Delayed Visual Loss and Its Surgical Rescue Following Extracranial-Intracranial Arterial Bypass and Native Internal Carotid Artery Sacrifice.

Abstract:
BACKGROUND
High-flow extracranial-intracranial (EC-IC) bypass followed by sacrifice of the native internal carotid artery (ICA) is a recognized treatment option for giant ICA aneurysm and skull base tumor involving the ICA. Distal clipping at the supraclinoid portion of the ICA is technically straightforward, but it can potentially compromise ophthalmic artery (OA) perfusion. Because of the extensive EC-IC anastomoses with the OA, visual symptoms are fortunately uncommon. We report a patient who developed complete blindness after distal trapping of the supraclinoid ICA; it was reversed after emergency clip removal.

CASE DESCRIPTION
Our patient is a 47-year-old man with recurrent nasopharyngeal carcinoma in close proximity to the left petrosal ICA. The first stage of the procedure involved an EC-IC bypass using radial artery graft, followed by a second stage with combined craniofacial excision. Trapping of the native ICA was achieved using a permanent aneurysm clip placed at the supraclinoid ICA distal to the origin of the OA. He complained of a new onset of complete left eye visual loss approximately 6 hours after the distal aneurysm clip was applied. He was immediately sent to the operating theatre for the removal of the supraclinoid aneurysm clip. On the next day, his vision improved and left pupil became reactive again.

DISCUSSION
OA flow following ICA trapping is complicated and precarious. Delayed onset of visual loss is possible. Prompt action by direct exploration and clip removal is needed and can be effective in reversing blindness.

Li|Lai-Fung|LF|
Leung|Gilberto Ka-Kit|GK|
Lui|Wai-Man|WM|

Blindness
Cerebral revascularization
Ischemic
Optic neuropathy


Identifying the neural substrates of intrinsic motivation during task performance.

Abstract: Intrinsic motivation is the inherent tendency to seek out novelty and challenge, to explore and investigate, and to stretch and extend one's capacities. When people imagine performing intrinsically motivating tasks, they show heightened anterior insular cortex (AIC) activity. To fully explain the neural system of intrinsic motivation, however, requires assessing neural activity while people actually perform intrinsically motivating tasks (i.e., while answering curiosity-inducing questions or solving competence-enabling anagrams). Using event-related functional magnetic resonance imaging, we found that the neural system of intrinsic motivation involves not only AIC activity, but also striatum activity and, further, AIC-striatum functional interactions. These findings suggest that subjective feelings of intrinsic satisfaction (associated with AIC activations), reward processing (associated with striatum activations), and their interactions underlie the actual experience of intrinsic motivation. These neural findings are consistent with the conceptualization of intrinsic motivation as the pursuit and satisfaction of subjective feelings (interest and enjoyment) as intrinsic rewards.

Functional magnetic resonance imaging (fMRI)


Sex Differences in the Association Between Measures of General and Central Adiposity and the Risk of Myocardial Infarction: Results From the UK Biobank.

Abstract:
BACKGROUND
There are substantial differences in the distribution of adipose tissue between women and men. We assessed the sex-specific relationships and their differences between measures of general and central adiposity and the risk of incident myocardial infarction (MI).

METHODS AND RESULTS
Between 2006 and 2010, the UK Biobank recruited over 500 000 participants aged 40 to 69 years across the United Kingdom. During 7 years of follow-up, 5710 cases of MI (28% women) were recorded among 265 988 women and 213 622 men without a history of cardiovascular disease at baseline. Cox regression models yielded adjusted hazard ratios for MI associated with body mass index, waist circumference, waist-to-hip ratio, and waist-to-height ratio. There was an approximate log-linear relationship between measures of general and central adiposity and the risk of MI in both sexes. A 1-SD higher in body mass index, waist circumference, waist-to-hip ratio, and waist-to-height ratio, respectively, were associated with hazard ratios (confidence intervals) for MI of 1.22 (1.17; 1.28), 1.35 (1.28; 1.42), 1.49 (1.39; 1.59), and 1.34 (1.27; 1.40) in women and of 1.28 (1.23; 1.32), 1.28 (1.23; 1.33), 1.36 (1.30; 1.43), and 1.33 (1.28; 1.38) in men. The corresponding women-to-men ratios of hazard ratios were 0.96 (0.91; 1.02), 1.07 (1.00; 1.14), 1.15 (1.06; 1.24), and 1.03 (0.97; 1.09).

CONCLUSIONS
Although general and central adiposity measures each have profound deleterious effects on the risk of MI in both sexes, a higher waist circumference and waist-to-hip ratio conferred a greater excess risk of MI in women than in men. Waist-to-hip ratio was more strongly associated with the risk of MI than body mass index in both sexes, especially in women.

Peters|Sanne A E|SAE|
Bots|Sophie H|SH|
Woodward|Mark|M|

myocardial infarction
adipose tissue
women
men


Discovery of novel simplified isoxazole derivatives of sampangine as potent anti-cryptococcal agents.

Abstract: Cryptococcus neoformans is the leading cause of cryptococcal meningitis, which is associated with high mortality due to lack of effective treatment. Herein a series of tricyclic isoxazole derivatives with excellent anti-cryptococcal activities were identified by structural simplification and scaffold hopping of antifungal natural product sampangine. Particularly, compound 8a showed promising features as an anti-cryptococcal lead compound. It was highly active against C. neoformans (MIC80 = 0.031 μg/mL), which was more potent than fluconazole and voriconazole. Moreover, compound 8a showed potent fungicidal activity and had potent inhibitory effects against important virulence factors (i.e. biofilm, melanin and urease) of C. neoformans. Preliminary antifungal mechanism investigation revealed that compound 8a induced apoptosis of C. neoformans cells and arrested the cell cycle at the G1/S phase.

Li|Zhuang|Z| Liu|Na|N| Tu|Jie|J| Ji|Changjin|C| Han|Guiyan|G| Wang|Yan|Y| Sheng|Chunquan|C|

D006576:Heterocyclic Compounds, 4 or More Rings

Anti-cryptococcal
Structural simplification
Fungicidal activity
Virulence factors
Antifungal mechanism


Pembrolizumab plus chemotherapy-induced pneumonitis in chemo-naïve patients with non-squamous non-small cell lung cancer: A multicentre, retrospective cohort study.

Abstract:
INTRODUCTION
Despite the extensive use of the combination of cytotoxic chemotherapy and programmed cell death protein 1/programmed death-ligand 1 checkpoint inhibitors for cancer treatment, the incidence and characteristics of pneumonitis caused by this combination therapy have not been examined in clinical settings.

METHODS
We conducted a 36-centre, retrospective cohort study in patients with chemo-naïve advanced non-squamous non-small cell lung cancer who received a combination of platinum, pemetrexed and pembrolizumab between December 2018 and June 2019.

RESULTS
The study comprised 299 patients. The most frequent grade ≥3 non-hematologic adverse event was pneumonitis. There were 37 patients (12.4%, 95% CI 8.9-16.7) with all-grade pneumonitis and 10 (3.3%, 95% CI 1.6-6.1) with grade ≥3 pneumonitis. Of these, 21 (7.0%, 95% CI 4.4-10.5) and 9 patients (3.0%, 95% CI 1.4-5.6) developed all-grade and grade ≥3 pneumonitis within 90 days after initiating the combination therapy, respectively. The median time to treatment failure and progression-free survival was 5.9 (95% CI 5.0-6.8) and 7.5 (95% CI 6.5-8.7) months, respectively. In the survival analysis after adjusting for immortal time bias, pneumonitis was independently associated with shorter progression-free survival (HR 1.99, 95% CI 1.07-3.69, P = 0.03) and overall survival (HR 3.03, 95% CI 1.12-8.20, P = 0.03).

CONCLUSIONS
Treatment-related pneumonitis occurred at a higher rate in the real-world population than that reported previously; it led to worse survival outcomes. Pneumonitis requires more attention. Additional studies are required to improve the safety of this combination therapy.

TRIAL REGISTRATION NUMBER
UMIN000038084.

Fujimoto|Daichi|D| Miura|Satoru|S| Yoshimura|Kenichi|K| Wakuda|Kazushige|K| Oya|Yuko|Y| Yokoyama|Toshihide|T| Yokoi|Takashi|T| Asao|Tetsuhiko|T| Tamiya|Motohiro|M| Nakamura|Atsushi|A| Yoshioka|Hiroshige|H| Haratani|Koji|K| Teraoka|Shunsuke|S| Tokito|Takaaki|T| Murakami|Shuji|S| Tamiya|Akihiro|A| Itoh|Shoichi|S| Yokouchi|Hiroshi|H| Watanabe|Satoshi|S| Yamaguchi|Ou|O| Tomii|Keisuke|K| Yamamoto|Nobuyuki|N|

D000971:Antineoplastic Combined Chemotherapy Protocols

Pneumonitis
Non-small cell lung cancer
Immune checkpoint inhibitor
PD-1
PD-L1
Pneumonia


Ultrasonic monitoring of drug loaded Pluronic F127 micellular hydrogel phase behaviour.

Abstract: Pluronic hydrogels composed of PEO-PPO-PEO tri-block copolymers have received a lot of attention for their applicability to drug delivery. These systems can be injected into the body in a liquid form and then, in response to temperature changes, self-assemble into nano-sized micelles which ultimately aggregate to form a gel. The phase behaviour and effectiveness of Pluronic hydrogels as drug carriers is affected by the local thermal and ionic environment which is likely to be different from patient to patient. There is a current need for in vivo techniques to study the phase behaviour of Pluronic hydrogels and this work demonstrates an ultrasound approach for the study of drug loaded Pluronic F127 hydrogels. Ultrasound velocity and attenuation were both found to change with temperature and through validation with fluorescence spectroscopy it was determined that the temperature dependent micellation transition in the Pluronic solutions could be identified through relative changes in ultrasound velocity and attenuation as a function of temperature. This phase transition was more clearly detected through examination of the first and second derivatives of both ultrasound parameters with respect to temperature. Further this work demonstrates for the first time to our knowledge ultrasound characterisation studies on drug loaded Pluronics.

Farrugia|Mario|M|
Morgan|Stephen P|SP|
Alexander|Cameron|C|
Mather|Melissa L|ML|

D020136:Hydrogel, Polyethylene Glycol Dimethacrylate

Pluronic
Hydrogel
Drug delivery
Ultrasound


Checkpoint Inhibition May Trigger the Rare Variant of Anti-LAD-1 IgG-Positive, Anti-BP180 NC16A IgG-Negative Bullous Pemphigoid.

Abstract: Bullous pemphigoid (BP) is an autoimmune blistering skin disease characterized by an autoimmune response to type XVII collagen (BP180). The generation of anti-BP180-NC16A IgG autoantibodies is considered to be central to the pathogenesis of BP, in part due to the close correlation between serum concentration and disease activity. However, ~60% of BP patients also generate IgG autoantibodies against LAD-1, the soluble 120 kDa ectodomain of BP180. Whilst the pathogenic significance of anti-LAD-1 IgG remains unclear, it may be sufficient to precipitate the development of BP, even in the absence of anti-BP180-NC16A IgG, based on several case reports in Japanese patients. There is increasing recognition that immune-checkpoint inhibitors may trigger and/or exacerbate BP as an immune-related adverse event (irAE). Until now, all of these cases have been associated with the induction of anti-BP180-NC16A IgG. Here, we report the case of a female Caucasian patient who developed BP during treatment with the programmed cell death protein 1 (PD-1) inhibitor nivolumab. Intriguingly, the patient exclusively generated anti-LAD-1 IgG, suggesting that anti-LAD-1 IgG was responsible for the development of her autoimmune blistering dermatosis. This is the first such case documented in a non-Japanese patient, thus, lending further support to the pathogenic relevance of anti-LAD-1 IgG in BP.

