 4 weeks from the onset. All patients responded to aggressive parenteral Vitamin B1 and B12 replacement therapy. These cases highlight the fact that bariatric surgery although is a promising option to treat morbid obesity; it is certainly not devoid of potential neurological complications due to micronutrient deficiencies. Delay in the diagnosis of acute polyneuropathy may worsen its long-term sequelae. A multidisciplinary team management with careful nutritional monitoring at regular interval is crucial in all patients for early recognition and intervention to avoid these complications after bariatric surgery.

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Levodopa: History and therapeutic applications

Sujith Ovallath, Bahiya Sulthana

Annals of Indian Academy of Neurology 2017 20(3):185-189

Levodopa – the aromatic amino acid L-3,4–dihydroxy phenylalanine has held the attention of neurologists and pharmacologists alike for more than half a century. Even though extensive research has been done across the globe in treatment of Parkinson's disease, with different molecules, none could replace the gold standard treatment or provide complete relief for the debilitated. Although research brought us better tips and tricks to modulate the dopamine blood levels to balance between the desired and deleterious effects, it could never replace the basic substrate. From simple oral preparation to more advanced treatment like duodenal dopa administration for better efficacy and compliance, L-dopa has sure undergone scrutiny and stayed strong as the fundamental neurotransmitter replacement therapy to pave path for many more new therapeutic strategies. So as a token of gratitude to the revolutionary agent and pioneers behind it, a trip down the memory lane is in order.

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Relationship between factor V leiden gene variant and risk of ischemic stroke: A case–control study

Amit Kumar, Shubham Misra, Ram Sagar, Pradeep Kumar, Arun K Yadav, Pumanshi Talwar, Ritesh Raj, Kameshwar Prasad

Annals of Indian Academy of Neurology 2017 20(3):284-288

Background: Factor V Leiden is the most common genetic variation among the blood coagulation pathway which leads to prothrombotic state, therefore, is considered an important gene for understating the stroke mechanism. Aim: The aim of the present study is to determine the relationship between single nucleotide polymorphism at G1691A position of Factor V gene and risk of ischemic stroke (IS) in North Indian population. Materials and Methods: In a retrospective case–control study, 250 patients with IS and 250 age- and gender-matched controls were enrolled in the period of October 2012 to September 2014 from in- and out-patient department of Neurology, All India Institute of Medical Sciences, New Delhi, India. Deoxyribonucleic acid for each case and control was isolated from peripheral blood using phenol-chloroform extraction method. Polymerase chain reaction-restriction fragment length polymorphism method was used to determine the polymorphism. Data were analyzed using STATA Software Version 13. Results: The mean age of IS patient was 52.8 ± 12.5 years and in control group was 50.97 ± 12.7 years. Genotypic frequency distributions were in accordance with Hardy–Weinberg equilibrium in both cases and controls. As expected hypertension, diabetes, dyslipidemia, smoking, heavy alcohol intake, family history of stroke, and poor economic status were significantly associated with the risk of IS. Multivariate analysis revealed 5.17 times higher odds for developing the risk of large vessel subtype of IS in patients carrying Factor V Leiden G1691A gene variation as compared to control subjects (OR, 5.17; 95% CI, 1.32–20.3, P= 0.01). Conclusion: The present study suggests that Factor V Leiden G1691A polymorphism may be significantly associated with the risk of large vessel subtype of IS. Large sample size studies using prospective cohort designs are required to corroborate the present findings.

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Levodopa-induced dyskinesia: Clinical features, pathophysiology, and medical management

Sanjay Pandey, Prachaya Srivanitchapoom

Annals of Indian Academy of Neurology 2017 20(3):190-198

Levodopa-induced dyskinesia (LID) is commonly seen in Parkinson's disease patients treated with levodopa. This side effect is usually encountered after long duration of treatment, but occasionally, this may be seen even after few days or months of treatment. LID is broadly classified as peak-dose dyskinesia, wearing-off or off-period dyskinesia, and diphasic dyskinesia. Pathogenesis of LID is complex, and different neurotransmitters such as dopamine, glutamine, adenosine, and gamma-aminobutyric acid play important role altering the normal physiology of direct and indirect pathway of cortico-basal ganglia-thalamic loop responsible for fine motor control. Treatment of LID requires careful history taking and clinical examination to find the type of dyskinesia as different approach is required for different types. Changes in dopaminergic medication including continuous dopaminergic stimulation are very helpful in the management of peak-dose dyskinesia. Different types of surgical approaches including unilateral pallidotomy and deep brain stimulation have given very good result in patients, who cannot be managed by medications alone. The surgical management of LID is dealt with in detail in another review in this series.

