Evaluation of depression and social anxiety symptoms in obese children

2016-03-31T06-28-48Z
Source: Düşünen Adam: The Journal of Psychiatry and Neurological Sciences
Esra Akyuz Ozkan, Ali Irfan Gul, Zeynep Tuba Ozdemir, Hasim Husrevsahi, Zehra Yildirim, Esra Domur, Ummugulsum Aliye Gecit.
Objective: The present study aimed to assess depression and social anxiety symptoms in obese children. Methods: The Childrens Depression Inventory (CDI) and the Social Anxiety Scale for Children - Revised (SASC-R) were administered to 80 obese children and 82 controls. Results: The obese group consisted of 42 male and 38 female children, mean age 12.48±2.70 years (range 7-17 years), mean body mass index (BMI) was 27.47±3.72 kg/m2; controls were 43 male, 39 female children, mean age 12.93±2.32 years (range 9-17 years), mean BMI was 16.92±5.17 kg/m2. Mean social anxiety scores were higher in the obese group than in the control group. Mean depression scores were significantly higher in the obese group than in the control group. The mean depression scores were higher in obese females compared to control females as well as in males. The mean social anxiety scores were higher in obese females than in controls as well as in males. There was no correlation between BMI and depression and social anxiety scores in obese males and females. Among obese childeren 21.5% and among the control group 14.3% had a value of CDI above the cut-off point, and this was statistically significant. Among obese childeren 15.2% of females and 10.4% of males had a value above the cut-off point, but the difference between sexes was not statistically significant. Discussion: Depression and social anxiety symptoms were more common in obese children and did not relate to the degree of obesity. The prevention of childhood obesity is important in both sexes for reducing the risk of psychological disorder in adulthood.


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Relation of the Nine Types of Temperament Model with personality disorders

2016-03-31T06-28-48Z
Source: Düşünen Adam: The Journal of Psychiatry and Neurological Sciences
Enver Demirel Yilmaz, Ali Gorkem Gencer, Ozge Unal, Mehmet Palanci, Mehmet Kandemir, Ziya Selcuk, Omer Aydemir.
Objective: Aim of this study is to determine the correspondence between personality categories and the types making up the Nine Types of Temperament Model (NTTM) a new temperament model which evaluates personality disorders within the context of temperament traits and maladaptive personality features- and conceptualization of NTTM types. Method: The sample group is composed of 117 participants with a personality disorder. SCID II and Nine Types of Temperament Scale (NTTS) were applied to participants. Results: According to the findings, all NTTM types have shown significant correlation with at least one personality disorder. According to the regression analysis results, it was determined that the NTTM types were explained by personality disorders at a rate of 19-41%. Conclusions: In this study, it is found that knowing the temperament features that form the basis of an individuals personality structure is helpful to diagnose and to determine the tendency to develop personality disorders that are pathological responses to personality characteristics. In addition, this study brings up questions such as whether the individual differences between patients with the same personality disorders can be evaluated on the basis of temperament and whether it is possible to determine therapy and treatment approaches according to an individuals temperament type.


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Psychometric properties of the Inventory of Interpersonal Problems Circumplex Scales short form: a reliability and validity study

2016-03-31T06-28-48Z
Source: Düşünen Adam: The Journal of Psychiatry and Neurological Sciences
Miray Akyunus, Tulin Gencoz.
Objective: Considering the lack of an instrument in Turkish to measure individuals interpersonal difficulties, our aim was to adapt a short version of the Inventory of Interpersonal Problems Circumplex Scales (IIP-C) for Turkish culture, and we studied the psychometric properties of the scale. Method: Our study included 1298 adult participants from the normal population (411 females and 887 males) between the ages of 18 and 68. In order to establish reliability and validity of the Turkish version of the IIP-C, internal consistency, test-retest reliability, split-half reliability coefficients, and concurrent and criterion validity studies were conducted. The validity study analyzed correlations with the Positive and Negative Affect Schedule, the Brief Symptom Inventory, the Multidimensional Scale of Perceived Social Support and the Basic Personality Traits Inventory. Results: The results of the study indicated good internal consistency, test-retest and split-half reliability coefficients of the IIP-C, assessing overall level of interpersonal difficulty and distress due to various interpersonal problems. Moreover, findings supported concurrent and criterion validity of the inventory, in addition to the two-factor structures consistent with the original inventory. Conclusion: The psychometric properties of IIP-C seem to be acceptable; therefore, the instrument can be utilized for research and clinical purposes in Turkey.


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Review of the diagnosis and treatment of pregnant psychiatric inpatients

2016-03-31T06-28-48Z
Source: Düşünen Adam: The Journal of Psychiatry and Neurological Sciences
Kader Semra Karatas, Julide Guler, Aytul Hariri, Feride Ezgi Buyuksahin Unal.



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Analysis of gene expression in mouse brain regions after exposure to 1.9 GHz radiofrequency fields

10.3109/09553002.2016.1159353<br/>James P. McNamee

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A case of patch stage of Kaposi’s sarcoma and discussion of the differential diagnosis

A 55-year-old HIV positive male had a skin lesion biopsy which showed atypical vascular proliferation within the superficial and deep dermis with mild atypia of lining endothelial cells. A sparse lymphoplasmacytic infiltrate surrounding the irregular vascular channels was noted. Immunohistochemistry highlighted the atypical blood vessels with the vascular markers CD31, CD34 and Factor VIII. The differential diagnosis included unusual vascular or lymphatic proliferations, stasis dermatitis, kaposiform hemangioendothelioma, progressive lymphangioma and angiosarcoma with focal Kaposi's sarcoma features. Characteristic human herpes virus-8 positive staining helped support the diagnosis of patch stage of Kaposi's sarcoma. Herein, we discuss the case findings, differential diagnosis and characteristic histological findings associated with the patch stage of Kaposi's sarcoma which can be an elusive diagnosis.

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Influence of different fixation protocols on the preservation and dimensions of cardiac tissue

Abstract

Recent extensive progress in invasive cardiac procedures has triggered a wave of dozens of heart morphometric anatomical studies that are carried out largely using autopsied samples fixed in formaldehyde solution prior to observations and measurements. In reality, very little is known about changes in heart tissue dimensions during fixation. The aim of this study was therefore to investigate how fixation affects the dimensions of cardiac tissue, and if different types and concentrations of reagents affect this phenomenon. A total of 40 pig heart samples were investigated, and seven different measuring sites were permanently marked in every heart prior to fixation. Four study groups (n = 10 each) were assembled that differed only in concentration and the type of fixative: (i) 2% formaldehyde solution; (ii) 4% formaldehyde solution (formalin); (iii) 10% formaldehyde solution; (iv) alcoholic formalin. The samples were measured before and after fixation at the following time points: 24 h, 72 h and 168 h. It was found that different fixatives significantly affected different parameters. Almost all of the heart dimensions that were measured stabilized after 24 h; later changes were statistically insignificant in the point-to-point comparison. Change in the length of the interatrial septum surface was not altered significantly in any of the fixatives after 24 h of preservation. It was found that 10% formaldehyde increased the thickness of muscular tissue only after 24 h; this thickening was reduced after 72 h and was insignificant at 168 h. Other heart parameters in this group do not present significant changes over the entire fixation time duration. In conclusion, the 10% formaldehyde phosphate-buffered solution appeared to be the best fixative among the fixatives that were studied for cardiac morphometric purposes; this solution caused the smallest changes in tissue dimensions. Measurements should be obtained at least after 1 week of preservation when most parameters exhibit the smallest changes compared with the non-preserved samples.

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Non-metric variation of the middle phalanges of the human toes (II–V): long/short types and their evolutionary significance

Abstract

The human lateral toes are characterised by extreme reduction compared with other primates, and in particular other hominoids. Some phalangeal non-metric variants have been well identified in humans, in particular: triphalangeal/biphalangeal patterns, and the presence/absence of phalangeal secondary centres of ossification. The purpose of the present study was to describe and analyse an original non-metric variation of the middle phalanges of the lateral toes. The material consisted of 2541 foot radiographs that came from 2541 different European adult individuals. Two morphological types of the middle phalanx were defined as a simple binary trait: long type (L) and short type (S). In feet with a triphalangeal pattern in all lateral toes (1413 cases), a mediolateral increasing gradient was observed in the occurrence of type S: 8.1% in II; 30.7% in III; 68.4% in IV; and 99.1% in V. In feet with a biphalangeal pattern in one or more lateral toes (III–V; 1128 cases), type S occurred more frequently than in triphalangeal feet. Of the 30 theoretical arrangements of the L/S types in the lateral toes (II–V) in a complete foot, only 13 patterns were observed. Seven patterns represented 95.6% of the population: LLSS (20.9%), LLLS (17.1%), LSS (15.9%), SSS (14.5%), LSSS (12.7%), LLS (10.1%) and SSSS (4.4%). Type L can be interpreted as the primitive pattern (plesiomorphy), and type S as a derived pattern (apomorphy) that seems specific to the human species (i.e. autapomorphy). Within the specific evolution of the human foot in relation to the acquisition of constant erect posture and bipedalism, the short type of the middle phalanges can reasonably be considered as directly linked to the reduction of the lateral toes.

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Monastic Leadership as 'Immaterial Resource': a look at reformist abbots of the tenth to early twelfth centuries

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De taalbescherming van de anderstalige die naar de rechter stapt

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Assessment throughout a whole fishing year of the dominant microbiota of peeled brown shrimp (Crangon crangon) stored for 7 days under modified atmosphere packaging at 4 °C without preservatives

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Estimation of the optimum dose of vitamin D for disease prevention in older people: rationale, design and baseline characteristics of the BEST-D trial.

Related Articles

Estimation of the optimum dose of vitamin D for disease prevention in older people: rationale, design and baseline characteristics of the BEST-D trial.