Sadik|Christian D|CD|
Langan|Ewan A|EA|
Grätz|Victoria|V|
Zillikens|Detlef|D|
Terheyden|Patrick|P|

bullous pemphigoid
LAD-1
nivolumab
checkpoint inhibitors
melanoma
skin inflammation


Dermatomyositis revealing breast cancer: report of a case.

Abstract: Dermatomyositis (DM) is a rare connective corresponding to an inflammatory disease of skeletal muscles. Paraneoplastic origin must always be sought, primarily gynecological tumor in women, but the investigations are often made difficult by the fact that a primary tumor is often not detectable at the time of the cutaneous manifestations. This approach includes in addition to the monitoring report at regular intervals of 6 to 12 months for two years after diagnosis. We report a case of Dermatomyositis revealing breast cancer.

Lamquami|Safae|S| Errarhay|Sanae|S| Mamouni|Nisrine|N| Bouchikhi|Chahrazad|C| Banani|Abdelaziz|A|

Dermatomyositis
breast cancer
paraneoplastic syndromes


The polymorphisms in the thyroid peroxidase gene were associated with the development of autoimmune thyroid disease and the serum levels of anti-thyroid peroxidase antibody.

Abstract: Graves' disease (GD) and Hashimoto's disease (HD) are well known autoimmune thyroid diseases (AITDs), and the severity and intractability of AITDs varies among patients. Thyroid peroxidase (TPO) is a thyroid-specific antigen. The levels of anti-thyroid peroxidase antibody (TPOAb) were higher in patients with HD and may be associated with thyroid destruction. In this study, we genotyped eight single nucleotide polymorphisms (SNPs) in the TPO gene to clarify the association of TPO gene polymorphisms with the development, severity and intractability of AITD. We genotyped TPO rs2071399G/A, rs2071400C/T, rs2071402A/G, rs2071403A/G, rs1126799C/T, rs1126797T/C, rs732609A/C, and rs2048722A/G polymorphisms in 145 patients with GD, 147 patients with HD and 92 healthy controls by PCR-RFLP method. TPO rs2071400 T carriers (CT + TT genotypes) were more frequent in AITD, GD, and HD patients (p=0.0079, 0.0041, and 0.0488, respectively). The TPO rs2071403 GG genotype was more frequent in AITD, GD, and HD patients (p=0.0227, 0.0465, and 0.0305, respectively). There was no significant association between the SNPs and the prognosis of AITD. Serum levels of TPOAb were significantly higher in AITD patients with TPO rs2071400 T carriers (CT + TT genotypes) than in those with the CC genotype (p=0.0295), and were also significantly higher in AITD patients with TPO rs2048722 T carriers (CT + TT genotypes) than in those with the CC genotype (p=0.0056). In conclusion, TPO rs2071400 and rs2071403 polymorphisms were associated with the development of HD and GD, but not with the prognosis. Moreover, TPO rs2071400 and rs2048722 polymorphisms were associated with the serum levels of TPOAb.

Tomari|Saki|S| Watanabe|Mikio|M| Inoue|Naoya|N| Mizuma|Tomoyo|T| Yamanaka|Chika|C| Hidaka|Yoh|Y| Iwatani|Yoshinori|Y|

D020022:Genetic Predisposition to Disease

Polymorphism
Anti-thyroid peroxidase antibody
Severity
Graves’ disease
Hashimoto’s disease


REal-time Assessment of Community Transmission (REACT) of SARS-CoV-2 virus: Study protocol.

Abstract: Background: England, UK has one of the highest rates of confirmed COVID-19 mortality globally. Until recently, testing for the SARS-CoV-2 virus focused mainly on healthcare and care home settings. As such, there is far less understanding of community transmission. Protocol: The REal-time Assessment of Community Transmission (REACT) programme is a major programme of home testing for COVID-19 to track progress of the infection in the community. REACT-1 involves cross-sectional surveys of viral detection (virological swab for RT-PCR) tests in repeated samples of 100,000 to 150,000 randomly selected individuals across England. This examines how widely the virus has spread and how many people are currently infected. The age range is 5 years and above. Individuals are sampled from the England NHS patient list. REACT-2 is a series of five sub-studies towards establishing the seroprevalence of antibodies to SARS-CoV-2 in England as an indicator of historical infection. The main study (study 5) uses the same design and sampling approach as REACT-1 using a self-administered lateral flow immunoassay (LFIA) test for IgG antibodies in repeated samples of 100,000 to 200,000 adults aged 18 years and above. To inform study 5, studies 1-4 evaluate performance characteristics of SARS-CoV-2 LFIAs (study 1) and different aspects of feasibility, usability and application of LFIAs for home-based testing in different populations (studies 2-4). Ethics and dissemination: The study has ethical approval. Results are reported using STROBE guidelines and disseminated through reports to public health bodies, presentations at scientific meetings and open access publications. Conclusions: This study provides robust estimates of the prevalence of both virus (RT-PCR, REACT-1) and seroprevalence (antibody, REACT-2) in the general population in England. We also explore acceptability and usability of LFIAs for self-administered testing for SARS-CoV-2 antibody in a home-based setting, not done before at such scale in the general population.

SARS-CoV-2
virus
COVID-19
antibody
lateral flow immunoassay
prevalence
PCR
point-of-care diagnostics


Incursions of sea lamprey, Petromyzon marinus, and striped bass, Morone saxatilis, in Labrador waters: Episodic events or evidence of a northward range expansion?

Abstract: We describe observations of sea lamprey (Petromyzon marinus) and striped bass (Morone saxatilis) incursions into Labrador, Canada. While P. marinus have been periodically observed in similar latitudes, their numbers have conspicuously increased in estuarine environments in 2020. In contrast, M. saxatilis were not observed from Labrador until 2017 but appear to be declining after the initial surge in abundance that peaked in 2018. It remains unclear whether spawning populations of either species exist. Given the potential to negatively affect species of commercial and cultural importance through predation, follow-up surveys are warranted.

sea lamprey
Petromyzon marinus
striped bass
Morone saxatilis
Labrador
range expansion
climate change
invasive species


Reduced Periodontal Support for Lower Central Incisor - A 3D Finite Element Analysis of Compressive Stress in the Periodontium.

Abstract:
BACKGROUND
The aim of this study was to assess the stress concentration in simulated periodontal alveolar bone containing healthy teeth with and without attachment loss.

METHODS
Six 3-D models of a lower central incisor were created simulating the teeth structure, cancellous and cortical bone and periodontal ligament. Each model presented a 1mm increasing distance between cement-enamel junction (CEJ) and alveolar bone crest (ABC) (1 to 6mm). A 100N, 45-degree load was applied to the buccal face of the lower central incisor. The effects of Minimum Principal Stress (MPS) on lamina dura (LD) and ABC were analyzed.

RESULTS
The results showed an increase of MPS in the surrounding bone (ABC and LD) due to periodontal attachment loss. The 6mm attachment loss model showed the highest (p less than 0.001) magnitude in MPS. Each millimeter increase in CEJ-ABC distance generated a 12% pattern of attachment loss and an increase at least of 65.7% for ABC and 33.6% for LD.

CONCLUSION
Under simulated conditions, attachment loss increases stress concentration in the surrounding bone suggesting a partly explanation regarding bone resorption risk for teeth with periodontal attachment loss.

da Rocha|Milena Cerqueira|MC|
da Rocha|Daniel Maranha|DM|
Tribst|João Paulo Mendes|JPM|
Borges|Alexandre Luiz Souto|ALS|
Alvim-Pereira|Fabiano|F|

incisor
finite element analysis
Periodontium
bone


In- vitro-activity of additive application of hydrogen peroxide in antimicrobial photodynamic therapy using LED in the blue spectrum against bacteria and biofilm associated with periodontal disease.

Abstract:
BACKGROUND
Although antimicrobial photodynamic therapy (aPDT) has been shown to be efficient in killing planktonic periodontopathogenic bacteria, its activity on established biofilms is very limited. The aim of the present in-vitro study was to evaluate the potential effect of hydrogen peroxide as a pretreatment for aPDT.

METHODS
aPDT consisting of riboflavin as photosensitizer and illumination by a LED lamp emitting in the blue spectrum for 30 s and 60 s (aPDT60) was combined with a pretreatment with 0.25% and 3% hydrogen peroxide. The antimicrobial activity of these treatments was determined against eight oral species (incl. Porphyromonas gingivalis and Tannerella forsythia) and against eight-species biofilms. Treatment of biofilms in an artificial pocket model included a mechanical removal of the biofilm.

RESULTS
Against planktonic bacteria, pretreatment with hydrogen peroxide increased killing of planktonic bacteria, after aPDT60 no viable bacteria were detected in 7 of 8 strains. In biofilms formed on well-plates, aPDT60 reduced bacterial counts only by 0.53 log10 cfu, whereas reduction was closed to 4 log10 or higher when 3% hydrogen peroxide was used. When biofilms were treated in the periodontal-pocket model, reduction of cfu was less than 0.5 log10 after mechanical therapy or aPDT60 only, however no bacteria were detected after mechanical biofilm removal followed by the use 3% of hydrogen peroxide and aPDT60.

CONCLUSIONS
aPDT using riboflavin and blue LED light applied after mechanical removal of biofilm and adjunctive 3% hydrogen peroxide solution appears to represent an alternative for antimicrobial periodontal therapy.

Kunz|Daniel|D| Wirth|Jessica|J| Sculean|Anton|A| Eick|Sigrun|S|

D000900:Anti-Bacterial Agents
D000890:Anti-Infective Agents
D018441:Biofilms
D006861:Hydrogen Peroxide
D066298:In Vitro Techniques
D010510:Periodontal Diseases
D010778:Photochemotherapy
D017319:Photosensitizing Agents
D012256:Riboflavin

Hydrogen peroxide
Antimicrobial photodynamic therapy
Biofilms
Periodontopathogens
Riboflavin


Bidirectional Transradial and Transfemoral Approach for Stent-Assisted Coil Embolization of Right Subclavian Artery Saccular Aneurysm.

Abstract: Subclavian artery aneurysms are rare lesions that usually require treatment for complications. Bidirectional stent-assisted coil embolization is the most effective treatment of complex wide-necked aneurysms. The stents provide a rigid scaffold that allows coil deposition with reduced risk of coil herniation into the parent vessel lumen. Bidirectional transradial and transfemoral approaches contribute to stable procedure. We report a successful bidirectional stent-assisted coil embolization of a saccular aneurysm of the subclavian artery as an alternative to stent graft implantation to diminish the risk of right vertebral artery occlusion.

coil embolization
subclavian artery
aneurysm


Overview of gastrointestinal cancer prevention in Asia.