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Leptomeningeal carcinomatosis presenting as cauda equina syndrome

Bhagyadhan A Patel, Rahul T Chakor, Swaleha Nadaf, Kaumil V Kothari

Annals of Indian Academy of Neurology 2017 20(3):320-321

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Surgical treatment of levodopa-induced dyskinesia in parkinson's disease

Syam Krishnan, Krishnakumar Kesava Pisharady

Annals of Indian Academy of Neurology 2017 20(3):199-206

The treatment of motor manifestations of Parkinson's disease (PD) is essentially a trade-off between adequate relief of motor symptoms and prevention and control of motor complications, particularly levodopa-induced dyskinesia (LID). Progression of PD is paralleled by a progressive difficulty in achieving the balance. Functional neurosurgical procedures provide sustained relief of LID in carefully selected patients when further tailoring of medical therapy fails to achieve this goal. Though deep brain stimulation (DBS) has superseded lesioning surgeries, pallidotomy still has a role in those patients in whom DBS is not feasible for financial or other reasons.

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The prevalence and severity of autonomic dysfunction in chronic inflammatory demyelinating polyneuropathy

Suresh Babu Pasangulapati, TV Murthy, Ajith Sivadasan, L Rynjah Gideon, AT Prabhakar, Aaron Sanjith, Vivek Mathew, Mathew Alexander

Annals of Indian Academy of Neurology 2017 20(3):274-277

Introduction: In chronic inflammatory demyelinating polyneuropathy (CIDP), emphasis has been on motor disabilities, and autonomic dysfunction in these patients has not been addressed systematically. Materials and Methods: Autonomic function was prospectively analyzed in 38 patients with CIDP. Quantitative autonomic function testing was done using Finometer® PRO and severity of adrenergic and cardiovagal dysfunction graded according to composite autonomic severity score and sudomotor dysfunction assessed using sympathetic skin response. Results: Thirty-four (89%) patients had features of autonomic dysfunction. Thirty-three (86%) patients had cardiovagal dysfunction, 21 (55%) had adrenergic dysfunction, and 24 (63%) had sudomotor dysfunction. Autonomic dysfunction was mild to moderate in the majority (86%). Conclusions: Autonomic dysfunction in CIDP is underreported and potentially amenable to therapy. Our cohort had a high proportion of adrenergic dysfunction compared to previous studies.

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James wenceslaus papez, his circuit, and emotion

Kalyan B Bhattacharyya

Annals of Indian Academy of Neurology 2017 20(3):207-210

James Papez worked on the anatomical substrates of emotion and described a circuit, mainly composed of the hippocampus, thalamus and cingulum, and published his observations in 1937. However, such an idea existed before him, as evidenced by the rudimentary indications from Paul Broca, and Paul MacLean added some other structures like, septum, amygdala, and hypothalamus in its ambit and called it the limbic system. Paul Ivan Yakovlev, proposed a circuit which also referred to orbitofrontal, insular, anterior temporal lobe, and other nuclei of thalamus. Further works hinted at cerebellar projections into this system and the clinical picture of aggression, arousal and positive feeding responses with stimulation of cerebellar nuclei, attests its possible role. Finally, the work of Heinrich Klüver and Paul Bucy of the United States of America on ablating the temporal lobes and amygdala and the resultant behaviour of the animals, almost incontrovertibly adduced evidence for the operation of a neural circuitry in the genesis of emotion. Additionally, Papez circuit may also be concerned with memory and damage to its various components in Parkinson's disease, Alzheimer's disease, Korsakoff's syndrome, semantic dementia, and global amnesia, where cognitive disturbance is almost universal, lends credence to its putative role.

