Characterization of intratumor magnetic nanoparticle distribution and heating in a rat model of metastatic spine disease.

Abstract:
OBJECT
The goal of this study was to optimize local delivery of magnetic nanoparticles in a rat model of metastatic breast cancer in the spine for tumor hyperthermia while minimizing systemic exposure.

METHODS
A syngeneic mammary adenocarcinoma was implanted into the L-6 vertebral body of 69 female Fischer rats. Suspensions of 100-nm starch-coated iron oxide magnetic nanoparticles (micromod Partikeltechnologie GmbH) were injected into tumors 9 or 13 days after implantation. For nanoparticle distribution studies, tissues were harvested from a cohort of 36 rats, and inductively coupled plasma mass spectrometry and histopathological studies with Prussian blue staining were used to analyze the samples. Intratumor heating was tested in 4 anesthetized animals with a 20-minute exposure to an alternating magnetic field (AMF) at a frequency of 150 kHz and an amplitude of 48 kA/m or 63.3 kA/m. Intratumor and rectal temperatures were measured, and functional assessments of AMF-exposed animals and histopathological studies of heated tumor samples were examined. Rectal temperatures alone were tested in a cohort of 29 rats during AMF exposure with or without nanoparticle administration. Animal studies were completed in accordance with the protocols of the University Animal Care and Use Committee.

RESULTS
Nanoparticles remained within the tumor mass within 3 hours of injection and migrated into the bone at 6, 12, and 24 hours. Subarachnoid accumulation of nanoparticles was noted at 48 hours. No evidence of lymphoreticular nanoparticle exposure was found on histological investigation or via inductively coupled plasma mass spectrometry. The mean intratumor temperatures were 43.2°C and 40.6°C on exposure to 63.3 kA/m and 48 kA/m, respectively, with histological evidence of necrosis. All animals were ambulatory at 24 hours after treatment with no evidence of neurological dysfunction.

CONCLUSIONS
Locally delivered magnetic nanoparticles activated by an AMF can generate hyperthermia in spinal tumors without accumulating in the lymphoreticular system and without damaging the spinal cord, thereby limiting neurological dysfunction and minimizing systemic exposure. Magnetic nanoparticle hyperthermia may be a viable option for palliative therapy of spinal tumors.

Zadnik|Patricia L|PL|
Molina|Camilo A|CA|
Sarabia-Estrada|Rachel|R|
Groves|Mari L|ML|
Wabler|Michele|M|
Mihalic|Jana|J|
McCarthy|Edward F|EF|
Gokaslan|Ziya L|ZL|
Ivkov|Robert|R|
Sciubba|Daniel|D|

ICP-MS = inductively coupled plasma mass spectrometry


Extrusion-based 3D (Bio)Printed Tissue Engineering Scaffolds: Process-Structure-Quality Relationships.

Abstract: Biological additive manufacturing (Bio-AM) has emerged as a promising approach for the fabrication of biological scaffolds with nano- to microscale resolutions and biomimetic architectures beneficial to tissue engineering applications. However, Bio-AM processes tend to introduce flaws in the construct during fabrication. These flaws can be traced to material nonhomogeneity, suboptimal processing parameters, changes in the (bio)printing environment (such as nozzle clogs), and poor construct design, all with significant contributions to the alteration of a scaffold's mechanical properties. In addition, the biological response of endogenous and exogenous cells interacting with the defective scaffolds could become unpredictable. In this review, we first described extrusion-based Bio-AM. We highlighted the salient architectural and mechanotransduction parameters affecting the response of cells interfaced with the scaffolds. The process phenomena leading to defect formation and some of the tools for defect detection are reviewed. The limitations of the existing developments and the directions that the field should grow in order to overcome said limitations are discussed.

Gerdes|Samuel|S|
Ramesh|Srikanthan|S|
Mostafavi|Azadeh|A|
Tamayol|Ali|A|0000-0003-1801-2889
Rivero|Iris V|IV|
Rao|Prahalada|P|

D040542:Mechanotransduction, Cellular
D023822:Tissue Engineering
D054457:Tissue Scaffolds

tissue engineering
scaffolds
Bio-AM
defects
3D printing
material rheology


Biocontrol of rats in an urban environment in Southeast Asia using Sarcocystis singaporensis.

Abstract:
BACKGROUND
Upon request of the local administration a control campaign targeting commensal rats (Rattus rattus, R. exulans) was conducted in 30 sub-districts (villages) of the World Heritage town Luang Prabang, Northern Laos, using rat bait containing lethal quantities of the parasitic protist Sarcocystis singaporensis. The associated investigations assessed the short-term control efficacy, willingness of residents to co-operate (community approach), and temporal and spatial changes of the urban rat population in response to treatment.

RESULTS
Biological rodent control significantly reduced rodent activity (percentage of positive tracking patches) in the town, from a mean of 25.3% (±12.8% SD) before (January-February) down to 8.0% (±4.4%) after (June) treatment. Reduction of rodent activity relative to three untreated villages was 83%. Similarly, residents observed significantly fewer rats on their properties after the campaign (mean percentage of households (HHs) per village with sightings), whereby reduction of sightings amounted to 57%. There was significant correlation between residents' observation rates and rodent activity. Among 94 rats trapped before and after treatment each, proportions of adult R. exulans and juvenile R. rattus were higher after rodent control, suggesting that a considerable part of the adult house rat population had been removed. Furthermore, a 5% post-campaign incidence of infection suggested that few rats had survived bait uptake.

CONCLUSION
S. singaporensis may be used successfully as tactical biocontrol agent for culling of rats in urban environments. We propose additional components of a long-term rodent management strategy for the town, without which the impact of culling campaigns would be limited. © 2019 Society of Chemical Industry.

biocontrol
Sarcocystis singaporensis
Rattus rattus
northern Laos
biological rodent control
Rattus exulans
Rattus tanezumi
town of Luang Prabang
urban rodent control


Correlation between the blood level of irisin and the severity of acute myocardial infarction in exercise-trained rats.

Abstract: Background Acute myocardial infarction is a major cause of death all over the world. Irisin is a novel myokine released after exercise. This work aimed to study the correlation between the serum irisin level and the severity of the acute myocardial infarction in the exercise-trained rats. Methods Forty-eight male rats were classified into four groups (12 for each): group I, control sedentary (C); group II, exercise-trained (EX) (swimming for 8 weeks); group III, isoprenaline-induced infarct (MI); and group IV, exercise-trained infarct (EX-MI) (swimming for 8 weeks followed by isoprenaline-induced infarction). ECG was recorded at start and end of the study, before and after induction of infarction. The serum level of irisin, lipid peroxidation [malondialdehyde (MDA)], total antioxidant status (TAS), creatine phosphokinase-MB (CK-MB), and troponin I was determined. The hearts were excised for histopathology and immunohistochemistry for caspase-3. Results The infarct rats showed significant prolongation in QTc interval and elevation in the ST segment as well as significant elevation of serum CK-MB, troponin I, and MDA, whereas TAS and serum irisin level were significantly decreased. With exercise, we observed a high positive correlation between the serum irisin and QRS duration (+0.643), amplitude (+0.860), and TAS (+0.887). In addition, there was a high negative correlation between the serum irisin and ST elevation (-0.865), QTc (-0.886), CK-MB (-0.891), troponin (-0.882), and MDA (-0.868). This was confirmed by the negative correlation between serum irisin and both collagen deposition and caspase-3 expression (-0.823 and -0.822, respectively). Conclusions We recommend regular exercise or taking recombinant irisin as a supplement to protect at-risk individuals against acute myocardial infarction.

Bashar|Shaimaa M|SM|
Samir El-Sherbeiny|Shereen M|SM|
Boraie|Mohamed Z|MZ|

irisin
myocardial infarction
exercise
ECG
isoprenaline


Iowa Gambling Task Performance in Parkinson Disease Patients with Impulse Control Disorders.

Abstract:
OBJECTIVE
A subgroup of patients with Parkinson disease (PD) develops impulse control disorders (ICD) associated with their dopamine replacement therapy. Patients and their families may be reluctant to report ICD symptoms or unaware these symptoms are related to PD medication, which can make detecting an ICD difficult for clinicians. Ideally, a behavioral measure that is sensitive to ICD could be employed to ensure that patients with these behaviors are identified and treated. The Iowa Gambling Task (IGT), a standardized decision-making task, has proven sensitive in other populations with impulse control problems. We hypothesized that the IGT would differentiate between PD patients with and without ICD.

METHODS
We compared IGT performance and disease variables in 24 PD patients with ICD and 24 PD patients without ICD. Patient groups were matched in terms of age, sex, and duration of PD.

RESULTS
There were no significant differences in IGT scores between PD groups. IGT performance declined with increasing age, but the majority of patients performed within normal limits based on published age- and education-corrected normative data.

CONCLUSIONS
The IGT did not distinguish between PD patients with and without ICD. Increasing age negatively impacted performance in both groups. Other studies have found that IGT performance may decline in normal aging. Our results suggest that the IGT lacks the sensitivity and specificity needed to differentiate between age-related deficits and disruption in frontal-subcortical circuits underlying ICD associated with PD medications. Therefore, the IGT is not an appropriate behavioral measure for ICD in PD patients.

Biars|Julia W|JW|
Johnson|Nicole L|NL|
Nespeca|Michelle|M|
Busch|Robyn M|RM|
Kubu|Cynthia S|CS|
Floden|Darlene P|DP|

D007174:Disruptive, Impulse Control, and Conduct Disorders

Elderly/geriatrics/aging
Executive functions
Parkinson’s disease


Occurrence of Soil Fungi in Antarctic Pristine Environments.

Abstract: The presence of fungi in pristine Antarctic soils is of particular interest because of the diversity of this microbial group. However, the extreme conditions that coexist in Antarctica produce a strong selective pressure that could lead to the evolution of novel mechanisms for stress tolerance by indigenous microorganisms. For this reason, in recent years, research on cold-adapted microorganisms has increased, driven by their potential value for applications in biotechnology. Cold-adapted fungi, in particular, have become important sources for the discovery of novel bioactive secondary metabolites and enzymes. In this study, we studied the fungal community structure of 12 soil samples from Antarctic sites, including King George Island (including Collins Glacier), Deception Island and Robert Island. Culturable fungi were isolated and described according to their morphological and phenotypical characteristics, and the richness index was compared with soil chemical properties to describe the fungal community and associated environmental parameters. We isolated 54 fungal strains belonging to the following 19 genera: Penicillium, Pseudogymnoascus, Lambertella, Cadophora, Candida, Mortierella, Oxygenales, Geomyces, Vishniacozyma, Talaromyces, Rhizopus, Antarctomyces, Cosmospora, Tetracladium, Leptosphaeria, Lecanicillium, Thelebolus, Bjerkandera and an uncultured Zygomycete. The isolated fungi were comprised of 70% Ascomycota, 10% Zygomycota, 10% Basidiomycota, 5% Deuteromycota and 5% Mucoromycota, highlighting that most strains were associated with similar genera grown in cold environments. Among the culturable strains, 55% were psychrotrophic and 45% were psychrophilic, and most were Ascomycetes occurring in their teleomorph forms. Soils from the Collins Glacier showed less species richness and greater species dominance compared with the rest of the sites, whereas samples 4, 7, and 10 (from Fildes Bay, Coppermine Peninsula and Arctowski Station, respectively) showed greater species richness and less species dominance. Species richness was related to the C/N ratio, whereas species dominance was inversely related to C and N content. Thus, the structure of the fungal community was mainly related to soil chemical parameters more than sample location and altitude.