Abstract: "War on cancer" was declared through the National Cancer Act by President Richard Nixon in 1971, but cancer statistics from the American Cancer Society and other sources indicated the failure of this war, suggesting instead focus on the message that a "prevention strategy" might be much more effective than cancer treatment. While cancer statistics notoriously showed sharp increases in incidence as well as in mortality concurrent with economic growth in Asia, fortunately Asian countries benefit from plentiful resources of natural compounds, which can prevent cancer. Just like cancer chemotherapeutics targeted to kill cancer cells in Western countries, natural agents activating molecular mechanisms for cancer prevention, reversion of premalignant tumors, and even ablation of cancer stem cells, are very abundant in Asia. Currently, these natural agents are under very active investigations targeting the hallmarks of cancer prevention, including selective induction of apoptosis in cancer cells, suppression of growth factors or their signaling, suppression of cell proliferation and of cancer-promoting angiogenesis, induction of mesenchymal-epithelial transition, and disruption of the tumor microenvironment, developing promising cancer preventive agents. However, Asia is the most populous continent in the world and some Asian countries do not have the resources to implement cancer screening programs for early detection or treatment. In addition, despite the excellent cancer preventive screening strategies in some Asian countries, well-designed clinical trials for cancer prevention are somewhat delayed compared to Western countries. In this review article, several phytochemicals/phytoceuticals produced and studied in different Asian countries will be introduced, including Korean red ginseng (pride of Korea), curcumin (Indian spice for life), black or green tea (popular in Japan/Sri Lanka), genistein from tofu (famous Chinese food), diallylsulfide or S-allylcysteine (garlic, popularly consumed as a food ingredient in many Asian countries), capsaicin, 6-gingerol, flavopiridol, and silymarin (abundant in various Asian foods). Whereas in Western countries cancer chemotherapeutics involve strategies not only to block the growth of the primary tumor, but also to inhibit its progression to metastatic disease, the endless pursuit of effective agents for cancer prevention may be a unique and featured strategy in Asia. More active efforts for clinical application of these principles should be supported.

Park|Jong-Min|JM|
Lee|Ho-Jae|HJ|
Yoo|Jun Hwan|JH|
Ko|Weon Jin|WJ|
Cho|Joo Young|JY|
Hahm|Ki Baik|KB|

Chemotherapeutics
Clinical trials
Phytoceuticals
Chemoprevention
Molecular targeted prevention


The "ivory vertebra" sign.

Abstract: The ivory verterba sign is indicative of diffuse sclerosis of a vertebral body. Though classically associated with osteoblastic metastatic disease, the appearance has also been described with multiple other conditions. Observable on Compute tomography or standard radiography, this sign can serve as a important clue to a systemic disease process.

D003937:Diagnosis, Differential
D006801:Humans
D013122:Spinal Diseases

Ivory Vertebra Sign Osteoblastic Sclerotic Spine


Molecular and biochemical characterization of the OLE-1 high-oleic castor seed (Ricinus communis L.) mutant.

Abstract: The natural OLE-1 high-oleic castor mutant has been characterized, demonstrating that point mutations in the FAH12 gene are responsible for the high-oleic phenotype. The contribution of each mutation was evaluated by heterologous expression in yeast, and lipid studies in developing OLE-1 seeds provided new evidence of unusual fatty acids channeling into TAGs. Ricinus communis L. is a plant of the Euphorbiaceae family well known for producing seeds whose oil has a very high ricinoleic (12-hydroxyoctadecenoic) acid content. Castor oil is considered the only commercially renewable source of hydroxylated fatty acids, which have many applications as chemical reactants. Accordingly, there has been great interest in the field of plant lipid biotechnology to define how ricinoleic acid is synthesized, which could also provide information that might serve to increase the content of other unusual fatty acids in oil crops. Accordingly, we set out to study the biochemistry of castor oil synthesis by characterizing a natural castor bean mutant deficient in ricinoleic acid synthesis (OLE-1). This mutant accumulates high levels of oleic acid and displays remarkable alterations in its seed lipid composition. To identify enzymes that are critical for this phenotype in castor oil, we cloned and sequenced the oleate desaturase (FAD2) and hydroxylase (FAH12) genes from wild-type and OLE-1 castor bean plants and analyzed their expression in different tissues. Heterologous expression in yeast confirmed that three modifications to the OLE-1 FAH12 protein were responsible for its weaker hydroxylase activity. In addition, we studied the expression of the genes involved in this biosynthetic pathway at different developmental stages, as well as that of other genes involved in lipid biosynthesis, both in wild-type and mutant seeds.

Venegas-Calerón|Mónica|M|
Sánchez|Rosario|R|
Salas|Joaquín J|JJ|
Garcés|Rafael|R|
Martínez-Force|Enrique|E|

D018506:Gene Expression Regulation, Plant

D044925:Oxidoreductases Acting on CH-CH Group Donors

D020133:Reverse Transcriptase Polymerase Chain Reaction

Ricinus
Fatty acids
Castor bean
Oleate desaturase
Lipid synthesis
OLE-1 mutant
Oleate 12-hydroxylase
Triacylglycerol


The Arabidopsis thaliana mitogen-activated protein kinases MPK3 and MPK6 target a subclass of 'VQ-motif'-containing proteins to regulate immune responses.

Abstract: Mitogen-activated protein kinase (MAPK) cascades play key roles in plant immune signalling, and elucidating their regulatory functions requires the identification of the pathway-specific substrates. We used yeast two-hybrid interaction screens, in vitro kinase assays and mass spectrometry-based phosphosite mapping to study a family of MAPK substrates. Site-directed mutagenesis and promoter-reporter fusion studies were performed to evaluate the impact of substrate phosphorylation on downstream signalling. A subset of the Arabidopsis thaliana VQ-motif-containing proteins (VQPs) were phosphorylated by the MAPKs MPK3 and MPK6, and renamed MPK3/6-targeted VQPs (MVQs). When plant protoplasts (expressing these MVQs) were treated with the flagellin-derived peptide flg22, several MVQs were destabilized in vivo. The MVQs interact with specific WRKY transcription factors. Detailed analysis of a representative member of the MVQ subset, MVQ1, indicated a negative role in WRKY-mediated defence gene expression - with mutation of the VQ-motif abrogating WRKY binding and causing mis-regulation of defence gene expression. We postulate the existence of a variety of WRKY-VQP-containing transcriptional regulatory protein complexes that depend on spatio-temporal VQP and WRKY expression patterns. Defence gene transcription can be modulated by changing the composition of these complexes - in part - through MAPK-mediated VQP degradation.

Pecher|Pascal|P| Eschen-Lippold|Lennart|L| Herklotz|Siska|S| Kuhle|Katja|K| Naumann|Kai|K| Bethke|Gerit|G| Uhrig|Joachim|J| Weyhe|Martin|M| Scheel|Dierk|D| Lee|Justin|J|

D020929:Mitogen-Activated Protein Kinase Kinases

pathogen-associated molecular pattern (PAMP)


Exploring patterns of beta-diversity to test the consistency of biogeographical boundaries: A case study across forest plant communities of Italy.

Abstract:
Aim
To date, despite their great potential biogeographical regionalization models have been mostly developed on descriptive and empirical bases. This paper aims at applying the beta-diversity framework on a statistically representative data set to analytically test the consistency of the biogeographical regionalization of Italian forests.

Location
Italy.

Taxon
Vascular plants.

Methods
Forest plant communities were surveyed in 804 plots made in a statistically representative sample of forest communities made by 201 sites of Italian forests across the three biogeographical regions of the country: Alpine, Continental, and Mediterranean. We conducted an ordination analysis and an analysis of beta-diversity, decomposing it into its turnover and nestedness components.

Results
Our results provide only partial support to the consistency of the biogeographical regionalization of Italy. While the differences in forest plant communities support the distinction between the Alpine and the other two regions, differences between Continental and Mediterranean regions had lower statistical support. Pairwise beta-diversity and its turnover component are higher between- than within-biogeographical regions. This suggests that different regional species pools contribute to assembly of local communities and that spatial distance between-regions has a stronger effect than that within-regions.

Main conclusions
Our findings confirm a biogeographical structure of the species pools that is captured by the biogeographical regionalization. However, nonsignificant differences between the Mediterranean and Continental biogeographical regions suggest that this biogeographical regionalization is not consistent for forest plant communities. Our results demonstrate that an analytical evaluation of species composition differences among regions using beta-diversity analysis is a promising approach for testing the consistency of biogeographical regionalization models. This approach is recommended to provide support to the biogeographical regionalization used in some environmental conservation polices adopted by EU.

forest plant communities
Italy
biogeographical regionalization
turnover
nestedness
ICP Forests
beta‐diversity


Ultrastructural morphology of goblet cells of the conjunctiva of dogs.

Abstract:
OBJECTIVE
To describe the morphology of goblet cells of the eyelid conjunctiva in dogs using transmission and scanning electron microscopy.

ANIMAL STUDIED
Ten dogs, both male and female of different breeds, with no ocular changes were examined (20 eyes).

PROCEDURES
Ten samples of conjunctiva were collected and processed for scanning and transmission electron microscopy (SEM and TEM), while another 10 samples were stained with Schiff's periodic stain (SPA) and alcian blue, pH 2.5, and analyzed using light microscopy.

RESULTS
Scanning electron microscopy revealed several points of mucus extrusion in the free apical portion of the goblet cells as well as a wide distribution of lymphoid follicles and macrophages intermingling with the microvilli of palpebral epithelium cells. TEM revealed normal goblet cells that were predominantly oval with wide cytoplasm of different diameters, and large vesicles with heterogeneous granules and free edges, suggesting the release of mucus content onto the conjunctival surface. Cytoplasmic organelles, such as the Golgi apparatus, endoplasmic reticulum, and a high number of mitochondria were also observed. All the samples were positive for SPA and alcian blue staining.

CONCLUSION
This is the first study to evaluate the goblet cells of the eyelid conjunctiva in healthy dogs using electron microscopy techniques. These results are useful for comparing the palpebral conjunctiva of dogs without ocular changes to palpebral conjunctiva of dogs and other species with ocular changes.

goblet cells
dogs
electron microscopy
keratoconjunctivitis sicca
ocular surface


Idiopathic granulomatous interstitial nephritis responsive to mycophenolate mofetil therapy.

Abstract: Granulomatous interstitial nephritis (GIN) is a rare histologic disease. Various causes have been reported in the literature, including drugs, sarcoidosis, and infections. Other incidents have no discernible cause and are identified as idiopathic. We report a 68-year-old white man who presented with acute kidney injury and was given a diagnosis of idiopathic GIN. Mycophenolate mofetil treatment was elected because of steroid toxicity. He responded well to mycophenolate mofetil and has been in remission for more than 3 years. To our knowledge, this is the first report of successful treatment with mycophenolate mofetil of an adult patient with idiopathic GIN.

Leeaphorn|Napat|N|
Stokes|Michael B|MB|
Ungprasert|Patompong|P|
Lecates|William|W|


FUS mutation is probably the most common pathogenic gene for JALS, especially sporadic JALS.