Maturitas. 2015 Apr;80(4):426-31

Authors: Clarke R, Newman C, Tomson J, Hin H, Kurien R, Cox J, Lay M, Sayer J, Hill M, Emberson J, Armitage J

Abstract
BACKGROUND: Previous large trials of vitamin D for prevention of fractures and other disease outcomes have reported conflicting results, possibly because the doses tested were insufficient to maintain optimum blood levels of vitamin D (25[OH]D) predicted by the observational studies. This report describes the design and baseline characteristics of the BEST-D (Biochemical Efficacy and Safety Trial of vitamin D) trial which aims to establish the best dose of vitamin D to assess in a future large outcome trial.
METHODS: The BEST-D trial will compare the biochemical and other effects of daily dietary supplementation with 100 μg or 50 μg vitamin D3 or placebo, when administered for 12 months, in 305 ambulant community-dwelling older people living in Oxfordshire, England. The primary analyses will compare 12-month mean plasma concentrations of 25(OH)D as well as the proportion of participants with a 12-month concentration >90 nmol/L between participants allocated 100 μg and participants allocated 50 μg daily. Secondary analyses will compare the two active doses (both separately and when combined) with placebo. Additional end-points include biochemical assessments of safety, blood pressure, arterial stiffness, falls, fractures, heel and wrist bone density, grip strength and physical performance and echocardiographic assessments of cardiac function in a random sample of participants.
RESULTS: About one-third of eligible participants agreed to participate in the trial. The mean age was 72 (SD 6) years with equal numbers of men and women. About one third reported a prior history of fracture or hypertension, one-fifth reported a prior cardiovascular event, and one tenth reported diabetes or a fall in the previous 6 months.
CONCLUSIONS: The results of this trial will help determine the optimum dose of vitamin D to test in a larger trial investigating whether vitamin D supplementation can reduce the risk of fractures, cardiovascular disease or cancer.

PMID: 25721698 [PubMed - indexed for MEDLINE]

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“Chain of Beads” Appearance of the Superior Mesenteric Artery

Publication date: Available online 30 March 2016
Source:European Journal of Vascular and Endovascular Surgery
Author(s): H.Y. Zhang, C.L. Chen




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Randomized Phase III study of gemcitabine plus S-1 versus gemcitabine plus cisplatin in advanced biliary tract cancer: Japan Clinical Oncology Group Study (JCOG1113, FUGA-BT).

Randomized Phase III study of gemcitabine plus S-1 versus gemcitabine plus cisplatin in advanced biliary tract cancer: Japan Clinical Oncology Group Study (JCOG1113, FUGA-BT).

Jpn J Clin Oncol. 2016 Apr;46(4):385-8

Authors: Mizusawa J, Morizane C, Okusaka T, Katayama H, Ishii H, Fukuda H, Furuse J, Hepatobiliary and Pancreatic Oncology Group of the Japan Clinical Oncology Group

Abstract
A Phase II selection design trial was conducted to identify the most promising regimen for comparison with standard therapy in chemo-naive patients with unresectable or recurrent biliary tract cancer (JCOG0805). Gemcitabine plus S-1 therapy showed better efficacy than S-1 monotherapy with acceptable safety in JCOG0805 study. Based on this result, a randomized Phase III trial was started in May 2013 to confirm the non-inferiority of gemcitabine plus S-1 therapy relative to gemcitabine plus cisplatin therapy, which is the current standard treatment for chemo-naive patients with unresectable or recurrent biliary tract cancer. A total of 350 patients will be accrued from 32 Japanese institutions within 4 years. The primary endpoint is overall survival, while the secondary endpoints are progression-free survival, adverse events, serious adverse events, clinically significant adverse events, response rate and %planned dose. This trial has been registered with the UMIN Clinical Trials Registry (http://ift.tt/1lXJedE) and the registration number is UMIN000010667.

PMID: 27025903 [PubMed - in process]

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tDCS and Robotics on Upper Limb Stroke Rehabilitation: Effect Modification by Stroke Duration and Type of Stroke

Objective. The aim of this exploratory pilot study is to test the effects of bilateral tDCS combined with upper extremity robot-assisted therapy (RAT) on stroke survivors. Methods. We enrolled 23 subjects who were allocated to 2 groups: RAT + real tDCS and RAT + sham-tDCS. Each patient underwent 10 sessions (5 sessions/week) over two weeks. Outcome measures were collected before and after treatment: (i) Fugl-Meyer Assessment-Upper Extremity (FMA-UE), (ii) Box and Block Test (BBT), and (iii) Motor Activity Log (MAL). Results. Both groups reported a significant improvement in FMA-UE score after treatment (). No significant between-groups differences were found in motor function. However, when the analysis was adjusted for stroke type and duration, a significant interaction effect () was detected, showing that stroke duration (acute versus chronic) and type (cortical versus subcortical) modify the effect of tDCS and robotics on motor function. Patients with chronic and subcortical stroke benefited more from the treatments than patients with acute and cortical stroke, who presented very small changes. Conclusion. The additional use of bilateral tDCS to RAT seems to have a significant beneficial effect depending on the duration and type of stroke. These results should be verified by additional confirmatory studies.

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Associations between heart failure and physical function in U.S. adults.

Associations between heart failure and physical function in U.S. adults.

QJM. 2016 Mar 29;

Authors: Churilla JR, Richardson MR, Pinkstaff SO, Fletcher BJ, Fletcher GF

Abstract
BACKGROUND: There is a paucity of nationally representative data in the area of heart failure (HF) and physical function (PF).
AIM: Examine the relationship(s) between HF and PF in a nationally representative sample of United States (U.S.) adults.
DESIGN: Cross-Section analysis of U.S. Adults.
METHODS: Sample (n=6,623) included adult (≥40 years of age) participants from the 1999-2006 National Health and Nutrition Examination Survey. Participants reporting HF answered questions related to their abilities to accomplish specific upper extremity and lower extremity tasks, and household chores.
RESULTS: Prevalence estimates of reporting much difficulty or the inability to stand from an armless chair was 9.9% and 4.3% (P=0.002) in those with and without HF, respectively. Similar estimates were revealed for much difficulty or inability to lift or carry 10 lbs. (16.8% and 8.6%, P=0.0004) and much difficulty or inability to do household chores (13.3% and 6.1%, P=0.0008). Following adjustments participants reporting HF had significantly greater odds of reporting much difficulty or the inability to stand from an armless chair (OR 1.93; 95% CI 1.25, 2.96), much difficulty or the inability to lift or carry 10 lbs. (OR 1.90; 95% CI 1.36, 2.65), and much difficulty or inability to do household chores (OR 2.06; 95% CI 1.41, 3.02) compared to participants not reporting HF.
CONCLUSIONS: Findings suggest U.S. adults reporting HF are more likely to report poorer PF.

PMID: 27026699 [PubMed - as supplied by publisher]

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Cognitive impairment and reduced quality of life among old-age groups in Southern Urban India: home based community residents, free and paid old-age home residents.

Cognitive impairment and reduced quality of life among old-age groups in Southern Urban India: home based community residents, free and paid old-age home residents.

QJM. 2016 Mar 29;

Authors: Samuel R, McLachlan CS, Mahadevan U, Isaac V

Abstract
AIM: The purpose of the study were a) to screen for cognitive impairment using Mini-Mental Status Examination among three old-age groups based on dwelling types in Chennai, India i.e., residential paid old-age homes, residential free (charitable) homes and home-based community-dwelling residents; b) secondly to investigate factors (demographic, psychological, medical, and disability) associated with cognitive impairment in the these old-age; c) thirdly, to investigate the independent association between cognitive impairment and health-related quality of life (QOL) among elderly across aged care dwelling types.
METHODS: A total of 499 elderly from three old-age groups were interviewed in this cross-sectional study (173 elderly home-based community-dwellers, 176 paid-home and 150 free-home residents). All the participants were interviewed for their socio-economic condition, medical morbidity, self-reported worry and anxiety, disability and QOL.
RESULTS: 42.7% free-home elderly residents were found to have cognitive impairment, while 32.4% of paid-home and 21.9% of community-dwelling elderly had cognitive impairment. The residents of free-home were less educated, had lower income and reported higher incidence of worry, anxiety, disability and poor QOL than community-dwelling or paid-home residents. Increasing age, low education, female gender, high blood pressure and disability was associated with cognitive impairment. Cognitive impairment had significant negative effect on their health-related QOL (b=-0.10, p=0.01), independent of age, gender, education, chronic illness and dwelling type.
CONCLUSION: The burden of cognitive impairment was high in all aged-care dwelling types in urban India; with free charitable home residents being worse affected. Cognitive impairment was associated with disability and poor health-related QOL in these age-care settings.

PMID: 27026698 [PubMed - as supplied by publisher]

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Two teachers and a book.

Two teachers and a book.

QJM. 2016 Mar 29;

Authors: Seaton A

PMID: 27026697 [PubMed - as supplied by publisher]

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Cerebral Toxoplasmosis.

Cerebral Toxoplasmosis.

QJM. 2016 Mar 29;

Authors: Ozaras R, Karaismailoglu B, Hasiloglu Z, Sahin S, Vatan A, Oz B

PMID: 27026696 [PubMed - as supplied by publisher]

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Hertoghe sign: an hallmark of lepromatous leprosy.

Hertoghe sign: an hallmark of lepromatous leprosy.

QJM. 2016 Mar 29;

Authors: Parrino D, Di Bella S

PMID: 27026695 [PubMed - as supplied by publisher]

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A novel mutation in KLHL3 gene causes Familial Hyperkalemic Hypertension.

A novel mutation in KLHL3 gene causes Familial Hyperkalemic Hypertension.

QJM. 2016 Mar 29;

Authors: Kelly D, Rodzlan MR, Jeunemaitre X, Wall C

PMID: 27026694 [PubMed - as supplied by publisher]

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Chondrocalcinosis and Gitelman syndrome.

Chondrocalcinosis and Gitelman syndrome.

QJM. 2016 Mar 29;

Authors: Iqbal Z, Sayer JA

PMID: 27026693 [PubMed - as supplied by publisher]

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What can imaging tell us about cognitive impairment and dementia?

What can imaging tell us about cognitive impairment and dementia?