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Spectrum of visual impairment in cerebral venous thrombosis: Importance of tailoring therapies based on pathophysiology

Sanjith Aaron, Anupriya Arthur, AT Prabakhar, Pavitra Mannam, NK Shyamkumar, Sunithi Mani, Vivek Mathew, Jeyanthi Peter, Ajith Sivadasan, Anika Alexander, M Karthik, Rohith Ninan Benjamin, Mathew Alexander

Annals of Indian Academy of Neurology 2017 20(3):294-301

Visual impairment can complicate cerebral venous thrombosis (CVT). Here, we describe the various pathophysiological mechanisms and treatments available. A retrospective chart review of all patients treated for CVT in a large quaternary teaching hospital was done, and cases with visual impairment due to CVT were identified. The various mechanisms causing visual impairment in CVT were (1) raised intracranial pressure (ICP) caused by venous thrombosis without venous infarcts resulting in a benign intracranial hypertension-like presentation of CVT, (2) venous infarcts involving the occipital cortex, (3) raised ICP following the development of a secondary dural arteriovenous (AV) fistula, and (4) arterial occipital infarcts due to posterior cerebral artery compression secondary to herniation in large venous infarcts. Apart from using systemic anticoagulants to attempt recanalization and drugs with carbonic anhydrase inhibitor activity to reduce the ICPs, treatment modalities employed to save vision were (1) recanalization by local thrombolysis, stenting, or mechanical devices; (2) cerebrospinal fluid diversion procedures such as theco-periotoneal shunting; (3) optic nerve sheath fenestration; and (4) specific treatment for conditions such as dural AV fistula occurring as a late complication. CVT can cause visual impairment through different pathophysiological mechanisms. Depending on the mechanism, treatment strategies need to be tailored. Furthermore, very close monitoring is needed both in the acute and in the follow-up period, as new pathophysiological mechanisms can arise, compromising the vision. This may require a different treatment approach. Literature on this aspect of CVT is lacking.

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Acute ischemic stroke treatment using mechanical thrombectomy: A study of 137 patients

Rakeshsingh K Singh, Vishal Annaji Chafale, Rakesh Shyam Lalla, Keyurkumar Chandrakantbhai Panchal, Anil Pandurang Karapurkar, Satish Vasant Khadilkar, Pawan K Ojha, Yogesh Godge, Rakesh K Singh, Rajesh Benny

Annals of Indian Academy of Neurology 2017 20(3):211-216

Background: Mechanical thrombectomy (MT) is the most effective treatment in large vessel occlusion (LVO). We have analyzed our initial experience of MT of 137 patients in anterior circulation (AC) and posterior circulation (PC) LVO using Solitaire stent retriever device. Methods: Retrospective cohort analysis of 112 AC and 25 PC acute ischemic strokes was done considering various baseline characteristics, risk factors, National Institute of Health Stroke Scale (NIHSS) change, revascularization rate, complications, and functional outcome at 3 months using modified Rankin score. Results: Out of 137 patients, occlusion was found in M1 segment (44.5%), carotid T occlusion (37.2%), and basilar artery (18.2%). Atrial fibrillation was important risk factor for Carotid T occlusion. 50.4% patients received intravenous thrombolysis. Baseline mean NIHSS in AC was 15.5 (±4.32), and PC was 19 (±5.5). Tandem lesions were noted in 14.6%. There was significant difference in mean door-to-needle time for AC and PC (220 ± 80.6 and 326 ± 191.8 min, respectively). Mean time to revascularization for AC (39.5 ± 14.1) and PC (42.2 ± 19.4) was similar. Procedural success (modified thrombolysis in cerebral infarction ≥2b) observed in AC and PC was 92.9% and 84%, respectively (P = 0.154). NIHSS at admission between 5 and 15 and immediate postprocedure NIHSS improvement >4 was associated with significant better clinical outcome at 3 months. Overall complication rate was about 15.3% including symptomatic intracranial hemorrhage in 8.1% and 6.6% deaths. Conclusion: MT is safe treatment and equally effective for both AC and PC LVO. With careful patient selection, clinical outcome in PC was comparable to AC despite delayed presentation and higher baseline NIHSS.

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Hyper acute demyelinating encephalomyelitis of childhood: A rare entity

Suman Kushwaha, Ashutosh Gupta, Neha Agarwal, Sujata Chaturvedi, Deepak Jha

Annals of Indian Academy of Neurology 2017 20(3):316-318

A young child with catastrophic neurological illness diagnosed as a rare variant of acute demyelinating encephalomyelitis (ADEM). She succumbed to her illness despite of aggressive and appropriate management. Malignant demyelinating encephalomyelitis should be considered in children who are refractory to the treatment of ADEM.