Abstract: Juvenile amyotrophic lateral sclerosis (JALS) is a rare and severe form of ALS. The development of gene sequencing methods has resulted in increased reports of JALS cases in recent years, and additional gene mutations in FUS have been identified. Fused in sarcoma (FUS) mutations, appeared rarely in classical ALS but indeed were the most frequent pathogenic mutations in JALS, especially in sporadic JALS. After studied the reports in the last 10 years about JALS cases, the case characteristics caused by FUS mutations and the commonality of the mutation sites were summarized in this review. FUS mutation associated with more than half of JALS and the very majority of sporadic JALS. It's worth noting that almost all of the mutations occur in nuclear localization signal (NLS) of FUS in sporadic JALS. This discovery emphasized a new perspective focus on NLS for the diagnosis and etiology of sporadic JALS as well as for further study about new treatment.

Sporadic juvenile amyotrophic lateral sclerosis


Self-expanding apical closure device for full-percutaneous closed-chest transapical valve procedures with large-sized introducer sheaths: first study in an animal model.

Abstract:
OBJECTIVES
Available apical occluders do not fulfil requirements for full-percutaneous transapical valve procedures with large-sized introducer sheaths. A self-expanding closure device designed for closed-chest transapical valve procedures was tested in an animal model to verify safety, efficacy and thrombogenicity.

METHODS
Large-sized 21-Fr introducer sheaths (Certitude™ system for Sapien™ valves) were percutaneously placed in the ventricles of nine 3-month old minipigs. To seal the apical access, delivery catheters carrying folded self-expanding plugs were inserted. Then, the plugs were deployed while sheaths were removed. Echocardiograms verified tamponade and cardiac function, drains were not placed and a 3-month long aspirin therapy was administered. After 6 and 9 months, animals were euthanized and organs were analysed for macroembolic lesions search. Histological analysis was also performed.

RESULTS
Nine minipigs (weight: 28±3 kg) were used for this study. Eight plugs were successfully deployed in 8 ventricles without cardiac tamponade or ventricular dysfunction (success rate: 88.9%). In a failed procedure (the animal died after 1 month of cardiac tamponade), the outer disc of the apical plug got stuck in the intercostal space and did not correctly deploy. Post-mortem analysis in 8 minipigs at 6 (n = 4) and 9 months (n = 4) confirmed full deployment and good fixation of all plugs with internal surfaces covered by new endocardium. Macroscopic analysis of myocardium and vital organs showed absence of embolic lesions. Histological analysis showed absence of significant inflammatory infiltration and thrombosis.

CONCLUSIONS
In this animal model, self-expanding closure devices sealed 21-Fr large percutaneous apical accesses without acute tamponade, thrombosis or embolization. Further tests to evaluate full-percutaneous closed-chest apical procedures are required.

Hong|Nanchao|N|
Lu|Yanan|Y|
Hu|Hanbo|H|
Sun|Jing|J|
Sun|Kun|K|
von Segesser|Ludwig Karl|LK|
Berdajs|Denis|D|
Chen|Sun|S|
Ferrari|Enrico|E|

D019918:Heart Valve Prosthesis Implantation

Apical closure device
Percutaneous heart valve procedures
Transapical valve implantation


An E2F5-TFDP1-BRG1 Complex Mediates Transcriptional Activation of MYCN in Hepatocytes.

Abstract: Liver regeneration is characterized by cell cycle reentrance of hepatocytes. N-Myc, encoded by MYCN, is a member of the Myc family of transcription factors. Elevation of MYCN expression has been noted in the course of liver regeneration whereas the underlying mechanism remains unclear. Here we describe that up-regulation of MYCN expression, as measured by quantitative PCR, Western blotting, and immunohistochemical staining, paralleled liver regeneration in animal and cell models. MYCN expression was up-regulated as a result of transcriptional activation. Ingenuity pathway analysis (IPA) revealed several up-stream transcriptional regulators for MYCN and RNA interference validated E2F5 and TFDP1 as essential for hepatocyte growth factor (HGF)-induced MYCN trans-activation. Further examination showed that deficiency of BRG1, a chromatin remodeling protein, attenuated MYCN induction during liver regeneration. BRG1 interacted with and was recruited by E2F5/TFDP1 to the MYCN promoter. Mechanistically, BRG1 might play a role regulating histone H3 acetylation and H3K4 trimethylation and facilitating/stabilizing the binding of RNA polymerase II surrounding the MYCN promoter. Over-expression of ectopic MYCN in BRG1-null hepatocytes overcame deficiency of proliferation. Importantly, a positive correlation between MYCN expression and BRG1/E2F5/TFDP1 expression was observed in human liver specimens. In conclusion, our data identify a novel epigenetic pathway where an E2F5-TFDP1-BRG1 complex regulates MYCN transcription to promote liver regeneration.

Fan|Zhiwen|Z| Kong|Ming|M| Miao|Xiulian|X| Guo|Yan|Y| Ren|Haozhen|H| Wang|Jinglin|J| Wang|Shuai|S| Tang|Ning|N| Shang|Longcheng|L| Zhu|Zhengyi|Z| Liu|Hanyi|H| Zhu|Wei|W| Shi|Xiaolei|X|

hepatocyte
liver regeneration
transcriptional regulation
chromatin remodeling protein
proliferation
epigenetics


Heterologous expression and purification of plantaricin NC8, a two-peptide bacteriocin against Salmonella spp. from Lactobacillus plantarum ZJ316.

Abstract: Bacteriocin, which is produced by lactic acid bacteria (LAB), has the potential to act as natural preservatives in the food industry. To develop strategies to overproduce such peptides, plantaricin NC8, a class IIb LAB bacteriocin that consists of two peptides, PLNC8α and PLNC8β, was successfully heterologously expressed in Escherichia coli BL21 (DE3). PLNC8α and PLNC8β peptides were expressed as His6-tag fusion proteins and were separated by Ni(2+) chelating affinity chromatography. To get the PLNC8α and PLNC8β peptides without extra amino acids in the N-terminus, the fusion proteins were cleaved by enterokinase and further purified using the Ni-NTA Sefinose™ Resin Kit. The molecular masses of peptides were checked using Tricine-SDS-PAGE and MALDI-TOF-MS. The yield of purified PLNC8α was around 2-2.5 mg/L, and the yield of PLNC8β was around 1.5-2 mg/L. The antimicrobial spectrum of cleaved peptides was detected and the synergistic action of PLNC8α and PLNC8β was preliminarily confirmed. It was found that E. coli was a suitable host for heterologous expression of plantaricin NC8 with a significant yield. Importantly, the bacteriocin appeared to be very active for controlling and inhibiting the food-borne pathogenic Gram-negative bacteria Salmonella spp., and might be useful as a natural preservative candidate.

D000900:Anti-Bacterial Agents
D001430:Bacteriocins
D004926:Escherichia coli
D015870:Gene Expression
D048191:Lactobacillus plantarum
D011994:Recombinant Proteins
D012475:Salmonella

Heterologous expression
Plantaricin NC8
Salmonella spp
Escherichia coli


Analysis of mutation of the c-Kit gene and PDGFRA in gastrointestinal stromal tumors.

Abstract: The aim of the present study was to investigate mutation status of the c-Kit gene (KIT) and PDGFRA in patients with a gastrointestinal stromal tumor (GIST). In total, 93 patients with a GIST were included in the study, in which polymerase chain reaction amplification and gene sequencing were used to detect the sequences of exons 9, 11, 13 and 17 in KIT and exons 12 and 18 in PDGFRA. KIT mutations were detected in 64 cases (68.82%), of which exon 11 mutations were detected in 56 cases (60.22%), exon 13 mutations were detected in three cases (3.23%) and one case (1.08%) was shown to have a mutation in exon 17. The most common mutation in exon 11 was a deletion, which accounted for 55.36% (31/56) of the cases, followed by a point mutation observed in 26.79% (15/56) of the cases, while an insertion (tandem repeats) was identified in 14.29% (8/56) of the cases, and 3.57% (2/56) of the exon 11 mutations were deletions associated with a point mutation. The majority of the mutations were heterozygous, with only a few homozygous mutations. Mutational analysis revealed the mutations to be more concentrated in the classic hot zone at the 5'-end, followed by the tandem repeat frame at the 3'-end. In four cases, a mutation was detected in exon 18 of PDGFRA, of which one was associated with a mutation in KIT. The remaining three cases (10.34%, 3/29) were not associated with mutations in KIT and accounted for 37.5% (3/8) of the CD117-negative GIST cases. Therefore, the majority of the GIST cases were characterized by mutations in KIT or PDGFRA, which were directly associated with the disease. Pairs of different mutations in the same exon of KIT, or KIT mutations coupled with pairs of mutations in PDGFRA, were detected in a small number of patients. Imatinib is a small molecule tyrosine kinase inhibitor and is the first line targeted treatment for GIST, resulting in markedly improved survival rates. Thus, gene mutation genotyping may provide inspiration and guidance for imatinib-based targeted cancer therapy.

Xu|Chun-Wei|CW| Lin|Shan|S| Wang|Wu-Long|WL| Gao|Wen-Bin|WB| Lv|Jin-Yan|JY| Gao|Jing-Shan|JS| Zhang|Li-Ying|LY| Li|Yang|Y| Wang|Lin|L| Zhang|Yu-Ping|YP| Tian|Yu-Wang|YW|

c-Kit
PDGFRA
gastrointestinal stromal tumors
gene mutation
molecular detection


Facilitated ion transfer of protonated primary organic amines studied by square wave voltammetry and chronoamperometry.

Abstract: The transfer of the protonated forms of heptylamine, octylamine, decylamine, procaine and procainamide facilitated by dibenzo-18-crown-6 from water to a solvent polymeric membrane has been investigated by using cyclic square wave voltammetry. The experimental voltammograms obtained are in good agreement with theoretical predictions. The values of the standard ion transfer potential, complexation constant and diffusion coefficient in water have been obtained from these experiments, and have been used to draw some conclusions about the lipophilicity of these species and the relative stability of the organic ammonium complexes with dibenzo-18-crown-6. The results have been compared with those provided by linear sweep voltammetry. Calibration graphs were obtained with both techniques. An interesting chronoamperometric method for the determination of the diffusion coefficient of the target ion in the membrane has been developed and applied to all these protonated amines.

Torralba|E|E|
Ortuño|J A|JA|
Molina|A|A|
Serna|C|C|
Karimian|F|F|

Facilitated ion transfer
Protonated primary organic amines
Cyclic square wave voltammetry
Liquid membranes


Neuromodulation in migraine: state of the art and perspectives.

Abstract: Migraine is a highly prevalent and disabling disease. The drugs prescribed for migraine prophylaxis can have intolerable side effects or can be ineffective. Neuromodulation techniques are increasingly used in neurology. Transcutaneous supraorbital nerve stimulation is effective in episodic migraine prevention, whereas vagus nerve stimulation provides interesting results in acute migraine therapy. Transcranial stimulation techniques gave variable, and sometimes contradictory, results. The visual cortex is the target of choice in migraine: studies in migraine prevention and aura acute treatment are encouraging. These noninvasive therapies appear safe with a low rate of side effects. Available studies of invasive occipital nerve stimulation in chronic migraine gave modest results; but invasive occipital nerve stimulation offers a new hope to highly disabled patients who failed to respond to any other treatment. In the future, neuromodulation will probably take an increasing place in migraine treatment, as add-on therapy or alternative to medications, especially because of its attractive safety profile.

