Acetylshikonin from Zicao attenuates cognitive impairment and hippocampus senescence in D-galactose-induced aging mouse model via upregulating the expression of SIRT1

Publication date: Available online 9 January 2018
Source:Brain Research Bulletin
Author(s): Qisen Li, Jiacheng Zeng, Meiling Su, Yu He, Banghao Zhu
Zicao acts as a pleiotropic medicine in various diseases due to its particular pharmacological properties, including anti-inflammatory, anti-tumor, anti-oxidative, and wound healing effects. However, few studies have focused on the function in neurodegenerative diseases of Zicao. In this study, we investigated the neuroprotective effect of Acetylshikonin (AS) from Zicao on the hippocampus of the D-galactose (D-gal)-induced sub-acute aging mouse model of Alzheimer's disease (AD). The aging model was established in male Kunming mice by subcutaneous injection of D-gal (150 mg/kg/d) for 60 days, and the mice were given AS (270, 540 and 1080 mg/kg/d) or distilled water intragastrically for 30 days after 30 days of D-gal injection. The behavioral results test by Morris Water Maze (MWM) revealed that chronic AS treatment alleviated D-gal-induced learning and memory deficits compared with the D-gal-treated mice. In addition, AS also ameliorated the oxidative stress and neuroinflammation induced by D-gal through decreasing the level of interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), malondialdehyde (MDA) and enhancing the activity of the antioxidant enzymes superoxide dismutase (SOD). Moreover, western blot results showed that AS can up-regulate the expression of Sirtuin 1 (SIRT1) and inhibit D-gal-induced activation of p53/p21 signaling pathway in the hippocampus of mice. These results suggest that AS can execute the prevention and treatment of D-gal-induced brain aging by SIRT1/P53/P21 pathway.



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Serum Haptoglobin in Chinese Patients with Alzheimer’s Disease and Mild Cognitive Impairment: A Case-Control Study

Publication date: Available online 9 January 2018
Source:Brain Research Bulletin
Author(s): Cen-Jing Zhu, Guo-Xin Jiang, Jin-Mei Chen, Zhi-Ming Zhou, Qi Cheng
BackgroundSerum level of Haptoglobin (Hp) maybe associated with Alzheimer's disease (AD) and mild cognitive impairment (MCI).ObjectiveTo investigate associations between serum Hp and AD, as well as between Hp and MCI.MethodsSerum levels of Hp were measured and analyzed for 51 patients with AD, 139 patients with MCI and their healthy controls matched with sex and age. All study subjects were from a survey among residents aged 60 years and over in a community located in the southwest suburb of Shanghai.ResultsSerum levels of Hp were observed significantly higher in AD and MCI cases than controls (both p < 0.0001). A significant positive correlation was found between Hp and Activities of Daily Living (ADL) score (rs = 0.430, p = 0.007), as well as between Hp and Clinical Dementia Rating (CDR) score (rs = 0.359, p = 0.027) in all AD patients. According to the receiver operating characteristic (ROC) curve analysis, the optimal cut-off point for Hp was found to be 67.50 μg/ml (sensitivity, 0.902; specificity, 0.745) in AD patients, and 44.76 μg/ml (sensitivity, 0.986; specificity, 0.403) in MCI patients.ConclusionElevated serum levels of Hp were observed in AD and MCI patients than controls. In addition, Hp may correlate with the severity of AD.



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Harmine enhances GABAergic transmission onto basoamygdala projection neurons in mice

Publication date: Available online 9 January 2018
Source:Brain Research Bulletin
Author(s): Wei-Zhu Liu, Bo-Wei Huang, Wen-Jie You, Ping Hu, Xue-Hui Wang, Jun-Yu Zhang, Xiao-Bin Xu, Zong-Yong Zhang, Bing-Xing Pan, Wen-Hua Zhang
Emerging evidence indicates that loss of inhibitory tone in amygdala with its subsequent overactivation contributes to the development of multiple mental disorders such as anxiety disorders and post-traumatic stress disorder (PTSD). Harmine is a member of natural β-carboline alkaloids which can readily cross the blood brain barrier and displays significant antidepressant and anxiolytic effects in rodents. However, the underlying neurobiological mechanisms are largely unknown. Here, by using whole-cell patch clamp recordings in in vitro amygdala slices, we examined the effect of harmine on glutamatergic and GABAergic transmission onto basal amygdala (BA) projection neurons (PNs). Our results showed that harmine affected neither the amplitude nor the frequency of spontaneous and miniature excitatory postsynaptic currents (sEPSCs/mEPSCs) of PNs. By contrast, it markedly increased both the amplitude and frequency of the spontaneous inhibitory postsynaptic currents (sIPSCs). For mIPSCs, only an increase of their frequency but not amplitude was observed following harmine perfusion, suggesting that harmine might act through presynaptic mechanism. In parallel, a reduction of paired-pulse ratio of evoked IPSCs emerged in the presence of harmine. Furthermore, the intrinsic excitability of PNs was dramatically decreased upon harmine treatment. Together, our study suggests that harmine selectively potentiates the inhibitory but not excitatory transmission onto BA PNs, which may contribute to its antidepressant and anxiolytic influence.



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Larval infestation of chronic ischaemic leg ulcer

Description

Several cases of obligatory wound myiasis have been reported in the medical literature.1–3 For a long time, such infestation was perceived as a complication of poor quality wound care in patients with chronic ulcers. There are only three cases of wound myiasis reported in the literature. Demirel et al reported on a 68-year-old male patient with larvae infestations of diabetic wound that were discovered during surgical debridement.3 Another two cases of traumatic larval infestation associated with Bowen carcinoma and with chronic leg ulcer were reported.3 Up to date, there is no report of chronic ulcer with massive larvae infestation as in this patient.

Figure 1 with video capture (video 1) demonstrates a massive larvae infestation of severe chronic ischaemic ulcer in a 60-year-old homeless male patient with HIV, who presented with unilateral leg pain without systemic or...

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Bilateral haemorrhagic basal ganglia infarction associated with early-onset group B streptococcus meningitis

A 2-day-old infant presented with poor feeding and grunting. Investigations revealed a raised C reactive protein of 164. Full septic screen was done, which subsequently confirmed a diagnosis of group B streptococcus meningitis. Baby was apyrexial and haemodynamically stable. There were no obvious neurological manifestations, and a routine cranial ultrasound scan was done, which revealed echogenic changes in the basal ganglia and thalami. MRI brain showed extensive haemorrhagic infarction within the lentiform and caudate nuclei with involvement of both posterior limbs of the internal capsule. This was followed by triventricular hydrocephalus needing shunt procedure. The clinical course was complicated by infantile spasms, which were treated with vigabatrin and steroids and subsequent global developmental delay and cerebral palsy.

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Hepatic amyloidosis: a cause of rapidly progressive jaundice

Description

An 83-year-old man presented with an acute history of weight loss and jaundice. He had a history of type 2 diabetes mellitus and hypertension. He consumed 30 units of alcohol per week.

The patient was cachectic and jaundiced with non-tender hepatomegaly and no evidence of chronic liver disease. There was evidence of hypoalbuminaemia (albumin 25 g/L, reference 34–51 g/L), hyperbilirubinaemia (bilirubin 188 μmol/L, reference <22 μmol/L) and a raised alkaline phosphatase (629 IU/L, reference 35–105 IU/L). Full blood count, coagulation tests and the remaining liver function tests were normal. An estimated Glomerular filtration rate (eGFR) was 71 mL/min/1.73 m². Autoantibodies and immunoglobulins were normal. Hepatitis viral serology was negative. Serum light chain measurements revealed kappa chain concentration of 13.3 (reference 3.3–19.4 mg/L) and lambda chain concentration of 28.5 (reference 5.7–26.6 mg/L) with a ratio of 0.47 (reference 0.26–1.75). A CT abdomen revealed hepatomegaly and ascites. He subsequently had a liver biopsy (figures 1–3

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Extraocular muscle cysticercosis: never skip steroids

DescriptionCase description

A 16-year-old girl presented with a 2-month history of recurrent (three episodes) right upper eyelid drooping and oedema (figure 1A). Examination showed fullness in the right upper eyelid along with elevation deficit. Visual acuity was 20/20 in each eye, and anterior and posterior segments were essentially within normal limits in both the eyes. To explain the cause, ultrasonography of the orbit for extraocular muscles revealed a large cyst in the superior rectus muscle along with a central hyperechoic spot corresponding to the scolex (figure 1B). Non-contrast CT of the orbit and brain revealed inflammatory thickening of the superior rectus muscle with the central cystic area harbouring the scolex without any intracranial foci (figure 1C). Based on the history and imaging findings a diagnosis of myocysticercosis was confirmed and the patient was started on tablet prednisolone 1mg/kg body weight from day 1 and tablet albendazole 15 mg/kg from day 3. The patient...

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Coats disease with exudative retinal detachment simulating cysticercus cyst: misleading ultrasonography!

Description

A 5-year-old boy was brought to our clinic when parents noticed white reflex and divergent squint in the left eye. Snellen visual acuity was 20/20 in the right eye and inaccurate projection of rays in the left eye along with a 30 prism dioptre divergent squint in the latter. Anterior segment was within normal limits in both eyes on slit lamp evaluation. As the child was uncooperative for detailed fundus examination, we performed an ocular ultrasonography. Ocular ultrasonography of the left eye showed an intraocular cystic mass with a localised hyperechoic area adjacent to cyst wall which is typical of a cysticercus cyst with scolex (figure 1). On Optomap ultra-wide-field fundus photography (Optos, Scotland, UK) we found that the cystic mass on ultrasonography was actually a localised exudative retinal detachment and the scolex-like area of hyperechogenicity was a large confluent exudate collection in the subretinal...

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Brain abscess in a patient with chronic sinusitis

Description

A middle-aged patient with a previous history of chronic sinusitis and arterial hypertension was admitted because of altered mental status. Two days earlier, symptoms such as fever, chills, nasal obstruction and headache slowly developed. On examination, the patient was febrile and with stiff neck. The remainder of the physical examination was normal. CT scan (figure 1A,B) and T1-MRI (figure 2A–C) were both performed; besides signs of sinusitis, a 2 cm right periatrial expansive lesion surrounded by vasogenic oedema was found being compatible with brain abscess. A thorough investigation was done to exclude infectious endocarditis, including echocardiography and blood cultures which were all negative. Viral serologies, including HIV, were negative. Based on the brain lesion characteristics (size and peculiar location), a conservative approach with broad-spectrum antibiotics (ceftriaxone, metronidazole and vancomycin) was initially suggested by Neurosurgery. However, 20 days after, the patient presented with neurological deterioration....