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Short version of the bilingual aphasia test in Malayalam

Gopee Krishnan, Reema Elizabeth Mathew

Annals of Indian Academy of Neurology 2017 20(3):217-219

Background: Brain damage can impair the use of all languages in bilingual persons. For effective management of aphasia (i.e., impaired language) in such persons, assessment of all languages is essential. The most widely used test for this purpose – the Bilingual Aphasia Test (BAT) – is cumbersome and requires a considerable amount of time for administration. To overcome this limitation, a short version of the BAT has been recommended. Objective: The objective of this study was to derive a short version of BAT for Malayalam-English bilingual persons with aphasia and to establish the test–retest reliability as well as the content and construct validities of this version. Methods: Following the recommendations of the test developers, we used seven subtests from the draft of an adapted full version of Malayalam BAT. These subtests in Malayalam and their counterparts in English were administered on a group of 22 Malayalam-English bilingual participants with aphasia. The scores obtained from these two languages were used to establish content and construct validities of the short version of the BAT in Malayalam. Further, we readministered the short version of BAT in a group of ten participants with aphasia to examine the test–retest reliability within 14 days from the date of first administration. Results: The short version of BAT in Malayalam revealed high test–retest reliability as well as content and construct validities. The administration time ranged between 30 and 45 min. Conclusions: Thus, the short version of the BAT in Malayalam can be considered a valid and reliable language test that can be quickly administered in Malayalam-English bilingual persons with aphasia.

http://ift.tt/2vmtxel

Surgical interventions for task-specific dystonia (writer's dystonia)

Paresh K Doshi, Raghvendra Vijay Ramdasi, Bharati Karkera, Dilraj B Kadlas

Annals of Indian Academy of Neurology 2017 20(3):324-327

Objectives: Writer's cramp is a focal dystonia producing abnormal postures during selective motor activities. Thalamotomy or globus pallidus internus deep brain stimulation (GPi DBS) has been used as a surgical treatment in patients not responding to medical treatment. Materials and Methods: Eight patients (all men, age 16–47 years) with refractory focal hand dystonia underwent either ventrooralis (Vo) thalamotomy (seven patients) or GPi DBS (one patient) using stereotactic techniques. Preoperative video recordings, Writing movment score for dystonic posture and latency of dystonia (WMS), and symptom severity scores (SSSs) were evaluated at baseline and latest follow-up ranging from 1 to 4 years. Results: All patients had difficulty in performing their most common tasks. The duration of symptoms ranged from 6 months to 12 years. All patients obtained immediate postoperative relief from the dystonic symptoms, and the effect was sustained during the follow-up period. The WMS (range 0–28) improved from a mean of 14.5 before surgery to 2, whereas the SSS (maximum 43 and minimum 10) improved from a mean of 15.3 before surgery to 2 at the last follow-up. There were no surgical complications, morbidity, or mortality. Conclusion: Vo thalamotomy or GPi DBS offers successful symptom relief in patients with task-specific dystonia.

http://ift.tt/2wx9Qz2

Long-term response of cerebrospinal fluid pressure in patients with idiopathic intracranial hypertension – A prospective observational study

V Abdul Gafoor, B Smita, James Jose

Annals of Indian Academy of Neurology 2017 20(3):220-224

Background: Idiopathic intracranial hypertension (IIH) is increased intracranial pressure (ICP) with normal cerebrospinal fluid (CSF) contents, in the absence of an intracranial mass, hydrocephalus, or other identifiable causes. The current knowledge of the treatment outcome of IIH is limited, and the data on the natural history of this entity are scant. Objective: The objective of the study is to study the treatment response of IIH by serially measuring the CSF opening pressure and to delineate the factors influencing the same. Materials and Methods: A prospective observational study in a cohort of fifty patients with IIH in whom CSF opening pressure was serially measured at pre-specified intervals. Results: The mean CSF opening pressure at baseline was 302.4 ± 51.69 mm of H2O (range: 220–410). Even though a higher body mass index (BMI) showed a trend toward a higher CSF opening pressure, the association was not significant (P = 0.168). However, the age of the patient had a significant negative correlation with the CSF pressure (P = 0.006). The maximum reduction in CSF pressure occurred in the first 3 months of treatment, and thereafter it plateaued. Remission was attained in 12 (24%) patients. BMI had the strongest association with remission (P = 0.001). Conclusions: In patients with IIH, treatment response is strongly related to BMI. However, patients with normal BMI are also shown to relapse and hence should have continuous, long-term follow-up. The reduction in CSF pressure attained in the first 3 months could reflect the long-term response to treatment.