D004561:Transcutaneous Electric Nerve Stimulation

neuromodulation
migraine
supraorbital nerve
treatment
occipital nerve
direct current stimulation
magnetic stimulation
peripheral nerve


Current analytical methods for porcine identification in meat and meat products.

Abstract: Authentication of meat products is critical in the food industry. Meat adulteration may lead to religious apprehensions, financial gain and food-toxicities such as meat allergies. Thus, empirical validation of the quality and constituents of meat is paramount. Various analytical methods often based on protein or DNA measurements are utilized to identify meat species. Protein-based methods, including electrophoretic and immunological techniques, are at times unsuitable for discriminating closely related species. Most of these methods have been replaced by more accurate and sensitive detection methods, such as DNA-based techniques. Emerging technologies like DNA barcoding and mass spectrometry are still in their infancy when it comes to their utilization in meat detection. Gold nanobiosensors have shown some promise in this regard. However, its applicability in small scale industries is distant. This article comprehensively reviews the recent developments in the field of analytical methods used for porcine identification.

Zia|Qamar|Q|
Alawami|Mohammad|M|
Mokhtar|Nur Fadhilah Khairil|NFK|
Nhari|Raja Mohd Hafidz Raja|RMHR|
Hanish|Irwan|I|

Loop-mediated isothermal amplification (LAMP)


Measuring language lateralisation with different language tasks: a systematic review.

Abstract: Language lateralisation refers to the phenomenon in which one hemisphere (typically the left) shows greater involvement in language functions than the other. Measurement of laterality is of interest both to researchers investigating the neural organisation of the language system and to clinicians needing to establish an individual's hemispheric dominance for language prior to surgery, as in patients with intractable epilepsy. Recently, there has been increasing awareness of the possibility that different language processes may develop hemispheric lateralisation independently, and to varying degrees. However, it is not always clear whether differences in laterality across language tasks with fMRI are reflective of meaningful variation in hemispheric lateralisation, or simply of trivial methodological differences between paradigms. This systematic review aims to assess different language tasks in terms of the strength, reliability and robustness of the laterality measurements they yield with fMRI, to look at variability that is both dependent and independent of aspects of study design, such as the baseline task, region of interest, and modality of the stimuli. Recommendations are made that can be used to guide task design; however, this review predominantly highlights that the current high level of methodological variability in language paradigms prevents conclusions as to how different language functions may lateralise independently. We conclude with suggestions for future research using tasks that engage distinct aspects of language functioning, whilst being closely matched on non-linguistic aspects of task design (e.g., stimuli, task timings etc); such research could produce more reliable and conclusive insights into language lateralisation. This systematic review was registered as a protocol on Open Science Framework: https://osf.io/5vmpt/.

Bradshaw|Abigail R|AR|
Thompson|Paul A|PA|
Wilson|Alexander C|AC|
Bishop|Dorothy V M|DVM|
Woodhead|Zoe V J|ZVJ|

Language
Lateralisation
Systematic review
Task design


Clinical and therapeutic outcomes of COVID-19 intensive care units (ICU) patients: a retrospective study in Ghana.

Abstract: The COVID-19 pandemic had caused significant morbidity and mortality, with over a million deaths recorded to date. Mortality recorded among severe-critically ill patients admitted to intensive care units (ICU) has been significantly high, especially in most COVID-19 epicenters. Reports on the unique clinical characteristics and outcomes from the ICU admissions are on-going with isolated studies in Africa. This study was a retrospective single-centre study involving all polymerase chain reaction (PCR) confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients admitted to the medical intensive care unit (MICU) of the department of medicine and therapeutics, Korle-Bu Teaching Hospital, over the period of 13th April - 28th June 2020. Twenty-two (22) patients in total fulfilled the inclusion criteria and are included in this report. Patients' socio-demographic characteristics, clinical and laboratory parameters outcomes as well as treatment modalities employed were extracted from their respective medical records and analyzed using STATA version 14. Dyspnoea, fever and cough were most common associated symptoms. The mean duration of admission at the ICU was 4.1 ± 3.0 days with five deaths (22.7%). About 91% (20/22) had at least one comorbidity with hypertension as the most prevalent. The median oxygen saturation/fraction of inspired oxygen (SpO2/FiO2) level was significantly higher in persons with only COVID-19 pneumonia compared to those with complicated respiratory failure (p<0.001). Six (27.3%) out of the 22 patients had non-invasive ventilation, with only 1/22 (4.5%) receiving mechanical ventilation. Although non-significant, the mean duration of ICU stay was relatively shorter in patients who received therapeutic doses of anticoagulation (p=0.32). Duration of treatment with methylprednisolone was significantly associated with patient outcomes (p=0.04) and serum ferritin levels had a tendency to negatively affect outcome (p=0.06). Clearly there are still no specific targeted medications for COVID-19 treatment, except for empirically symptoms-guided treatments and management of mild to critically ill patients. Early use of systemic corticosteroids for severe to critically ill patients in the ICU using S/F ratio and CRP levels may improve outcomes.

Afriyie-Mensah|Jane|J|
Aboagye|Elvis Twumasi|ET|
Ganu|Vincent Jessey|VJ|
Bondzi|Samuel|S|
Tetteh|Dennis|D|
Kwarteng|Ernest|E|
Akamah|Joseph|J|
Doku|Alfred|A|
Adjei|Patrick|P|


Foot Length Growth as a Novel Marker of Early Puberty.

Abstract: Foot growth is part of overall pubertal growth but its relation to other anthropometric and hormonal changes is unclear. Our objective was to determine how foot length changes relate to changes in other growth parameters (height and weight), Tanner stage, and serum hormones. Adolescents (n = 342) were recruited to a 3-year longitudinal cohort study, underwent annual anthropometric assessments (height, weight, and foot length), and provided self-rated Tanner staging. They also provided blood samples that were analyzed using liquid chromatography-tandem mass spectrometry for serum testosterone and estradiol and classified as pre-pubertal or pubertal based on circulating hormone levels. Average annual percent increase in foot length was greater for pre-pubertal adolescents compared with pubertal. Increased foot length was associated with increases in height, weight, Tanner stage, and serum hormones in males and pre-menarcheal females but not post-menarcheal females. Foot length offers a novel, noninvasive, cost-effective, and easily demonstrable marker of early pubertal changes.

Balzer|Ben W R|BWR|0000-0001-7116-2339
Cheng|Hoi Lun|HL|
Garden|Frances|F|
Luscombe|Georgina M|GM|
Paxton|Karen T|KT|
Hawke|Catherine I|CI|
Handelsman|David J|DJ|
Steinbeck|Katharine S|KS|

foot length
puberty
adolescence
testosterone
estradiol


Anti-proliferative activity of Ensete superbum Roxb. Cheesman extract and its active principles on human colorectal cancer cell lines.

Abstract: Ensete superbum Roxb. Cheesman (wild banana) is a plant traditionally used for the treatment of fever and diarrhea. On a preliminary screening, the ripe peel aqueous extract (PA) exhibited higher cytotoxicity (cell viability of 49% against HCT-15 at 75 µg/ml; and 46% against Caco2 at 50 µg/ml), superior anti-inflammatory (IC50 of 0.49 µg/ml), and greater anti-mutagenic activity at 500 µg/plate compared to the aqueous extracts of seed (SA), flower (FA) and bract (BA). Therefore, we further evaluated the anti-proliferative activity of PA and its fractions. The ability to inhibit the growth of cell lines (HCT-15 and Caco2) was used for the bio-guided fractionation and isolation of active compounds in PA using chromatographic techniques. Multiple extractions of the PA yielded the peel dioxane fraction (PD), and column fractionation of PD yielded eight compounds, of which three (Compound D-PDD, Compound E-PDE, and Compound G-PDG) possessed higher cytotoxic activity. At 10 µg/ml, the cell viability of HCT-15 was 50.1%, 46.5%, and 61.9%, respectively; Caco2 was 98.2%, 62.9%, and 64.7%, respectively, for PDD, PDE, and PDG. These compounds also showed apoptotic effect as evidenced by measuring the mitochondrial membrane potential, dual staining (acridine orange/ethidium bromide), DNA fragmentation, and the ROS status in colorectal cell lines. The UPLC-HRMS/MS, FTIR, and NMR data revealed the active compounds as quercetin-3-O-rutinoside, 3,5-dimethoxy-4-hydroxybenzoic acid, and 4',5,7-trihydroxyflavone. These findings indicate the anti-proliferative potential of PA, and warrant further investigation of its active principles in the amelioration of colorectal cancer in in vivo models. PRACTICAL APPLICATION: The potential of an underutilized crop as a source of therapeutic agents for colon cancer was established, as the study showed a high cytotoxic activity of wild bananas against HCT-15 and Caco2 cell lines. Bioactivity guided fractionation of peel fraction identified the active compounds present in wild banana, and their anticancer activity was attributed to the induction of cell death. The study indicated that wild banana has the potential to inhibit the growth of colon cancer cells.

D000970:Antineoplastic Agents
D018938:Caco-2 Cells
D002470:Cell Survival
D015179:Colorectal Neoplasms
D006801:Humans
D010936:Plant Extracts

Ensete superbum
anti-inflammatory
anti-mutagenic
cytotoxic activity
phenolics


Stress influences the dynamics of hippocampal structural remodeling associated with fear memory extinction.

Abstract: Fear extinction is defined as a decline in fear-conditioned responses following non-reinforced exposure to a fear conditioned stimulus, therefore the conditioned stimulus gains new predictive properties. Patients with anxiety related disorders (e.g.: PTSD) subjected to extinction-like exposure treatments often experience a relapse of symptoms. Stress is a risk factor for those psychiatric disorders and a critical modulator of fear learning that turns the memory resistant to the extinction process. Dendritic spines are the anatomical sites where neuronal activity reshapes brain networks during learning and memory processes. Thus, we planned to characterize the dynamics of synaptic remodeling before and after contextual fear extinction in the dorsal hippocampus (DH), and how this process is affected by a previous stress experience. Animals with or without previous stress were contextually fear conditioned and one day later trained in an extinction paradigm. Rats were sacrificed one day after conditioning (pre-extinction) or one day after extinction for spine density analysis in the DH. We confirmed that stress exposure induced a deficit in extinction learning. Further, a higher density of dendritic spines, particularly mature ones, was observed in the DH of non-stressed conditioned animals at pre-extinction. Interestingly, after extinction, the spine levels returned to the control values. Conversely, stressed animals did not show such spines boost (pre-extinction) or any other change (post-extinction). In contrast, such standard dynamics of dendritic changes as well as the behavioral extinction was recovered when stressed animals received an intra-basolateral amygdala infusion of midazolam prior to stress. Altogether, these findings suggest that stress hinders the normal dynamic of dendritic remodeling after fear extinction and this could be part of the neurobiological substrate that makes those memories resistant to be extinguished.