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Acute-on-chronic mesenteric ischaemia by early and diffuse atherosclerosis in a young adult patient

Description

A 48-year-old Caucasian man with gypsy ethnicity had smoking habits (35 pack-years) and previous alcohol consumption (10 g/day; abstinent for 3 years). There was no relevant personal/family cardiovascular disease, history of illicit drug abuse, non-steroidal anti-inflammatory drug use or other previous/current medications. He had a 3-year history of chronic diarrhoea (3–4 bowel movements/day), abdominal pain and weight loss (25.9% of usual weight; body mass index=13.7 kg/m²). In the last month, an exacerbation of abdominal pain occurred with excruciating postprandial episodes requiring opioid analgesia. Laboratory analysis showed leucocytosis (34.8; N: 4–11x10⁹/L), neutrophilia (90.6%), normocytic/normochromic anaemia (haemoglobin: 8.0; N: 13–17 g/dL), high Erythrocyte sedimentation rate (ESR) (54; N<20 mm/hour), faecal calprotectin (4890; n<50 mg/kg) and C-reactive protein (CRP) (10.7; N<0.5 mg/dL). Oesophagogastroduodenoscopy and ileocolonoscopy with biopsies showed multiple Helicobacter pylori-negative gastroduodenal ulcers (figure 1A,B) and non-specific mild ulceration of the terminal ileum and proximal colon, without granulomas. CT enterography showed distended small bowel loops without...

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Birt-Hogg-Dube syndrome: spontaneous pneumothorax as a first symptom

Birt-Hogg-Dubé syndrome (BHDS) is a rare hereditary autosomal dominant condition characterised by benign cutaneous lesions, lung cysts, increased risk of spontaneous pneumothorax and renal cancer. It shows great heterogenous presentation within and between affected families. We report a case of a Danish female patient with recurrent pneumothoraces as the first symptom of BHDS. Over the years, she developed skin changes, and a family history of skin changes, pneumothoraces and renal cancer was discovered. BHDS was suspected, a genetic analysis was performed and a pathogenic variation c.1285delC in FLCN gene was detected in the patient. As we stated the diagnosis BHDS, we discovered several undiagnosed family members all of them now entering a lifelong follow-up programme with abdominal imaging because of the increased risk of developing renal cancer. BHDS should be known to oncologists, dermatologists and pulmonologists as the patients most often present to these medical disciplines.

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Iatrogenic foreign body in an adult with presbyacusis

Description

Foreign bodies in the external auditory meatus are a common presentation to Otolaryngology both to clinic and as an emergency.1 Most objects referred to Otolaryngology are round and hard such as beads and are more difficult to remove.1While many patients are aware of what might be in their ear, some do not. The causative event can be missed, and the symptoms can be non-specific.2 They may present with a foreign body sensation, a feeling of fullness in the ear, otalgia and recurrent otitis externa. Many of these symptoms can be applied to a presentation of impacted cerumen.

These images refer to a 67-year-old man who presented to Otolaryngology having been referred by his General Practitioner. On presentation to the clinic, he had persistent otalgia in the left ear and reduced hearing for the past 3 months. He also described a feeling of fullness...

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Morphological and Functional Characterization of Non-fast-Spiking GABAergic Interneurons in Layer 4 Microcircuitry of Rat Barrel Cortex

Abstract

GABAergic interneurons are notorious for their heterogeneity, despite constituting a small fraction of the neuronal population in the neocortex. Classification of interneurons is crucial for understanding their widespread cortical functions as they provide a complex and dynamic network, balancing excitation and inhibition. Here, we investigated different types of non-fast-spiking (nFS) interneurons in Layer 4 (L4) of rat barrel cortex using whole-cell patch-clamp recordings with biocytin-filling. Based on a quantitative analysis on a combination of morphological and electrophysiological parameters, we identified 5 distinct types of L4 nFS interneurons: 1) trans-columnar projecting interneurons,2) locally projecting non-Martinotti-like interneurons, 3) supra-granular projecting Martinotti-like interneurons,4) intra-columnar projecting VIP-like interneurons,and5) locally projecting neurogliaform-like interneurons. Trans-columnar projecting interneurons are one of the most striking interneuron types, which have not been described so far in Layer 4. They feature extensive axonal collateralization not only in their home barrel but also in adjacent barrels. Furthermore, we identified that most of the L4 nFS interneurons express somatostatin, while few are positive for the transcription factor Prox1. The morphological and electrophysiological characterization of different L4 nFS interneuron types presented here provides insights into their synaptic connectivity and functional role in cortical information processing.

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Reassessing the Evidence for Capacity Limits in Neural Signals Related to Working Memory

Abstract

In 2004, two landmark studies described the discovery of brain imaging (functional magnetic resonance imaging and electroencephalography) signals that increase with the number of items held in visual working memory (WM). These studies claimed that the signals leveled off (plateaued) once the number of memoranda reached the capacity of WM, as estimated by the prevailing model of the time. However, alternative models were not considered, and changing concepts of WM in the more than a decade since these studies were published necessitate a re-evaluation of their findings; newer models that provide the most accurate account of behavioral data do not incorporate a fixed limit on the number of items stored. Furthermore, an important claim made about the original studies, that signals plateau at each individual's estimated capacity, has never been tested. Here, we pit the plateau model of signal strength against an alternative, saturation model, a biophysically plausible account in which signals increase continuously without plateau. We show that the saturation model provides a better description of the original data, challenging the assumption that imaging results provide evidence for a fixed item limit in WM.

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Heterogeneous Redistribution of Facial Subcategory Information Within and Outside the Face-Selective Domain in Primate Inferior Temporal Cortex

Abstract

The inferior temporal cortex (ITC) contains neurons selective to multiple levels of visual categories. However, the mechanisms by which these neurons collectively construct hierarchical category percepts remain unclear. By comparing decoding accuracy with simultaneously acquired electrocorticogram (ECoG), local field potentials (LFPs), and multi-unit activity in the macaque ITC, we show that low-frequency LFPs/ECoG in the early evoked visual response phase contain sufficient coarse category (e.g., face) information, which is homogeneous and enhanced by spatial summation of up to several millimeters. Late-induced high-frequency LFPs additionally carry spike-coupled finer category (e.g., species, view, and identity of the face) information, which is heterogeneous and reduced by spatial summation. Face-encoding neural activity forms a cluster in similar cortical locations regardless of whether it is defined by early evoked low-frequency signals or late-induced high-gamma signals. By contrast, facial subcategory-encoding activity is distributed, not confined to the face cluster, and dynamically increases its heterogeneity from the early evoked to late-induced phases. These findings support a view that, in contrast to the homogeneous and static coarse category-encoding neural cluster, finer category-encoding clusters are heterogeneously distributed even outside their parent category cluster and dynamically increase heterogeneity along with the local cortical processing in the ITC.

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An Orientation Map for Disparity-Defined Edges in Area V4

Abstract

Binocular disparity information is an important source of 3D perception. Neurons sensitive to binocular disparity are found in almost all major visual areas in nonhuman primates. In area V4, disparity processes are suggested for the purposes of 3D-shape representation and fine disparity perception. However, whether neurons in V4 are sensitive to disparity-defined edges used in shape representation is not clear. Additionally, a functional organization for disparity edges has not been demonstrated so far. With intrinsic signal optical imaging, we studied functional organization for disparity edges in the monkey visual areas V1, V2, and V4. We found that there is an orientation map in V4 activated by edges purely defined by binocular disparity. This map is consistent with the orientation map obtained with regular luminance-defined edges, indicating a cue-invariant edge representation in this area. In contrast, such a map is much weaker in V2 and totally absent in V1. These findings reveal a hierarchical processing of 3D shape along the ventral pathway and the important role that V4 plays in shape-from-disparity detection.

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Effects of Anodal Transcranial Direct Current Stimulation Over the Ventrolateral Prefrontal Cortex on Episodic Memory Formation and Retrieval

Abstract

In the past decade, several studies have investigated the effects of transcranial direct current stimulation (tDCS) on episodic memory abilities. However, the specific conditions under which tDCS affects memory remain largely unclear. Here, we report data from 4 experiments aimed at investigating the effects of anodal tDCS over the left ventrolateral prefrontal cortex (VLPFC) on verbal episodic memory. We evaluated tDCS-induced effects as a function of time of administration, nature of the memory encoding task, and age of the participants. A robust enhancement of memory performance was only found when anodal tDCS was delivered during intentional memorization. This enhancement was evident in young and older adults. tDCS applied during incidental memorization or during retrieval did not induce any modulation of memory performance, and memory was unaffected by offline administration before encoding or retrieval. These results show that the modulation of episodic memory functions by anodal tDCS over the left VLPFC is dependent upon the time of administration and the nature of the memory task. The findings may help profile the optimal stimulation protocols for neurorehabilitation interventions on individuals with memory decline.

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Overexpression of CTNNB1: Clinical implication in Chinese de novo acute myeloid leukemia

Publication date: Available online 9 January 2018
Source:Pathology - Research and Practice
Author(s): Xi-xi Li, Hong Guo, Jing-dong Zhou, De-hong Wu, Ji-chun Ma, Xiang-mei Wen, Wei Zhang, Zi-jun Xu, Jiang Lin, Jun Qian
CTNNB1 expression has been identified in numerous solid tumors. The present study was designed to determine CTNNB1 expression and its clinical significance in Chinese de novo acute myeloid leukemia (AML) patients. Real-time quantitative PCR was carried out to detect the pattern of CTNNB1 expression in 140 AML patients and 46 controls. The level of CTNNB1 transcript in AML patients was significantly up-regulated compared with controls (P < 0.001). CTNNB1^high patients showed significantly older age than CTNNB1^low patients (P < 0.05). The frequency of high CTNNB1 expression was significantly observed in patients with intermediate/poor karyotypes. CTNNB1^high patients had a significantly lower complete remission (CR) rate than CTNNB1^low patients (P = 0.004). Among cytogenetically normal AML (CN-AML), CTNNB1^high patients presented significantly shorter overall survival (OS, P = 0.004) and leukemia-free survival (LFS, P = 0.038) than CTNNB1^low patients. Multivariate analysis confirmed that CTNNB1 expression was an independent prognostic factor in affecting OS among CN-AML. Moreover, our study revealed that CTNNB1 level significantly decreased after CR in 59 AML patients (P = 0.032) and increased in 28 relapsed AML patients (P = 0.015). Our findings suggest that Wnt/β-catenin is overexpressed and confers a poor prognosis in AML, and could be used in the monitoring of CN-AML.