Durán|Paola|P|
Barra|Patricio J|PJ|
Jorquera|Milko A|MA|
Viscardi|Sharon|S|
Fernandez|Camila|C|
Paz|Cristian|C|
Mora|María de la Luz|ML|
Bol|Roland|R|

Antarctica
fungal community
biodiversity index
cold desert
extreme environment


Long-Term Aortic Valve Function in Patients With or Without Surgical Treatment for Discrete Subaortic Stenosis.

Abstract: The purpose of this study was to evaluate the long-term function of the aortic valve in patients with discrete subaortic stenosis (DSS), and its prognostic implications. 34 patients with the diagnosis of isolated DSS were treated at our pediatric heart center between 1992 and 2019. Demographic, echocardiographic and surgical data were analyzed. 26 patients had surgery to remove the subaortic membrane. The primary endpoint of this study was a change in the aortic valve function, secondary outcomes included functional class, aortic valve replacement, and reoperation due to recurrence of DSS. The mean post-operative follow-up time was 7.07 years (1-22.5). At the time of the most recent follow up, in the surgical group 11 patients (46%) had echocardiographic evidence of deterioration in their aortic valve insufficiency (AI) (p < 0.002). The deterioration was associated with a pre-operative left ventricular outflow tract (LVOT) gradient greater than 49 mmHg (p < 0.022). 8 patients with DSS were followed for a mean of 12.9 years (6.8-21.3), without meeting the criteria for surgical intervention, none showed any change in the aortic valve function during follow-up time. DSS resection may not prevent worsening of aortic valve insufficiency over time. Patients with stable AI and low LVOT gradient may not require surgery. Given these findings, it may be appropriate to carefully follow patients with new onset AI and low LVOT gradient, delaying surgical intervention.

Subaortic stenosis
Membrane
Aortic insufficiency


Developing Customizable Cancer Information Extraction Modules for Pathology Reports Using CLAMP.

Abstract: Natural language processing (NLP) technologies have been successfully applied to cancer research by enabling automated phenotypic information extraction from narratives in electronic health records (EHRs) such as pathology reports; however, developing customized NLP solutions requires substantial effort. To facilitate the adoption of NLP in cancer research, we have developed a set of customizable modules for extracting comprehensive types of cancer-related information in pathology reports (e.g., tumor size, tumor stage, and biomarkers), by leveraging the existing CLAMP system, which provides user-friendly interfaces for building customized NLP solutions for individual needs. Evaluation using annotated data at Vanderbilt University Medical Center showed that CLAMP-Cancer could extract diverse types of cancer information with good F-measures (0.80-0.98). We then applied CLAMP-Cancer to an information extraction task at Mayo Clinic and showed that we can quickly build a customized NLP system with comparable performance with an existing system at Mayo Clinic. CLAMP-Cancer is freely available for academic use.

Soysal|Ergin|E|
Warner|Jeremy L|JL|
Wang|Jingqi|J|
Jiang|Min|M|
Harvey|Krysten|K|
Jain|Sandeep Kumar|SK|
Dong|Xiao|X|
Song|Hsing-Yi|HY|
Siddhanamatha|Harish|H|
Wang|Liwei|L|
Dai|Qi|Q|
Chen|Qingxia|Q|
Du|Xianglin|X|
Tao|Cui|C|
Yang|Ping|P|
Denny|Joshua Charles|JC|
Liu|Hongfang|H|
Xu|Hua|H|

D016247:Information Storage and Retrieval

Natural Language Processing
Electronic Health Records
Information Storage and Retrieval


8-O-Acetyl Shanzhiside Methylester From Lamiophlomis Rotata Reduces Neuropathic Pain by Inhibiting the ERK/TNF-α Pathway in Spinal Astrocytes.

Abstract: Lamiophlomis rotata (L. rotata; Benth.) Kudo is an effective traditional herb in the clinical treatment of chronic pain syndromes in China. 8-O-acetyl shanzhiside methylester (8-OaS), a chief component in L. rotata, possesses potent immunosuppressive activities and favorable analgesic effects. This study was proposed to compare the analgesic effects of 8-OaS with those of lidocaine and ketamine in a spinal nerve ligation (SNL) model by behavioral tests, and then investigated its effects upon the expression of spinal glial fibrillary acidic protein (GFAP), phosphorylated extracellular regulated protein kinases (pERK) and tumor necrosis factor-alpha (TNF-α) via immunofluorescence staining and western blot analyses. The data showed consecutive intrathecal injection of 8-OaS for 2 weeks brought about remarkable palliation of neuropathic pain (NP), possessing similar anti-allodynia effects with those of lidocaine and ketamine. Two weeks after surgery, pERK within the spinal dorsal horn was mainly expressed in astrocytes more than neurons and microglia, and 8-OaS inhibited spinal astrocytic activation and TNF-α expression. Finally, co-treatment of 8-OaS and PD98059 (an Extracellular signal-regulated kinase, ERK inhibitor) did not lead to remarkable increase in pain relief or TNF-α expression comparing to rats treated with 8-OaS or PD98059 alone. In conclusion, the anti-nociceptive effects of 8-OaS in the condition of NP relied on the inhibition of SNL-induced astrocyte activation, probably via the down-regulation of the ERK/TNF-α pathway.

Zhang|Wei|W| Bai|Yang|Y| Qiao|Yu|Y| Wang|Jian|J| Li|Meng-Ying|MY| Wang|Jing-Wen|JW| Jia|Na|N| Chen|Tao|T| Li|Yun-Qing|YQ| Wen|Ai-Dong|AD|

8-O-acetyl shanzhiside methylester
neuropathic pain
ERK
astrocytes
SNL
spinal dorsal horn


Uremic encephalopathy with isolated brainstem involvement revealed by magnetic resonance image: a case report.

Abstract:
BACKGROUND
Uremic Encephalopathy (UE) is a neurological complication associated with acute or chronic renal failure. Imaging findings of UE may present involvement of the basal ganglia, cortical or subcortical regions, and white matter. We report a rare case of UE caused by neurogenic bladder with isolated brainstem involvement revealed by magnetic resonance imaging (MRI). Immediate therapy resulted in full recovery of neurological signs and changes on MRI.

CASE PRESENTATION
A 14-year-old Han Chinese woman with a history of chronic renal failure caused by neurogenic bladder. On admission, she was unconscious and her pupils presented different sizes, while her vital signs were normal. MRI showed high signal in the dorsal pontine base and in the mid brain on fluid-attenuated inversion-recovery (FLAIR) imaging and on T2-weighted imaging while the signal was normal on diffusion-weighted images (DWI). Blood analysis revealed renal failure and acidosis. After urinary retention treatment and acidosis correction, the patient soon recovered. Follow-up MRI 2 months after the discharge revealed complete resolution of UE in the brainstem.

CONCLUSION
We reported a rare case of a patient with UE that had unusual imaging manifestations for whom timely diagnosis and treatment assured recovery.

D038524:Diffusion Magnetic Resonance Imaging

Posterior reversible encephalopathy syndrome


Sleeping through COVID-19: a longitudinal comparison of 2019 and 2020 infant auto-videosomnography metrics.

Abstract:
BACKGROUND
With the outbreak of the COVID-19 pandemic, pediatric experts called attention to the potential adverse effects of living restrictions (e.g., lockdown) on child well-being, but at the same time- acknowledged their possible benefits. To date, only few data-driven reports have been published on child sleep during COVID-19, and all have been based on parent- or self-reports. This study used auto-videosomnography to capture the effects of COVID-19 stay-at-home orders imposed in the USA on objectively measured infant sleep.

METHODS
Auto-videosomnography metrics of infants assessed nightly between January and May 2020 were compared with metrics of an equivalent infant cohort, assessed in the corresponding 2019 period. A total of 610 infants (50.7% girls) aged 6-18 months (M = 11.8, SD = 3.6) were included, with 71,472 analyzed nights. Multilevel models were applied to assess differences between 2019 and 2020 infant sleep pre- and during-lockdown.

RESULTS
Whereas infant cohorts were equivalent in demographic and January-March/April sleep characteristics, during the 2020 lockdown infants had longer nighttime sleep durations (Mdifference  = 11.0 min, p = .01), later morning rise times (Mdifference  = 9.5 min, p = .008), and later out-of-crib times (Mdifference  = 12.3 min, p < .0001), compared to the equivalent 2019 period. In addition, weekday-weekend differences in sleep onset and midpoint times were diminished during 2020 home-confinement compared to the equivalent 2019 period (2019: Mdifference  = 5.5 min, p < .0001; Mdifference  = 4.5 min, p < .0001; 2020: Mdifference  = 2.3 min, p = .01; Mdifference  = 3.1 min, p < .0001, respectively).

CONCLUSIONS
Notwithstanding the negative implications of COVID-19 living restrictions in other domains, our findings indicate that there might be a silver lining-in promoting longer and more consistent infant sleep. These benefits should be considered in determining policy for the current and future pandemics.

Sleep home-confinement coronavirus infancy videosomnography


Germline and somatic mutations of the APC gene in papillary thyroid carcinoma associated with familial adenomatous polyposis: Analysis of three cases and a review of the literature.

Abstract: Patients with familial adenomatous polyposis (FAP), which is caused by the dysfunction of the adenomatous polyposis coli (APC) protein, have the possibility of developing extracolonic manifestations, including thyroid cancer (TC), congenital hypertrophy of the retinal pigment epithelium, desmoid tumors, and gastric and duodenal adenomas. The pathogenesis of these disorders associated with FAP is considered to be affected by the site of the germline mutation on the APC gene as a genotype-phenotype correlation. Moreover, β-catenin binding sites consist of 20-amino acid repeats (20-AARs) in the APC protein, and they are essential for the development of colorectal adenomas and certain other extracolonic manifestations. The present study retrospectively analyzed the germline and somatic mutations of the APC gene in three papillary TC patients with FAP to analyze the association between the remaining number of 20-AARs and the development of TC. The mutation sites of two TCs did not include 20-AARs in each allele. In one patient, the remaining number of 20-AARs was two in the germline mutation and zero in the somatic mutation. Together with the data on 13 FAP-associated thyroid cancerous lesions in 3 FAP patients reported previously, the majority of the remaining numbers of 20-AARs was zero in the TC patients with FAP (13/16; 81.3%). Consequently, the APC/β-catenin signaling pathway may be strongly involved with the pathogenesis of TC with FAP. Further accumulation of FAP patients with TC will be required to confirm the molecular pathogenesis of TC.

Kumamoto|Kensuke|K| Ishida|Hideyuki|H| Ohsawa|Tomonori|T| Ishibashi|Keiichiro|K| Ushiama|Mineko|M| Yoshida|Teruhiko|T| Iwama|Takeo|T|

APC
familial adenomatous polyposis
thyroid cancer


Scanning electrochemical microscopy and its potential for studying biofilms and antimicrobial coatings.