World J Radiol. 2016 Mar 28;8(3):240-254

Authors: Narayanan L, Murray AD

Abstract
Dementia is a contemporary global health issue with far reaching consequences, not only for affected individuals and their families, but for national and global socio-economic conditions. The hallmark feature of dementia is that of irreversible cognitive decline, usually affecting memory, and impaired activities of daily living. Advances in healthcare worldwide have facilitated longer life spans, increasing the risks of developing cognitive decline and dementia in late life. Dementia remains a clinical diagnosis. The role of structural and molecular neuroimaging in patients with dementia is primarily supportive role rather than diagnostic, American and European guidelines recommending imaging to exclude treatable causes of dementia, such as tumor, hydrocephalus or intracranial haemorrhage, but also to distinguish between different dementia subtypes, the commonest of which is Alzheimer's disease. However, this depends on the availability of these imaging techniques at individual centres. Advanced magnetic resonance imaging (MRI) techniques, such as functional connectivity MRI, diffusion tensor imaging and magnetic resonance spectroscopy, and molecular imaging techniques, such as 18F fluoro-deoxy glucose positron emission tomography (PET), amyloid PET, tau PET, are currently within the realm of dementia research but are available for clinical use. Increasingly the research focus is on earlier identification of at risk preclinical individuals, for example due to family history. Intervention at the preclinical stages before irreversible brain damage occurs is currently the best hope of reducing the impact of dementia.

PMID: 27029053 [PubMed - as supplied by publisher]

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Molecular imaging of movement disorders.

Molecular imaging of movement disorders.

World J Radiol. 2016 Mar 28;8(3):226-239

Authors: Lizarraga KJ, Gorgulho A, Chen W, De Salles AA

Abstract
Positron emission tomography measures the activity of radioactively labeled compounds which distribute and accumulate in central nervous system regions in proportion to their metabolic rate or blood flow. Specific circuits such as the dopaminergic nigrostriatal projection can be studied with ligands that bind to the pre-synaptic dopamine transporter or post-synaptic dopamine receptors (D1 and D2). Single photon emission computerized tomography (SPECT) measures the activity of similar tracers labeled with heavy radioactive species such as technetium and iodine. In essential tremor, there is cerebellar hypermetabolism and abnormal GABAergic function in premotor cortices, dentate nuclei and ventral thalami, without significant abnormalities in dopaminergic transmission. In Huntington's disease, there is hypometabolism in the striatum, frontal and temporal cortices. Disease progression is accompanied by reduction in striatal D1 and D2 binding that correlates with trinucleotide repeat length, disease duration and severity. In dystonia, there is hypermetabolism in the basal ganglia, supplementary motor areas and cerebellum at rest. Thalamic and cerebellar hypermetabolism is seen during dystonic movements, which can be modulated by globus pallidus deep brain stimulation (DBS). Additionally, GABA-A receptor activity is reduced in motor, premotor and somatosensory cortices. In Tourette's syndrome, there is hypermetabolism in premotor and sensorimotor cortices, as well as hypometabolism in the striatum, thalamus and limbic regions at rest. During tics, multiple areas related to cognitive, sensory and motor functions become hypermetabolic. Also, there is abnormal serotoninergic transmission in prefrontal cortices and bilateral thalami, as well as hyperactivity in the striatal dopaminergic system which can be modulated with thalamic DBS. In Parkinson's disease (PD), there is asymmetric progressive decline in striatal dopaminergic tracer accumulation, which follows a caudal-to-rostral direction. Uptake declines prior to symptom presentation and progresses from contralateral to the most symptomatic side to bilateral, correlating with symptom severity. In progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), striatal activity is symmetrically and diffusely decreased. The caudal-to-rostral pattern is lost in PSP, but could be present in MSA. In corticobasal degeneration (CBD), there is asymmetric, diffuse reduction of striatal activity, contralateral to the most symptomatic side. Additionally, there is hypometabolism in contralateral parieto-occipital and frontal cortices in PD; bilateral putamen and cerebellum in MSA; caudate, thalamus, midbrain, mesial frontal and prefrontal cortices in PSP; and contralateral cortices in CBD. Finally, cardiac sympathetic SPECT signal is decreased in PD. The capacity of molecular imaging to provide in vivo time courses of gene expression, protein synthesis, receptor and transporter binding, could facilitate the development and evaluation of novel medical, surgical and genetic therapies in movement disorders.

PMID: 27029029 [PubMed - as supplied by publisher]

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Simultaneous whole body (18)F-fluorodeoxyglucose positron emission tomography magnetic resonance imaging for evaluation of pediatric cancer: Preliminary experience and comparison with (18)F-fluorodeoxyglucose positron emission tomography computed tomography.

Simultaneous whole body (18)F-fluorodeoxyglucose positron emission tomography magnetic resonance imaging for evaluation of pediatric cancer: Preliminary experience and comparison with (18)F-fluorodeoxyglucose positron emission tomography computed tomography.

World J Radiol. 2016 Mar 28;8(3):322-330

Authors: Pugmire BS, Guimaraes AR, Lim R, Friedmann AM, Huang M, Ebb D, Weinstein H, Catalano OA, Mahmood U, Catana C, Gee MS

Abstract
AIM: To describe our preliminary experience with simultaneous whole body (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography and magnetic resonance imaging (PET-MRI) in the evaluation of pediatric oncology patients.
METHODS: This prospective, observational, single-center study was Health Insurance Portability and Accountability Act-compliant, and institutional review board approved. To be eligible, a patient was required to: (1) have a known or suspected cancer diagnosis; (2) be under the care of a pediatric hematologist/oncologist; and (3) be scheduled for clinically indicated (18)F-FDG positron emission tomography-computed tomography (PET-CT) examination at our institution. Patients underwent PET-CT followed by PET-MRI on the same day. PET-CT examinations were performed using standard department protocols. PET-MRI studies were acquired with an integrated 3 Tesla PET-MRI scanner using whole body T1 Dixon, T2 HASTE, EPI diffusion-weighted imaging (DWI) and STIR sequences. No additional radiotracer was given for the PET-MRI examination. Both PET-CT and PET-MRI examinations were reviewed by consensus by two study personnel. Test performance characteristics of PET-MRI, for the detection of malignant lesions, including FDG maximum standardized uptake value (SUVmax) and minimum apparent diffusion coefficient (ADCmin), were calculated on a per lesion basis using PET-CT as a reference standard.
RESULTS: A total of 10 whole body PET-MRI exams were performed in 7 pediatric oncology patients. The mean patient age was 16.1 years (range 12-19 years) including 6 males and 1 female. A total of 20 malignant and 21 benign lesions were identified on PET-CT. PET-MRI SUVmax had excellent correlation with PET-CT SUVmax for both benign and malignant lesions (R = 0.93). PET-MRI SUVmax > 2.5 had 100% accuracy for discriminating benign from malignant lesions using PET-CT reference. Whole body DWI was also evaluated: the mean ADCmin of malignant lesions (780.2 + 326.6) was significantly lower than that of benign lesions (1246.2 + 417.3; P = 0.0003; Student's t test). A range of ADCmin thresholds for malignancy were evaluated, from 0.5-1.5 × 10(-3) mm(2)/s. The 1.0 × 10(-3) ADCmin threshold performed best compared with PET-CT reference (68.3% accuracy). However, the accuracy of PET-MRI SUVmax was significantly better than ADCmin for detecting malignant lesions compared with PET-CT reference (P < 0.0001; two-tailed McNemar's test).
CONCLUSION: These results suggest a clinical role for simultaneous whole body PET-MRI in evaluating pediatric cancer patients.

PMID: 27028112 [PubMed - as supplied by publisher]

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Multidetector computed tomography features of pancreatic metastases from leiomyosarcoma: Experience at a tertiary cancer center.

Multidetector computed tomography features of pancreatic metastases from leiomyosarcoma: Experience at a tertiary cancer center.

World J Radiol. 2016 Mar 28;8(3):316-321

Authors: Suh CH, Keraliya A, Shinagare AB, Kim KW, Ramaiya NH, Tirumani SH

Abstract
AIM: To describe the multidetector computed tomography features of pancreatic metastasis from leiomyosarcoma (LMS).
METHODS: Between January 1995 and December 2012, 13 consecutive patients (11 women, 2 men; mean age of 57 years; range, 38-78 years) with pancreatic metastases from LMS were included in our study. Imaging features including location, number, largest dimension, tumor attenuation and enhancement characteristics, presence of necrosis, pancreatic ductal dilatation, common bile duct (CBD) dilatation, presence of pancreatitis, and atrophy were documented.
RESULTS: The most common site of origin of the pancreatic metastases from LMS was uterus (38.5%), followed by retroperitoneum (30.8%) and extremity (23.1%). None of the patients in our study had pancreas as the first site of metastasis. All patients developed pancreatic metastases at a median interval of 24 mo. Pancreatic metastases from LMS were solitary in 8/13 patients and multiple in 5/13 patients, had no predilection for any part of the pancreas, were hypovascular on arterial phase in 10/13 patients and associated with pancreatic duct dilatation in 3/13 patients. None had CBD dilatation. None of the pancreatic metastases in LMS cohort caused pancreatitis, and atrophy. Median duration of follow-up was 19 mo for LMS cohort during which two patients underwent resection of metastasis (median survival 45 mo) while the remaining underwent systemic therapy (median survival 13 mo).
CONCLUSION: Pancreatic metastases from LMS are often solitary and hypovascular masses and less commonly associated with pancreatic ductal dilatation, CBD dilatation, pancreatitis or pancreatic atrophy. Surgical resection of solitary LMS pancreatic metastasis can be considered due to the long survival of these patients.

PMID: 27027985 [PubMed - as supplied by publisher]

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Angiographic and volumetric effects of mammalian target of rapamycin inhibitors on angiomyolipomas in tuberous sclerosis.

Angiographic and volumetric effects of mammalian target of rapamycin inhibitors on angiomyolipomas in tuberous sclerosis.