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MiR-21-5p, miR-34a, and human telomerase RNA component as surrogate markers for cervical cancer progression

Publication date: Available online 9 January 2018
Source:Pathology - Research and Practice
Author(s): Yue Zhu, Ying Han, Tian Tian, Peihong Su, Guan Jin, Juan Chen, Yungui Cao
ObjectiveThis study aimed to demonstrate the predictive value of miR-21-5p, miR-34a, and human telomerase RNA component (hTERC) in cervical cancer (CC) development and evaluated their potential possibility for future clinical applications.MethodsSpecimens were collected from the normal cervix, cervical intraepithelial neoplasia (CIN) I, CIN II/III, cervical squamous cell carcinoma. Cytological evaluations and histopathologic examinations were conducted in all subjects, along with the assessment of human papillomavirus (HPV) DNA. The expression levels of the miR-21-5p and miR-34a were detected by RT-PCR. hTERC amplification was detected by dual-color interphase fluorescence in situ hybridization (FISH). Then miRNA, hTERC expressions were compared with the cytological and histologic examination.ResultsCompared to that in the benign samples, the expression of miR-21-5p and miR-34a in abnormal samples was significantly upregulated and downregulated, gradually corresponding to the severity of cervical lesions (P < 0.05). There was a trend toward an increasing amplification of hTERC with the increasing severity of cervical lesions. miR-21-5p and miR-34a expression, and hTERC amplification were more specific than HPV positivity in differentiating low-grade cervical disorders from high-grade ones (P < 0.05).ConclusionsMiR-21-5p upregulation, miR-34a downregulation, and hTERC amplification were associated with the aggressive progression of CC, which suggests that miR-21-5p, miR-34a and hTERC might serve as surrogate markers for CC progression and potential molecular targets for blockage of the development of CC.



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Superficial mycosis of the foot caused by Cladophialophora boppii

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Modification of the Fitzpatrick system of skin phototype classification for the Indian population, and its correlation with narrowband diffuse reflectance spectrophotometry

Summary

Background

The Fitzpatrick classification for skin phototyping is widely used, but its usefulness in dark-skinned populations has been questioned by some researchers. Recently, skin colour measurement has been proposed for phototyping skin colour objectively.

Aims

To modify the Fitzpatrick system of skin phototyping for the Indian population and to study its correlation with skin colour using narrowband diffuse reflectance spectrophotometry

Methods

Answer choices for three items (eye colour, hair colour, colour of unexposed skin) out of 10 in the original Fitzpatrick questionnaire were modified, followed by self-administration of the original and the modified Fitzpatrick questionnaire by 70 healthy Indian volunteers. Skin colour (melanin and erythema indices) was measured from two photoexposed and two photoprotected sites using a narrowband reflectance spectrophotometer.

Results

The mean ± SD scores for the original and modified Fitzpatrick questionnaires were 25.40 ± 4.49 and 23.89 ± 4.82, respectively (r = 0.97, P < 0.001). The two items related to tanning habits were deemed irrelevant based on the subjects' response and were removed from the modified questionnaire. The Melanin Index (MI) of all sites correlated moderately well with both the modified (r = 0.61–0.64, P < 0.001) and original Fitzpatrick questionnaire scores (r = 0.64–0.67, P < 0.001), while the Erythema Index showed poor correlation with both. An MI value of ≧42 was found to be the cut-off between skin phototypes I–III and IV, and ≥ 47 between IV and V–VI.

Conclusions

Our modification of the Fitzpatrick questionnaire makes it more relevant to the Indian population. Spectrophotometry can be a useful objective tool for skin phototyping.

http://ift.tt/2CWxX0J

Modification of the Fitzpatrick system of skin phototype classification for the Indian population, and its correlation with narrowband diffuse reflectance spectrophotometry

Summary

Background

The Fitzpatrick classification for skin phototyping is widely used, but its usefulness in dark-skinned populations has been questioned by some researchers. Recently, skin colour measurement has been proposed for phototyping skin colour objectively.

Aims

To modify the Fitzpatrick system of skin phototyping for the Indian population and to study its correlation with skin colour using narrowband diffuse reflectance spectrophotometry

Methods

Answer choices for three items (eye colour, hair colour, colour of unexposed skin) out of 10 in the original Fitzpatrick questionnaire were modified, followed by self-administration of the original and the modified Fitzpatrick questionnaire by 70 healthy Indian volunteers. Skin colour (melanin and erythema indices) was measured from two photoexposed and two photoprotected sites using a narrowband reflectance spectrophotometer.

Results

The mean ± SD scores for the original and modified Fitzpatrick questionnaires were 25.40 ± 4.49 and 23.89 ± 4.82, respectively (r = 0.97, P < 0.001). The two items related to tanning habits were deemed irrelevant based on the subjects' response and were removed from the modified questionnaire. The Melanin Index (MI) of all sites correlated moderately well with both the modified (r = 0.61–0.64, P < 0.001) and original Fitzpatrick questionnaire scores (r = 0.64–0.67, P < 0.001), while the Erythema Index showed poor correlation with both. An MI value of ≧42 was found to be the cut-off between skin phototypes I–III and IV, and ≥ 47 between IV and V–VI.

Conclusions

Our modification of the Fitzpatrick questionnaire makes it more relevant to the Indian population. Spectrophotometry can be a useful objective tool for skin phototyping.

http://ift.tt/2CWxX0J

Dermoscopic characterization of cutaneous lymphomas: a pilot survey

Abstract

Background

While substantial dermoscopic analysis of melanocytic lesions has been performed, dermoscopic characterization of cutaneous lymphoid proliferations has been limited. Cutaneous lymphoma, particularly early mycosis fungoides (MF) and its variants, is often challenging to clinically and pathologically distinguish from inflammatory processes of the skin. This study aimed to survey the dermoscopic findings of cutaneous lymphomas and to discern whether any patterns might potentially serve as specific signatures.

Methods

Fifteen patients with an established diagnosis of cutaneous lymphoma were prospectively recruited and seen in the university multidisciplinary cutaneous lymphoma program with MF, an MF- variant, CD30-positive lymphoproliferative disorder, or cutaneous B-cell lymphomas and were included in our study. Dermoscopic findings, histologic features, clinical characteristics, and demographic data were analyzed.

Results

Patch stage MF was characterized by interconnected white structureless patches encircling small fine linear vessels, yielding an overall trabeculated to fenestrated pattern under dermoscopy. Corresponding histopathologic findings for these patterns included epidermotropism, atypical pleomorphic cells, and lichenoid infiltrates. Folliculotropic mycosis fungoides (FMF) was characterized by folliculocentric erosions surrounded by dotted and fine linear vessels, loss of terminal follicles, comedo-like openings, and interconnected regular-appearing structureless patches. Corresponding histopathologic findings in these FMF cases were typical of FMF. Notably, these changes were not appreciated in lymphomatoid papulosis. Primary cutaneous follicle center B cell lymphoma showed crystalline structures and vascular pseudopods.

Conclusions

Cutaneous lymphomas appear to demonstrate characteristic dermoscopic patterns, reflective of the specific lymphoma type and its corresponding histopathology, which have not been seen in inflammatory skin conditions, such as psoriasis and eczematous dermatitis.

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The early repigmentation pattern of vitiligo is related to the source of melanocytes and by the choice of therapy: a retrospective cohort study

Abstract

Background

Patients with vitiligo present with different repigmentation patterns in the early recovery stage.

Objectives

To analyze the relationships between early repigmentation patterns in vitiliginous patches, their clinical characteristics, and therapeutic choices.

Methods

Patients with vitiligo seen in the Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University from 2010 to 2015, were included, and their clinical records, especially photographs and medical treatments, were reviewed.

Results

One hundred and sixteen patients were included in this study, and 326 lesions with different degrees of depigmentation, locations, stages, distributions, therapies, and repigmentation patterns were included and analyzed. Perifollicular repigmentation occurred more frequently in lesions with complete depigmentation (P = 0.005), in non-sun exposed areas (P < 0.001), a stable stage (P = 0.008), and lesions treated with narrow band ultraviolet B (NB-UVB) (P < 0.001, despite lesion distributions). Marginal repigmentation is more frequent in lesions with complete depigmentation (P = 0.016), lesions treated without NB-UVB (P = 0.002), and facial lesions treated with topical vitamin D analogs (TVDAs) monotherapy (P = 0.022). Diffuse repigmentation is the predominant pattern in lesions with incomplete depigmentation (P < 0.001), in sun-exposed areas (P < 0.001), progressive stage (P = 0.044), and truncal lesions treated with TVDAs (P < 0.001).

Conclusions

The different repigmentation patterns of vitiligo lesions depend on the different source and status of melanocytes and their abilities to produce melanin on the choice of therapy.

http://ift.tt/2CMeGv1

Interested in global health? Here is where to start: a checklist for United States dermatology residents

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Isolation and molecular characterization of zoonotic Buffalopox virus from skin lesions of humans in India

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Hypopigmented mycosis fungoides: a 20-case retrospective series

Abstract

Background

Hypopigmented mycosis fungoides (hMF) is a rare subtype of mycosis fungoides. The aim of this study was to identify the clinical–epidemiological profile of our patient group and also to provide additional information about treatment responses and prognosis.

Methods

This is a cross-sectional retrospective observational study, with exploratory analysis. The outcome variables were disease progression and related death.

Results

Twenty patients with hMF were selected from a group of 102 patients diagnosed with MF. There was no gender difference (10 females and 10 males). Mean age at diagnosis was 43.85 years, and most patients had mixed or black skin color. The mean time between the onset of the lesions and the diagnosis was 66.75 months. Patients were equally distributed in stages IA (50%) and IB (50%). Photochemotherapy (psoralen and ultraviolet A) was the predominant therapeutic modality. The mean follow-up time was 7.25 years. In 10%, disease progression was observed. Death related to the disease occurred in one patient.

Conclusions

The clinical and epidemiological profile of patients with hypopigmented MF found in our sample is in agreement with what is described in the literature, with the exception of the age at diagnosis, higher than expected. Diagnostic delay time, despite long, is also consistent with the medical literature; however, in this sample, we had two cases of disease progression, with death of one patient, despite the treatment, which is extremely important since hypopigmented MF is usually associated with good prognosis.

http://ift.tt/2CP1yF6

The usefulness of nail plate and intraoperative dermoscopy in subungual glomus tumor

http://ift.tt/2DeCKro

Eruptive keratoacanthomas secondary to nivolumab immunotherapy

http://ift.tt/2CP1wNu

Idiopathic chilblains in myelomonocytic leukemia: not a simple association

http://ift.tt/2Dgw1x1

Evaluation of ICAM-1 expression and vascular changes in the skin of patients with plaque, pustular, and erythrodermic psoriasis

Abstract

Background

Psoriasis is a chronic inflammatory disease. Pustular, erythrodermic, and extensive plaque psoriasis are responsible for systemic complications. Systemic capillary leak syndrome is the complication with greater progression to death and occurs due to vascular changes.

Purpose

The aim of this study was to evaluate vascular changes through the expression of CD34 and ICAM-1 in plaque, pustular, and erythrodermic psoriasis.

Methods

The sample consisted of seven patients with erythrodermic psoriasis, 24 with moderate-severe plaque psoriasis, 14 with mild plaque psoriasis and 13 with pustular psoriasis. Patients were submitted to physical examination and skin biopsy for histopathological examination and immunohistochemical analysis with anti-CD34 and anti-ICAM-1 antibodies. Subsequently, tissue fragments were organized by groups using the Tissue Macroarray (TMA) technique to perform immunohistochemistry.