Abstract: Biofilms are known to be well-organized microbial communities embedded in an extracellular polymeric matrix, which supplies bacterial protection against external stressors. Biofilms are widespread and diverse, and despite the considerable large number of publications and efforts reported regarding composition, structure and cell-to-cell communication within biofilms in the last decades, the mechanisms of biofilm formation, the interaction and communication between bacteria are still not fully understood. This knowledge is required to understand why biofilms form and how we can combat them or how we can take advantage of these sessile communities, e.g. in biofuel cells. Therefore, in situ and real-time monitoring of nutrients, metabolites and quorum sensing molecules is of high importance, which may help to fill that knowledge gap. This review focuses on the potential of scanning electrochemical microscopy (SECM) as a versatile method for in situ studies providing temporal and lateral resolution in order to elucidate cell-to-cell communication, microbial metabolism and antimicrobial impact, e.g. of antimicrobial coatings through the study of electrochemical active molecules. Given the complexity and diversity of biofilms, challenges and limitations will be also discussed.

Scanning electrochemical microscopy
Biofilm
Antimicrobial
Bacteria
Quorum sensing


Diagnostic impact of integrated 18F-FDG PET/MRI in cerebral staging of patients with non-small cell lung cancer.

Abstract: Background Integrated positron emission tomography/magnetic resonance imaging (PET/MRI) systems are increasingly being available and used for staging examinations. Brain metastases (BM) are frequent in patients with non-small cell lung cancer (NSCLC) and decisive for treatment strategy. Purpose To assess the diagnostic value of integrated 18F-2-fluoro-2-deoxy-D glucose (18F-FDG) PET/MRI in initial staging in patients with NSCLC for BM in comparison to MRI alone. Material and Methods Eighty-three patients were prospectively enrolled for an integrated 18F-FDG PET/MRI examination. The 3 T MRI protocol included a fluid-attenuated inversion-recovery sequence (FLAIR) and a contrast-enhanced three-dimensional magnetization prepared rapid acquisition GRE sequence (MPRAGE). Two neuroradiologists evaluated the datasets in consensus regarding: (i) present lesions; (ii) size of lesions; and (iii) number of lesions detected in MRI alone, compared to the PET component when reading the 18F-FDG PET/MRI. Results Based on MRI alone, BM were detected in 15 out of the 83 patients, comprising a total of 39 metastases. Based on PET alone, six patients out of the 83 patients were rated positive for metastatic disease, revealing a total of 15 metastases. PET detected no additional BM. The size of the BM correlated positively with sensitivity of detection in PET. Conclusion The sensitivity of PET in detection of BM depends on their size. 18F-FDG PET/MRI does not lead to an improvement in diagnostic accuracy in cerebral staging of NSCLC patients, as MRI alone remains the gold standard.

Deuschl|Cornelius|C|
Nensa|Felix|F|
Grueneisen|Johannes|J|
Poeppel|Thorsten D|TD|
Sawicki|Lino M|LM|
Heusch|Philipp|P|
Gramsch|Carolin|C|
Mönninghoff|Christoph|C|
Quick|Harald H|HH|
Forsting|Michael|M|
Umutlu|Lale|L|
Schlamann|Marc|M|

D000328:Adult
D000368:Aged
D000369:Aged, 80 and over
D002289:Carcinoma, Non-Small-Cell Lung
D003287:Contrast Media
D005260:Female
D019788:Fluorodeoxyglucose F18
D006801:Humans
D021621:Imaging, Three-Dimensional
D008175:Lung Neoplasms
D008279:Magnetic Resonance Imaging
D008297:Male
D008875:Middle Aged
D064847:Multimodal Imaging
D009367:Neoplasm Staging
D049268:Positron-Emission Tomography
D019275:Radiopharmaceuticals
D012680:Sensitivity and Specificity

staging
Lung cancer
18F-FDG-PET
cerebral metastases
integrated PET/MRI
magnetic resonance imaging (MRI)


Examining Land Use Changes to Evaluate the Effects of Land Management in a Complex, Dynamic Landscape.

Abstract: Anthropogenic alterations to landscapes have increased as the human population continues to rise, leading to detrimental changes in natural habitats. Ecological restoration assists in recovery by altering habitats to improve conditions and foster biodiversity. We examined land cover changes over time within a complex, dynamic region in the Midwest to assess the long-term effects of conservation. We used Landsat 8 bands for a 15-class land cover map of Oak Openings Region using supervised classification. We validated our map and achieved an overall accuracy of 71.2% from correctly classified points out of total visited points. Change over 10 years, from 2006 to 2016, was explored by comparing class statistics from FRAGSTATS between our map and original land cover map. We found that natural land, i.e., forest and early successional, covered 33%, with 10% permanently protected, while human-modified land, i.e., agricultural and developed, covered 67% of the region. Over 10 years, natural classes increased, and cultural classes decreased by 5.8%. There were decreases for the three forest communities and increases for the two early successional communities. These changes are likely the result of natural recovery and disturbance, and conservation efforts by the Green Ribbon Initiative. Changes in habitat also came with distribution changes, e.g., increased fragmentation for some classes, which was readily visible. Our useful method measured functionality by emphasizing changes in composition and configuration. Our approach provides a tool for assessing cumulative regional-scale effects from site-level management and conservation. This large-scale view for conservation is needed to effectively mitigate future changes.

D003247:Conservation of Natural Resources

Land cover change
Conservation
Oak Openings Region
Urbanization
Vegetation classification


Mechanistic simulation of bioconcentration kinetics of waterborne Cd, Ag, Pd, and Pt in the zebra mussel Dreissena polymorpha.

Abstract: Mechanistic models based on chemical properties of metals and body size have received substantial attention for their potential application to various metals and to different conditions without required calibration. This advantage has been demonstrated for a number of metals, such as Cd and Ag. However, the capacity of metal-specific chemical properties to explain variations in the accumulation for platinum-group elements (PGEs) has not been investigated yet, although emission of these metals is of increasing concern. Once being released, PGEs exist in the environment in mixtures with other metals. The present study attempted to model the accumulation of Pd and Pt in mixtures with Ag and Cd in the zebra mussel (Dreissena polymorpha) from the aqueous phase; and to investigate the potential application of mechanistic models to Pd and Pt. The present study showed statistically insignificant differences in metal accumulation among size groups in a narrow range of shell length (16-22 mm). Kinetic models could simulate well the accumulation of Cd, Ag, and Pt when metal-specific responses of zebra mussels are taken into consideration. These responses include enhanced immobilisation as a detoxifying mechanism and exchange between soft tissues and shells via the extrapallial fluid. Environmental conditions, e.g. the presence of abiotic ligands such as chloride, might also play an important role in metal accumulation. Significant relationships between the absorption efficiency and the covalent index indicate the potential application of mechanistic models based on this chemical property to Pt.

Yen Le|T T|TT|
García|Míriam R|MR|
Grabner|Daniel|D|
Nachev|Milen|M|
Balsa-Canto|Eva|E|
Hendriks|A Jan|AJ|
Zimmermann|Sonja|S|
Sures|Bernd|B|

Bioconcentration
Mechanistic model
Covalent index
Bivalves
Platinum
Trace metals


Expression of Cry1Ac in transgenic Bt soybean lines and their efficiency in controlling lepidopteran pests.

Abstract:
BACKGROUND
Two transgenic lines of the soybean Glycine max, MON87701 expressing the Cry1Ac protein and MON87701RR2Y expressing Cry1Ac +  EPSPS proteins, were evaluated for their resistance to four lepidopteran pests in the laboratory using detached-leaf bioassays throughout the soybean growth seasons (before anthesis, during anthesis and after anthesis) in China. Enzyme-linked immunosorbent assays (ELISAs) were used to monitor the Cry1Ac expression in soybean leaves.

RESULTS
The bioassay results revealed that both transgenic soybean lines exhibited significantly high resistance against Helicoverpa armigera (Hübner) throughout the soybean growing seasons. The survival rates of H. armigera larvae ranged from 5.4 to 24.4% when feeding on the transgenic soybean leaves, significantly lower than the survival rates when feeding on control leaves (71.1-94.9%). Limited resistance was found for both transgenic soybean lines against Spodoptera litura (Fabricius), although the survival rates and weight of S. litura larvae as well as female fecundity were significantly decreased when feeding on Bt soybean leaves compared with feeding on control leaves. In contrast, both transgenic soybean lines provided almost no resistance to Spodoptera exigua (Hübner) and Agrotis ypsilon (Rottemberg). Cry1Ac expression in the leaves of both transgenic soybean lines was relatively stable throughout the soybean growing season, with a peak occurring at V6 -8 and V11 -12 before anthesis. The ELISA results were positively correlated with the results from the insect bioassays.

CONCLUSIONS
The results show that, while Cry1Ac-expressing Bt soybeans may provide good protection against H. armigera, alternative control measures are required to manage S. exigua, S. litura and A. ypsilon.

Yu|Huilin|H| Li|Yunhe|Y| Li|Xiangju|X| Romeis|Jörg|J| Wu|Kongming|K|

Bt soybean
ELISA
Helicoverpa armigera
Spodoptera litura
Spodoptera exigua
Agrotis ypsilon


Pharmacological classification of herbal extracts by means of comparison to spectral EEG signatures induced by synthetic drugs in the freely moving rat.

Abstract: Herbal extracts targeting at the brain remain a continuous challenge to pharmacology. Usually, a number of different animal tests have to be performed in order to find a potential clinical use. Due to manifold possibly active ingredients biochemical approaches are difficult. A more holistic approach using a neurophysiological technique has been developed earlier in order to characterise synthetic drugs. Stereotactic implantation of four semi-microelectrodes into frontal cortex, hippocampus, striatum and reticular formation of rats allowed continuous wireless monitoring of field potentials (EEG) before and after drug intake. After frequency analysis (Fast Fourier Transformation) electric power was calculated for 6 ranges (delta, theta, alpha1, alpha2, beta1 and beta2). Data from 14 synthetic drugs - tested earlier and representative for different clinical indications - were taken for construction of discriminant functions showing the projection of the frequency patterns in a six-dimensional graph. Quantitative analysis of the EEG frequency pattern from the depth of the brain succeeded in discrimination of drug effects according to their known clinical indication (Dimpfel and Schober, 2003). Extracts from Valerian root, Ginkgo leaves, Paullinia seed, Hop strobile, Rhodiola rosea root and Sideritis scardica herb were tested now under identical conditions. Classification of these extracts based on the matrix from synthetic drugs revealed that Valerian root and hop induced a pattern reminiscent of physiological sleep. Ginkgo and Paullinia appeared in close neighbourhood of stimulatory drugs like caffeine or to an analgesic profile (tramadol). Rhodiola and Sideritis developed similar frequency patterns comparable to a psychostimulant drug (methylphenidate) as well to an antidepressive drug (paroxetine).

Pharmacological classification
Herbal extract
Spectral EEG signature
Field potential
In-vivo EEG model


Identification and functional analysis of GCK gene mutations in 12 Chinese families with hyperglycemia.

Abstract:
AIMS/INTRODUCTION
To investigate the clinical and genetic characteristics of Chinese patients with a phenotype consistent with maturity-onset diabetes of the young type 2 and explore the pathogenic mechanism of their hyperglycemia.

MATERIALS AND METHODS
We studied 12 probands and their extended families referred to our center for screening mutations in the glucokinase gene (GCK). Clinical data were collected and genetic analysis was carried out. The recombinant wild-type and mutant glucokinase were generated in Escherichia coli. The kinetic parameters and thermal stability of the enzymes were determined in vitro.