http://ift.tt/2vmHw3F

Epidemiology of peripheral neuropathy: An Indian perspective

Sweety Trivedi, Alak Pandit, Goutam Ganguly, Shyamal Kumar Das

Annals of Indian Academy of Neurology 2017 20(3):173-184

Peripheral neuropathy (PN) is a common disorder and presents as diagnostic and therapeutic challenge to physicians and neurologists. In epidemiological studies from India from various regions the overall prevalence of PN varied from 5 to 2400 per 10,000 population in various community studies. India is composed of a multiethnic, multicultural population who are exposed to different adverse environmental factors such as arsenic and lead. Use of different chemotherapeutic agents with propensity to affect peripheral nerves, increasing methods of diagnosis of connective tissue disorders and use of immunomodulating drugs, growing aging population is expected to change the spectrum and burden of peripheral neuropathy in the community. The other important aspect of peripheral neuropathies is in terms of the geographical and occupational distribution especially of toxic neuropathies like arsenic which is common in eastern belt; lead, mercury and organo-phosphorous compounds where occupational exposures are major sources. Inflammatory neuropathies either due to vasculitis or G B Syndrome, chronic inflammatory polyradiculopathies are another major group of neuropathies which is increasing due to increase longevity of Indian subjects and immunological impairment, also adds to morbidity of the patients and are potentially treatable. Leprous neuropathy is common in India and although its frequency is significantly decreasing because of national control program yet pure neuritic form still remains a cause of concern and similar is the case with another infective cause like diptheric neurpathy. Thus this article is an attempt to cover major categories and also highlight the areas where further studies are needed.

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Hospital-based retrospective study of cryptococcal meningitis in a large cohort from India

Karkal Ravishankar Naik, Aralikatte Onkarappa Saroja, Darshan Kiran Doshi

Annals of Indian Academy of Neurology 2017 20(3):225-228

Background: Cryptococcal meningitis is an important and a fatal neuroinfection. Early diagnosis and treatment is of utmost importance in reducing morbidity and mortality. Materials and Methods: Data of patients with laboratory-confirmed cryptococcal meningitis seen in tertiary care hospital were reviewed. Details of demographic profile, clinical data, laboratory parameters, complications, and in-hospital mortality were studied. Results: Among 97 patients with cryptococcal meningitis (79 men, 18 women), 88 were HIV-positive, two were diabetic, and seven were sporadic. Their age ranged from 23 to 67 years (39.16 ± 9.49). Additional pathogens for meningitis were identified in 24 patients. Headache was the most common symptom (91%) followed by fever (66%), vomiting (51%), altered sensorium (31%), and seizures (20%). Neurological deficits included cranial nerve palsies (28), motor deficits (11), sphincter disturbances (5), and sensory involvement in four patients. Complications included renal dysfunction (20%), dyselectrolytemia (20%), seizures (16%), hypersensitivity (7%), and hepatic dysfunction (5%). Favorable outcome was seen in 72 patients, 13 remained unchanged, and 12 died. Rapid clinical progression, low cerebrospinal fluid (CSF) cell count and protein were associated with higher mortality. CSF cell count and protein were lower in patients who had isolated cryptococcal meningitis compared to those with additional pathogen. Mean sugar levels were higher and duration of illness was shorter in HIV-negative individuals. Conclusion: Cryptococcal meningitis is common in patients with AIDS. Effective and early antifungal treatment carries a good prognosis. On rapid evolution of the disease, decreased CSF cell count and protein heralds poor prognosis and warrants initiation of early specific treatment.

http://ift.tt/2vlQrSP

Clinical spectrum, therapeutic outcomes, and prognostic predictors in sjogren's syndrome-associated neuropathy

Ajith Sivadasan, Karthik Muthusamy, Bimal Patel, Rohit Ninan Benjamin, AT Prabhakar, Vivek Mathew, Sanjith Aaron, Mathew Alexander