World J Radiol. 2016 Mar 28;8(3):308-315

Authors: Sheth RA, Feldman AS, Paul E, Thiele EA, Walker TG

Abstract
AIM: To investigate the angiographic and volumetric effects of mammalian target of rapamycin (mTOR) inhibitors on angiomyolipomas (AMLs) in a case series of patients with tuberous sclerosis complex.
METHODS: All patients who underwent catheter angiography prior to and following mTOR inhibitor therapy (n = 3) were evaluated. All cross-sectional imaging studies were analyzed with three-dimensional volumetrics, and tumor volume curves for all three tissue compartments (soft tissue, vascular, and fat) were generated. Segmentation analysis tools were used to automatically create a region of interest (ROI) circumscribing the AML. On magnetic resonance images, the "fat only" map calculated from the in- and opposed-phase gradient recalled echo sequences was used to quantify fat volume within tumors. Tumor vascularity was measured by applying a thresholding tool within the ROI on post-contrast subtraction images. On computed tomography images, volume histogram analysis of Hounsfield unit was performed to quantify tumor tissue composition. The angiography procedures were also reviewed, and tumor vascularity based on pre-embolization angiography was characterized in a semi-quantitative manner.
RESULTS: Patient 1 presented at the age of 15 with a 6.8 cm right lower pole AML and a 4.0 cm right upper pole AML. Embolization was performed of both tumors, and after a few years of size control, the tumors began to grow, and the patient was initiated on mTOR inhibitor therapy. There was an immediate reduction in the size of both lesions. The patient then underwent repeat embolization and discontinuation of mTOR inhibition, after which point there was a substantial regrowth in both tumors across all tissue compartments. Patient 2 presented at the age of 18 with a right renal AML. Following a brief period of tumor reduction after embolization, she was initiated on mTOR inhibitor therapy, with successful reduction in tumor size across all tissue compartments. As with patient 1, however, there was immediate rebound growth following discontinuation of inhibitor therapy, without sustained control despite repeat embolization. patient 3 presented at the age of 5 with a left renal AML and underwent two embolization procedures without lasting effect prior to starting mTOR inhibition. As with patients 1 and 2, following discontinuation of therapy, there was immediate rebound growth of the tumor. Repeat embolization, however, was notable for a substantial reduction in intratumoral aneurysms and vascularity.
CONCLUSION: AML volume reduction as well as post-treatment rebound growth due to mTOR inhibitors involves all three tissue components of the tumor.

PMID: 27027863 [PubMed - as supplied by publisher]

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Paget’s Disease of Bone

Figure 1.

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Case 10-2016: A 22-Year-Old Man with Sickle Cell Disease, Headache, and Difficulty Speaking

Presentation of Case. Dr. Todd M. Herrington (Neurology): A 22-year-old right-handed man was admitted to this hospital because of the acute onset of headache and difficulty speaking. The patient had been well until approximately noon on the day of admission, when a dull, diffuse headache developed;…

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Carotid–Cavernous Sinus Fistula

Figure 1.

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Opioid Abuse in Chronic Pain — Misconceptions and Mitigation Strategies

Chronic pain not caused by cancer is among the most prevalent and debilitating medical conditions but also among the most controversial and complex to manage. The urgency of patients' needs, the demonstrated effectiveness of opioid analgesics for the management of acute pain, and the limited…

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Randomized Trial of Longer-Term Therapy for Symptoms Attributed to Lyme Disease

Patients with Lyme disease, which is caused by the Borrelia burgdorferi sensu lato complex (including B. afzelii and B. garinii in Europe), often report persistent symptoms. These symptoms are also referred to as the post–Lyme disease syndrome or chronic Lyme disease and may occur after…

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Extended-Release Naltrexone to Prevent Opioid Relapse in Criminal Justice Offenders

Opioid-use disorder is a chronic relapsing condition that has serious public health consequences. Opioid dependence disproportionately affects U.S. criminal justice system populations, and relapse and overdose deaths occur at high rates after release from incarceration. Evidence-based opioid…

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Time for a Different Approach to Lyme Disease and Long-Term Symptoms

The condition of most patients with Lyme disease improves after initial antibiotic therapy; however, 10 to 20% of treated patients may have lingering symptoms of fatigue, musculoskeletal pains, disrupted sleep, and lack of customary mental functions. The plausible idea that additional antimicrobial…

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Case 10-2016: A 22-Year-Old Man with Sickle Cell Disease, Headache, and Difficulty Speaking

Presentation of Case. Dr. Todd M. Herrington (Neurology): A 22-year-old right-handed man was admitted to this hospital because of the acute onset of headache and difficulty speaking. The patient had been well until approximately noon on the day of admission, when a dull, diffuse headache developed;…

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Carotid–Cavernous Sinus Fistula

Figure 1.

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Extended-Release Naltrexone to Prevent Opioid Relapse in Criminal Justice Offenders

Opioid-use disorder is a chronic relapsing condition that has serious public health consequences. Opioid dependence disproportionately affects U.S. criminal justice system populations, and relapse and overdose deaths occur at high rates after release from incarceration. Evidence-based opioid…

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Opioid Abuse in Chronic Pain — Misconceptions and Mitigation Strategies

Chronic pain not caused by cancer is among the most prevalent and debilitating medical conditions but also among the most controversial and complex to manage. The urgency of patients' needs, the demonstrated effectiveness of opioid analgesics for the management of acute pain, and the limited…

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Case 10-2016: A 22-Year-Old Man with Sickle Cell Disease, Headache, and Difficulty Speaking

Presentation of Case. Dr. Todd M. Herrington (Neurology): A 22-year-old right-handed man was admitted to this hospital because of the acute onset of headache and difficulty speaking. The patient had been well until approximately noon on the day of admission, when a dull, diffuse headache developed;…

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Carotid–Cavernous Sinus Fistula

Figure 1.

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Perceptions of Urologists About the Conversational Elements Leading to Treatment Decision-Making Among Newly Diagnosed Prostate Cancer Patients

Abstract

Widespread adoption and use of the practice of shared decision-making among health-care providers, especially urologists, has been limited. This study explores urologists' perceptions about their conversational practices leading to decision-making by newly diagnosed prostate cancer patients facing treatment. Semi-structured, in-depth interviews were conducted with 12 community and academic urologists practicing in the St. Louis, MO, region. Data were analyzed using a consensus coding approach. Urologists reported spending 30–60 min with newly diagnosed prostate cancer patients when discussing treatment options. They frequently encouraged family members' involvement in discussions about treatment, especially patients' spouses and children. Participants perceived these conversations to be difficult given the emotional burden associated with a cancer diagnosis, and encouraged patients to postpone their decisions or to get a second opinion before finalizing their treatment of choice. Initial discussions included a presentation of treatment options relevant to the patient's condition, side effects, outcome probabilities, and next steps. Urologists seldom used statistics while talking about treatment outcome probabilities and preferred to explain outcomes in terms of the patient's practical, emotional, and social experiences. Their styles to elicit the patient's preferences ranged from explicitly asking questions to making assumptions based on clinical experience and subtle patient cues. In conclusion, urologists' routine conversations included most elements of shared decision-making. However, shared decision-making required urologists to have nuanced discussions and be skilled in elicitation methods and risk discussions which requires further training. Further research is required to explore roles of family and clinical staff as participants in this process.

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Carotid–Cavernous Sinus Fistula

Figure 1.

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Case 10-2016: A 22-Year-Old Man with Sickle Cell Disease, Headache, and Difficulty Speaking

Presentation of Case. Dr. Todd M. Herrington (Neurology): A 22-year-old right-handed man was admitted to this hospital because of the acute onset of headache and difficulty speaking. The patient had been well until approximately noon on the day of admission, when a dull, diffuse headache developed;…

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Asparagus cochinchinensis Extract Alleviates Metal Ion-Induced Gut Injury in Drosophila: An In Silico Analysis of Potential Active Constituents

Metal ions and sulfate are components of atmospheric pollutants that have diverse ways of entering the human body. We used Drosophila as a model to investigate the effect of Asparagus cochinchinensis (A. cochinchinensis) extracts on the gut and characterized gut homeostasis following the ingestion of metal ions (copper, zinc, and aluminum). In this study, we found that the aqueous A. cochinchinensis extract increased the survival rate, decreased epithelial cell death, and attenuated metal ion-induced gut morphological changes in flies following chronic exposure to metal ions. In addition, we screened out, by network pharmacology, six natural products (NPs) that could serve as putative active components of A. cochinchinensis that prevented gut injury. Altogether, the results of our study provide evidence that A. cochinchinensis might be an effective phytomedicine for the treatment of metal ion-induced gut injury.

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Pediatric Radiology Continuing Medical Education Activity

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Hermes

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Case 10-2016: A 22-Year-Old Man with Sickle Cell Disease, Headache, and Difficulty Speaking

Presentation of Case. Dr. Todd M. Herrington (Neurology): A 22-year-old right-handed man was admitted to this hospital because of the acute onset of headache and difficulty speaking. The patient had been well until approximately noon on the day of admission, when a dull, diffuse headache developed;…

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The impact of participation in strategic planning on managers' creation of budgetary slack: the mediating role of autonomous motivation and affective organisational commitment

This study investigates the impact of participative strategic planning on managers' creation of budgetary slack. Specifically, we draw on self-determination and organisational commitment theory to examine whether and how the degree of managerial participation in strategic planning relates to the creation of budgetary slack. The hypotheses are empirically tested with survey data obtained from 247 managers in a cross-section of West-European organisations. The results from a structural equation model, with controls for budget participation and slack detection, suggest that increased participation in strategic planning leads to lower budgetary slack creation through the suggested path of heightened affective organisational commitment. In addition, the results indicate that budget participation decreases the creation of budgetary slack through the mediating effect of autonomous budget motivation, suggesting that both elements of the organisational planning process are related to the creation of budgetary slack. Our study contributes to the growing research exploring the interface between accounting and strategy by recognizing the importance of participative strategic planning for understanding managers' creation of budgetary slack.