Results

In 58 patients, analysis of vessels using anti-CD34 demonstrated vascular immunostaining in superficial dermis and between dermal papillae. There were more blood vessels in erythrodermic psoriasis, followed by plaque psoriasis. In erythrodermic psoriasis, there were small and few tortuous blood vessels with great dilatation, while plaque psoriasis presented larger vessels that were less dilated and more tortuous. There was an intense and localized expression of ICAM-1 in endothelial and lymphocytic cells in all groups, with significant differences.

Conclusions

Vascular alterations are important in psoriasis, with an increase in the number of blood vessels and ICAM-1 overexpression, especially in erythrodermic form. Therefore, vascular changes and the expression of intercellular adhesion molecules could help to diagnose the erythrodermic form of psoriasis.

http://ift.tt/2Dexzry

Dermoscopy of childhood flexural comedones: description of 4 cases

http://ift.tt/2CNvIZs

Remission of refractory metastatic Crohn's disease achieved with dapsone

http://ift.tt/2DfNnu6

Clinico-etiologic profile of hand dermatitis and patch response of patients at a tertiary hospital in Lagos, Nigeria: results of a prospective observational study

Abstract

Background

Hand dermatitis is an acute or chronic inflammation of the skin of the hands from a multifactorial cause which may be endogenous, exogenous, or a combination of both. With a wide range in severity and recurrent periods of flares, it has significant impact on the quality of life of its sufferers. A history of atopy predisposes patients to hand dermatitis, but contact dermatitis, either allergic or irritant, is the more commonly implicated factor in the etiology of hand dermatitis. Patch testing is an important tool in identifying the allergen responsible for allergic hand dermatitis, and this knowledge will contribute to improved management.

Aim and Objectives

This study was undertaken to evaluate the clinical and etiologic profile and review the patch responses of patients who presented with hand dermatitis at a foremost tertiary skin clinic in the most populous state of the most populous country in Africa.

Methods

A prospective, observational study in which consecutive walk-in patients who fulfilled the inclusion criteria were enrolled. Ethical clearance was obtained. Study tools included self-administered questionnaires, physical examination, and patch tests (European Hermal series), amongst others. The patch tests were carried out. Results were documented, and treatment was individualized based on clinical and investigation findings. The results were collated and analyzed with SPSS^® 17.0 edition (SPSS II).

Results

Hand dermatitis was seen in 177 (13.3%) patients who presented during the study period. The mean age was 34.6 + 17.4 years. Almost two-thirds of patients (119; 67.2%) had chronic hand dermatitis, while 53 (32.8%) presented acutely. Patch responses were positive in 65 (36.7%) patients with paraphenylenediamine identified as the most frequent cause. Respondents had at least one (+) response to 20 of the 28 allergens, while there was no response to eight of the allergens in the European series.

Conclusion

The study reveals that hand dermatitis is present in a younger age group and a variety of subtypes coexist. Locally sourced allergens are needed to improve the yield of patch responses.

http://ift.tt/2CP1tRO

Nail changes in alopecia areata: an update and review

Abstract

Nail changes are a common feature of alopecia areata (AA) and are a significant source of cosmetic disfigurement and functional impairment. This review provides an update of the prevalence, clinical and histopathological features, pathogenesis, differential diagnosis, clinical course, prognosis, and management of nail changes in patients with AA. Searches for peer-reviewed journal articles were conducted using the PubMed/MEDLINE database with the search terms "nail changes alopecia areata," "alopecia areata nails," and specific searches on "trachyonychia alopecia areata" and "pitting alopecia areata." Other sources of articles included the reference lists of retrieved articles. Nail changes are a common feature of AA, with an average prevalence of 30%, and can cause significant disfigurement and loss of function. Pitting and trachyonychia were by far the most common manifestations of AA, with an average prevalence of 20 and 8%, respectively. Red spotted lunulae, onycholysis, and punctate leukonychia were other reported findings. Other etiologies, such as onychomycosis or lichen planus, may coexist with or confound the diagnosis. There is limited published data on the clinical manifestations of AA-associated nail changes and therapeutic options. Larger controlled trials are necessary to guide treatment decisions.

http://ift.tt/2DfNndA

Giant panda foraging and movement patterns in response to bamboo shoot growth

Abstract

Diet plays a pivotal role in dictating behavioral patterns of herbivorous animals, particularly specialist species. The giant panda (Ailuropoda melanoleuca) is well-known as a bamboo specialist. In the present study, the response of giant pandas to spatiotemporal variation of bamboo shoots was explored using field surveys and GPS collar tracking. Results show the dynamics in panda-bamboo space-time relationships that have not been previously articulated. For instance, we found a higher bamboo stump height of foraged bamboo with increasing elevation, places where pandas foraged later in spring when bamboo shoots become more fibrous and woody. The time required for shoots to reach optimum height for foraging was significantly delayed as elevation increased, a pattern which corresponded with panda elevational migration patterns beginning from the lower elevational end of Fargesia robusta distribution and gradually shifting upward until the end of the shooting season. These results indicate that giant pandas can respond to spatiotemporal variation of bamboo resources, such as available shoots. Anthropogenic interference of low-elevation F. robusta habitat should be mitigated, and conservation attention and increased monitoring should be given to F. robusta areas at the low- and mid-elevation ranges, particularly in the spring shooting season.

http://ift.tt/2mktCdz

Analysis of the evolution of gross alpha and gross beta activities in airborne samples in Valencia (Spain)

Publication date: March 2018
Source:Journal of Environmental Radioactivity, Volume 183
Author(s): Marina Sáez-Muñoz, María del Carmen Bas, Josefina Ortiz, Sebastián Martorell
Gross alpha (Aα) and gross beta activities (Aβ) were measured weekly in the airborne of the Universitat Politècnica de Valencia campus (in the east of Spain) during the period 2009–2015 (7 years). The geometric mean values of weekly Aα and Aβ were 0.53·10⁻⁴ Bq m⁻³ and 5.77·10⁻⁴ Bq m⁻³, respectively; with an average ratio Aα/Aβ of 0.097. This study highlights the heterogeneity of gross alpha and gross beta activities depending on the different periods of the year. Data show seasonal variations with the highest activity in summer months and the lowest one in winter months. Several atmospheric factors were considered in order to explain this intra-annual variation (wind speed, temperature, relative humidity, precipitations, dust content and prevailing wind directions). Multiple Linear Regression Analysis were performed in order to obtain information on significant atmospheric factors that affect gross α and gross β variability, which could be useful in identifying meteorological or atmospheric changes that could cause deviations in gross α and gross β activity depending on the seasons considered. Models obtained explain more than 60% of variability for global data, and also for winter and spring-autumn months. However, more research is needed to explain gross α and gross β variability in summer months, because the atmospheric factors considered in the MLR explain less than 35% of variability.



http://ift.tt/2mfzZxU

Linking dynamic patterns of neural activity in orbitofrontal cortex with decision making

Publication date: April 2018
Source:Current Opinion in Neurobiology, Volume 49
Author(s): Erin L Rich, Frederic M Stoll, Peter H Rudebeck
Humans and animals demonstrate extraordinary flexibility in choice behavior, particularly when deciding based on subjective preferences. We evaluate options on different scales, deliberate, and often change our minds. Little is known about the neural mechanisms that underlie these dynamic aspects of decision-making, although neural activity in orbitofrontal cortex (OFC) likely plays a central role. Recent evidence from studies in macaques shows that attention modulates value responses in OFC, and that ensembles of OFC neurons dynamically signal different options during choices. When contexts change, these ensembles flexibly remap to encode the new task. Determining how these dynamic patterns emerge and relate to choices will inform models of decision-making and OFC function.



http://ift.tt/2D0s7vh

Boron-chelating membranes based in hybrid mesoporous silica nanoparticles for water purification

Publication date: 5 March 2018
Source:Materials & Design, Volume 141
Author(s): Federica Albertini, Tânia Ribeiro, Sérgio Alves, Carlos Baleizão, José Paulo S. Farinha
Boron is a key element for some biological processes,but it becomes toxic for humans and plants in concentrations above a few ppm. We have design a new approach for boron scavenging, based in hybrid membranes of functional mesoporous silica nanoparticles immobilized in cellulose acetate. The mesoporous silica nanoparticles, with diameters around 150nm, were functionalized with vicinal diol groups that complex boron very efficiently. The functional nanoparticles were covalently immobilized in a cellulose acetate membrane using a di-terminated alkoxisilane that react with the remaining silanol groups at the nanoparticles surfaces and with the hydroxyl groups of the cellulose. The functional nanoparticles and the hybrid membranes show boron removal efficiencies of phenyl boronic acid of up to 93%. The membranes can be used in multistage filtering systems, with sequential membranes modules in continuous operation, in a cheap, simple and efficient process for boron scavenging.

Graphical abstract

http://ift.tt/2CXfUqh

Extension induced phase separation and crystallization in semidilute solutions of ultra high molecular weight polyethylene

Publication date: 31 January 2018
Source:Polymer, Volume 136
Author(s): Sara Lindeblad Wingstrand, Luna Imperiali, Roman Stepanyan, Ole Hassager
We investigate the influence of controlled uniaxial extension on various flow induced phenomena in semidilute solutions of ultra high molecular weight polyethylene. Concentrations range from 9w% to 29w% and the choice of solvent is paraffin oil. The start-up extensional behavior is measured at various Hencky strain rates ε˙ and at two different temperatures (150∘C and 170∘C) well above the melting point. For Hencky strains ε>0.9 the qualitative behavior of the samples differ significantly depending on the imposed conditions and the concentration of the samples. Overall we propose two flow scenarios: Scenario 1 - flow induced phase separation resulting in an unstable bulky filament and Scenario 2 - flow induced phase separation and crystallization resulting in a stable deformation and a smooth strongly strain hardening filament. Scenario 2 is observed only at 150∘C at high ε˙ and high concentrations. Scenario 1, observed at both temperatures, is most pronounced at low rates and/or high concentrations.

Graphical abstract

http://ift.tt/2FmVju4

Comparative evaluation of skin moisture after topical application of 10% and 30% lactobionic acid

Summary

Background

Dry skin is characterized by symptoms such as itching, redness, excessive exfoliation. These symptoms cause discomfort and contribute to secondary bacterial infections. Dry skin treatments are based on topical applications of various formulations. Among many of them are polyhydroxy acids, which recently gained more attention.

Aims

The aim of this study was a comparative assessment of hydration level (corneometric) after application of lactobionic acid (LA) in the form of peel at concentrations of 10% and 30%.

Material and Methods

The study involved 10 Caucasian individuals aged 26-73 years. Eight treatments were performed at weekly intervals. The peels were applied using the "Split face" method—on the left side of the face 10% LA, and the right side 30% LA which consisted of specified concentration of LA, deionized water, xanthan gum, ethoxydiglycol. The test subjects received a 5% LA cream for overnight use. The cream consisted of deionized water, LA, isopropyl palmitate, ascorbyl palmitate, methylparaben. The products for this study were provided by Grehen Ltd. Celestynów, Poland. Prior to each procedure, the skin hydration level was measured using Corneometer CM 825 from Courage + Khazaka electronic GmbH.