RESULTS
In the 12 families, 11 GCK mutations (R43C, T168A, K169N, R191W, Y215X, E221K, M235T, R250H, W257X, G261R and A379E) and one variant of uncertain significance (R275H) were identified. R191W was detected in two unrelated families. Of the 11 GCK mutations, three mutations (c.507G>C, K169N; c.645C>A, Y215X; c.771G>A, W257X; NM_000162.3, NP_000153.1) are novel. Basic kinetics analysis explained the pathogenicity of the five mutants (R43C, K169N, R191W, E221K and A379E), which showed reduced enzyme activity with relative activity indexes between ~0.001 and 0.5 compared with the wild-type (1.0). In addition, the thermal stabilities of these five mutants were also decreased to varying degrees. However, for R250H and R275H, there was no significant difference in the enzyme activity and thermal stability between the mutants and the wild type.

CONCLUSIONS
We have identified 11 GCK mutations and one variant of uncertain significance in 12 Chinese families with hyperglycemia. For five GCK mutations (R43C, K169N, R191W, E221K and A379E), the changes in enzyme kinetics and thermostability might be the pathogenic mechanisms by which mutations cause hyperglycemia.

Maturity-onset diabetes of the young
Glucokinase
Enzyme kinetics


If a trauma patient is tachycardic, should we call for a counsellor?

Abstract:
BACKGROUND
It has been suggested in the literature that raised heart rate in the early period after trauma is associated with the development of post-traumatic psychopathology, but little account has been taken of the potential confounding effect of injury severity.

MATERIALS AND METHODS
A cohort of 154 patients, studied as part of a wider investigation of trauma outcomes, was included. Initial heart rate in the accident & emergency department, and injury severity score and new injury severity scores were recorded. Patients completed the General Health Questionnaire (GHQ-28) as a measure of psychopathology at presentation and again at two- and six-month follow-up.

RESULTS
There was no relationship between psychopathology at presentation and initial heart rate or injury severity. Raised heart rate was associated with post-traumatic psychopathology at two months but not at six months. When the potential confounding effect of injury severity was controlled for, there was no independent correlation between heart rate and post-traumatic psychopathology. Injury severity score and new injury severity scores were strongly associated with GHQ-28 caseness.

CONCLUSION
Post-traumatic tachycardia is not associated with development of psychopathology, but injury severity is. Previous studies that have suggested a link between tachycardia and development of psychopathology are flawed because they have not considered the confounding effect of severity of injury.

Sutherland|A G|AG|
Senthilkumaran|S|S|
Alexander|D A|DA|
Hutchison|J D|JD|

D011569:Psychiatric Status Rating Scales

Trauma psychopathology outcomes tachycardia


Acute and subchronic toxicological evaluation of Stachys lavandulifolia aqueous extract in Wistar rats.

Abstract: Stachys lavandulifolia (S. lavandulifolia) is a plant that has been widely used as an herbal medicine in Iran. Unfortunately, despite the prevalent medicinal uses of the plant, there are no reports on the possible toxic effects of S. lavandulifolia. In the present study the potential toxicity of S. lavandulifolia after acute and subchronic administration in rats was evaluated. Rats were orally treated with single doses of S. lavandulifolia aqueous extract and screened for signs of toxicity two weeks after administration. In the sub-chronic toxicity study, S. lavandulifolia was administered for 45 days. Mortality, clinical signs, body weight changes were assayed during the study. After 45 days animals were sacrificed and hematological and biochemical parameters, as well as weight of some organs were measured. All of the rats treated with different concentrations of water extracts of S. lavandulifolia were alive for all 14 days of observation. No hematological changes were observed a part from significant increase in WBC and neutrophils counts. Moreover, serum aspartate aminotransferase (AST) and creatinine significantly increased. Histopathological examinations showed fatty change, degeneration of hepatocytes and renal glomerular atrophy in the male rats. In the female rats, atrophy of hepatocytes and dilatation of sinusoids in liver, hyperemia and degeneration of renal epithelium mostly in cortical region were observed. Based on the results of this study no observed adverse effect level (NOAEL) of the total aqueous extract of S. lavandulifolia considered to be 250 and 100 mg/kg/day for the male and female rats, respectively.

Modarresi|M|M|
Hosseinzadeh|L|L|
Nematy|N|N|
Siavash-Haghighi|Z M|ZM|
Ghanbari|K|K|

Acute
Subchronic
Stachys lavandulifolia
Rat
Toxicity


Patient-specific and intra-operatively modifiable factors assessed by computer navigation predict maximal knee flexion one year after TKA.

Abstract:
PURPOSE
There are multiple factors affecting maximal knee flexion (MKF) after total knee arthroplasty (TKA). The aim of the study was to investigate whether patient-specific factors (PSF) and surgically modifiable factors (SMF), measured by means of a computer-assisted navigation system, can predict the MKF after TKA.

METHODS
Data from 99 patients collected during a randomized clinical trial were used for this secondary data analysis. The MKF of the patients was measured preoperatively and 1-year post-surgery. Multiple regression analyses were performed to investigate which combination of variables would be the best to predict the 1-year MKF.

RESULTS
When considering SMF alone, the combination of three factors significantly predicted the 1-year MKF (p = 0.001), explaining 22 % of its variation. When considering only PSF, the combination of pre-op MKF and BMI significantly predicted the 1-year MKF (p < 0.001), explaining 23 % of its variation. When considering both groups of potential predictors simultaneously, the combination of five SMF with two PSF significantly predicted the 1-year MKF (p = 0.001), explaining 32 % of its variation.

CONCLUSIONS
Computer navigation variables alone could explain 22 % of the variance in the 1-year MKF. The larger proportion (32 %) of the 1-year MKF variation could be explained with a combination of SMF and PSF. The results of studies in this area could be used to identify patients at risk of poor outcomes.

LEVEL OF EVIDENCE
Level II, Prognostic study.

Lampe|Frank|F|
Marques|Carlos J|CJ|
Fiedler|Franziska|F|
Sufi-Siavach|Anusch|A|
Carita|Ana I|AI|
Matziolis|Georg|G|

Computer-assisted surgery
Joint range of motion
Prognosis
Total knee replacement


A comparison study between 3D T2-weighted SPACE and conventional 2D T2-weighted turbo spin echo in assessment of carotid plaque.

Abstract: The aim of this study was to compare 3D T2-weighted sampling perfection with application optimized contrast using different flip angle evolutions (T2w SPACE) with conventional 2D T2w turbo-spin echo (TSE) in plaque imaging of carotid artery. 45 patients underwent 3.0-T MRI for carotid arteries imaging. MR sequences included T2w SPACE, T2w TSE, Time of flight (TOF) and T1-weighted (T1w) TSE. The signal intensity of intra-plaque hemorrhage (IPH), lipid-rich necrotic core (LRNC), and loose matrix (LM) were measured and their contrast ratios (CRs) against adjacent muscle were calculated. CRs from T2w SPACE and T2w TSE were compared to each other. CRs of LM, LRNC, and IPH measured on T2w SPACE were 1.74-3.04 (2.44), 0.98-1.66 (1.39), and 1.91-2.93 (2.51), respectively. CRs of LM, LRNC, and IPH on T2w TSE were 1.97-3.41 (2.44), 1.18-1.73 (1.43), and 2.26-3.75 (2.26), respectively. There was no significant difference of CR of the carotid plaques between T2w SPACE and T2w TSE (p = 0.455). Markedly significant differences of CRs were found between LM and LRNC (p < 0.001), and between LRNC and IPH (p < 0.001) on T2w SPACE and T2w TSE. T2w SPACE was comparable with conventional T2w TSE in characterization of carotid plaque.

Lv|Peng|P| Dai|Yuanyuan|Y| Lin|Jiang|J| Zhang|Weisheng|W| Liu|Hao|H| Liu|Hui|H| Tang|Xiao|X|

Plaque
Carotid artery
Atherosclerosis
Magnetic resonance imaging


Biological activity of mannosylerythritol lipids on the mammalian cells.

Abstract: Mannosylerythritol lipids (MEL) are glycolipids mainly produced by pseudo-yeasts. These molecules present remarkable biological activities widely explored in many fields, including medicine, pharmaceuticals, and cosmetics. This review presents the main biological activity of MEL on the HL60, K562, B16, PC12, and skin cells. There is strong evidence that MEL changes the levels of glycosphingolipids of HL-60 lineage, which induce differentiation into granulocytic cells. Regarding B16 cells, MEL can trigger both apoptosis (10 μM) and cell differentiation (5 μM), in which the MEL concentration is related to each metabolic pathway. MEL can also trigger differentiation in PC12 cells due to the increase in the GalCer content. In this specific case, the effects are transient, and the differentiated cells are unstable and tend to apoptosis. MEL-B can particularly maintain skin hydration and moisture due to their self-assembled structures that resemble the tissue cells. Moreover, MEL-B repair aquaporin expression in the HaCaT keratinocytes damaged with UVA irradiation, whereas MEL-C suppresses the expression of COX-2 protein in fibroblasts, indicating that these glycolipids activate the cellular antioxidant mechanism. Recent findings denoted the anti-melanogenic activity of MEL since they suppress tyrosinase enzyme at mRNA levels in B16 and NHMs cells. MEL act effectively on mammalian cells; however, there is no clear pattern of their metabolic effects. Also, gene expression levels seem to be related to two main factors: chemical structure and concentration. However, the specific signaling cascades that are induced by MEL remain inconclusive. Thus, further investigations are vital to understanding these mechanisms clearly. KEY POINTS: • The four MEL homologs promote different biological responses in mammalian cells. • MEL modifies the pattern of glycosphingolipids in the plasma membrane of tumor cells. • Activation/deactivation of phosphorylation of serine/threonine kinase proteins.

Glycosphingolipids
Anti-melanogenic activity
Cellular differentiation
Moisturizing action


Applying dental implant therapy in patients with oral lichen planus: a review of literature.

Abstract: Lichen planus (LP) is a violent, paranormal inflammatory disease that can affect the skin or any lining of the mucous membrane. LPs are a branch of immune-mediated inflammatory disease (IMID) that collaborates with the function and structure of the immune system that are precipitated through various etiological infectious agents. Oral lichen planus (OLP) is one of the most common kinds of IMID. These traumas might limit the normal life of patients and, in some cases, can be treated spontaneously. In patients who are affected by OLP, the dental clinicians must be capable of the proper diagnosis of the disorder. Dental implants are progressively applied for the treatment of partial or complete edentulism. Implant rehabilitation in OLP patients is one of the main challenges for patients and dental clinicians. There is not enough knowledge about this condition, and also medical documents are limited. In this study, by conducting a comprehensive review of literature, we tried to collect related data around the safety and success rate of implant rehabilitation in patients who suffer from OLP disorder. There proved to be no relation between implant survival rate and OLP diseases, but it is proven that some factors such as bone quality and fracture resistance, parafunctional habits, and resection of the marginal mandible could powerfully affect it. For evaluation of the advantages and disadvantages of applying implants in patients with OLP disorders, implementation of controlled studies is required.

Dental implants
Oral lichen planus
Lichen planus
Oral mucosa


Sweet Cherry (Prunus avium L.) PaPIP1;4 Is a Functional Aquaporin Upregulated by Pre-Harvest Calcium Treatments that Prevent Cracking.