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Myelin-reactive antibodies initiate T cell-mediated CNS autoimmune disease by opsonization of endogenous antigen

Abstract

In the pathogenesis of central nervous system (CNS) demyelinating disorders, antigen-specific B cells are implicated to act as potent antigen-presenting cells (APC), eliciting waves of inflammatory CNS infiltration. Here, we provide the first evidence that CNS-reactive antibodies (Ab) are similarly capable of initiating an encephalitogenic immune response by targeting endogenous CNS antigen to otherwise inert myeloid APC. In a transgenic mouse model, constitutive production of Ab against myelin oligodendrocyte glycoprotein (MOG) was sufficient to promote spontaneous experimental autoimmune encephalomyelitis (EAE) in the absence of B cells, when mice endogenously contained MOG-recognizing T cells. Adoptive transfer studies corroborated that anti-MOG Ab triggered activation and expansion of peripheral MOG-specific T cells in an Fc-dependent manner, subsequently causing EAE. To evaluate the underlying mechanism, anti-MOG Ab were added to a co-culture of myeloid APC and MOG-specific T cells. At otherwise undetected concentrations, anti-MOG Ab enabled Fc-mediated APC recognition of intact MOG; internalized, processed and presented MOG activated naïve T cells to differentiate in an encephalitogenic manner. In a series of translational experiments, anti-MOG Ab from two patients with an acute flare of CNS inflammation likewise facilitated detection of human MOG. Jointly, these observations highlight Ab-mediated opsonization of endogenous CNS auto-antigen as a novel disease- and/or relapse-triggering mechanism in CNS demyelinating disorders.

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Iodine-125-labeled DNA-Triplex-forming oligonucleotides reveal increased cyto- and genotoxic effectiveness compared to Phosphorus-32

10.3109/09553002.2016.1160157<br/>Volker Dahmen

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Efficacy of nasal corticosteroid in preventing regrowth after adenoidectomy

Publication date: Available online 29 March 2016
Source:Auris Nasus Larynx
Author(s): Yavuz Selim Yildirim, Erol Senturk, Sabri Baki Eren, Remzi Dogan, Selahattin Tugrul, Orhan Ozturan
ObjectiveOne of the most frequent reasons of nasal obstruction and sleep apnea in pediatrics is adenoid hypertrophy. Remaining adenoid tissue can reoccur following hypertrophied adenoid removal and a second operation may be needed. Nasal corticosteroids are utilized in order to reduce adenoid hypertrophy and eliminate adenoidectomy operation. The purpose of our study is to assess the effect of nasal corticosteroid administration after adenoidectomy on adenoid regrowth and symptom scores.Material and methodSeventy patients who had adenoidectomy were enrolled in our study. Patients were divided into two groups. Group I (35 patients) received Mometasone furoate (40mcg/day per nostril) intranasal spray for 6 months, starting at postoperative week 3 after wound healing. As for Group II (35 patients), they received intranasal saline spray. Patients were followed up for one year. Every patient had flexible nasal endoscopy at postoperative week 3 and one year after the operation. Choana was scored according to its occlusion level by the adenoid tissue. Additionally, nasal obstruction symptoms (nasal congestion, dry mouth, snoring, nasal speaking, apnea and night coughing) were scored.ResultsRemaining adenoid tissue in the nasopharynx was comparable in flexible endoscopic assessment and no significant difference was seen between postoperative week 3 nasal obstruction scores. In the flexible endoscopic assessment completed in the twelfth month of the study, significant reduction was found in Group 1 compared to Group 2 in terms of adenoid size. When patients in both groups were compared, statistically significant reduction was observed in nasal obstruction symptom scores at the twelfth month.ConclusionThis study has demonstrated that the use of steroid nasal spray following adenoidectomy significantly prevents regrowth and reduces nasal obstruction symptoms in the early period.



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Radical and Atom Transfer Halogenation (RATH): A Facile Route for Chemical and Polymer Functionalization

This work demonstrates a new halogenation reaction through sequential radical and halogen transfer reactions, named as "radical and atom transfer halogenation" (RATH). Both benzoxazine compounds and poly(2,6-dimethyl-1,4-phenylene oxide) have been demonstrated as active species for RATH. Consequently, the halogenated compound becomes an active initiator of atom transfer radical polymerization. Combination of RATH and sequential ATRP provides an convenient and effective approach to prepare reactive and crosslinkable polymers. The RATH reaction opens a new window both to chemical synthesis and molecular design and preparation of polymeric materials.

A new radical and atom transfer halogenation (RATH) has been explored, showing great ability to generate the active sites of atom transfer radical polymerization and provide a versatile and convenient approach to design and synthesis of reactive/crosslinkable linear polymers and graft copolymers.

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Initiator and Photocatalyst-Free Visible Light Induced One-Pot Reaction: Concurrent RAFT Polymerization and CuAAC Click Reaction

A new, visible light-catalyzed, one-pot and one-step reaction is successfully employed to design well-controlled side-chain functionalized polymers, by the combination of ambient temperature revisible addtion-fragmentation chain transfer (RAFT) polymerization and click chemistry. Polymerizations are well controlled in a living way under the irradiation of visible light-emitting diode (LED) light without photocatalyst and initiator, using the trithiocarbonate agent as iniferter (initiator-transfer agent-terminator) agent at ambient temperature. Fourier transfer infrared spectroscopy (FT-IR), NMR, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) data confirm the successful one-pot reaction. Compared to the reported zero-valent metal-catalyzed one-pot reaction, the polymerization rate is much faster than that of the click reaction, and the visible light-catalyzed one-pot reaction can be freely and easily regulated by turning on and off the light.

The visible light induced one-pot reaction is successfully achieved between a clickable monomer and a clickable agent under the irradiation of visible light in the presence of trithiocarbonate agent and CuBr₂/ligand, which avoids the use of initiator and photocatalyst.

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Dendritic Cells in Systemic Lupus Erythematosus: From Pathogenic Players to Therapeutic Tools

System lupus erythematosus (SLE) is a multifactorial systemic autoimmune disease with a wide variety of presenting features. SLE is believed to result from dysregulated immune responses, loss of tolerance of CD4 T cells and B cells to ubiquitous self-antigens, and the subsequent production of anti-nuclear and other autoreactive antibodies. Recent research has associated lupus development with changes in the dendritic cell (DC) compartment, including altered DC subset frequency and localization, overactivation of mDCs and pDCs, and functional defects in DCs. Here we discuss the current knowledge on the role of DC dysfunction in SLE pathogenesis, with the focus on DCs as targets for interventional therapies.

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Learning from the “Tsunami” of immune checkpoint inhibitors in 2015

Publication date: Available online 30 March 2016
Source:Critical Reviews in Oncology/Hematology
Author(s): Hampig Raphael Kourie, Gil Awada, Ahmad Hussein Awada
2015 was marked by the tsunami of immune checkpoint inhibitors revealed by numerous FDA approvals, publications and abstracts in relation with these drugs in different cancers and settings. First, we reported all new indications of anti-CTLA4 and anti-PD1 approved by the FDA, the positive clinical trials published and the abstracts with promising results at important scientific meetings during 2015. Then, we discussed different critical issues of these new agents going from their predictive factors, combination therapies, tumor response patterns, efficacy in particular settings, side effect management to cost and economic burden.



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KvLEA, a New Isolated Late Embryogenesis Abundant Protein Gene from Kosteletzkya virginica Responding to Multiabiotic Stresses

The LEA proteins are a kind of hydrophilic proteins, playing main functions in desiccation tolerance. However, their importance as a kind of stress proteins in abiotic stress is being clarified little by little. In this study we isolated, cloned, and identified the first KvLEA gene in Kosteletzkya virginica. Bioinformatic analysis showed that the protein encoded by this gene had common properties of LEA proteins and the multiple sequences alignment and phylogenetic analysis further showed that this protein had high homology with two Arabidopsis LEA proteins. Gene expression analysis revealed that this gene had a higher expression in root and it was induced obviously by salt stress. Moreover, the transcripts of KvLEA were also induced by other abiotic stresses including drought, high temperature, chilling, and ABA treatment. Among these abiotic stresses, ABA treatment brought about the biggest changes to this gene. Collectively, our research discovered a novel LEA gene and uncovered its involvement in multiabiotic stresses in K. virginica. This research not only enriched studies on LEA gene in plant but also would accelerate more studies on K. virginica in the future.

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Cell Cycle Arrest and Apoptosis Induction via Modulation of Mitochondrial Integrity by Bcl-2 Family Members and Caspase Dependence in Dracaena cinnabari-Treated H400 Human Oral Squamous Cell Carcinoma

Dracaena cinnabari Balf.f. is a red resin endemic to Socotra Island, Yemen. Although there have been several reports on its therapeutic properties, information on its cytotoxicity and anticancer effects is very limited. This study utilized a bioassay-guided fractionation approach to determine the cytotoxic and apoptosis-inducing effects of D. cinnabari on human oral squamous cell carcinoma (OSCC). The cytotoxic effects of D. cinnabari crude extract were observed in a panel of OSCC cell lines and were most pronounced in H400. Only fractions DCc and DCd were active on H400 cells; subfractions DCc15 and DCd16 exhibited the greatest cytotoxicity against H400 cells and D. cinnabari inhibited cells proliferation in a time-dependent manner. This was achieved primarily via apoptosis where externalization of phospholipid phosphatidylserine was observed using DAPI/Annexin V fluorescence double staining mechanism studied through mitochondrial membrane potential assay cytochrome enzyme-linked immunosorbent and caspases activities revealed depolarization of mitochondrial membrane potential (MMP) and significant activation of caspases 9 and 3/7, concomitant with S phase arrest. Apoptotic proteins array suggested that MMP was regulated by Bcl-2 proteins family as results demonstrated an upregulation of Bax, Bad, and Bid as well as downregulation of Bcl-2. Hence, D. cinnabari has the potential to be developed as an anticancer agent.