Results

There was a statistically significant improvement in hydration level after 8 treatments for all measuring points and both concentrations. The difference of the skin hydration level between 10% LA and 30% LA could not be determined.

Conclusions

Lactobionic acid is a highly moisturizing agent. There was no significant difference in moisturizing effect between 10% LA concentration and 30% LA concentration.

http://ift.tt/2mffUHV

Comparative evaluation of skin moisture after topical application of 10% and 30% lactobionic acid

Summary

Background

Dry skin is characterized by symptoms such as itching, redness, excessive exfoliation. These symptoms cause discomfort and contribute to secondary bacterial infections. Dry skin treatments are based on topical applications of various formulations. Among many of them are polyhydroxy acids, which recently gained more attention.

Aims

The aim of this study was a comparative assessment of hydration level (corneometric) after application of lactobionic acid (LA) in the form of peel at concentrations of 10% and 30%.

Material and Methods

The study involved 10 Caucasian individuals aged 26-73 years. Eight treatments were performed at weekly intervals. The peels were applied using the "Split face" method—on the left side of the face 10% LA, and the right side 30% LA which consisted of specified concentration of LA, deionized water, xanthan gum, ethoxydiglycol. The test subjects received a 5% LA cream for overnight use. The cream consisted of deionized water, LA, isopropyl palmitate, ascorbyl palmitate, methylparaben. The products for this study were provided by Grehen Ltd. Celestynów, Poland. Prior to each procedure, the skin hydration level was measured using Corneometer CM 825 from Courage + Khazaka electronic GmbH.

Results

There was a statistically significant improvement in hydration level after 8 treatments for all measuring points and both concentrations. The difference of the skin hydration level between 10% LA and 30% LA could not be determined.

Conclusions

Lactobionic acid is a highly moisturizing agent. There was no significant difference in moisturizing effect between 10% LA concentration and 30% LA concentration.

http://ift.tt/2mffUHV

Post-herpes zoster sarcoidosis as a recurrence

http://ift.tt/2CWgjcD

Metabolic Reprogramming via Targeting CD38 NADase Augments Adoptive T Cell Therapy

Publication date: 9 January 2018
Source:Cell Metabolism, Volume 27, Issue 1
Author(s): Mario R. Fernandez, John L. Cleveland
One strategy to improve the potency of adoptive T cell therapy is to augment the function and persistence of anti-tumor T cells. In this issue of Cell Metabolism, Chatterjee et al. (2018) demonstrate that intratumoral CD4⁺ T cell functions and memory can be improved by targeting a CD38-NAD⁺-Sirt1-Foxo1 metabolic circuit.

Teaser

One strategy to improve the potency of adoptive T cell therapy is to augment the function and persistence of anti-tumor T cells. In this issue of Cell Metabolism, Chatterjee et al. (2018) demonstrate that intratumoral CD4⁺ T cell functions and memory can be improved by targeting a CD38-NAD⁺-Sirt1-Foxo1 metabolic circuit.


http://ift.tt/2ALMy9e

Apoptotic Regulatory T Cells Retain Suppressive Function through Adenosine

Publication date: 9 January 2018
Source:Cell Metabolism, Volume 27, Issue 1
Author(s): Ulf H. Beier
Regulatory T cells maintain tolerance and prevent autoimmunity, but their suppressive effects can hinder immune responses against cancer. In Nature Immunology, Maj et al., 2017 report that regulatory T cells can execute these actions through the nucleoside adenosine even after cell death.

Teaser

Regulatory T cells maintain tolerance and prevent autoimmunity, but their suppressive effects can hinder immune responses against cancer. In Nature Immunology, Maj et al., 2017 report that regulatory T cells can execute these actions through the nucleoside adenosine even after cell death.


http://ift.tt/2CWDZP1

SERCA2b Cycles Its Way to UCP1-Independent Thermogenesis in Beige Fat

Publication date: 9 January 2018
Source:Cell Metabolism, Volume 27, Issue 1
Author(s): Emilio P. Mottillo, Vanesa D. Ramseyer, James G. Granneman
A new study in Nature Medicine, by Ikeda et al. (2017), reports that calcium cycling in beige adipocytes elevates energy expenditure and glucose oxidation in the absence of uncoupling protein 1. Thermogenic calcium cycling in beige fat is mediated by SERCA2b and improves cold tolerance and metabolic status.

Teaser

A new study in Nature Medicine, by Ikeda et al. (2017), reports that calcium cycling in beige adipocytes elevates energy expenditure and glucose oxidation in the absence of uncoupling protein 1. Thermogenic calcium cycling in beige fat is mediated by SERCA2b and improves cold tolerance and metabolic status.


http://ift.tt/2ALEUf1

Aminoacylation of Proteins: New Targets for the Old ARSenal

Publication date: 9 January 2018
Source:Cell Metabolism, Volume 27, Issue 1
Author(s): Seyed Mehdi Jafarnejad, Sung-Hoon Kim, Nahum Sonenberg
Besides charging tRNAs with their cognate amino acids, aminoacyl-tRNA synthetases (ARSs) are involved in a plethora of non-canonical functions, including development, immune response, and angiogenesis. In this issue of Cell Metabolism, He et al. (2018) report a novel biochemical function of ARSs: posttranslational addition of amino acids to lysine residues in proteins.

Teaser

Besides charging tRNAs with their cognate amino acids, aminoacyl-tRNA synthetases (ARSs) are involved in a plethora of non-canonical functions, including development, immune response, and angiogenesis. In this issue of Cell Metabolism, He et al. (2018) report a novel biochemical function of ARSs: posttranslational addition of amino acids to lysine residues in proteins.


http://ift.tt/2CW931a

Repression of Adipose Tissue Fibrosis through a PRDM16-GTF2IRD1 Complex Improves Systemic Glucose Homeostasis

Publication date: 9 January 2018
Source:Cell Metabolism, Volume 27, Issue 1
Author(s): Yutaka Hasegawa, Kenji Ikeda, Yong Chen, Diana L. Alba, Daniel Stifler, Kosaku Shinoda, Takashi Hosono, Pema Maretich, Yangyu Yang, Yasushi Ishigaki, Jingyi Chi, Paul Cohen, Suneil K. Koliwad, Shingo Kajimura
Adipose tissue fibrosis is a hallmark of malfunction that is linked to insulin resistance and type 2 diabetes; however, what regulates this process remains unclear. Here we show that the PRDM16 transcriptional complex, a dominant activator of brown/beige adipocyte development, potently represses adipose tissue fibrosis in an uncoupling protein 1 (UCP1)-independent manner. By purifying the PRDM16 complex, we identified GTF2IRD1, a member of the TFII-I family of DNA-binding proteins, as a cold-inducible transcription factor that mediates the repressive action of the PRDM16 complex on fibrosis. Adipocyte-selective expression of GTF2IRD1 represses adipose tissue fibrosis and improves systemic glucose homeostasis independent of body-weight loss, while deleting GTF2IRD1 promotes fibrosis in a cell-autonomous manner. GTF2IRD1 represses the transcription of transforming growth factor β-dependent pro-fibrosis genes by recruiting PRDM16 and EHMT1 onto their promoter/enhancer regions. These results suggest a mechanism by which repression of obesity-associated adipose tissue fibrosis through the PRDM16 complex leads to an improvement in systemic glucose homeostasis.

Graphical abstract

Teaser

Hasegawa et al. identify GTF2IRD1 as a cold-inducible transcription factor that represses adipose tissue fibrosis through a PRDM16-EHMT1 complex. Repression of adipose tissue fibrosis by the complex improves systemic glucose homeostasis independent of UCP1-mediated thermogenesis and body weight. In humans, GTF2IRD1 expression inversely correlates with subcutaneous WAT fibrosis and visceral adiposity.


http://ift.tt/2CYrUsL

Three-Dimensional Adipose Tissue Imaging Reveals Regional Variation in Beige Fat Biogenesis and PRDM16-Dependent Sympathetic Neurite Density

Publication date: 9 January 2018
Source:Cell Metabolism, Volume 27, Issue 1
Author(s): Jingyi Chi, Zhuhao Wu, Chan Hee J. Choi, Lily Nguyen, Saba Tegegne, Sarah E. Ackerman, Audrey Crane, François Marchildon, Marc Tessier-Lavigne, Paul Cohen
While the cell-intrinsic pathways governing beige adipocyte development and phenotype have been increasingly delineated, comparatively little is known about how beige adipocytes interact with other cell types in fat. Here, we introduce a whole-tissue clearing method for adipose that permits immunolabeling and three-dimensional profiling of structures including thermogenic adipocytes and sympathetic innervation. We found that tissue architecture and sympathetic innervation differ significantly between subcutaneous and visceral depots. Subcutaneous fat demonstrates prominent regional variation in beige fat biogenesis with localization of UCP1⁺ beige adipocytes to areas with dense sympathetic neurites. We present evidence that the density of sympathetic projections is dependent on PRDM16 in adipocytes, providing another potential mechanism underlying the metabolic benefits mediated by PRDM16. This powerful imaging tool highlights the interaction of tissue components during beige fat biogenesis and reveals a previously undescribed mode of regulation of the sympathetic nervous system by adipocytes.

Graphical abstract

Teaser

Chi et al. use Adipo-Clear, a whole-tissue clearing method that permits immunolabeling and three-dimensional profiling, to identify differences in tissue architecture and sympathetic innervation between subcutaneous and visceral adipose depots. Localized beigeing of subcutaneous fat correlates with areas of dense sympathetic neurites, highlighting adipocyte regulation of the sympathetic nervous system.


http://ift.tt/2CXQs57

Extracellular Vesicles Provide a Means for Tissue Crosstalk during Exercise

Publication date: 9 January 2018
Source:Cell Metabolism, Volume 27, Issue 1
Author(s): Martin Whitham, Benjamin L. Parker, Martin Friedrichsen, Janne R. Hingst, Marit Hjorth, William E. Hughes, Casey L. Egan, Lena Cron, Kevin I. Watt, Rhiannon P. Kuchel, Navind Jayasooriah, Emma Estevez, Tim Petzold, Catherine M. Suter, Paul Gregorevic, Bente Kiens, Erik A. Richter, David E. James, Jørgen F.P. Wojtaszewski, Mark A. Febbraio
Exercise stimulates the release of molecules into the circulation, supporting the concept that inter-tissue signaling proteins are important mediators of adaptations to exercise. Recognizing that many circulating proteins are packaged in extracellular vesicles (EVs), we employed quantitative proteomic techniques to characterize the exercise-induced secretion of EV-contained proteins. Following a 1-hr bout of cycling exercise in healthy humans, we observed an increase in the circulation of over 300 proteins, with a notable enrichment of several classes of proteins that compose exosomes and small vesicles. Pulse-chase and intravital imaging experiments suggested EVs liberated by exercise have a propensity to localize in the liver and can transfer their protein cargo. Moreover, by employing arteriovenous balance studies across the contracting human limb, we identified several novel candidate myokines, released into circulation independently of classical secretion. These data identify a new paradigm by which tissue crosstalk during exercise can exert systemic biological effects.