Abstract: The involvement of aquaporins in rain-induced sweet cherry (Prunus avium L.) fruit cracking is an important research topic with potential agricultural applications. In the present study, we performed the functional characterization of PaPIP1;4, the most expressed aquaporin in sweet cherry fruit. Field experiments focused on the pre-harvest exogenous application to sweet cherry trees, cultivar Skeena, with a solution of 0.5% CaCl2, which is the most common treatment to prevent cracking. Results show that PaPIP1;4 was mostly expressed in the fruit peduncle, but its steady-state transcript levels were higher in fruits from CaCl2-treated plants than in controls. The transient expression of PaPIP1;4-GFP in tobacco epidermal cells and the overexpression of PaPIP1;4 in YSH1172 yeast mutation showed that PaPIP1;4 is a plasma membrane protein able to transport water and hydrogen peroxide. In this study, we characterized for the first time a plasma membrane sweet cherry aquaporin able to transport water and H2O2 that is upregulated by the pre-harvest exogenous application of CaCl2 supplements.

D000595:Amino Acid Sequence
D020346:Aquaporins
D002118:Calcium
D003001:Cloning, Molecular
D019295:Computational Biology
D005638:Fruit
D010940:Plant Proteins
D000068220:Prunus avium
D017422:Sequence Analysis, DNA

aquaporins
4
PaPIP1
calcium application
fruit-cracking
sweet-cherry


Clinical utility of late-night and post-overnight dexamethasone suppression salivary cortisone for the investigation of Cushing's syndrome.

Abstract:
INTRODUCTION
There is a pressing need to identify diagnostic testing for Cushing's syndrome that can be achieved with ease and at low cost. This study aimed to explore the usefulness of late-night and post-overnight 1-mg dexamethasone suppression salivary cortisone, as measured by liquid chromatography-tandem mass spectrometry, for investigation of hypercortisolism.

METHODS
Salivary cortisone data of subjects were investigated according to a pre-specified protocol. Subjects were classified as having 'hypercortisolism' or 'eucortisolism' on the basis of histological or biochemical criteria. Receiver operating characteristic curves were drawn to identify the cut-off values and study their performance characteristics. We measured 24-hour urinary free cortisol; late-night salivary cortisol and cortisone; and post-overnight 1-mg dexamethasone suppression serum cortisol, and salivary cortisol and cortisone. Saliva and urine samples were assayed by liquid chromatography-tandem mass spectrometry.

RESULTS
In this study, 21 subjects were classified as having hypercortisolism and 78 as having eucortisolism. A late-night salivary cortisone cut-off of 13.50 nmol/L had a sensitivity of 94.7% and a specificity of 87.2%. After taking 1-mg dexamethasone the night before, a salivary cortisol cut-off of 0.85 nmol/L had a sensitivity of 76.2% and a specificity of 96.2%; a salivary cortisone cut-off of 7.45 nmol/L had a sensitivity of 85.7% and a specificity of 94.9%, while a salivary cortisone cut-off of 3.25 nmol/L had a sensitivity of 95.2% and a specificity of 79.5%. Many salivary cortisol samples were below the detection limit of liquid chromatography-tandem mass spectrometry. In comparison with salivary cortisol, salivary cortisone had a better correlation with total serum cortisol and better diagnostic performance following dexamethasone suppression.

CONCLUSIONS
Both late-night and post-overnight dexamethasone suppression salivary cortisone levels are of diagnostic value in the investigation of hypercortisolism.

Ng|C M|CM|
Lam|T K|TK|
Au Yeung|Y C|YC|
Choi|C H|CH|
Iu|Y P|YP|
Shek|C C|CC|
Tiu|S C|SC|

Dexamethasone
Cortisone
Cushing syndrome


Prognostic significance of CD56 and CD7 in acute myeloid leukaemia and their outcome.

Abstract:
BACKGROUND
The expression of CD7 and CD56 in Acute Myeloid Leukaemia was considered to be a poor prognostic factor for overall survival, complete remission but the result were limited and more prognostic parameter need to study. The importance of validating new prognostic parameters in acute myeloid leukaemia was the reason to investigate the prognostic significance of CD7 and CD56.

MATERIAL AND METHODS
Study involving patients who had newly diagnosed AML. Imunophenotyping was carried out at diagnosis and after induction therapy also compared with molecular and cytogenetics studies. End points were the leukaemia free survival, relapse-free survival, and overall survival.

RESULT
All 87 patients that were included in the study were divided into 4 groups based on expression of CD56 and CD7 as Group 1 (CD7+, CD56+), group 2 (CD7-, CD56+), group 3 (CD7+, CD56-) and group 4 (CD7-, CD56-) and were compared clinically and immunophenotypically. The clinical parameters that were correlated were age, sex, LFS (leukaemia free survival), Overall survival (OS) and Relapse Free survival (RFS) and were followed up with MRD at day 30 along with Molecular abnormalities and cytogenetic karyotyping.

CONCLUSION
The study data suggest that prognostic significance of CD7 and CD56 expression in patients of acute myeloid leukaemia could be indicative of poor prognosis as it was also associated with the adverse prognostic parameter (Minimal Residual Disease, high risk, shorter overall survival).

Acute myeloid leukaemia
overall survival
leukaemia free survival
relapse free survival
minimal residual disease
leukaemia-associated immunophenotypes


Seizures Prior to Radiotherapy of Gliomas: Prevalence, Risk Factors and Survival Prognosis.

Abstract:
BACKGROUND/AIM
Seizures represent a common manifestation of gliomas. This study evaluated the prevalence of pre-radiotherapy seizures, potential risk factors and associations with survival.

PATIENTS AND METHODS
Eight factors were analyzed in 222 patients for associations with seizures including number, size and location of glioma, World Health Organization (WHO) grade, performance score, gender, age and upfront resection. These factors plus pre-radiotherapy symptoms and seizures were assessed for survival.

RESULTS
Prevalence of pre-radiotherapy seizures was 29.3%. A significant correlation was found for grade II (p=0.002), trends for age ≤59 years (p=0.123) and lack of upfront resection (p=0.113). Unifocal gliomas (p<0.001), grade II (p=0.045) and upfront resection (p<0.001) showed significant associations with survival (univariate analyses). A trend was found for seizures (p=0.075) and age ≤59 years (p=0.091). In the multivariate analysis, grade II (p=0.002) and upfront resection (p=0.004) maintained significance; unifocal gliomas showed a trend (p=0.062).

CONCLUSION
Pre-radiotherapy seizures appeared to be correlated with WHO grade, age and lack of upfront resection, and with better survival.

Witteler|Jaspar|J|
Kjaer|Troels W|TW|
Tvilsted|Soeren|S|
Schild|Steven E|SE|
Rades|Dirk|D|

seizures
Glioma
prevalence
risk factors
survival
radiation therapy


Identification of an Autophagy-Related Signature Predicting Overall Survival for Papillary Thyroid Carcinoma.

Abstract:
Background
Papillary thyroid carcinoma usually shows an excellent prognosis. However, its recurrence or persistence rate is high. In this study, we used bioinformatics to identify autophagy-related genes (ARGs) and establish a novel scoring system for papillary thyroid carcinoma.

Methods
We collected ARGs sequencing data of patients with papillary thyroid carcinoma from The Cancer Genome Atlas database. Differentially expressed ARGs were identified by the "Limma" package in R language. After univariate and multivariate Cox regression analysis, an ARG signature was developed. The established prognostic signature was evaluated by Kaplan-Meier curve and time-dependent receiver operating characteristic.

Results
A sum of 26 differentially expressed ARGs were identified. Gene set enrichment analysis revealed that several significantly oncological signatures were enriched, such as autophagy, p53 signaling pathway, apoptosis, human cytomegalovirus infection, and platinum drug resistance. After univariate and multivariate analysis, 3 ARGs (ITPR1, CCL2, and CDKN2A) were selected to develop autophagy-related signature. Patients with high risk had significantly shorter overall survival than those with low risk. The areas under the curve indicated that the signature showed good accuracy of prediction.

Conclusions
We established a novel scoring system based on 3 ARGs, which provides a promising tool for the development of personalized therapy.

papillary thyroid carcinoma
autophagy-related genes
prognostic signature
RNA-seq


Tribute to Dr Jacques Rogge: muscle activity and fatigue during hiking in Olympic dinghy sailing.

Abstract: 'A tribute to Dr J. Rogge' aims to systematically review muscle activity and muscle fatigue during sustained submaximal quasi-isometric knee extension exercise (hiking) related to Olympic dinghy sailing as a tribute to Dr Rogge's merits in the world of sports. Dr Jacques Rogge is not only the former President of the International Olympic Committee, he was also an orthopaedic surgeon and a keen sailor, competing at three Olympic Games. In 1972, in fulfilment of the requirements for the degree of Master in Sports Medicine, he was the first who studied a sailors' muscle activity by means of invasive needle electromyography (EMG) during a specific sailing technique (hiking) on a self-constructed sailing ergometer. Hiking is a bilateral and multi-joint submaximal quasi-isometric movement which dinghy sailors use to optimize boat speed and to prevent the boat from capsizing. Large stresses are generated in the anterior muscles that cross the knee and hip joint, mainly employing the quadriceps at an intensity of 30-40% maximal voluntary contraction (MVC), sometimes exceeding 100% MVC. Better sailing level is partially determined by a lower rate of neuromuscular fatigue during hiking and for ≈60% predicted by a higher maximal isometric quadriceps strength. Although useful in exercise testing, prediction of hiking endurance capacity based on the changes in surface EMG in thigh and trunk muscles during a hiking maintenance task is not reliable. This could probably be explained by the varying exercise intensity and joint angles, and the great number of muscles and joints involved in hiking. Highlights Dr Jacques Rogge, former president of the International Olympic Committee and Olympic Finn sailor, was the first to study muscle activity during sailing using invasive needle EMG to obtain his Master degree in Sports Medicine at the Ghent University. Hiking is a critical bilateral and multi-joint movement during dinghy racing, accounting for >60% of the total upwind leg time. Hiking generates large stresses in the anterior muscles that cross the knee and hip joint. Hiking is considered as a quasi-isometric bilateral knee extension exercise. Muscle activity measurements during sailing, recorded by means of EMG, show a mean contraction intensity of 30-40% maximal voluntary contraction with peaks exceeding 100%. Hiking performance is strongly related to the development of neuromuscular fatigue in the quadriceps muscle. Since maximal strength is an important determinant of neuromuscular fatigue during hiking, combined strength and endurance training should be incorporated in the training program of dinghy sailors.

Bourgois|Jan G|JG|
Dumortier|Jasmien|J|
Callewaert|Margot|M|
Celie|Bert|B|
Capelli|Carlo|C|
Sjøgaard|Gisela|G|
De Clercq|Dirk|D|
Boone|Jan|J|

muscle activity
hiking
Sailing
muscle fatigue
electromyography


Tilburg frailty indicator. German translation and psychometric testing.

Abstract:
BACKGROUND
The Tilburg frailty indicator (TFI) is a self-report measurement instrument which integrates the physical, psychological and social domains to assess frailty in older adults. The aim of this study was the adaptation of the TFI to a German version and testing of the psychometric properties.

MATERIAL AND METHODS
This study surveyed 210 individuals aged 64-91 years living at home. The mean age of participants was M = 75.3±5.7 years with 62 % females. The internal consistency was tested with Cronbach's alpha. The test-retest reliability was calculated after 20 weeks. The German TFI was validated using alternative measures for assessment of the quality of life, e.g. Eurohis-QoL-8 and short form health survey (SF-12), the patient health questionnaire (PHQ), the geriatric anxiety inventory short form (GAI-SF), the social support scale (F-Soz-U-K-14) and the resilience scale (RS-11).