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Urinary 3-(3-Hydroxyphenyl)-3-hydroxypropionic Acid, 3-Hydroxyphenylacetic Acid, and 3-Hydroxyhippuric Acid Are Elevated in Children with Autism Spectrum Disorders

Autism spectrum disorders (ASDs) are a group of mental illnesses highly correlated with gut microbiota. Recent studies have shown that some abnormal aromatic metabolites in autism patients are presumably derived from overgrown Clostridium species in gut, which may be used for diagnostic purposes. In this paper, a GC/MS based metabolomic approach was utilized to seek similar biomarkers by analyzing the urinary information in 62 ASDs patients compared with 62 non-ASDs controls in China, aged 1.5–7. Three compounds identified as 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA), 3-hydroxyphenylacetic acid (3HPA), and 3-hydroxyhippuric acid (3HHA) were found in higher concentrations in autistic children than in the controls (). After oral vancomycin treatment, urinary excretion of HPHPA (), 3HPA (), and 3HHA () decreased markedly, which indicated that these compounds may also be from gut Clostridium species. The sensitivity and specificity of HPHPA, 3HPA, and 3HHA were evaluated by receiver-operating characteristic (ROC) analysis. The specificity of each compound for ASDs was very high (>96%). After two-regression analysis, the optimal area under the curve (AUC, 0.962), sensitivity (90.3%), and specificity (98.4%) were obtained by ROC curve of Prediction probability based on the three metabolites. These findings demonstrate that the measurements of the three compounds are strong predictors of ASDs and support the potential clinical utility for identifying a subgroup of ASDs subjects.

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Does Unilateral Oocyte Retrieval due to Transvaginally Inaccessible Ovaries, Contrary to Common Beliefs, Affect IVF/ICSI Treatment Outcomes That Much?

Objective. To investigate in vitro fertilization (IVF) treatment outcomes of unilateral oocyte retrieval in patients with transvaginally inaccessible ovaries. Study Design. Ninety-two women who underwent unilateral oocyte retrieval were retrospectively matched for age, antral follicle count, and body mass index with 184 women who underwent bilateral oocyte retrieval. Each patient in bilateral oocyte retrieval group had the same number of cumulus oophorus complexes (COCs) from single ovary and had comparable number of follicles (±2) on contralateral site where follicular aspiration was performed. Results. The number of COCs, metaphase-2 oocytes, 2-pronuclei, and top-quality embryos was significantly lower in unilateral oocyte retrieval group. However, proportion of patients with an embryo transfer of at least one top-quality embryo was found to be comparable between unilateral and bilateral oocyte retrieval. Subsequently, clinical pregnancy and live birth rates were found to be similar between the groups. The ROC curve analysis revealed (AUC = 0.74, 95% CI 0.63–0.86, ) that retrieved COCs ≥ 5 from single ovary had sensitivity of 76.0% and specificity of 64.2% for occurrence of a clinical pregnancy. Conclusion. The patients with unilateral oocyte retrieval have reasonable chance of success with IVF. The retrieval of ≥5 COCs from accessible ovary might result in better treatment outcomes among these patients.

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Stabilization of 11/9-Helical [small alpha]/[small beta]-Peptide Foldamers in Protic Solvents

Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C6CC01189F, Communication

Mihye Lee, Jihyun Shim, Philjae Kang, Moon-Gun Choi, Soo Hyuk Choi
[small alpha]/[small beta]-Peptides with alternating [small alpha]-amino acid and cis-2-aminocyclohexanecarboxylic acid (cis-ACHC) residues adopts 11/9-helical conformations, of which folding propensity decreases as solvent polarity increases. We report a modifed cis-ACHC residue, cis-2-amino-cis-4-methylcyclohexanecarboxylic acid,...
The content of this RSS Feed (c) The Royal Society of Chemistry

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Open source non-invasive prenatal testing platform and its performance in a public health laboratory

Abstract

Objective

To introduce NIPT for fetal autosomal trisomies and gender in a Danish public health setting, using semi-conductor sequencing and published open source scripts for analysis.

Methods

Plasma derived DNA from a total of 375 pregnant women (divided into 3 datasets) was whole-genome sequenced on the Ion Proton™ platform and analyzed using a pipeline based on WISECONDOR for fetal autosomal aneuploidy detection and SeqFF for fetal DNA fraction estimation. We furthermore validated a fetal sex determination analysis.

Results

The pipeline correctly detected 27/27 trisomy 21, 4/4 trisomy 18 and 3/3 trisomy 13 fetuses. Neither false negatives nor false positives (chromosomes 13, 18 and 21) were observed in our validation dataset. Fetal sex was identified correctly in all but one triploid fetus (172/173). SeqFF showed a strong correlation (R² = 0.72) to Y-chromosomal content of the male fetus samples.

Discussion

We have implemented NIPT into Danish health care using published open source scripts for autosomal aneuploidy detection and fetal DNA fraction estimation showing excellent false negative and false positive rates. SeqFF provides a good estimation of fetal DNA fraction. This coupled with an analysis of fetal sex provides a complete NIPT workflow, which may easily be adapted for implementation in other public health laboratories.

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Three-dimensional manometry of the upper esophageal sphincter in swallowing and nonswallowing tasks

The Laryngoscope

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An in-depth analysis of patient-reported outcomes in patients with chronic hepatitis C treated with different anti-viral regimens

The American Journal of Gastroenterology

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Reasonable decision of anesthesia methods in patients who underwent endoscopic submucosal dissection for superficial esophageal carcinoma: A retrospective analysis in a single Japanese institution

The Turkish Journal of Gastroenterology

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Iron intake, serum iron indices and risk of colorectal adenomas: a meta-analysis of observational studies

European Journal of Cancer Care

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Outcome of acute intestinal failure

British Journal of Surgery

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Randomized double blind placebo-controlled trial of Saccharomyces cerevisiae CNCM I-3856 in irritable bowel syndrome: improvement in abdominal pain and bloating in those with predominant constipation

United European Gastroenterology Journal

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Hepatic oleate regulates liver stress response partially through PGC-1α during high-carbohydrate feeding

Journal of Hepatology

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Prospective study of glycemic load, glycemic index, and carbohydrate intake in relation to risk of biliary tract cancer

The American Journal of Gastroenterology

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Mortality from laparoscopic antireflux surgery in a nationwide cohort of the working-age population

British Journal of Surgery

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Metabolic syndrome in relation to Barrett’s esophagus and esophageal adenocarcinoma: Results from a large population-based case-control study in the Clinical Practice Research Datalink

Cancer Epidemiology

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Estimating postoperative survival of gastric cancer patients and factors affecting it in Iran: Based on a TNM-7 Staging System

Acta Medica Iranica

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Irritable bowel syndrome: a clinical review

Current Rheumatology Reviews

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Treatment satisfaction, preferences and perception gaps between patients and physicians in the ulcerative colitis CARES study: A real world-based study

Digestive and Liver Diseases

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New treatments for hepatitis C virus (HCV): Scope for preventing liver disease and HCV transmission in England

Journal of Viral Hepatitis

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Drug–resin drug interactions in patients with delayed gastric emptying: What is optimal time window for drug administration?

Neurogastroenterology & Motility

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An update on the management of hepatitis C virus-infected patients with stage 4-5 chronic kidney disease while awaiting the revised KDIGO Guidelines

Nephrology Dialysis Transplantation

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Prevalence of celiac disease among the Iranian population: A systematic review and meta-analysis of observational studies

The Turkish Journal of Gastroenterology

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Outcomes of lung transplantation in recipients with hepatitis C virus infection

American Journal of Transplantation

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Preoperative serum -fetoprotein and prognosis after hepatectomy for hepatocellular carcinoma

British Journal of Surgery

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Toxins, Vol. 8, Pages 95: ADAM10 Cell Surface Expression but Not Activity Is Critical for Staphylococcus aureus α-Hemolysin-Mediated Activation of the NLRP3 Inflammasome in Human Monocytes

The Staphylococcus aureus toxin, α-hemolysin, is an important and well-studied virulence factor in staphylococcal infection. It is a soluble monomeric protein that, once secreted by the bacterium, forms a heptameric pore in the membrane of a broad range of host cell types. Hemolysin was recently discovered to bind and activate a disintegrin and metalloprotease 10 (ADAM10). In epithelial and endothelial cells, ADAM10 activation is required for the toxin's activity against these cells. In host monocytic cells, α-hemolysin activates the nucleotide-binding domain and leucine-rich repeat containing gene family, pyrin domain containing 3 (NLRP3) inflammasome leading to production of pro-inflammatory cytokines and cell death. We now show that ADAM10 is critical for α-hemolysin-mediated activation of the NLRP3 inflammasome in human monocytes as siRNA knockdown or chemical blockade of ADAM10-α-hemolysin interaction leads to diminished inflammasome activation and cell death by reducing the available ADAM10 on the cell surface. Unlike epithelial cell and endothelial cell damage, which requires α-hemolysin induced ADAM10 activation, ADAM10 protease activity was not required for NLRP3 inflammasome activation. This work confirms the importance of ADAM10 in immune activation by α-hemolysin, but indicates that host cell signal induction by the toxin is different between host cell types.

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Sandra Bem’s Gender Schema Theory After 34 Years: A Review of its Reach and Impact

Abstract

One of Sandra Bem's important contributions was the development of gender schema theory (GST; Bem 1981a). Through an analysis of journal articles referencing GST, we explored the breadth of the theory's reach and the ways in which its use has changed over time. More specifically, we analyzed how often GST reached journals outside psychology as well as journals and research populations outside the United States, even though Bem was a U.S. psychologist whose empirical work was primarily with U.S. populations. We also assessed the range of research topics that have used a GST framework. We found that 34 years later, GST continues to be cited frequently, with a broad reach beyond U.S. psychology, particularly into international as well as communication and business journals. We found five primary novel uses of the theory: development, discrimination/stereotyping, occupations, historically marginalized populations, and mental health and trauma. We conclude that GST has been a generative theory. For the future, we recommend that GST be used to frame the study of intersectionality, for research-based activism, and as part of a project of theory-bridging.