Bender|Crhistian Luis|CL|
Giachero|Marcelo|M|
Comas-Mutis|Ramiro|R|
Molina|Victor Alejandro|VA|
Calfa|Gastón Diego|GD|

Stress
Fear memory
Dendritic spines
Dorsal hippocampus
Basolateral amygdala


Case formulation and the therapeutic relationship: the role of therapist self-reflection and self-revelation.

Abstract: This article examines the role of the therapist's self-reflection and self-revelation in case formulation. We believe that a collaboratively constructed case formulation must always be considered in the context of an evolving therapeutic relationship. Further, self-reflection and self-revelation on the part of the therapist are critical for a more elaborate and nuanced case formulation and for understanding the patient. This highlights the importance of attunement to the here and now and the evolving therapeutic relationship. From this attunement, the therapist's self-reflection and self-revelation can emerge further, which can lead to the patient's personal growth and increased self-other awareness. To illustrate our point, we present an integrative, relational model in the case of a patient who has been in treatment.

case formulation
therapeutic relationship
self-reflection
self-revelation
intersubjectivity


Abdominal pain caused by a giant liver hydatid cyst and the management of the residual cavity in a tertiary public hospital in Greece.

Abstract: Diagnosis and treatment of liver hydatid cysts may be challenging. Many surgical techniques have been proposed for the treatment of liver hydatid cysts, but the problem of the residual cavity still remains controversial and challenging, especially in giant liver hydatid cysts which are rare entities that have not been widely described in the literature so far. Capitonnage, external tube drainage and omentoplasty are the most commonly used techniques. Herein, we report the case of a 70-year-old man with a mild upper quadrant pain that proved to have a giant liver hydatid cyst, 21*14 cm2, occupying the entire right lobe of the liver. We describe a successful surgical approach with cyst unroofing and careful evacuation of the multiple daughter cysts by aspiration, and the effective management of the residual cavity by the combination of all three aforementioned techniques.

Syllaios|Athanasios|A| Schizas|Dimitrios|D| Koutras|Antonios|A| Zotos|Prokopis-Andreas|PA| Davakis|Spyridon|S| Vailas|Michail|M| Hasemaki|Natasha|N| Triantafyllou|Evangelia|E| Georgiou|Christos|C|

liver
residual cavity
capitonnage
external tube drainage
omentoplasty
Giant hydatid cyst
echinococcosis


Knowledge of blood transfusion among nurses.

Abstract:
AIMS AND OBJECTIVES
To measure nurses' knowledge of blood transfusion in the United Arab Emirates.

BACKGROUND
Blood transfusion is a fundamental aspect of nursing practice and nurses' knowledge of it is essential for safe practice. Yet little is known about their blood transfusion practice and the knowledge that underpins it. The few studies that have investigated this topic previously have shown deficiencies in both knowledge and practice. To date, no such study has been carried out in the Middle East.

DESIGNS
A descriptive, cross-sectional study.

METHODS
A random sample of 248 nurses from two general hospitals in the Emirate of Abu Dhabi. The response rate was 94AE3%. A knowledge questionnaire comprising six sections and 49 items was developed for this study. Data were analysed using descriptive and inferential statistics.

RESULTS
The overall knowledge scores of nurses were generally low ranging from 27-56 of a possible score of 70. Data analysis revealed knowledge deficits in several key aspects of blood transfusion. There were statistically significant relationship between nurses' knowledge and the work setting, the country where they trained and type of qualifications.

CONCLUSION
This survey highlighted knowledge deficits which could be detrimental to patient safety. These results have implications for nursing education, policy and practice.

RELEVANCE TO CLINICAL PRACTICE
Nurses have the responsibility to update their knowledge of and skills in carrying out blood transfusion. The tool developed in this study may be useful for educators and managers to identify gaps in knowledge and inform decisions to address them.

Hijji|Belal|B|
Parahoo|Kader|K|
Hussein|Mohammad Moshaddeque|MM|
Barr|Owen|O|

knowledge
nurses
survey
practice development
questionnaire development


Impact of Bio-Carrier Immobilized with Marine Bacteria on Self-Healing Performance of Cement-Based Materials.

Abstract: The present study evaluated the self-healing efficiency and mechanical properties of mortar specimens incorporating a bio-carrier as a self-healing agent. The bio-carrier was produced by immobilizing ureolytic bacteria isolated from seawater in bottom ash, followed by surface coating with cement powder to prevent loss of nutrients during the mixing process. Five types of specimens were prepared with two methods of incorporating bacteria, and were water cured for 28 days. To investigate the healing ratio, the specimens with predefined cracks were treated by applying a wet-dry cycle in three different conditions, i.e., seawater, tap water, and air for 28 days. In addition, a compression test and a mercury intrusion porosimetry analysis of the specimens were performed to evaluate their physico-mechanical properties. The obtained results showed that the specimen incorporating the bio-carrier had higher compressive strength than the specimen incorporating vegetative cells. Furthermore, the highest healing ratio was observed in specimens incorporating the bio-carrier. This phenomenon could be ascribed by the enhanced bacterial viability by the bio-carrier.

Kim|Hayeon|H|
Son|Hyeongmin|H|
Seo|Joonho|J|0000-0002-8027-492X
Lee|H K|HK|

bio-carrier
immobilization
self-healing efficiency
ureolytic bacteria
microbial viability


Communal therapeutic mobility in group walking: A meta-ethnography.

Abstract: Increased attention to links between walking, health and wellbeing have contributed to a growth in the number of walking groups meeting on a regular basis to offer short, social walks. Walking group interventions are known to increase physical activity and to have wide-ranging health benefits, and there is evidence that drop out is generally low. The aim of this paper is to synthesise qualitative research on experiences and perceptions of group walking in order to develop a new conceptual understanding of the group walking experience. We conducted a systematic search of the literature and identified 22 such studies which we synthesised using meta-ethnography. Included studies were conducted in the UK, USA, Australia and Ireland. Most reported research was undertaken with outdoor walking groups, some of which catered specifically for people who shared a disease experience or a disability. A smaller number of studies examined indoor mall walking groups, while two looked at perceptions of non-participants of group walking as a potential activity. From the original constructs identified in the papers we derived five higher order constructs: seeking and enjoying health and fitness, attachment to walking, providing purpose and confidence, mobile companionship and a peaceful and contemplative shared respite from everyday life. We argue that participating in a walking group provides a set of experiences that together constitute a specific form of shared or communal therapeutic mobility that is not simply the accumulation of the constructs we have outlined. Rather, we suggest that an initial instrumental and disciplinary focus on health and fitness is transformed through the experience of group walking into a shared meaningful and enjoyable practice; an emergent communal therapeutic mobility, which recruits and retains large numbers of group walkers. However, this communal therapeutic mobility is not equally accessible to all.

Pollard|Tessa M|TM|
Guell|Cornelia|C|
Morris|Stephanie|S|

Therapeutic mobilities
Walking
Meta-ethnography
Walking groups
Communitas
Pilgrimage
Qualitative synthesis


Proteomic analysis of changes in the Kandelia candel chloroplast proteins reveals pathways associated with salt tolerance.

Abstract: The plant chloroplast is one of the most sensitive organelles in response to salt stress. Chloroplast proteins extracted from seedling leaves were separated by two-dimensional gel electrophoresis (2-DE). More than 600 protein spots could be distinguished on each gel. Fifty-eight differentially expressed protein spots were detected, of which 46 could be identified through matrix-assisted laser desorption ionization time-of-flight/time-of-flight mass spectrometry (MALDI-TOF/TOF-MS). These proteins were found to be involved in multiple aspects of chloroplast metabolism pathways such as photosynthesis, ATP synthesis, detoxification and antioxidation processes, nitrogen assimilation and fixation, protein metabolism, and tetrapyrrole biosynthesis. The results indicated that K. candel could withstand up to 500 mM NaCl stress for a measured period of 3 days, by maintaining normal or high photosynthetic electron transfer efficiency and an only slightly stimulated Calvin cycle. Meanwhile, we found that ROS scavenging, nitrogen assimilation, protein degradation and chaperone function in chloroplasts were also of importance for salt tolerance of K. candel. The ultrastructural and physiological data agree with chloroplast proteome results. These findings allow further exploration of our knowledge on salt adaptation in woody halophytes and may contribute to the development of more salt-tolerant plants in the future.

Wang|Lingxia|L| Pan|Dezhuo|D| Li|Jian|J| Tan|Fanglin|F| Hoffmann-Benning|Susanne|S| Liang|Wenyu|W| Chen|Wei|W|

D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Kandelia candel
Salt stress
Photosynthesis
Antioxidation
Nitrogen assimilation
Chloroplast proteome


Xanthoangelol and 4-Hydroxyderricin Are the Major Active Principles of the Inhibitory Activities against Monoamine Oxidases on Angelica keiskei K.

Abstract: Monoamine oxidase inhibitors (MAOI) have been widely used as antidepressants. Recently, there has been renewed interest in MAO inhibitors. The activity-guided fractionation of extracts from Angelica keiskei Koidzumi (A. keiskei K.) led to the isolation of two prenylated chalcones, xanthoangelol and 4-hydroxyderricin and a flavonoid, cynaroside. These three isolated compounds are the major active ingredients of A. keiskei K. to inhibit the MAOs and DBH activities. Xanthoangelol is a nonselective MAO inhibitor, and a potent dopamine β-hydroxylase (DBH) inhibitor. IC50 values of xanthoangelol to MAO-A and MAO-B were calculated to be 43.4 μM, and 43.9 μM. These values were very similar to iproniazid, which is a nonselective MAO inhibitor used as a drug against depression. The IC50 values of iproniazid were 37 μM, and 42.5 μM in our parallel examination. Moreover, IC50 value of xanthoangelol to DBH was calculated 0.52 μM. 4-Hydroxyderricin is a potent selective MAO-B inhibitor and also mildly inhibits DBH activity. The IC50 value of 4-hydroxyderricin to MAO-B was calculated to be 3.43 μM and this value was higher than that of deprenyl (0.046 μM) used as a positive control for selective MAO-B inhibitor in our test. Cynaroside is a most potent DBH inhibitor. The IC50 value of cynaroside to DBH was calculated at 0.0410 μM. Results of this study suggest that the two prenylated chalcones, xanthoangelol and 4-hydroxyderricin isolated from A. keiskei K., are expected for potent candidates for development of combined antidepressant drug. A. keiskei K. will be an excellent new bio-functional food material that has the combined antidepressant effect.

Kim|Ji Ho|JH|
Son|Yeon Kyung|YK|
Kim|Gun Hee|GH|
Hwang|Keum Hee|KH|

Xanthoangelol
4-hydroxyderricin
Monoamine oxidase inhibitor
Angelica keiskei Koidzumi
Cynaroside
Dopamine β-hydroxylase inhibitor


Effects of physical activity and exercise on the cognitive function of patients with Alzheimer disease: a meta-analysis.

Abstract:
BACKGROUND
Alzheimer's disease (AD), as the most common cause of dementia, brings huge economic burden for patients and social health care systems, which motivates researchers to study multiple protective factors, among which physical activity and exercise have been proven to be both effective and economically feasible.