RESULTS
The internal consistency was acceptable with a value for Cronbach's alpha of 0.67. The test-retest reliability was good after 5 months α = 0.87 (physical domain r = 0.85, psychological domain r = 0.75 and social domain r = 0.84). The inter-item correlations ranged between - 0.06 and 0.57. Correlations with alternative frailty measures showed good convergent and divergent validity.

CONCLUSION
This study showed acceptable psychometric properties of the German adaptation of the TFI which was found to be age and frailty sensitive. The results of the validity of the TFI support the three domains integrated in the frailty score. Further application and testing of the German TFI in primary care and clinical settings are suggested to consolidate the findings.

Freitag|S|S|
Schmidt|S|S|
Gobbens|R J J|RJ|

Tilburg frailty indicator
German translation
Psychometric properties
Reliability
Validity


Efficacy and safety of sorafenib for advanced renal cell carcinoma: real-world data of patients with renal impairment.

Abstract:
Background
We retrospectively analysed the efficacy and safety of sorafenib in patients with advanced renal cell carcinoma with renal impairment.

Methods
Patients were divided into two groups by an estimated glomerular filtration rate (eGFR) cut-off of 45 mL/min/1.73 m2. Background factors considered to affect prognosis were well balanced by propensity score matching between the groups. Demographics, dose modification, adverse events, tumour response, progression-free survival, and renal function (eGFR) were evaluated.

Results
Among 935 and 2008 patients with an eGFR of <45 and ≥45, respectively, 613 pairs were matched. The mean starting dose was significantly lower in patients with an eGFR of <45; however, the mean daily dose, median treatment duration, progression-free survival, and tumour response were similar between the groups. In terms of safety, no significant differences were found in serious adverse events, although cytopaenia (16.6% vs 10.6%) and renal dysfunction (4.4% vs 0.7%) were higher in patients with an eGFR of <45 than ≥45 in all adverse events. There were also no differences in dose modification, including dose reduction, dose interruption, and treatment discontinuation.

Conclusion
Throughout the 12-month observation period, sorafenib in patients with an eGFR of <45 and ≥45 showed similar safety and efficacy, and treatment was continued without affecting renal function.

Tatsugami|Katsunori|K| Oya|Mototsugu|M| Kabu|Koki|K| Akaza|Hideyuki|H|

sorafenib
real-world data
eGFR
propensity score matching
advanced RCC


Genre-typical narrative arcs in films are less appealing to lay audiences and professional film critics.

Abstract: People tend to like stimuli-ranging from human faces to text-that are prototypical, and thus easily processed. However, recent research has suggested that less typical stimuli may be preferred in creative contexts, such as fine art or music lyrics. In an archival sample of movie scripts, we tested whether genre-typicality predicted film ratings as a function of rater role (novice audience member or expert film critic). Genre-typicality was operationalized as the profile correlations between linguistic arcs (across five segments, or acts) for each script and within-genre averages. We predicted (1) that critics would prefer more disfluent (genre-atypical) films and general audiences would prefer fluent (genre-typical) films, and (2) that these differences would be most pronounced for genres expected to be more entertaining (e.g., action/adventure) than challenging (e.g., tragedy). Partly consistent with our hypotheses, the results showed that critics gave higher ratings to action/adventure films with less typical positive emotion arcs. However, regardless of audience-member or professional-critic status, higher ratings were attributed to films that were more genre-atypical (or disfluent), in terms of analytic thinking, narrative action, and emotional tone, across all genres except family/kids films. Such findings support the growing literature on the appeal of disfluency in the arts and have relevance for researchers in psychology and computer science who are interested in computational linguistic approaches to attitudes, film, and literature.

Film
Prototypicality
Genre
Computerized text analysis
Language


Antifungal prophylaxis with anidulafungin to minimize drug interactions with an antiepileptic treatment in a hematopoietic stem cell transplant recipient.

Abstract:
WHAT IS KNOWN AND OBJECTIVE
Invasive fungal infections are a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). This provides a clear rationale for antifungal prophylaxis in this population. A concern is the potential for drug interactions, given that most of antifungals are metabolized through the P450 cytochrome system.

CASE SUMMARY
We present a case of a 33-year-old woman, with a past history of high-risk epilepsy, who underwent allogeneic HSCT for a myelodysplastic syndrome. Anidulafungin was successfully used as antifungal prophylaxis to minimize drug interactions with her antiepileptic treatment.

WHAT IS NEW AND CONCLUSION
This is the first reported case of antifungal prophylaxis with this echinocandin in HSCT. Anidulafungin may be an option in transplant recipients with multiple risk factors for drug interactions.

Feliu|J|J|
Del Pozo|J L|JL|
Azanza|J R|JR|
García-Muñoz|R|R|
Zabalza|A|A|
Gorosquieta|A|A|
Pérez-Equiza|E|E|
Olavarría|E|E|

antifungal prophylaxis
anidulafungin
drug interactions
hematopoietic stem cell transplantation


Exploration of joint redundancy but not task space variability facilitates supervised motor learning.

Abstract: The number of joints and muscles in a human arm is more than what is required for reaching to a desired point in 3D space. Although previous studies have emphasized how such redundancy and the associated flexibility may play an important role in path planning, control of noise, and optimization of motion, whether and how redundancy might promote motor learning has not been investigated. In this work, we quantify redundancy space and investigate its significance and effect on motor learning. We propose that a larger redundancy space leads to faster learning across subjects. We observed this pattern in subjects learning novel kinematics (visuomotor adaptation) and dynamics (force-field adaptation). Interestingly, we also observed differences in the redundancy space between the dominant hand and nondominant hand that explained differences in the learning of dynamics. Taken together, these results provide support for the hypothesis that redundancy aids in motor learning and that the redundant component of motor variability is not noise.

Singh|Puneet|P| Jana|Sumitash|S| Ghosal|Ashitava|A| Murthy|Aditya|A|

reaching
minimum-intervention principle
motor control
motor noise
supervised learning


Multi-valvular infective endocarditis from Gemella morbillorum.

Abstract: Gemella morbillorum is increasingly implicated in infectious endocarditis. Our patient presented with anaemia and renal failure with evidence of infarcts and embolic disease. He was found to have endocarditis with an organism that could not speciate with standard culture methods requiring matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) for identification and susceptibilities. While involvement of mitral and aortic valves can be expected with Gemella, he had rare involvement of the pulmonic valve in a structurally normal heart. Although bacteriological cure was achieved, due to the locally destructive nature of Gemella, he ultimately required valve replacements for heart failure resolution. Workup for commonly implicated pathologies associated with G. morbillorum led to suspicion of gastrointestinal malignancy with findings of occult bleeding prompting an ongoing evaluation. With improved access to advanced diagnostics, G. morbillorum has been increasingly identified in infectious endocarditis. Given its destructive nature, it is important for clinicians to consider this organism is difficult to identify isolates.

heart failure
drugs: infectious diseases
infectious diseases
medical management
valvar diseases


Optimization of a Labeling and Kit Preparation Method for Ga-68 Labeled DOTATATE, Using Cation Exchange Resin Purified Ga-68 Eluates Obtained from a Tin Dioxide 68Ge/68Ga Generator.

Abstract:
PURPOSE
The aim of this study was to optimize a radiolabeling method using cationic processed Ga-68 eluates from a SnO2-based 68Ge/68Ga generator, followed by the development of DOTA-Tyr3-Thre8-octreotide (DOTATATE) kits.

PROCEDURES
Diluted generator eluates were adsorbed on a SCX resin and desorbed with acidified 5 M NaCl solution. Optimized labeling conditions were determined by variation of pH, using 35 μg DOTATATE and sodium acetate buffer. DOTATATE kits were developed based on optimized radiolabeling conditions, were labeled, and evaluated.

RESULTS
Optimized labeling conditions resulted in a radiolabeling efficiency of around 99 % and radiochemical yield of almost 85 %. Different kit preparation methods did not significantly influence the radiolabeling results. Kits were found to be stable over 3 months.

CONCLUSION
A labeling method using SCX-processed Ga-68 eluates was optimized. DOTATATE kits specifically for these SCX-processed Ga-68 eluates were successfully formulated. A post-labeling Sep-Pak C18 purification should be optional.

Kits
DOTATATE
Cation exchange resin
Ga-68 eluate
SnO2-based 68Ge/68Ga generator
Radiolabeling efficiency
Radiochemical yields


The role of the JAK/STAT signal pathway in rheumatoid arthritis.

Abstract: Proinflammatory cytokine activation of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signal transduction pathway is a critical event in the pathogenesis and progression of rheumatoid arthritis. Under normal conditions, JAK/STAT signaling reflects the influence of negative regulators of JAK/STAT, exemplified by the suppressor of cytokine signaling and protein inhibitor of activated STAT. However, in rheumatoid arthritis (RA) both of these regulators are dysfunctional. Thus, continuous activation of JAK/STAT signaling in RA synovial joints results in the elevated level of matrix metalloproteinase gene expression, increased frequency of apoptotic chondrocytes and most prominently 'apoptosis resistance' in the inflamed synovial tissue. Tofacitinib, a JAK small molecule inhibitor, with selectivity for JAK2/JAK3 was approved by the United States Food and Drug Administration (US FDA) for the therapy of RA. Importantly, tofacitinib has demonstrated significant clinical efficacy for RA in the post-US FDA-approval surveillance period. Of note, the success of tofacitinib has spurred the development of JAK1, JAK2 and other JAK3-selective small molecule inhibitors, some of which have also entered the clinical setting, whereas other JAK inhibitors are currently being evaluated in RA clinical trials.


Computer and Experimental Simulation of Alloxazine Synthesis from Gamma Irradiation of Amino Acids on Iceland Spar: A Prebiotic Chemistry Perspective.

Abstract: On ancient Earth, environmental conditions favored prebiotic chemical reactions. In the Archean, some molecules with conjugated rings might have been synthesized, displaying structural stability in the Archean in the presence of ionizing radiation and hydration-dehydration events. Additionally, it is suggested that on ancient Earth, calcite was a common mineral promoting organic compound synthesis. In the present work a study of the interaction of amino acid mixtures with the (104) surface of calcite is presented. Our preliminary results show the abiotic synthesis of alloxazine (a flavin with relevant photochemical properties). Computer simulations were performed in HyperChem 8.0.1. by means of MM+ molecular mechanics and PM3 semi-empirical methods, in 27 possible amino acid trimers of alanine, glycine and lysine. Alloxazine formation is possible by the gamma irradiation of amino acids. The computer simulations show that trimers GGG and GGA promote the further transformation from diketopiperazines (DKP's) and KGK to alloxazine. The computer simulations with free radicals are not stable when alloxazine is interacting with the calcite surface. Experiments in anoxygenic environments with hydration-dehydration events in gamma irradiated samples allow the abiotic formation of flavins, DKP's and a heterocycle compound with possible relevance in prebiotic chemistry.