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Chronic exposure to Bisphenol A affects uterine function during early pregnancy in mice

Endocrinology, Early Release.


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De novo-synthesized retinoic acid in ovarian antral follicles enhances FSH-mediated ovarian follicular cell differentiation and female fertility

Endocrinology, Early Release.


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The effects of Bisphenol A exposure at different developmental time points in an androgen-sensitive neuromuscular system in male rats

Endocrinology, Early Release.


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High-level expression of periostin is significantly correlated with tumour angiogenesis and poor prognosis in osteosarcoma

Summary

Periostin (PN), originally named as osteoblast-specific factor-2 (OSF-2), has been involved in regulating adhesion and differentiation of osteoblasts. Recently many studies have shown that high-level expression of PN is correlated significantly with tumour angiogenesis and prognosis in many kinds of human cancer. However, whether and how periostin expression influences prognosis in osteosarcoma remains unknown. This study aimed to examine the expression of PN in patients with osteosarcoma and explore the relationship of PN expression with clinicopathologic factors, tumour angiogenesis and prognosis. Immunohistochemistry was performed to determine the expression of PN in osteosarcoma and osteochondroma respectively. Vascular endothelial growth factor (VEGF) and CD34 were also examined in tissues from the osteosarcoma patients mentioned above. The results showed that PN expression was significantly (P < 0.05) higher in osteosarcoma (80.9%) than in osteochondroma (14.7%). Increased PN protein expression was associated with histological subtype (P = 0.000), Enneking stage (P = 0.027) and tumour size (P = 0.009). The result also showed that high expression of PN correlated with VEGF expression (r = 0.285; P = 0.019) and that tumours with PN-positive expression significantly had higher microvessal density (44.6 ± 13.7 vs. 20.6 ± 6.5; P = 0.000) compared to those in normal bone tissues. Additionally, the expression of PN was found to be an independent prognostic factor in osteosarcoma patients. In conclusion, our findings suggest that PN may have an important role in tumour progression and may be used as a prognostic biomarker for patients with osteosarcoma.

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Prevalence of malnutrition and proportion of anaemia among the malnourished children aged 1-5 years in a rural tertiary care centre, South India

2016-03-30T01-12-18Z
Source: International Journal of Contemporary Pediatrics
Shibily Ruhman M., Sharanabasappa S. Dhanwadkar, Geethu Sukumarapilla.
Background: PEM is a disease of multiple deprivations and poverty, affecting nearly 150 million children under the age of five years in the world. Out of the 120 million children in India, over 75 million are estimated to suffer from visible PEM, which is indeed a matter of great concern. Numerous studies have been conducted time to time to know the prevalence of malnutrition, in order to target the at risk population so that effective intervention programmes can be implemented. To fight against malnutrition and PEM, we have to identify the malnourished so as to develop a target based intervention. For that, anthropometry provides the single most portable, universally applicable, inexpensive and non-invasive technique for assessing the size, proportions and composition of the human body. Methods: A cross sectional study was done among 400 children aged 1-5 years who attended OPD, based on systematic random selection. Socio economic profile of the subjects and anthropometric values were taken by trained staff and the measured values were compared with WHO reference values and classified as underweight, stunted, thin or having wasting as per different classifications. The data was analyzed using the statistical software, SPSS version 20. Results: Among the 400 children, 31% of the children were identified as underweight by IAP classification. As per weight for height criteria, using the z score system as per WHO criteria 27% of children were identified as having wasting. Conclusions: This study identifies that conventional IAP classification label more children as malnourished when compared with the classification based on wasting. The conventional use of underweight (low weight for age) instead of z score as the sole criterion for identifying undernourished children may underestimate the true incidence of severe Under nutrition in a community, so further research has to be done in to sort out the appropriate reference system for Indian population.


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Substance abuse among male adolescents in northern India

2016-03-30T01-12-18Z
Source: International Journal of Contemporary Pediatrics
Faizur Rahman, V.N. Tripathi.
Background: The rising burden of substance abuse among adolescents is a major public health challenge worldwide. The present study was undertaken to find out the prevalence of substance abuse among adolescents in Kanpur. Methods: This community based, cross-sectional study was conducted in among 539 male adolescents in the age group 10-18 years using simple random sampling. A pre-tested and pre-designed schedule was used to collect the relevant information after taking informed consent. The data was analyzed using SPSS software. Results: Substance abuse was found among 15.02% male adolescents. Smoking was prevalent among 10.95%, alcohol was used by 3.34% and other drugs were used by 0.75% male adolescents. There was an increase in prevalence of substance abuse with the increase in age. Conclusions: It is important to strengthen health education on substance abuse among the adolescents age group through mass media and school health programs.


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International Society of Urological Pathology (ISUP) Grading of Prostate Cancer.

No abstract available

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Monte Carlo simulation based prediction of blended oil composition containing mustard, rapeseed and soybean oil

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TCAD methodology for simulation of GaN-HEMT power devices

Gallium nitride (GaN) based High Electron Mobility Transistors (HEMTs) are candidates for the next generation of power electronic devices and are therefore subject of intense research activities worldwide. Technology CAD (TCAD) has proven a major impact on the optimization of silicon based device technologies. It is a logical follow up to provide accurate simulation tools, methods and models for GaN-based device technologies that are benchmarked against hardware data. This work presents a systematic investigation of GaN-HEMTs by TCAD, including process emulation, in plane and full stress simulation, and drift-diffusion device simulation.

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Worldwide policies on haemochromatosis and blood donation: a survey among blood services

Background and Objectives: Haemochromatosis (HC) is a disorder of iron metabolism, requiring frequent phlebotomy to normalize high serum iron levels. There is currently no consensus relating to the eligibility of these patients to donate blood for transfusion. To gain a better understanding of the policies worldwide, a survey amongst blood services was performed. Materials and Methods: A web-based questionnaire was developed and distributed among 44 blood services in 41 countries to identify the different policies relating to patients with HC and blood donation. Results: Respondents from 35 blood services (80%) of 33 countries completed the questionnaire. In 24 blood services among them (69%), individuals with genetic susceptibility for HC and/or patients with HC are accepted as blood donors. In approximately one-third of these blood centres (33%), genetic carriers/patients are allowed to donate blood more frequently than regular donors. Prescription from/approval by the patient's treating physician and/or a donor physician is required in the majority of the blood services (87%). Similar policies were identified in a few countries; however, in general, the policies regarding blood donation from patients with HC remain widely variable. Conclusion: The results of our survey demonstrate large differences in the blood donation policies regarding carriers/patients with HC illustrating the need for uniform evidence-based and cost-effective policies which could benefit both HC patients and the blood supply around the world.

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Quantitative in vivo microdialysis study on the influence of multidrug transporters on the blood-brain barrier passage of oxcarbazepine: concomitant use of hippocampal monoamines as pharmacodynamic markers for the anticonvulsant activity

Various antiepileptic drugs were shown to be substrates for multidrug transporters at the level of the blood-brain barrier. These ATP-dependent efflux pumps actively limit brain accumulation of xenobiotics and drugs. Intrahippocampal oxcarbazepine perfusion in rat was previously shown to exert anticonvulsant effects associated with increases in extracellular dopamine and serotonin levels. In contrast, preliminary studies in our laboratory revealed that no anticonvulsant or monoaminergic effects could be obtained after systemic oxcarbazepine administration. The present in vivo microdialysis study was conducted to investigate the impact of the transport kinetics of oxcarbazepine across the blood-brain barrier on the observed treatment refractoriness. More precisely, the influence of intra-hippocampal perfusion of verapamil, a P-glycoprotein inhibitor, and probenecid, a multidrug resistance protein inhibitor, on the blood-brain barrier passage and anticonvulsant properties of oxcarbazepine were investigated in the focal pilocarpine model for limbic seizures. Simultaneously, the effects on hippocampal monoamines were studied as pharmacodynamic markers for the anticonvulsant activity. Although systemic oxcarbazepine administration alone failed in preventing the animals from developing seizures, coadministration with verapamil or probenecid offered complete protection. Concomitantly, significant increases in extracellular hippocampal dopamine and serotonin levels were observed within our previously defined anticonvulsant monoamine range. The present data indicate that oxcarbazepine is a substrate for multidrug transporters at the blood-brain barrier. Coadministration with multidrug transporter inhibitors significantly potentiates the anticonvulsant activity of oxcarbazepine and offers opportunities for treatment of pharmacoresistant epilepsy.

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Steroids in intractable childhood epilepsy: clinical experience and review of the literature

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Anticonvulsant action of GBR-12909 and citalopram against acute experimentally induced limbic seizures

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An unconventional mechanism of hollow nanorod formation: asymmetric Cu diffusion in Au-Cu alloy nanorods during galvanic replacement reaction

Chem. Commun., 2016, Advance Article
DOI: 10.1039/C6CC00752J, Communication

Sravan Thota, Shutang Chen, Jing Zhao
Au-Cu alloy nanorods are used as templates in a galvanic replacement reaction to form hollow nanorods through an unconventional mechanism involving the asymmetric diffusion of Cu.
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry

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One-pot synthesis of mesoporous silica hollow spheres with Mn-N-C integrated into the framework for ethylbenzene oxidation

Chem. Commun., 2016, Advance Article
DOI: 10.1039/C6CC00907G, Communication

Lingling Fu, Sufang Zhao, Yuan Chen, Zhigang Liu
Mesoporous silica spheres with Mn-N-C materials integrated into the framework are synthesized via the surfactant (CTAB) template-assisted one-pot approach.
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry

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Taxonomy of rare genetic metabolic bone disorders

The Summary: This article reports a taxonomic classification of rare skeletal diseases based on metabolic phenotypes. It was prepared by The Skeletal Rare Diseases Working Group of the International Osteoporosis Foundation (IOF) and includes 116 OMIM phenotypes with 86 affected genes. Introduction: Rare skeletal metabolic diseases comprise a group of diseases commonly associated with severe clinical consequences. In recent years, the description of the clinical phenotypes and radiographic features of several genetic bone disorders was paralleled by the discovery of key molecular pathways involved in the regulation of bone and mineral metabolism. Including this information in the description and classification of rare skeletal diseases may improve the recognition and management of affected patients. Methods: IOF recognized this need and formed a Skeletal Rare Diseases Working Group (SRD-WG) of basic and clinical scientists who developed a taxonomy of rare skeletal diseases based on their metabolic pathogenesis. Results: This taxonomy of rare genetic metabolic bone disorders (RGMBDs) comprises 116 OMIM phenotypes, with 86 affected genes related to bone and mineral homeostasis. The diseases were divided into four major groups, namely, disorders due to altered osteoclast, osteoblast, or osteocyte activity; disorders due to altered bone matrix proteins; disorders due to altered bone microenvironmental regulators; and disorders due to deranged calciotropic hormonal activity. Conclusions: This article provides the first comprehensive taxonomy of rare metabolic skeletal diseases based on deranged metabolic activity. This classification will help in the development of common and shared diagnostic and therapeutic pathways for these patients and also in the creation of international registries of rare skeletal diseases, the first step for the development of genetic tests based on next generation sequencing and for performing large intervention trials to assess efficacy of orphan drugs.