Graphical abstract

Teaser

Using quantitative proteomic techniques and intravital imaging experiments, Whitham et al. characterize the exercise-induced secretion of proteins contained in extracellular vesicles (EVs) and identify several novel candidate myokines that are released into the circulation independently of classical secretion.


http://ift.tt/2CXx5Jh

An Adipose Tissue Atlas: An Image-Guided Identification of Human-like BAT and Beige Depots in Rodents

Publication date: 9 January 2018
Source:Cell Metabolism, Volume 27, Issue 1
Author(s): Fang Zhang, Guiyang Hao, Mengle Shao, Kien Nham, Yu An, Qiong Wang, Yi Zhu, Christine M. Kusminski, Gedaa Hassan, Rana K. Gupta, Qiwei Zhai, Xiankai Sun, Philipp E. Scherer, Orhan K. Oz
[¹⁸F]Fluorodeoxyglucose-PET/CT (¹⁸F-FDG-PET/CT) imaging has been invaluable for visualizing metabolically active adipose tissues in humans with potential anti-diabetic and anti-obesity effects. To explore whether mice display human-like fat depots in anatomically comparable regions, we mapped fat depots using glucose or fatty acid imaging tracers, such as ¹⁸F-FDG through PET/CT or [^123/125I]-β-methyl-p-iodophenyl-pentadecanoic acid with SPECT/CT imaging, to analogous depots in mice. Using this type of image analysis with both probes, we define a large number of additional areas of high metabolic activity corresponding to novel fat pads. Histological and gene expression analyses validate these regions as bona fide fat pads. Our findings indicate that fat depots of rodents show a high degree of topological similarity to those of humans. Studies involving both glucose and lipid tracers indicate differential preferences for these substrates in different depots and also suggest that fatty acid-based visualized approaches may reveal additional brown adipose tissue and beige depots in humans.

Graphical abstract

Teaser

¹⁸F-FDG-PET/CT imaging in humans has been invaluable for visualizing metabolically active adipose tissues. Using PET/CT and SPECT/CT for imaging glucose and lipid metabolism, respectively, in mice, Zhang et al. define an atlas of fat depots, topologically analogous to those observed in humans.


http://ift.tt/2ALMAy1

SnapShot: Niche Determines Adipocyte Character I

Publication date: 9 January 2018
Source:Cell Metabolism, Volume 27, Issue 1
Author(s): Devika P. Bagchi, Isabel Forss, Susanne Mandrup, Ormond A. MacDougald
Adipose tissues are complex organs, with central roles in energy homeostasis as well as local functions. Adipocytes develop in diverse, discrete locations throughout the body. Important regional differences in adipocytes exist, and diseases that affect adipose tissues often demonstrate depot-specific effects. Herein, we depict the widespread locations of major and minor rodent adipose depots. Depot-specific molecular and functional characteristics will be described in Part II.

Teaser

Adipose tissues are complex organs, with central roles in energy homeostasis as well as local functions. Adipocytes develop in diverse, discrete locations throughout the body. Important regional differences in adipocytes exist, and diseases that affect adipose tissues often demonstrate depot-specific effects. Herein, we depict the widespread locations of major and minor rodent adipose depots. Depot-specific molecular and functional characteristics will be described in Part II.


http://ift.tt/2CX0gMK

SnapShot: Niche Determines Adipocyte Character II

Publication date: 9 January 2018
Source:Cell Metabolism, Volume 27, Issue 1
Author(s): Devika P. Bagchi, Isabel Forss, Susanne Mandrup, Ormond A. MacDougald
The intrinsic cellular and metabolic properties of an adipocyte are shaped by the specific niche in which it resides. The diverse and discrete locations of major and minor rodent adipose depots are depicted in Part I. In Part II, the molecular and functional characteristics of four major types of adipocytes are described. Identified functions of relatively understudied but undoubtedly important depots are also highlighted.

Teaser

The intrinsic cellular and metabolic properties of an adipocyte are shaped by the specific niche in which it resides. The diverse and discrete locations of major and minor rodent adipose depots are depicted in Part I. In Part II, the molecular and functional characteristics of four major types of adipocytes are described. Identified functions of relatively understudied but undoubtedly important depots are also highlighted.


http://ift.tt/2AKXG6w

A Qualitative Assessment of Academic Radiation Oncology Department Chairs’ Insights on Diversity, Equity, and Inclusion: Progress, Challenges, and Future Aspirations

Publication date: Available online 9 January 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Rochelle D. Jones, Christina H. Chapman, Emma B. Holliday, Nafisha Lalani, Emily Wilson, James A. Bonner, Benjamin Movsas, Shalom Kalnicki, Silvia C. Formenti, Charles R. Thomas, Steve M. Hahn, Fei-Fei Liu, Reshma Jagsi
PurposeA lack of diversity has been observed in radiation oncology (RO), with women and certain racial/ethnic groups underrepresented as trainees, faculty, and practicing physicians. The authors sought to gain a nuanced understanding of how to best promote diversity, equity, and inclusion (DEI) based on the insights of RO department chairs, with particular attention given to the experiences of the few women and underrepresented minorities (URM) in these influential positions.MethodsIn March-June 2016, the authors conducted telephone interviews with 24 RO department chairs (of 27 invited). Purposive sampling was employed to invite all chairs who were women (n=13) or URM (n=3), along with 11 male chairs who were not URM. Multiple analysts coded verbatim transcripts.ResultsFive themes were identified: (1) commitment to DEI promotes quality healthcare and innovation, (2) gaps remain despite some progress with promoting diversity in RO, (3) women and URM faculty continue to experience challenges in various career domains, (4) solutions to DEI issues would be facilitated by acknowledging realities of gender and race, and (5) expansion of the career pipeline is needed.ConclusionsChairs' insights had policy-relevant implications. Bias training should broach tokenism, blindness, and intersectionality. Efforts to recruit and support diverse talent should be deliberate and proactive. Bridge programs could engage students before their application to medical school.

Teaser

This qualitative study sought to understand how to promote diversity, equity, and inclusion in radiation oncology. The authors conducted telephone interviews with department chairs, with attention to the experiences of the few women and underrepresented minorities in these positions. Chairs' insights had policy-relevant implications. Bias training should attempt to tap into the sensitive contextual areas of tokenism, blindness, and intersectionality. Efforts to recruit and support diverse talent should be deliberate and proactive. Bridge programs could engage diverse learners across the education spectrum.


http://ift.tt/2AKWkZa

Endoscopic Surgery for Delayed Sinonasal Complications of Radiotherapy for Nasopharyngeal Carcinoma: a Subjective Outcome

Publication date: Available online 9 January 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Rachel Shemesh, Eran E. Alon, Iris Gluck, Arkadi Yakirevitch
BackgroundDelayed sino-nasal complications of radiotherapy include choanal stenosis, osteoradionecrosis, chronic sinusitis and intranasal synechiae. There are only sporadic reports on their surgical treatment with equivocal results.MethodsThis is a prospective case series of all patients surgically treated for delayed sino-nasal complications of radiotherapy in our institution during the last 10 years. The inclusion criteria required at least a 6-month follow up after the surgery. Included patients were asked to fill a SNOT-16 questionnaire preoperatively and 6 months after the surgery.Resultsnine patients with history of radiotherapy for nasopharyngeal carcinoma were included in our series. In all cases partial or complete subjective improvement was seen.ConclusionIn select cases, endoscopic sinus surgery may be of benefit in the treatment of delayed sino-nasal complications of radiotherapy.

Teaser

Delayed sino-nasal complications of radiotherapy include choanal stenosis, osteoradionecrosis, chronic sinusitis and intranasal synechiae. Their incidence and burden on their quality of life are underestimated. Results of our prospective study show good subjective outcome of surgical treatment of these delayed sino-nasal complications. It should encourage clinicians to be cognizant of symptoms suspicious for this pathology and to be diligent in referring the patients for further evaluation and treatment.


http://ift.tt/2D0ixbN

Radiation Therapy to Sites of Metastatic Disease as Part of Consolidation in High-risk Neuroblastoma: Can Long-term Control be Achieved?

Publication date: Available online 9 January 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Dana L. Casey, Ken L. Pitter, Brian H. Kushner, Nai-Kong V. Cheung, Shakeel Modak, Michael P. LaQuaglia, Suzanne L. Wolden
BackgroundAs part of consolidative therapy in high-risk neuroblastoma, modern protocols recommend radiation therapy (RT) both to the primary site and to sites of metastatic disease that persist after induction chemotherapy. Although there is abundant data showing excellent local control with 21 Gy directed at the primary site, there is little data describing the feasibility and efficacy of RT directed at metastatic sites of disease as part of consolidation.MethodsAll patients with neuroblastoma who received RT to metastatic sites of disease as a part of consolidative therapy at a single institution between 2000 and 2015 were reviewed. Among 159 patients, 244 metastases were irradiated.ResultsMedian follow up among surviving patients was 7.4 years. Over 85% of the irradiated metastases were treated with 21 Gy (range 10.5 Gy - 36 Gy). Tumor recurrence occurred in 43 of 244 (18%) irradiated metastases. The 5-year local control (LC) of treated metastatic sites was 81%. Metastatic sites that cleared with induction chemotherapy had improved LC compared to sites with persistent uptake on MIBG (LC 92% vs 67%, p<0.0001). LC at irradiated metastatic sites did not differ based on total number of sites irradiated or site of disease irradiated (bone vs soft tissue). Patients with bulky, resistant disease who were treated with 30-36 Gy had worse LC (p=0.02). However, on multivariate analysis, only persistence after induction chemotherapy remained a significant prognostic factor for LC (hazard ratio = 3.7, p<0.0001). Patients with LC at irradiated metastatic sites had improved overall survival (OS) compared to those who did not (OS 71% vs 50%, p<0.0001).ConclusionsResponse to chemotherapy is an important prognostic factor for LC at irradiated metastatic sites in neuroblastoma. Overall, consolidative RT appears to be an effective modality of LC. Long-term disease control can be achieved with such an approach.

Teaser

Although radiation therapy to persistent sites of metastatic disease is recommended as part of consolidative therapy for high-risk neuroblastoma, there is little data evaluating the value of this approach in achieving long-term control. Our results show that irradiation of metastatic sites of disease is effective in achieving local control, and that response to induction chemotherapy is a significant prognostic factor for control at irradiated sites.