Mendoza-Torres|Ernesto|E| Cruz-Catañeda|Jorge|J| Negrón-Mendoza|Alicia|A| Heredia|Alejandro|A|0000-0002-3887-610X

D000596:Amino Acids
D003198:Computer Simulation
D018534:Earth, Planet
D019418:Evolution, Chemical
D005415:Flavins
D005720:Gamma Rays
D007055:Iceland
D008956:Models, Chemical
D000069497:Origin of Life

Alloxazine
MM+ molecular mechanics
PM3 semi-empirical method
Calcite mineral
Mineral surface
Prebiotic synthesis


Safety and tolerability of anifrolumab, a monoclonal antibody targeting type I interferon receptor, in Japanese patients with systemic lupus erythematosus: A multicenter, phase 2, open-label study.

Abstract: Objectives: This study evaluated the safety and tolerability of anifrolumab, a monoclonal antibody targeting the type I interferon (IFN) receptor, in Japanese patients with moderate-to-severe systemic lupus erythematosus (SLE).Methods: In this open-label, phase 2, dose-escalation study, patients received intravenous (IV) anifrolumab 100, 300, or 1000 mg every 4 weeks from days 29 to 337 (Stage 1). Patients who completed Stage 1 continued anifrolumab 300 mg every 4 weeks for 156 weeks (Stage 2). The primary objective was to evaluate the safety of anifrolumab for 48 weeks (Stage 1) and 156 weeks (Stage 2). The pharmacokinetics and pharmacodynamics of anifrolumab were also assessed.Results: Of 20 patients enrolled in Stage 1, 17 received IV anifrolumab 100 mg (n = 6), 300 mg (n = 5), or 1000 mg (n = 6). Adverse events (AE) and serious AE (SAE) incidences were similar between dose cohorts. SAEs occurred in 41% (Stage 1) and 33% (Stage 2) of patients; AEs leading to discontinuation occurred in 24% (Stage 1) and 22% (Stage 2) of patients. Anifrolumab had non-linear pharmacokinetics after the first and last dose and dose-dependently suppressed the IFN gene signature.Conclusion: Anifrolumab was well tolerated among Japanese patients with moderate-to-severe SLE.

Tanaka|Yoshiya|Y| Takeuchi|Tsutomu|T| Okada|Masato|M| Ishii|Tomonori|T| Nakajima|Hiroshi|H| Kawai|Shinichi|S| Nagashima|Takao|T| Hayashi|Nobuya|N| Wang|Liangwei|L| Tummala|Raj|R|

safety
Anifrolumab
systemic lupus erythematosus
intravenous
dose escalation


Measuring physical activity in pregnancy: a comparison of accelerometry and self-completion questionnaires in overweight and obese women.

Abstract:
OBJECTIVES
Increased physical activity in pregnancy may reduce the risk of gestational diabetes and pre-eclampsia, which occur more commonly in overweight and obese women. There is limited assessment of physical activity questionnaires in pregnancy. This study compares self-reported physical activity using two questionnaire methods with objectively recorded physical activity using accelerometry in overweight and obese pregnant women.

STUDY DESIGN
59 women with booking BMI≥25 kg/m(2) completed the Recent Physical Activity Questionnaire (RPAQ) and Australian Women's Activity Survey (AWAS) or recorded at least 3 days of accelerometry at median 12 weeks' gestation. Accelerometer thresholds of 100 counts/min and 1952 counts/min were used to define light and moderate or vigorous physical activity (MVPA) respectively.

RESULTS
48% of women were in their first pregnancy and 41% were obese. Median daily self-reported MVPA was significantly higher for both AWAS (127 min, p<0.001) and RPAQ (81 min, p<0.001) than that recorded by accelerometer (35 min). There was low or moderate correlation between questionnaire and accelerometer estimates of total active time (AWAS ρ=0.36, p=0.008; RPAQ ρ=0.53, p<0.001) but no significant correlation between estimates of time spent in MVPA.

CONCLUSIONS
These self-report questionnaires over-estimated MVPA and showed poor ability to discriminate women on the basis of MVPA. Accelerometry measurement was feasible and acceptable. Objective methods should be used where possible in studies measuring physical activity in pregnancy. Questionnaires remain valuable to define types of activity.

Bell|Ruth|R|
Tennant|Peter W G|PW|
McParlin|Catherine|C|
Pearce|Mark S|MS|
Adamson|Ashley J|AJ|
Rankin|Judith|J|
Robson|Stephen C|SC|

International Physical Activity Questionnaire

P P P P P P P P P P P U U U M U U U U U U M U U U P M


The effect of a statewide COVID-19 shelter-in-place order on shoulder arthroplasty for proximal humerus fracture volume and length of stay.

Abstract:
Background
Although the COVID-19 pandemic has disrupted elective shoulder arthroplasty throughput, traumatic shoulder arthroplasty procedures are less apt to be postponed. We sought to evaluate shoulder arthroplasty utilization for fracture during the COVID-19 pandemic and California's associated shelter-in-place order compared to historical controls.

Methods
We conducted a cohort study with historical controls, identifying patients who underwent shoulder arthroplasty for proximal humerus fracture in California using our integrated electronic health record. The time period of interest was following the implementation of the statewide shelter-in-place order: March 19, 2020-May 31, 2020. This was compared to three historical periods: January 1, 2020-March 18, 2020, March 18, 2019-May 31, 2019, and January 1, 2019-March 18, 2019. Procedure volume, patient characteristics, in-hospital length of stay, and 30-day events (emergency department visit, readmission, infection, pneumonia, and death) were reported. Changes over time were analyzed using linear regression adjusted for usual seasonal and yearly changes and age, sex, comorbidities, and postadmission factors.

Results
Surgical volume dropped from an average of 4.4, 5.2, and 2.6 surgeries per week in the historical time periods, respectively, to 2.4 surgeries per week after shelter-in-place. While no more than 30% of all shoulder arthroplasty procedures performed during any given week were for fracture during the historical time periods, arthroplasties performed for fracture was the overwhelming primary indication immediately after the shelter-in-place order. More patients were discharged the day of surgery (+33.2%, P = .019) after the shelter-in-place order, but we did not observe a change in any of the corresponding 30-day events.

Conclusions
The volume of shoulder arthroplasty for fracture dropped during the time of COVID-19. The reduction in volume could be due to less shoulder trauma due to shelter-in-place or a change in the indications for arthroplasty given the perceived higher risks associated with intubation and surgical care. We noted more patients undergoing shoulder arthroplasty for fracture were safely discharged on the day of surgery, suggesting this may be a safe practice that can be adopted moving forward.

Level of Evidence
Level III; Retrospective Case-control Comparative Study.

Dillon|Mark T|MT|
Chan|Priscilla H|PH|
Prentice|Heather A|HA|
Royse|Kathryn E|KE|
Paxton|Elizabeth W|EW|
Okike|Kanu|K|
Khatod|Monti|M|
Navarro|Ronald A|RA|

COVID-19
Shoulder arthroplasty
Proximal humerus fracture
Volume
Same-day discharge


Willingness to use smartphone apps for lifestyle management among patients with schizophrenia.

Abstract: Mobile technology is a popular intervention mode for patients with schizophrenia because of its accessibility and functionality. We examined patients' willingness to use smartphone apps for lifestyle management and its effect on self-reported lifestyle habits. Five hundred fifty-five inpatients from various mental health institutions participated. Willingness to use smartphone apps was associated with age, education, income, device type, and body mass index. Positive opinions on smartphone app use were significantly associated with willingness to use apps, which was significantly associated with dietary and living habits. Thus, improving willingness to use apps can help patients improve their lifestyle, potentially preventing relapse.

Lee|Kyunghee|K|
Bejerano|Ivy Lynne|IL|
Han|Mihwa|M|
Choi|Hyun Seok|HS|

D010342:Patient Acceptance of Health Care

Smartphone
Schizophrenia
Technology
Mobile health


First 2 Years of Experience of "Residential Care" at "Sakalawara Rehabilitation Services," National Institute of Mental Health and Neurosciences, Bengaluru, India.

Abstract:
Introduction
There is an unmet need for continuity-of-care is well known for those with severe mental disorders (SMDs) after acute care at hospitals in India. The "Sakalawara Rehabilitation Services (SRS)" functioned from March 2014 at "Sakalawara Community Mental Health Centre" (SCMHC) of "National Institute of Mental Health and Neurosciences," Bengaluru, India in the concepts of residential care (half-way-home) with the aim to develop a replicable model.

Aim
To review the inpatient records after the initial 2 years of experience in residential care at SCMHC.

Methodology
Retrospective file review of inpatients at SCMHC from March 2014 to March 2016 in a semi-structured proforma designed for the study. Ethical committee of NIMHANS Bengaluru has approved the study.

Results
The total number of inpatients during this period was 85. It was found that Schizophrenia spectrum disorders were the most common diagnosis among these patients. The activity of daily living and psycho-education were the most common individual interventions. The majority of families underwent structured family psycho-educational interventions. This review also demonstrated the feasibility of tele-aftercare in continuity of care after discharge of patients.

Conclusion
SRS kind of residential set-up is feasible and demonstrated effectiveness in maintaining continuity of care of SMDs. There is a need for better structured and customized interventions. There is further a scope for tele (video) aftercare for those with SMDs.

Manjunatha|Narayana|N|
Agarwal|Preeti Pansari|PP|
Shashidhara|Harihara N|HN|
Palakode|Mohan|M|
Raj|E Aravind|EA|
Mary Kapanee|Aruna Rose|AR|
Nattala|Prashanthi|P|
Kumar|C Naveen|CN|
Sudhir|Paulomi|P|
Thirthalli|Jagadisha|J|
Bharath|Srikala|S|
Sekar|Kasi|K|
Varghese|Mathew|M|

residential care
rehabilitation services
severe mental disorders
continuity of care
Aftercare


QSAR Studies, Synthesis and Antibacterial Assessment of New Inhibitors Against Multidrug-Resistant Mycobacterium tuberculosis.

Abstract:
BACKGROUND
The increasing rate of appearance of multidrug-resistant strains of Mycobacterium tuberculosis (MDR-TB) is a serious problem at the present time. MDR-TB forms do not respond to the standard treatment with the commonly used drugs and can take some years or more to treat with drugs that are less potent, more toxic and much more expensive.

OBJECTIVE
The goal of this work is to identify the novel effective drug candidates active against MDR-TB strains through the use of methods of cheminformatics and computeraided drug design.

METHODS
This paper describes Quantitative Structure-Activity Relationships (QSAR) studies using Artificial Neural Networks, synthesis and in vitro antitubercular activity of several potent compounds against H37Rv and resistant Mycobacterium tuberculosis (Mtb) strains.

RESULTS
Eight QSAR models were built using various types of descriptors with four publicly available structurally diverse datasets, including recent data from PubChem and ChEMBL. The predictive power of the obtained QSAR models was evaluated with a cross-validation procedure, giving a q2=0.74-0.78 for regression models and overall accuracy 78.9-94.4% for classification models. The external test sets were predicted with accuracies in the range of 84.1-95.0% (for the active/inactive classifications) and q2=0.80- 0.83 for regressions. The 15 synthesized compounds showed inhibitory activity against H37Rv strain whereas the compounds 1-7 were also active against resistant Mtb strain (resistant to isoniazid and rifampicin).

CONCLUSION
The results indicated that compounds 1-7 could serve as promising leads for further optimization as novel antibacterial inhibitors, in particular, for the treatment of drug resistance of Mtb forms.