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A multicenter study on dental trauma in permanent incisors among Special Olympics athletes in Europe and Eurasia

Objectives: Special Olympics athletes, as part of the population with intellectual disabilities, are reported to be more vulnerable to dental injuries due to poor lip closure, slow response to environmental obstacles, oral pathologic reflexes or dental features. The aim of this study was to assess the prevalence of dental trauma among Special Olympics athletes in countries of Europe and Eurasia. Material and Methods: A retrospective longitudinal multi centre study was performed with data collected through standardized Special Smiles screening forms and procedures from consenting 15.941 athletes participating in the annual Special Olympics held in 49 countries from Europe and Eurasia between 2007 and 2012. The data was compiled in an Excel worksheet and transferred to an SPSS data file in order to be analysed. Results: A total of 2190 athletes presented dental injury (13,02 %) with a std. deviation. of 5,02%. No significant differences (p= 0,136) in mean dental injury between age groups (One-way ANOVA test) were found. Conclusions: The present data suggest that dental trauma is an actual problem among individuals with special needs. The distribution of prevalence among the different countries had a remarkable variability, but it is evident that a relatively high proportion of this population is in need of a dental trauma preventive program. Clinical Relevance: Indication on an European large scale that dental trauma is a problem in the special needs population.

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The preclinical discovery of rituximab for the treatment of non-Hodgkin's lymphoma.

Related Articles

The preclinical discovery of rituximab for the treatment of non-Hodgkin's lymphoma.

Expert Opin Drug Discov. 2015 Jul;10(7):791-808

Authors: Smolewski P, Robak T

Abstract
INTRODUCTION: Monoclonal antibodies (MoAbs) were developed in the 1980s in order to treat malignancies. An important target for MoAbs was the CD20 B-cell lineage antigen. Rituximab (RTX) is a chimeric mouse anti-human MoAb that targets the CD20 antigen on the surface of malignant and normal B lymphocytes, and has rapidly become the widest used immunotherapeutic drug. RTX has had a significant impact on how B-cell non-Hodgkin's lymphomas (NHLs) and chronic lymphocytic leukemia is now treated.
AREAS COVERED: In this review, the authors demonstrate the mechanisms of action of RTX, and the preclinical data that have led to clinical trials and its final approval for the treatment of B-cell NHLs.
EXPERT OPINION: The discovery of RTX opened a new era for treatment of B-cell malignancies and became the starting point for the development of new, more active classes of anti-CD20 agents. Furthermore, it has contributed to the construction of a number of MoAbs specific for other antigens that target different types of neoplastic cells.

PMID: 26083358 [PubMed - indexed for MEDLINE]

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Rational drug discovery design approaches for treating Parkinson's disease.

Related Articles

Rational drug discovery design approaches for treating Parkinson's disease.

Expert Opin Drug Discov. 2015 Jul;10(7):713-41

Authors: Van der Schyf CJ

Abstract
INTRODUCTION: Parkinson's disease (PD) is a severe progressive neurodegenerative disorder. As yet, no therapeutic agent can prevent the characteristic neuronal cell loss in PD brain. The introduction of levodopa to the clinic several decades ago has greatly mitigated the symptomatic burden in PD patients. But the discovery of neuroprotective and disease-modifying therapies has lagged behind, becoming one of the most desired prizes in the drug discovery arms race for neurodegenerative disorders, including PD.
AREAS COVERED: In this review, the author provides an overview of the rational drug discovery approaches that are designed to prevent the onset or alter the course of the disease, and/or target its non-motor symptoms.
EXPERT OPINION: Largely due to the intertwined etiology that is a hallmark of PD's pathology, neuroprotective drug discovery is challenging, while very limited targeting strategies exist for the non-motor symptoms that afflict sufferers of PD. Rational approaches toward PD neurotherapeutics should target previously identified or emerging pathological pathways that are discovered in the course of investigating the underlying mechanisms in PD disease progression. Each of these pathways contributes to events that ultimately lead to the complex disease burden seen in PD and can form the basis for rational and highly targeted drug development.

PMID: 26054694 [PubMed - indexed for MEDLINE]

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Animal models for ebolavirus countermeasures discovery: what defines a useful model?

Related Articles

Animal models for ebolavirus countermeasures discovery: what defines a useful model?

Expert Opin Drug Discov. 2015 Jul;10(7):685-702

Authors: Shurtleff AC, Bavari S

Abstract
INTRODUCTION: Ebolaviruses are highly pathogenic filoviruses, which cause disease in humans and nonhuman primates (NHP) in Africa. The Zaire ebolavirus outbreak in 2014, which continues to greatly affect Western Africa and other countries to which the hemorrhagic fever was exported due to travel of unsymptomatic yet infected individuals, was complicated by the lack of available licensed vaccines or therapeutics to combat infection. After almost a year of research at an increased pace to find and test vaccines and therapeutics, there is now a deeper understanding of the available disease models for ebolavirus infection. Demonstration of vaccine or therapeutic efficacy in NHP models of ebolavirus infection is crucial to the development and eventual licensure of ebolavirus medical countermeasures, so that safe and effective countermeasures can be accelerated into human clinical trials.
AREAS COVERED: The authors describe ebolavirus hemorrhagic fever (EHF) disease in various animal species: mice, guinea pigs, hamsters, pigs and NHP, to include baboons, marmosets, rhesus and cynomolgus macaques, as well as African green monkeys. Because the NHP models are supremely useful for therapeutics and vaccine testing, emphasis is placed on comparison of these models, and their use as gold-standard models of EHF.
EXPERT OPINION: Animal models of EHF varying from rodents to NHP species are currently under evaluation for their reproducibility and utility for modeling infection in humans. Complete development and licensure of therapeutic agents and vaccines will require demonstration that mechanisms conferring protection in NHP models of infection are predictive of protective responses in humans, for a given countermeasure.

PMID: 26004783 [PubMed - indexed for MEDLINE]

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Privileged scaffolds in lead generation.

Related Articles

Privileged scaffolds in lead generation.

Expert Opin Drug Discov. 2015 Jul;10(7):781-90

Authors: Zhao H, Dietrich J

Abstract
INTRODUCTION: The term "privileged scaffold" was coined in 1988 and the strategy was to construct high-affinity ligands from core structures that can bind more than one receptor. Since then, the privileged scaffold-based design has evolved from a stand-alone technology to an integral component of various lead generation platforms.
AREAS COVERED: In this review, the authors discuss the applications of the privileged scaffold concept in current lead generation. Specifically, the authors cover the role that privileged scaffolds have played in the mass production of compounds to feed high-throughput screening (HTS) and its role in the design of ligands targeting protein-protein interactions, multiple ligands and warhead-based ligands. It is not the intention of the authors to review all privileged scaffolds known to date. Rather, the aim of this review is to highlight the strategic value of the concept of privileged scaffolds in various contemporary lead generation platforms.
EXPERT OPINION: The privileged scaffolds as described by the original definition proved abundant in the available chemical space. HTS and other screening methods, in addition to greatly enhanced compound collections, make privileged scaffold-based design less relevant in finding high-affinity ligands than originally envisioned. However, the principle of privileged scaffolds has greatly enhanced and empowered current lead generation technologies.

PMID: 25959748 [PubMed - indexed for MEDLINE]

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Challenges in early clinical drug development for ischemia-reperfusion injury in kidney transplantation.

Related Articles

Challenges in early clinical drug development for ischemia-reperfusion injury in kidney transplantation.

Expert Opin Drug Discov. 2015 Jul;10(7):753-62

Authors: O'Neill S, Gallagher K, Hughes J, Wigmore SJ, Ross JA, Harrison EM

Abstract
INTRODUCTION: In an effort to expand the donor pool, kidneys from donation after cardiac death (DCD) donors are increasingly utilised in renal transplantation. These kidneys suffer greater ischemia-reperfusion injury (IRI) and have a higher incidence of delayed graft function. In the last 25 years, relatively few pharmacological therapies to reduce IRI have been tested in randomised controlled trials in renal transplantation and currently no pharmacological agents are routinely utilised for this purpose.
AREAS COVERED: The authors look at why promising treatments in pre-clinical studies have not translated to significant clinical benefit in human trials. This may reflect a translational disconnect between the pre-clinical models used and clinical problems that are encountered in the transplant population. They also discuss the issues in conducting clinical trials and its implication on drug development.
EXPERT OPINION: Translating pharmacological strategies for reducing IRI is highly challenging at every stage of development from pre-clinical studies to clinical trials. Scientific knowledge of the complexity of IRI is rapidly evolving and new treatments are expected to emerge. There are ethical barriers that prevent donor treatments, particularly in the DCD setting. However, new clinical techniques such as normothermic regional and ex-vivo perfusion represent exciting opportunities to utilise pharmacological agents earlier in the process of transplantation.

PMID: 25947288 [PubMed - indexed for MEDLINE]

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