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Current and Future Initiatives for Radiation Oncology at the National Cancer Institute in the Era of Precision Medicine

Publication date: Available online 8 January 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Charles A. Kunos, C. Norman Coleman




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The radiation resistance of human multipotent mesenchymal stromal cells is independent of their tissue of origin

Publication date: Available online 9 January 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Alexander Rühle, Oliver Xia, Ramon Lopez Perez, Thuy Trinh, Wiltrud Richter, Anna Sarnowska, Patrick Wuchter, Jürgen Debus, Rainer Saffrich, Peter E. Huber, Nils H. Nicolay
PurposeHuman mesenchymal stromal cells (MSCs) may aid the regeneration of ionizing radiation-induced tissue damage. They can be harvested from different tissues for clinical purposes; however, the role of the tissue source on the radiation response of human MSCs remains unknown.Methods and MaterialsHuman MSCs were isolated from adipose tissue, bone marrow and umbilical cord, and cellular survival, proliferation and apoptosis were measured after irradiation. The influence of ionizing radiation (IR) on the defining functions of MSCs was assessed, and cell morphology, surface marker expression and the differentiation potential were examined. Western blot analyses were performed to assess the activation of DNA damage signaling and repair pathways.ResultsMSCs from adipose tissue, bone marrow and umbilical cord exhibited a relative radioresistance independent of their tissue of origin. Defining properties including cellular adhesion and surface marker expression were preserved, and irradiated MSCs maintained their potential for multi-lineage differentiation irrespective of their tissue source. Analysis of activated DNA damage recognition and repair pathways demonstrated an efficient repair of IR-induced DNA double-strand breaks in MSCs from different tissues, thereby influencing the induction of apoptosis.ConclusionsThese data show for the first time that MSCs are resistant to IR and largely preserve their defining functions after irradiation irrespective of their tissue of origin. Efficient repair of IR-induced DNA double-strand breaks and consecutive reduction of apoptosis induction may contribute to the tissue-independent radiation resistance of MSCs.

Teaser

Mesenchymal stromal cells (MSCs) from different tissues may aid the regeneration of radiation-induced organ lesions; however, the influence of ionizing radiation on tissue-specific human MSCs is unknown. Here we show that the radiation resistance of MSCs is independent of their tissue of origin, and irradiated MSCs from adipose tissue, bone marrow and umbilical cord preserved their defining characteristics. Efficient repair of radiation-induced DNA damage may contribute to this radiation resistance.


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The efficacy and safety of conventional and hypofractionated high-dose radiotherapy for prostate cancer in an elderly population: a subgroup analysis of the CHHiP trial

Publication date: Available online 9 January 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): James M. Wilson, David Dearnaley, Isabel Syndikus, Vincent Khoo, Alison Birtle, David Bloomfield, Ananya Choudhury, John Graham, Catherine Ferguson, Zafar Malik, Julian Money-Kyrle, Joe M. O'Sullivan, Miguel Panades, Chris Parker, Yvonne Rimmer, Christopher Scrase, John Staffurth, Andrew Stockdale, Clare Cruickshank, Clare Griffin, Emma Hall
IntroductionOutcome data on radiotherapy for prostate cancer in an elderly population are sparse. The CHHiP trial provides a large, prospectively collected, contemporary dataset in which to explore outcomes by age.Methods and MaterialsCHHiP participants received 3-6 months of androgen deprivation therapy and were randomly assigned (1:1:1) to receive 74Gy in 37 fractions (conventional fractionation), 60Gy in 20 fractions or 57Gy in 19 fractions. Toxicity was assessed using clinician-reported and patient-reported outcome (CRO/PRO) questionnaires. Participants were categorised as aged less than 75 (<75) or 75 years and older (75+).Outcomes were compared by age-group.Results491/3216 (15%) were 75+. There was no difference in biochemical or clinical failure (BCF) rates between the <75 and the 75+ group for any of the fractionation schedules. In the 75+ group BCF-free rates favoured hypofractionation and at 5 years were 74Gy: 84.7%, 60Gy: 91%, 57Gy: 87.7%. The incidence of CRO (G3) acute bowel toxicity was 2% in both age-groups. Grade 3 acute bladder toxicity was 8% and 7%. Five year cumulative incidence of CRO grade 2+ late bowel side effects was similar in both age groups. However, in the 75+ group, there was a suggestion of a higher cumulative incidence of bowel bother (≥small) with 60Gy compared to 74Gy and 57Gy. Patient-reported bladder bother was slightly higher in the 75+ group than the <75 group and there was a suggestion of a lower cumulative incidence of bladder bother with 57Gy compared to 74Gy and 60Gy in the 75+ group which was not evident in those <75.ConclusionHypofractionated radiotherapy appears to be well tolerated and effective in men over 75. The 57 Gy schedule has potential advantages in that it may moderate long term side effects without compromising treatment efficacy in this group.

Teaser

The efficacy and toxicity of radiotherapy for localised prostate cancer in CHHiP trial participants aged 75 and over was compared with patients younger than 75. There was no evidence of a difference in biochemical or clinical recurrence free survival or clinically significant toxicity between the older and younger patient groups. Hypofractionated radiotherapy is an effective and well tolerated treatment for localised prostate cancer in an elderly population with good performance status.


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The Role of Radiation Therapy in Patients with Relapsed/Refractory Hodgkin Lymphoma: Guidelines from the International Lymphoma Radiation Oncology Group

Publication date: Available online 9 January 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Louis S. Constine, Joachim Yahalom, Andrea K. Ng, David C. Hodgson, Andrew Wirth, Sarah A. Milgrom, N. George Mikhaeel, Hans Theodor Eich, Tim Illidge, Umberto Ricardi, Karin Dieckmann, Craig H. Moskowitz, Ranjana Advani, Peter M. Mauch, Lena Specht, Richard T. Hoppe
Relapsed and refractory Hodgkin lymphoma (HL) challenges clinicians to devise treatment strategies that are effective and safe. This problem is particularly prominent in an era when de-escalation trials are designed to minimize therapeutic toxicities in both early and advanced stage disease. Radiation therapy is the single most effective treatment modality for HL, and its integration into salvage regimens, or its independent use in select patients, must be understood in order to maximize our success in treating these patients. The complexity of treating relapsed/refractory HL derives from the spectrum of primary treatment approaches currently in use that creates heterogeneity in both treatment exposure and the potential toxicities of salvage therapy. Patients can have relapsed or refractory disease after limited or aggressive primary therapy (with or without radiation therapy), at early or delayed time points, with limited or extensive disease volumes, and with varying degrees of residual morbidity from primary therapy. Their response to salvage systemic therapy can be partial or complete, and the use of consolidative stem cell transplant is variably applied. New biologics and immunotherapeutic approaches have broadened but also complicated salvage treatment approaches. Through all of this, radiation therapy remains an integral component of treatment for many patients but it must be used effectively and judiciously. The purpose of this review is to describe the different treatment scenarios and provide guidance for radiation dose, volume, and timing in patients with relapsed or refractory HL.



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A Surgical Approach to the Harvest of the Vascularized Submandibular and Submental Lymph Node Flap: The "Through-the-Gland" Dissection Technique.

Related Articles

A Surgical Approach to the Harvest of the Vascularized Submandibular and Submental Lymph Node Flap: The "Through-the-Gland" Dissection Technique.

Ann Plast Surg. 2018 Jan 05;:

Authors: Nonomura H, Tan BK, Tan PWW, Goh T

Abstract
BACKGROUND: Extremity lymphedema is a pathological condition resulting from absence of lymph nodes and disease of lymphatic vessels, often due to oncologic clearance of lymph nodes. In recent years, vascularized lymph node transfer has become a rapidly emerging method of lymphatic reconstruction shown to lead to lymphatic regeneration. In particular, lymphatic flaps based on the submental artery have shown good results with its favorable donor site and available nodes. The lymph nodes here are in close relation to the submandibular gland and require careful dissection around and through the gland for safe harvest. We studied this region of the neck and describe the blood supply to the lymph nodes, their variable positions in relation to the gland, and our technique of dissecting through the submandibular gland while keeping the lymph nodes' hilar blood supply intact.
METHODS: We dissected 2 cadaver heads (4 sides of the neck) to study the submandibular and submental lymph nodes, where to locate them in relation to the submandibular gland and how best to dissect through the submandibular gland for access while keeping the hilar supply intact. We applied this knowledge in 6 clinical cases and provide a brief description of our "through-the-gland" dissection technique.
RESULTS: The submandibular lymph nodes may lie (1) superficial and posterior to the gland, (2) between the superficial and deep parts of the submandibular gland, or (3) anteriorly and submental. They are classified as superficial, deep, and submental, respectively. The through-the-gland dissection technique gave the surgeon improved access and exposure to the lymph nodes. It also facilitated safer dissection because their hilar blood supply is well visualized.
CONCLUSIONS: The through-the-gland technique of harvesting vascularized submandibular lymph node flaps is a safe technique that allows the surgeon to clearly identify and preserve blood supply of lymph nodes.

PMID: 29309323 [PubMed - as supplied by publisher]

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Clinical value of [18F]FDG-PET/CT and 3D-black-blood 3T-MRI for the diagnosis of large vessel vasculitis and single-organ vasculitis of the aorta.

Related Articles

Clinical value of [18F]FDG-PET/CT and 3D-black-blood 3T-MRI for the diagnosis of large vessel vasculitis and single-organ vasculitis of the aorta.

Q J Nucl Med Mol Imaging. 2018 Jan 02;:

Authors: Wenter V, Sommer NN, Kooijman H, Maurus S, Treitl M, Czihal M, Dechant C, Unterrainer M, Albert NL, Treitl KM

Abstract
BACKGROUND: We aimed to investigate the clinical value of a 3D-T1w turbo-spin-echo (TSE) sequence and [18F]fluorodeoxyglucose positron emission tomography / computed tomography ([18F]FDG- PET/CT) for the diagnosis of active large vessel vasculitis (LVV) and single-organ vasculitis (SOV) of the aorta.
METHODS: 24 patients with suspected vasculitis who underwent MRI and PET/CT were retrospectively evaluated. MRI was analyzed for concentric contrast enhancement and wall thickening, and flow artifact intensity (4-point-scales). PET/CT analysis comprised qualitative, quantitative and semiquantitative methods. Imaging findings were correlated with final diagnosis derived from the clinical follow-up data.
RESULTS: 15 of 24 patients had a clinically confirmed active vasculitis, two had inactive vasculitis and 7 no vasculitis. [18F]FDG-PET/CT and 3D-T1w TSE-MRI revealed both a high diagnostic accuracy of 88% and 83%, respectively. In patients in whom both PET/CT and MRI showed concordant findings (19 patients), the accuracy increased to 95% with a high positive predictive value (92%) and negative predictive value (100%); thus a correct diagnosis was obtained in 18 of 19 patients. Among the five patients with discordant findings PET/CT correctly identified the two patients without active vasculitis while rated false positive on MRI. Of the three remaining patients with active vasculitis, two were correctly identified by MRI and one by PET/CT.
CONCLUSIONS: 3D-T1w TSE-MRI and [18F]FDG-PET/CT are both useful in the diagnosis of active vasculitis with high diagnostic accuracies. The diagnostic accuracy was even optimized by combining the two analysis methods. Therefore, there might be substantial potential for the application of whole-body hybrid PET/MRI in the evaluation of vasculitis in future studies.