Annals of Indian Academy of Neurology 2017 20(3):278-283

Objectives: There are limited data regarding long-term follow-up and therapeutic outcomes in Sjogren's syndrome (SS)-associated peripheral neuropathy. In this study, we aim to study the clinical, electrophysiological spectrum and therapeutic responses among the different subtypes of SS-associated neuropathy. The predictors of suboptimal treatment response will be identified. Methods: The study included a retrospective cohort of patients with SS-associated neuropathy between January 2012 and November 2015. Baseline clinical, laboratory, electrophysiological data and details of treatment were noted. Therapeutic outcomes were assessed at follow-up and compared among the different subtypes. Prognostic predictors were determined using logistic regression analysis. Results: Fifty-four patients were included in the study. Sensory ataxic neuropathy (17, including 9 with sensory ganglionopathy) and radiculoneuropathy (11) were the main subtypes. Notable atypical presentations included acute neuropathies, pure motor neuropathies, and hypertrophic neuropathy. Concomitant autoimmune disorders were present in 24 (44.4%) patients. Most presentations were subacute-chronic (51, 94.4%). Minor salivary gland biopsy had a higher yield compared to serological markers (81.5 vs. 44.4%). Sensory ataxic neuropathy was associated with greater severity and autonomic dysfunction. Improvement was noted in 33 (61%) patients. Cranial neuropathy and radiculoneuropathy subtypes were associated with the best treatment responses. Chronicity, orthostatic hypotension, baseline severity, and marked axonopathy (nerve biopsy) were predictive of a suboptimal therapeutic response. Conclusions: The study highlights the heterogeneous spectrum, atypical presentations, and differential therapeutic responses. SS-associated neuropathy remains underdiagnosed. Early diagnosis and prompt initiation of immunotherapy before worsening axonal degeneration is paramount. SS-associated neuropathy need not necessarily be associated with a poor prognosis.

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Rituximab in neuromyelitis optica spectrum disorders: Our experience

Jui Dilip Jade, Srishti Bansi, Bhim Singhal

Annals of Indian Academy of Neurology 2017 20(3):229-232

Background: Neuromyelitis optica (NMO) is an inflammatory demyelinating central nervous system disease, with recurrent attacks of severe bilateral optic neuritis and longitudinally extensive transverse myelitis. Aggressive immunosuppression is essential to prevent clinical relapses and permanent disability. Rituximab, a monoclonal antibody to CD20, has been found effective in several reports and small uncontrolled studies. There is a paucity of data regarding its use in Indian patients. Objectives: The aim of this study was to report the results of rituximab treatment in NMO spectrum disorders (NMOSDs) in the Indian scenario. Methods: This study is a retrospective, observational study including 13 NMOSD patients treated with rituximab. After initial therapy in the acute episode with IV methylprednisolone and if needed plasma exchange, therapy was initiated as a cycle of intravenous rituximab, two doses 2 weeks apart of 1 g each. Subsequent cycles were advised at intervals of every 6 months. The primary outcome measure was annualized relapse rate (ARR), defined as a number of clinical attacks per year. Clinical adverse events were recorded throughout the study. Results: In the study, mean ARR reduced from 2.61 to 0.09 after therapy (P = 0.000685). Of 13 patients, 8 (61.54%) were completely relapse free after starting treatment with rituximab. Treatment was well tolerated and no serious adverse events were noted. Conclusions: The treatment of NMOSDs with rituximab in Indian patients reduces the frequency of relapses and is well tolerated.

http://ift.tt/2vmjgi1

Clinical features, risk factors, and short-term outcome of ischemic stroke, in patients with atrial fibrillation: Data from a population-based study

G William Akanksha, Kaur Paramdeep, Singh Gagandeep, Bansal Rajinder, S Paul Birinder, Singla Monika, Singh Shavinder, J Samuel Clarence, J Verma Shweta, Meenakshi Sharma, D Pandian Jeyaraj