Kovalishyn|Vasyl|V| Brovarets|Volodymyr|V| Blagodatnyi|Volodymyr|V| Kopernyk|Iryna|I| Hodyna|Diana|D| Chumachenko|Svitlana|S| Shablykin|Oleg|O| Kozachenko|Oleksandr|O| Vovk|Myhailo|M| Barus|Marianna|M| Bratenko|Myhailo|M| Metelytsia|Larysa|L|

QSAR
Mycobacterium tuberculosis
Drug design
Artificial Neural Networks


In vitro efficacy of a gene-activated nerve guidance conduit incorporating non-viral PEI-pDNA nanoparticles carrying genes encoding for NGF, GDNF and c-Jun.

Abstract:
Despite the success of tissue engineered nerve guidance conduits (NGCs) for the treatment of small peripheral nerve injuries, autografts remain the clinical gold standard for larger injuries. The delivery of neurotrophic factors from conduits might enhance repair for more effective treatment of larger injuries but the efficacy of such systems is dependent on a safe, effective platform for controlled and localised therapeutic delivery. Gene therapy might offer an innovative approach to control the timing, release and level of neurotrophic factor production by directing cells to transiently sustain therapeutic protein production in situ. In this study, a gene-activated NGC was developed by incorporating non-viral polyethyleneimine-plasmid DNA (PEI-pDNA) nanoparticles (N/P 7 ratio, 2 μg dose) with the pDNA encoding for nerve growth factor (NGF), glial derived neurotrophic factor (GDNF) or the transcription factor c-Jun. The physicochemical properties of PEI-pDNA nanoparticles, morphology, size and charge, were shown to be suitable for gene delivery and demonstrated high Schwann cell transfection efficiency (60 ± 13%) in vitro. While all three genes showed therapeutic potential in terms of enhancing neurotrophic cytokine production while promoting neurite outgrowth, delivery of the gene encoding for c-Jun showed the greatest capacity to enhance regenerative cellular processes in vitro. Ultimately, this gene-activated NGC construct was shown to be capable of transfecting both Schwann cells (S42 cells) and neuronal cells (PC12 and dorsal root ganglia) in vitro, demonstrating potential for future therapeutic applications in vivo.

STATEMENT OF SIGNIFICANCE
The basic requirements of biomaterial-based nerve guidance conduits have now been well established and include being able to bridge a nerve injury to support macroscopic guidance between nerve stumps, while being strong enough to withstand longitudinal tension and circumferential compression, in addition to being mechanically sound to facilitate surgical handling and implantation. While meeting these criteria, conduits are still limited to the treatment of small defects clinically and might benefit from additional biochemical stimuli to enhance repair for the effective treatment of larger injuries. In this study, a gene activated conduit was successfully developed by incorporating non-viral nanoparticles capable of efficient Schwann cell and neuronal cell transfection with therapeutic genes in vitro, which showed potential to enhance repair in future applications particularly when taking advantage of the transcription factor c-Jun. This innovative approach may provide an alternative to conduits used as platforms for the delivery neurotrophic factors or genetically modified cells (viral gene therapy), and a potential solution for the unmet clinical need to repair large peripheral nerve injury effectively.

Lackington|William A|WA|
Raftery|Rosanne M|RM|
O'Brien|Fergal J|FJ|

D051100:Glial Cell Line-Derived Neurotrophic Factor

Nerve guidance conduit
Non-viral gene therapy
Peripheral nerve repair


High risk HPV testing in the triage of repeat ASC-US and LSIL.

Abstract:
INTRODUCTION
The purpose of this study was to evaluate the real-life performance of high-risk (HR) HPV testing in the triage of repeat atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesions (LSIL).

MATERIAL AND METHODS
In 2004-2012, 127 women with repeat ASC-US and 118 women with LSIL were triaged with HPV testing using either a Hybrid Capture 2(®) or Abbott RealTime(®) HR-HPV test. The patient charts were retrospectively reviewed for performance of the tests.

RESULTS
In the repeat ASC-US group, 40.9% of the women were positive for HR-HPV. The prevalence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was 8.7%. The sensitivity of the HR-HPV testing for detection of CIN2+ was 90.9% (95% Cl 58.7-98.5%), with a specificity of 63.8% (95%CI 54.4-72.5%). In women ≥30 years old, the specificity was 70.4%, whereas in younger women it was only 27.8%. The negative predictive value to predict CIN3 was 100% (95% CI 95.2-100.0%). Of the women with LSIL, 68.6% were positive for HR-HPV and the prevalence of CIN2+ was 14.4%. The sensitivity of HR-HPV testing for detection of CIN2+ was 94.1% (95% CI 71.2-99.0%), and the specificity 35.6% (95% CI 26.4-45.8%), respectively. The negative predictive value to predict CIN3 was 100% (95% CI 90.4-100.0%).

CONCLUSION
HR-HPV testing seems to be beneficial in the triage of repeat ASC-US in women ≥30 years old, but a high prevalence of HR-HPV infection combined with poor specificity limit the use of HPV testing in the case of LSIL.

Veijalainen|Olga|O| Tuomisaari|Sanna|S| Luukkaala|Tiina|T| Mäenpää|Johanna|J|

D065309:Atypical Squamous Cells of the Cervix

D065310:Squamous Intraepithelial Lesions of the Cervix

ASC-US
LSIL
squamous intraepithelial lesions
CIN
HP triage
cervical cancer
cytology
human papillomavirus


Early Vertebroplasty versus Delayed Vertebroplasty for Acute Osteoporotic Compression Fracture : Are the Results of the Two Surgical Strategies the Same?

Abstract:
OBJECTIVE
In Korea, early vertebroplasty (EVP) or delayed vertebroplasty (DVP, which is performed at least 2 weeks after diagnosis) were performed for the treatment of acute osteoporotic compression fracture (OCF) of the spine. The present study compared the outcomes of two surgical strategies for the treatment of single-level acute OCF in the thoracolumbar junction (T12-L2).

METHODS
From 2004 to 2010, 23 patients were allocated to the EVP group (EVPG) and 27 patients to the DVP group (DVPG). Overall mean age was 68.3±7.9 and minimum follow-up period was 1.0 year. Retrospective study of clinical and radiological results was conducted.

RESULTS
No significant differences in baseline characteristics were observed between the two groups. As expected, mean duration from onset to vertebroplasty and mean duration of hospital stay were significantly longer in the DVPG (17.1±2.1 and 17.5±4.2) than in the EVPG (3.8±3.3 and 10.8±5.1, p=0.001). Final clinical outcome including visual analogue scale (VAS), Oswestry Disability Index, and Odom's criteria did not differ between the two groups. However, immediate improvement of the VAS after vertebroplasty was greater in the EVPG (5.1±1.3) than in the DVPG (4.0±1.0, p=0.002). The proportion of cement leakage was lower in the EVPG (30.4%) than in the DVPG (59.3%, p=0.039). In addition, semiquantitative grade of cement interdigitation was significantly more favorable in the EVPG than in the DVPG (p=0.003). Final vertebral body collapse and segmental kyphosis did not differ significantly between the two groups.

CONCLUSION
Our findings suggest that EVP achieves a better immediate surgical effect with more favorable cost-effectiveness.

Son|Seong|S| Lee|Sang-Gu|SG| Kim|Woo-Kyung|WK| Park|Chan-Woo|CW| Yoo|Chan-Jong|CJ|

Vertebroplasty
Compression fracture
Spine
Osteoporosis


In Search of Model Ecological Systems for Understanding Specialized Metabolism.

Abstract: Microbes occupy diverse habitats, forming interconnected, dynamic communities. Elucidating the principles of microbial community function is a grand challenge for microbiology, and it will entail experiments that engage microbiomes across multiple levels of complexity. For example, community-level hypotheses often require testing at the mechanistic and/or genetic levels, while mechanistic relationships require community-level evaluation to understand their importance in context. In this Perspective, we articulate the need for model microbiome systems that enable experimentation in both community and reductionist frameworks, with an emphasis on understanding the role of specialized metabolites in microbial communities. We consider essential criteria for developing such model microbiome systems and discuss potential future models that address the ecology of specialized metabolism.

specialized metabolism
microbiome
chemical ecology
interspecies interactions
microbial ecology
model systems


One-year outcomes and secondary prevention in patients after acute minor stroke: results from the China National Stroke Registry.

Abstract:
OBJECTIVES
Limited data are available on secondary preventive therapy use and patient outcomes after acute minor ischemic stroke in China. This study investigated secondary prevention strategies and outcomes up to 1 year after minor ischemic stroke.

METHODS
Patients from the China National Stroke Registry experienced a minor ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score ≤5) and admitted to hospital within 24 hours of symptom onset were included. One-year rates of recurrent stroke, stroke-related disability, and all-cause death were evaluated. Risk factors associated with 1-year stroke recurrence were examined in a multivariate model. The secondary prevention strategies in the acute phase were evaluated as combination of secondary prevention medication classes and the medications used in 1 year follow-up were examined.

RESULTS
The study included 1913 patients who had experienced acute minor ischemic stroke (mean age: 65.1 years; 67.3% men; mean NIHSS score: 2.5). Rates of recurrent stroke, disability, and death were 13.2, 17.0, and 6.3% at 1 year, respectively. History of hypertension, ischemic stroke, transient ischemic attack, and atrial fibrillation were independent predictors of one-year stroke recurrence. Rate of 1 year all-cause death in patients with triple combined therapy in acute phase was 4.1%, whereas in patients with none was 14.5%. At 1 year, only half patients continued the secondary prevention medications.

CONCLUSIONS
Outcomes in individuals in China who had experienced acute minor stroke were unfavorable, underscoring the importance of early, sustained preventive therapy in this patient population. Combination of secondary prevention medication classes was associated with a lower risk of death.

Tan|Ying|Y| Pan|Yuesong|Y| Liu|Liping|L| Wang|Yilong|Y| Zhao|Xingquan|X| Wang|Yongjun|Y| |||

outcomes
secondary prevention
Minor ischemic stroke
stroke recurrence
acute phase


Functionalization of [60]Fullerene through photochemical reaction for fulleropyrrolidine nanovectors synthesis: Experimental and theoretical approaches.

Abstract: To develop novel carbon-based nanocarriers, we proposed grafting on the [60]Fullerene (C60) biologically active molecules. In this process, the formed derivatives described another approach to use photo-cycloaddition reactions for developing the third nanovector generation. As a result, the photoexcitation of C60 and azomethine ylide (AZMYtrp), with visible light, was considered as the most promising pathway to synthesize fulleropyrrolidine (FPL). After complexation with sodium cation (Na+), the error masses of FPL mono-, bis- and tris-adducts were remarkably decreased to -85.93 %, -53.99 % and -99.42 %, respectively. The formed FPL-Na+ complexes presented a significant capacity for trapping OH and OOH free radicals. In fact, their antiradical properties increased when Na+ was bonded with FPL-Na+ mono-adduct carbonyl oxygens. Comparing FPL bis-adducts regioisomers, under three different AZMYtrp forms, the neutral and anionic-neutral forms of FPL cis1 isomer were considered as the most reactive bis-nanocarriers with mole fractions of about 61 % and 46 %, respectively, in contrast to FPL-Na+, when the mixture was dominated by the anionic-neutral form of cis2 isomer with 50.34 %.

[60]Fullerene
Fulleropyrrolidine
Free radicals
DFT calculation
Nnanocarrier