PMID: 29307167 [PubMed - as supplied by publisher]

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The effect of white matter hyperintensities on cognition is mediated by cortical atrophy

Publication date: April 2018
Source:Neurobiology of Aging, Volume 64
Author(s): Batool Rizvi, Atul Narkhede, Briana S. Last, Mariana Budge, Giuseppe Tosto, Jennifer J. Manly, Nicole Schupf, Richard Mayeux, Adam M. Brickman
White matter hyperintensities (WMH) have been linked to cognitive dysfunction and dementia, although the reasons are unclear. One possibility is that WMH promote neurodegeneration, which, in turn, affects cognition. We examined whether cortical thickness, a marker of neurodegeneration, mediates the relationship between WMH and cognition among 519 older adults. Using conditional process analysis modeling techniques, we examined the association between WMH volume and global cognition and tested whether cortical thickness mediates this relationship statistically. We also tested specific regional hypotheses to determine whether cortical thickness or volume in the medial temporal lobe mediates the relationship between WMH volume and memory. Increased total WMH volume was associated with poorer global cognition and memory. Global cortical thickness and medial temporal lobe thickness/volume mediated the relationship of WMH volume on global cognition and memory functioning. The mediating relationship was similar across racial and ethnic groups and across diagnostic groups (i.e., mild cognitive impairment/Alzheimer's disease). The findings suggest that WMH promote atrophy, which, in turn, drives cognitive decline and highlight a potential pathway in which small vessel cerebrovascular disease affects cognition by promoting neurodegenerative changes directly.



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Age-related differences in the neural correlates of empathy for pleasant and unpleasant touch in a female sample

Publication date: Available online 9 January 2018
Source:Neurobiology of Aging
Author(s): Federica Riva, Melanie Tschernegg, Patrizia Andrea Chiesa, Isabella C. Wagner, Martin Kronbichler, Claus Lamm, Giorgia Silani
Empathy is essential for successful social interactions and relationships. The neural underpinnings of empathy have predominantly been studied in the young adult population, while little is known about how they evolve across the life-span. In the present study, we used functional magnetic resonance imaging (fMRI) to investigate age-related differences of brain activity associated to empathy for positive and negative emotions. Female participants of three age groups – adolescents, young, and older adults- underwent an experimental paradigm inducing both first-hand and empathic experience of pleasant and unpleasant touch. Group comparisons and regression analyses revealed that older adults showed lower activation within the anterior insula with respect to young adults, during both empathy conditions. Further analyses provided evidence that years of education, Theory of Mind ability, grey matter volume, as well as first-hand affect processing did not account for these effects. These findings indicate that the neural bases of empathy change across different age groups, which selectively cover large parts of the human life span, from adolescence to old age, suggesting that the way in which we represent other's positive and negative emotions may go through important modifications throughout different ages.



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Elevated serum IGF-1 level enhances retinal and choroidal thickness in untreated acromegaly patients

Abstract

Purpose

1) To compare the retinal, choroidal, Haller's layer, and Sattler's/choriocapillaris thicknesses of untreated acromegaly patients without chiasm compression or diabetes mellitus and healthy controls. 2) To evaluate the correlations of retinal and choroidal thicknesses with serum growth hormone (GH) and insulin-like growth factor 1 (IGF) burden.

Methods

This prospective, case-control study included 27 untreated acromegaly patients and 27 sex-matched and age-matched controls. Subfoveal choroidal, Haller's layer and Sattler's/choriocapillaris thicknesses were determined by enhanced-depth imaging optical coherence tomography (EDI-OCT). Foveal and macular retinal thicknesses were determined with SD-OCT. GH and IGF-1 burdens were defined as the product of disease duration and treatment-naïve serum GH and IGF-1 levels.

Results

Compared with healthy controls, patients with acromegaly exhibited significantly increased foveal retinal (p = 0.003), subfoveal choroidal (p < 0.001), and Haller's layer (p < 0.001) thicknesses, with no differences in Sattler's/choriocapillaris layer thickness. Multiple point measurements in the posterior pole area showed equally increased nasal and temporal parts of the choroid. The retinal thickness maps of the two groups did not significantly differ. Correlation analysis indicated that choroidal thickness was significantly correlated with disease duration (p = 0.01), serum IGF-1 level (p = 0.03) and IGF-1 burden (p = 0.009). No significant correlations were detected between choroidal thickness and GH burden (p = 0.44). Retinal thickness was not significantly correlated with any factor.

Conclusion

The choroidal thickness of acromegaly patients was greater than that of healthy controls and was significantly correlated with disease duration, IGF-1 level and IGF-1 burden, indicating that excessive serum IGF-1 and its exposure time have a combined effect on choroidal thickness.

http://ift.tt/2mcBkW6

Elevated serum IGF-1 level enhances retinal and choroidal thickness in untreated acromegaly patients

Abstract

Purpose

1) To compare the retinal, choroidal, Haller's layer, and Sattler's/choriocapillaris thicknesses of untreated acromegaly patients without chiasm compression or diabetes mellitus and healthy controls. 2) To evaluate the correlations of retinal and choroidal thicknesses with serum growth hormone (GH) and insulin-like growth factor 1 (IGF) burden.

Methods

This prospective, case-control study included 27 untreated acromegaly patients and 27 sex-matched and age-matched controls. Subfoveal choroidal, Haller's layer and Sattler's/choriocapillaris thicknesses were determined by enhanced-depth imaging optical coherence tomography (EDI-OCT). Foveal and macular retinal thicknesses were determined with SD-OCT. GH and IGF-1 burdens were defined as the product of disease duration and treatment-naïve serum GH and IGF-1 levels.

Results

Compared with healthy controls, patients with acromegaly exhibited significantly increased foveal retinal (p = 0.003), subfoveal choroidal (p < 0.001), and Haller's layer (p < 0.001) thicknesses, with no differences in Sattler's/choriocapillaris layer thickness. Multiple point measurements in the posterior pole area showed equally increased nasal and temporal parts of the choroid. The retinal thickness maps of the two groups did not significantly differ. Correlation analysis indicated that choroidal thickness was significantly correlated with disease duration (p = 0.01), serum IGF-1 level (p = 0.03) and IGF-1 burden (p = 0.009). No significant correlations were detected between choroidal thickness and GH burden (p = 0.44). Retinal thickness was not significantly correlated with any factor.

Conclusion

The choroidal thickness of acromegaly patients was greater than that of healthy controls and was significantly correlated with disease duration, IGF-1 level and IGF-1 burden, indicating that excessive serum IGF-1 and its exposure time have a combined effect on choroidal thickness.

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Relationship of Vertigo and Postural Instability in Patients With Vestibular Schwannoma.

Related Articles

Relationship of Vertigo and Postural Instability in Patients With Vestibular Schwannoma.

Clin Exp Otorhinolaryngol. 2018 Jan 09;:

Authors: Nam GS, Jung CM, Kim JH, Son EJ

Abstract
Objectives: Growth of vestibular schwannomas (VS) causes progressive vestibular symptoms and postural instability. Since the tumor grows slowly, compensation of decaying vestibular input may decrease subjective symptoms of dizziness. This study aims to estimate the relationship of subjective vestibular symptoms and objective postural instability in patients with VS.
Methods: A retrospective review of 18 patients newly diagnosed with VS and with subjective vertigo symptoms was performed. The Results of vestibular function tests including the sensory organization test (SOT) using computerized dynamic posturography, caloric test, and self-report measures of subjective dizziness handicap (Dizziness Handicap Inventory) and visual analogue scale were compared according to the onset of vertigo symptoms.
Results: In VS patients, SOT showed decreased equilibrium score for all vestibular function related conditions, condition (C) 5 and 6, and composite (COMP) score. COMP scores were not correlated with visual analogue scale or Dizziness Handicap Inventory scores. Acute onset group included six patients and insidious onset group, 12 patients. Equilibrium scores for C5 and C6, and COMP scores were lower for insidious onset group, but the difference was not statistically significant.
Conclusion: Our findings confirmed postural instability is prevalent in VS patients. SOT parameters did not differ significantly between acute onset and insidious onset groups, but increased tumor size and canal weakness were noted in the insidious onset group. Clinicians should consider that postural instability is likely present even in patients who do not complain of acute vertigo, and appropriate counseling should be discussed with the patients.

PMID: 29307173 [PubMed - as supplied by publisher]

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Learning how to use IAM chromatography for predicting permeability

Publication date: 1 March 2018
Source:European Journal of Pharmaceutical Sciences, Volume 114
Author(s): Giuseppe Ermondi, Maura Vallaro, Giulia Caron
The interest for IAM (Immobilized Artificial Membranes) chromatography in the prediction of drug permeability is increasing. Here we firstly set-up a dataset of 253 molecules including neutral and ionized drugs and few organic compounds for which we either measured or retrieved from the literature IAM.PC.DD2 log Kw^IAM data. Then we applied block relevance (BR) analysis to extract from PLS models the relative contribution of intermolecular forces governing log Kw^IAM and Δlog Kw^IAM (a combined descriptor calculated from log Kw^IAM). Finally, the relationship between log Kw^IAM, Δlog Kw^IAM and passive permeability determined in both PAMPA and MDCK-LE systems was looked for. Models provided the basis for a rational application of IAM chromatography in permeability prediction.

Graphical abstract

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A trade-off between solubility enhancement and physical stability upon simultaneous amorphization and nanonization of curcumin in comparison to amorphization alone

Publication date: 1 March 2018
Source:European Journal of Pharmaceutical Sciences, Volume 114
Author(s): Jerome Jie Long Wong, Hong Yu, Li Ming Lim, Kunn Hadinoto
The numerous health benefits of curcumin (CUR) have not been fully realized due to its low aqueous solubility, resulting in poor bioavailability. While amorphization of CUR via amorphous solid dispersion (ASD) represents a well-established CUR solubility enhancement strategy, simultaneous amorphization and nanonization of CUR via amorphous CUR nanoparticles (or nano-CUR in short) have emerged only recently as the plausibly superior alternative to ASD. Herein we examined for the first time the amorphous nano-CUR versus the ASD of CUR in terms of their (1) in vitro solubility enhancement capability and (2) long-term physical stability. The ASD of CUR was prepared by spray drying with hydroxypropylmethylcellulose (HPMC) acting as crystallization inhibitor. The amorphous nano-CUR was investigated in both its (i) aqueous suspension and (ii) dry-powder forms in which the latter was prepared by spray drying with adjuvants (i.e. HPMC, trehalose, and soy lecithin). The results showed that the amorphous nano-CUR (in both its aqueous suspension and dry-powder forms) exhibited superior solubility enhancement to the ASD of CUR attributed to its faster dissolution rates. This was despite the ASD formulation contained a larger amount of HPMC. The superior solubility enhancement, however, came at the expense of low physical stability, where the amorphous nano-CUR showed signs of transformation to crystalline after three-month accelerated storage, which was not observed with the ASD. Thus, despite its inferior solubility enhancement, the conventional ASD of CUR was found to represent the more feasible CUR solubility enhancement strategy.

Graphical abstract

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