Annals of Indian Academy of Neurology 2017 20(3):289-293

Objectives: Atrial fibrillation (AF) is the most common sustained cardiac rhythm disorder associated with stroke. This study was done to describe risk factors, clinical features, and short-term outcomes of stroke patients with AF. Materials and Methods: This study was a part of the Indian Council of Medical Research funded "Ludhiana urban population based Stroke Registry." Data were collected using WHO STEPS stroke method. All patients ≥18 years of age, who developed ischemic stroke between March 26, 2011, and March 25, 2013, were included in this study. Data about demographic details, clinical features, and risk factors were collected. The outcome was assessed at 28 days using modified Rankin scale (mRs) (good outcome: mRS ≤2; poor outcome >2). The statistical measures calculated were descriptive statistics, Chi-square test, Fischer's exact test, and independent t-test. Results: Of the total 7199 patients enrolled in the registry, data of 1942 patients who fulfilled inclusion criteria were analyzed, and AF was seen in 203 (10%) patients. AF patients were older (AF 62 ± 14 vs. non-AF 60 ± 15 years, P= 0.01), had more hypertension (AF 176 [87%] vs. non-AF 1396 [80%], P= 0.03), hyperlipidemia (AF 60 [32%] vs. non-AF 345 [21%], P= 0.001), coronary artery disease (AF 60 [30%] vs. non-AF 195 [11%], P< 0.0001), and carotid stenosis (AF 14 [7%] vs. non-AF 57 (3%), P= 0.02). They had worse outcome (mRS >2; AF 90 [50%] vs. non-AF 555 [37%], P= 0.001). Conclusions: Ten percent of stroke patients had AF. They were older, had multiple risk factors and worse outcome. There was no gender difference in this large cohort.

http://ift.tt/2vpJMWm

A Case of Male Osteoporosis: A 37-Year-Old Man with Multiple Vertebral Compression Fractures.

A Case of Male Osteoporosis: A 37-Year-Old Man with Multiple Vertebral Compression Fractures.

Case Rep Endocrinol. 2017;2017:6328524

Authors: Radi S, Karaplis AC

Abstract
While the contributing role of testosterone to bone health is rather modest compared to other factors such as estradiol levels, male hypogonadism is associated with low bone mass and fragility fractures. Along with stimulating physical puberty by achieving virilization and a normal muscle mass and improving psychosocial wellbeing, the goals of testosterone replacement therapy in male hypogonadism also include attainment of age-specific bone mineral density. We report on a 37-year-old man who presented with multiple vertebral compression fractures several years following termination of testosterone replacement therapy for presumed constitutional delay in growth and puberty. Here, we discuss the management of congenital hypogonadotropic hypogonadism with hyposmia (Kallmann syndrome), with which the patient was ultimately diagnosed, the role of androgens in the acquisition of bone mass during puberty and its maintenance thereafter, and outline specific management strategies for patients with hypogonadism and high risk for fragility fractures.

PMID: 28791186 [PubMed]

http://ift.tt/2vIh7OC

The Typhoid Vaccine Acceleration Consortium (TyVAC): Vaccine effectiveness study designs: Accelerating the introduction of typhoid conjugate vaccines and reducing the global burden of enteric fever. Report from a meeting held on 26–27 October 2016, Oxford, UK

Publication date: Available online 10 August 2017
Source:Vaccine
Author(s): James E. Meiring, Malick Gibani
Typhoid fever is estimated to cause between 11.9–26.9 million infections globally each year with 129,000–216,510 deaths. Access to improved water sources have reduced disease incidence in parts of the world but the use of efficacious vaccines is seen as an important public health tool for countries with a high disease burden.A new generation of Vi typhoid conjugate vaccines (TCVs), licensed for use in young children and expected to provide longer lasting protection than previous vaccines, are now available. The WHO Strategic Advisory Group of Experts on Immunization (SAGE) has convened a working group to review the evidence on TCVs and produce an updated WHO position paper for all typhoid vaccines in 2018 that will inform Gavi, the Vaccine Alliance's future vaccine investment strategies for TCVs.The Typhoid Vaccine Acceleration Consortium (TyVAC) has been formed through a $36.9 million funding program from the Bill & Melinda Gates Foundation to accelerate the introduction of TCVs into Gavi-eligible countries.In October 2016, a meeting was held to initiate planning of TCV effectiveness studies that will provide the data required by policy makers and stakeholders to support decisions on TCV use in countries with a high typhoid burden.Discussion topics included (1) the latest evidence and data gaps in typhoid epidemiology; (2) WHO and Gavi methods and data requirements; (3) data on TCV efficacy; (4) cost effectiveness analysis for TCVs from mathematical models; (5) TCV delivery and effectiveness study design. Specifically, participants were asked to comment on study design in 3 sites for which population-based typhoid surveillance is underway.The conclusion of the meeting was that country-level decision making would best be informed by the respective selected sites in Africa and Asia vaccinating children aged from 9-months to 15-years-old, employing either an individual or cluster randomized design with design influenced by population characteristics, transmission dynamics, and statistical considerations.

http://ift.tt/2wwThTT

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