METHODS
A systematic literature search was performed for eligible studies published up to November 1st 2018 on three international databases (PubMed, Cochrane Library, and Embase) and two Chinese databases (Wanfang Data, China National Knowledge Infrastructure). All analyses were conducted using Stata 14.0. Due to heterogeneity between studies, a random-effects model was used for this meta-analysis. Meta-analysis was used to explore if physical activity and exercise can exert positive effects on cognition of elderly with AD and subgroup analyses were conducted to find out if there are dose-response effects.

RESULTS
A total of 13 randomized controlled trials were included with a sample size of 673 subjects diagnosed with AD. Intervention groups showed a statistically significant improvement in cognition of included subjects measured by the MMSE score (SMD = 1.12 CI:0.66~1.59) compared to the control groups. Subgroup analyses showed different amounts of physical activity and exercise can generate different effects.

CONCLUSIONS
As one of few meta-analyses comparing different quantities of physical activity and exercise interventions for AD in details, our study suggests that physical activity and exercise can improve cognition of older adults with AD. While the concomitant effects on cognition functions of high frequency interventions was not greater than that of low frequency interventions, the threshold remains to be settled. However, more RCTs with rigorous study design are needed to support our findings.

Jia|Rui-Xia|RX| Liang|Jing-Hong|JH| Xu|Yong|Y| Wang|Ying-Quan|YQ|

D016032:Randomized Controlled Trials as Topic

Physical activity
Exercise
Meta-analysis
Elderly
Older adults
Alzheimer’s disease, cognition


Integrating Prostate-specific Antigen Kinetics into Contemporary Predictive Nomograms of Salvage Radiotherapy After Radical Prostatectomy.

Abstract:
BACKGROUND
Salvage radiotherapy (SRT) is an established treatment for men with biochemical recurrence following radical prostatectomy (RP). There are several risk factors associated with adverse outcomes; however, the value of postoperative prostate-specific antigen (PSA) kinetics is less clear in the ultrasensitive PSA era.

OBJECTIVE
To characterize the impact of PSA kinetics on outcomes following SRT and generate nomograms to aid in identifying patients with an increased risk of adverse clinical outcomes.

DESIGN, SETTING, AND PARTICIPANTS
A multi-institutional analysis was conducted of 1005 patients with prostate cancer treated with SRT after RP, with a median follow-up of 5 years.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
Variables examined include immediate postoperative PSA, postoperative PSA doubling time (DT), and pre-SRT PSA, in addition to previously identified predictive factors. Multivariable survival analyses were completed using Fine-Gray competing risk regression. Rates of biochemical failure (BF), distant metastasis (DM), and prostate cancer-specific mortality (PCSM) were estimated by the cumulative incidence method. Nomograms were generated from multivariable competing risk regression with bootstrap cross-validation.

RESULTS AND LIMITATIONS
Factors associated with BF after SRT include PSA DT <6 mo, initial postoperative PSA ≥0.2 ng/ml, higher pre-SRT PSA, lack of androgen deprivation therapy, a higher Gleason score (GS), negative margins, seminal vesicle invasion, lack of pelvic nodal radiation, radiation total dose <66 Gy, a longer RP to SRT interval, and older age (p < 0.05 for each). Factors associated with DM include PSA DT <6 mo, pre-SRT PSA, a higher GS, and negative margins. Factors associated with PCSM include PSA DT not calculable or <6 mo and a higher GS. Nomograms were generated to estimate the risks of BF (concordance index [CI] 0.74), DM (CI 0.77), and PCSM (CI 0.77). Limitations include retrospective nature, broad treatment eras, institutional variations, and multiple methods available for the estimation of PSA DT.

CONCLUSIONS
Postoperative PSA kinetics, particularly pre-SRT PSA and PSA DT, are strongly associated with adverse oncologic outcomes following SRT and should be considered in management decisions.

PATIENT SUMMARY
In this report of men with prostate cancer who developed a prostate-specific antigen (PSA) recurrence after prostatectomy, we found that PSA levels after surgery and how quickly a PSA level doubles significantly impact the chance of prostate cancer recurrence after salvage radiation therapy. Based on this information, we created a tool to calculate a man's chance of cancer recurrence after salvage radiation therapy, and these estimations can be used to discuss whether additional treatment with radiation should be considered.

Campbell|Shauna R|SR|
Tom|Martin C|MC|
Agrawal|Shree|S|
Efstathiou|Jason A|JA|
Michalski|Jeff M|JM|
Abramowitz|Matthew C|MC|
Pollack|Alan|A|
Spratt|Daniel E|DE|
Hearn|Jason W D|JWD|
Stephans|Kevin L|KL|
Gao|Tianming|T|
Li|Jianbo|J|
Tendulkar|Rahul D|RD|

Prostate-specific antigen kinetics
Nomogram
Salvage radiation
Postprostatectomy outcomes
Prostate-specific antigen doubling time


Work or family or both? Value trajectories and their prediction over ten years.

Abstract: Previous studies have shown that values are developed during young adulthood. This study investigated whether and when developmental trajectories of values depend on gender, language region, cognitive competence, expected education duration, and ambition. Longitudinal data of 2620 adolescents in Switzerland were collected at eight waves of measurement over 10 years. Latent growth model analysis revealed that work values mainly increase between ages 16 and 20, whereas family values primarily increase after age 20. This pattern fits the major life and career roles sequence: Becoming established in one's career comes first, and focusing on family building follows later. The initial levels and development of values were essentially affected by gender, but other individual factors such as cognitive competence, expected education duration, and ambition also showed some effect, particularly on family values. These new insights into the development of values improve the understanding of the career decisions and career behavior of adolescents.

Tschopp|Cécile|C|
Keller|Anita C|AC|
Stalder|Barbara E|BE|

Value trajectories
Longitudinal data
Adolescents
Latent growth model
Family values
Intrinsic work values


Control by Low Levels of Calcium of Mammalian Cell Membrane Electropermeabilization.

Abstract: Electric pulses, when applied to a cell suspension, induce a reversible permeabilization of the plasma membrane. This permeabilized state is a long-lived process (minutes). The biophysical molecular mechanisms supporting the membrane reorganization associated to its permeabilization remain poorly understood. Modeling the transmembrane structures as toroidal lipidic pores cannot explain why they are long-lived and why their resealing is under the control of the ATP level. Our results describe the effect of the level of free Calcium ions. Permeabilization induces a Ca2+ burst as previously shown by imaging of cells loaded with Fluo-3. But this sharp increase is reversible even when Calcium is present at a millimolar concentration. Viability is preserved to a larger extent when submillimolar concentrations are used. The effect of calcium ions is occurring during the resealing step not during the creation of permeabilization as the same effect is observed if Ca2+ is added in the few seconds following the pulses. The resealing time is faster when Ca2+ is present in a dose-dependent manner. Mg2+ is observed to play a competitive role. These observations suggest that Ca2+ is acting not on the external leaflet of the plasma membrane but due to its increased concentration in the cytoplasm. Exocytosis will be enhanced by this Ca2+ burst (but hindered by Mg2+) and occurs in the electropermeabilized part of the cell surface. This description is supported by previous theoretical and experimental results. The associated fusion of vesicles will be the support of resealing.

Ciobanu|Florin|F| Golzio|Muriel|M| Kovacs|Eugenia|E| Teissié|Justin|J|0000-0002-7588-8062

Calcium
Electropermeabilization
Electroporation
Membrane repair


Mixed vitiligo of Blaschko lines: a newly discovered presentation of vitiligo responsive to combination treatment.

Abstract: Vitiligo, depigmenting disorder of the skin and mucous membranes, affects up to 1% of the population worldwide. It is classified into four major types: segmental, non-segmental, mixed, and unclassified type. Non-segmental vitiligo refers to non-dermatomal distribution of lesions, while dermatomal distribution of lesions is present in patients with segmental vitiligo. Segmental vitiligo can also follow Blaschko lines - pathways of epidermal cell migration and proliferation during the development of the fetus. Here, we present patient with segmental and non-segmental vitiligo following Blaschko lines with excellent therapeutic response to combined therapy. Prior to our report, a case of segmental and non-segmental vitiligo followed by Blaschko lines was never described, therefore we suggest the term "mixed vitiligo of Blaschko lines" to describe this entity. This is also a rare case in which 90% repigmentation was achieved in patient with segmental and nonsegmental vitiligo following Blaschko lines in only 2 months of combined therapy.

Kovacevic|Maja|M|
Stanimirovic|Andrija|A|
Vucic|Majda|M|
Goren|Andy|A|
Situm|Mirna|M|
Lukinovic Skudar|Vesna|V|
Lotti|Torello|T|


Debridement and implant retention in the management of hip periprosthetic joint infection: outcomes following guided and rapid treatment at a single centre.

Abstract:
AIMS
To analyse the effectiveness of debridement and implant retention (DAIR) in patients with hip periprosthetic joint infection (PJI) and the relationship to patient characteristics. The outcome was evaluated in hips with confirmed PJI and a follow-up of not less than two years.

PATIENTS AND METHODS
Patients in whom DAIR was performed were identified from our hip arthroplasty register (between 2004 and 2013). Adherence to criteria for DAIR was assessed according to a previously published algorithm.

RESULTS
DAIR was performed as part of a curative procedure in 46 hips in 42 patients. The mean age was 73.2 years (44.6 to 87.7), including 20 women and 22 men. In 34 hips in 32 patients (73.9%), PJI was confirmed. In 12 hips, the criteria for PJI were not fulfilled and antibiotics stopped. In 41 (89.1%) of all hips and in 32 (94.1%) of the confirmed PJIs, all criteria for DAIR were fulfilled. In patients with exogenous PJI, DAIR was performed not more than three days after referral. In haematogenous infections, the duration of symptoms did not exceed 21 days. In 28 hips, a single debridement and in six hips two surgical debridements were required. In 28 (87.5%) of 32 patients, the total treatment duration was three months. Failure was noted in three hips (9%). Long-term follow-up results (mean 4.0 years, 1.4 to 10) were available in 30 of 34 (88.2%) confirmed PJIs. The overall successful outcome rate was 91% in 34 hips, and 90% in 30 hips with long-term follow-up results.

CONCLUSION
Prompt surgical treatment with DAIR, following strict diagnostic and therapeutic criteria, in patients with suspected periprosthetic joint infection, can lead to high rates of success in eradicating the infection. Cite this article: Bone Joint J 2017;99-B:330-6.

Sendi|P||
Lötscher|P O|PO|
Kessler|B|B|
Graber|P|P|
Zimmerli|W|W|
Clauss|M|M|

D000328:Adult
D000368:Aged
D000369:Aged, 80 and over
D000900:Anti-Bacterial Agents
D019644:Arthroplasty, Replacement, Hip
D001424:Bacterial Infections
D003131:Combined Modality Therapy
D003646:Debridement
D005260:Female
D005500:Follow-Up Studies
D006621:Hip Joint
D006622:Hip Prosthesis
D006801:Humans
D008297:Male
D008875:Middle Aged
D060489:Prosthesis Retention
D016459:Prosthesis-Related Infections
D016896:Treatment Outcome

Debridement
Implant retention
Periprosthetic joint infection


The flavin transferase ApbE flavinylates the ferredoxin:NAD+-oxidoreductase Rnf required for N2 fixation in Azotobacter vinelandii.

Abstract: Azotobacter vinelandii, the model microbe in nitrogen fixation studies, uses the ferredoxin:NAD+-oxidoreductase Rnf to regenerate ferredoxin (flavodoxin), acting as an electron donor for nitrogenase. However, the relative contribution of Rnf to nitrogenase functioning is unknown because this bacterium contains another ferredoxin reductase, FixABCX. Furthermore, Rnf is flavinylated in the cell, but the importance and pathway of this modification reaction also remain largely unknown. We constructed A. vinelandii cells with impaired activities of FixABCX and/or putative flavin transferase ApbE. The ApbE-deficient mutant could not produce covalently flavinylated membrane proteins and demonstrated markedly decreased flavodoxin:NAD+ oxidoreductase activity and significant growth defects under diazotrophic conditions. The double ΔFix/ΔApbE mutation abolished the flavodoxin:NAD+ oxidoreductase activity and the ability of A. vinelandii to grow in the absence of a fixed nitrogen source. ApbE flavinylated a truncated RnfG subunit of Rnf1 by forming a phosphoester bond between flavin mononucleotide and a threonine residue. These findings indicate that Rnf (presumably its Rnf1 form) is the major ferredoxin-reducing enzyme in the nitrogen fixation system and that the activity of Rnf depends on its covalent flavinylation by the flavin transferase ApbE.

flavin transferase ApbE
ferredoxin:NAD+-oxidoreductase Rnf
Azotobacter vinelandii
nitrogen fixation
covalently bound flavin


Morphological De-com-pos-it-ion Helps Recognize Low-er Frequency Words in Typically Developing Spanish-Speaking Children.

Abstract: Several studies in Spanish and other languages have shown that, in a lexical decision task, children are more likely to accept pseudowords with a known morphological structure as words as compared to non-morphological pseudowords. Morphology also facilitates visual word recognition of actual words in children with reading difficulties. In the present study, we explored the role of morphology, frequency and reading proficiency (measured by school grade) in visual word recognition. Typically developing readers of Spanish from 2nd, 4th and 6th grades performed a lexical decision task in which the morphological complexity and the frequency of the words were factorially manipulated. Our results showed that morphology benefited the accuracy of visual word recognition for low frequency words only. We conclude that decomposition in morphemes occurs in Spanish only for less frequent words. These results in Spanish support models that posit the decomposition of morphologically complex words in the orthographic lexicon.

Spanish
Lexical decision
Literacy acquisition
Morphological processing
Word frequency


Publication of surgeon specific outcome data: a review of implementation, controversies and the potential impact on surgical training.

Abstract: Government-mandated publication of named surgeon-specific outcome data (SSD) has recently been introduced across nine surgical speciality areas in England. This move is the first time that such national data has been released in any country, and it promises to provide a significant advancement in health service transparency. Data is derived from nine preexisting national surgical audit databases. However, eight of these were not originally designed for this purpose, and there is considerable controversy surrounding data quality, risk adjustment, patient use and interpretation, and surgeons' subsequent case selection. Concerns also surround the degree to which these results truly reflect the individual consultant, or the wider hospital team and accompanying resources. The potential impact on surgical training has largely been overlooked. This paper investigated the background to SSD publication and controversies surrounding this, the potential impact on surgical training and the response to these concerns from medical and surgical leaders. As SSD collection continues to be refined, the most appropriate outcomes measurements need to be established, and risk adjustment requires ongoing improvement and validation. Prospective evaluation of changes in surgical training should be undertaken, as any degradation of will have both short and long-term consequences for patients and surgeons alike. It is important that the literature supporting the safety of supervised trainee practice is also promoted in order to counterbalance any potential concerns that might detract from trainee operating opportunities. Finally, it is important that outcomes data is communicated to patients in the most meaningful way in order to facilitate their understanding and interpretation given the complexities of the data and analysis involved.

Radford|P D|PD|
Derbyshire|L F|LF|
Shalhoub|J|J|
Fitzgerald|J E F|JEF|
|||


Elevated ROS depress mitochondrial oxygen utilization efficiency in cardiomyocytes during acute hypoxia.

Abstract: Mitochondria are important sites for the production of ATP and the generation of ROS in cells. However, whether acute hypoxia increases ROS generation in cells or affects ATP production remains unclear, and therefore, monitoring the changes in ATP and ROS in living cells in real time is important. In this study, cardiomyocytes were transfected with RoGFP for ROS detection and MitGO-Ateam2 for ATP detection, whereby ROS and ATP production in cardiomyocytes were respectively monitored in real time. Furthermore, the oxygen consumption rate (OCR) of cardiomyocytes was measured. Similar results were produced for adult and neonatal rat cardiomyocytes. Hypoxia (1% O2) reduced the basal OCR, ATP-linked OCR, and maximal OCR in cardiomyocytes compared with these OCR levels in the cardiomyocytes in the normoxic group (21% O2). However, ATP-linked OCR, normalized to maximal OCR, was increased during hypoxia, indicating that the electron leakage of complex III exacerbated the increase of ATP-linked oxygen consumption during hypoxia and vice versa. Combined with the result that cardiomyocytes expressing MitGO-Ateam2 showed a significant decrease in ATP production during hypoxia compared with that of normoxic group, acute hypoxia might depress the mitochondrial oxygen utilization efficiency of the cardiomyocytes. Moreover, cardiomyocytes expressing Cyto-RoGFP or IMS-RoGFP showed an increase in ROS generation in the cytosol and the mitochondrial intermembrane space (IMS) during hypoxia. All of these results indicate that acute hypoxia generated more ROS in complex III and increased mitochondrial oxygen consumption, leading to less ATP production. In conclusion, acute hypoxia depresses the mitochondrial oxygen utilization efficiency by decreasing ATP production and increasing oxygen consumption as a result of the enhanced ROS generation at mitochondrial complex III.

Zhao|Ru-Zhou|RZ| Wang|Xiao-Bo|XB| Jiang|Shuai|S| Ru|Ning-Yu|NY| Jiao|Bo|B| Wang|Yun-Ying|YY| Yu|Zhi-Bin|ZB|0000-0001-5357-9288

D000255:Adenosine Triphosphate
D000818:Animals
D015687:Cell Hypoxia
D002478:Cells, Cultured
D014450:Electron Transport Complex III
D008929:Mitochondria, Heart
D032383:Myocytes, Cardiac
D051381:Rats
D017207:Rats, Sprague-Dawley
D017382:Reactive Oxygen Species

Oxygen utilization efficiency
Cardiomyocyte
Hypoxia
ROS generation
ATP production
Mitochondrial oxygen consumption


Candidemia in pediatric burn patients: Risk factors and outcomes in a retrospective cohort study.

Abstract:
Background and Purpose
Despite advances in burn care and management, infections are still a major contributor to morbidity and mortality rates in patients with burn injuries. Regarding this, the present study was conducted to investigate the prevalence and importance of candidemia in pediatric burn patients.

Materials and Methods
Blood samples were collected from the patients and cultured in an automated blood culture system. Candida species were identified using specific culture media. The relationship between candidemia and possible risk factors was evaluated and compared to a control group.

Results
A total of 71 patients with the mean age of 4.52±3.63 years were included in the study. Blood cultures showed candidemia in 19 (27%) patients. Based on the results, C. albicans was the most common fungus among patients with and without candidemia. The results of statistical analysis also showed that candidemia was significantly correlated with total body surface area (TBSA), mechanical ventilation, duration of total parenteral nutrition, length of intensive care unit (ICU) stay, presence of neutropenia, and R-Baux score (all P≤0.001). In this regard, TBSA, length of ICU stay, R-Baux score, and Candida score were identified as the determinant factors for mortality due to candidemia.

Conclusion
Candidemia increases the mortality and morbidity rates associated with burn injuries. Prompt diagnostic and prevention measures can reduce the unfortunate outcomes via controlling the possible risk factors.

Sobouti|Behnam|B| Dahmardehei|Mostafa|M| Fallah|Shahrzad|S| Karrobi|Majid|M| Ghavami|Yaser|Y| Vaghardoost|Reza|R|

Candidemia
Pediatric burn
Burn injury
C. Glabrata
C. Krusei
Candida albicans


Reliability of Leg and Vertical Stiffness During High Speed Treadmill Running.

Abstract: In research, the accurate and reliable measurement of leg and vertical stiffness could contribute to valid interpretations. The current study aimed at determining the intraparticipant variability (ie, intraday and interday reliabilities) of leg and vertical stiffness, as well as related parameters, during high speed treadmill running, using the "sine-wave" method. Thirty-one males ran on a treadmill at 6.67 m∙s-1, and the contact and flight times were measured. To determine the intraday reliability, three 10-s running bouts with 10-min recovery were performed. In addition, to examine the interday reliability, three 10-s running bouts on 3 separate days with 48-h interbout intervals were performed. The reliability statistics included repeated-measure analysis of variance, average intertrial correlations, intraclass correlation coefficients (ICCs), Cronbach's α reliability coefficient, and the coefficient of variation (CV%). Both intraday and interday reliabilities were high for leg and vertical stiffness (ICC > 0.939 and CV < 4.3%), as well as related variables (ICC > 0.934 and CV < 3.9%). It was thus inferred that the measurements of leg and vertical stiffness, as well as the related parameters obtained using the "sine-wave" method during treadmill running at 6.67 m∙s-1, were highly reliable, both within and across days.

D003198:Computer Simulation
D055119:Elastic Modulus
D005080:Exercise Test
D006801:Humans
D007866:Leg
D008297:Male
D008954:Models, Biological
D005082:Physical Exertion
D015203:Reproducibility of Results
D012420:Running
D012680:Sensitivity and Specificity
D055815:Young Adult

contact and flight time
kinetics
reproducibility
step length and rate
“sine-wave”


Rhodium(III)-catalyzed three-component reaction of imines, alkynes, and aldehydes through C-H activation.

Abstract: An efficient rhodium(III)-catalyzed tandem three-component reaction of imines, alkynes and aldehydes through CH activation has been developed. High stereo- and regioselectivity, as well as good yields were obtained in most cases. The simple and atom-economical approach offers a broad scope of substrates, providing polycyclic skeletons with potential biological properties.

Huang|Ji-Rong|JR| Song|Qiang|Q| Zhu|Yu-Qin|YQ| Qin|Liu|L| Qian|Zhi-Yong|ZY| Dong|Lin|L|

CH activation
cyclization
multicomponent reactions
rhodium


Bowl Inversion in an Exo-type Supramolecule in the Solid State.

Abstract: Bowl inversion is a unique property of buckybowls. The polarity and assembly configuration of buckybowls are reversed after bowl inversion. So far, this unique phenomenon has been studied in solution and on surface, but not in solid state due to spatial constraint. Now a series of exo-type supramolecular assemblies of trithiasumanene and nanographene are investigated. Tuning the electron density of the nanogaphene component was found to directly affect the binding constant of the complex. Reversible bowl inversion in the solid state was then successfully achieved by subjecting the trithiasumanene-nanographene assembly with the weakest binding strength to repeated heating-cooling cycles, which was unambiguously observed by single crystal X-ray diffraction.

bowl inversion
buckybowls
exo-complex
supramolecular chemistry


Conductively coupled flexible silicon electronic systems for chronic neural electrophysiology.

Abstract: Materials and structures that enable long-term, intimate coupling of flexible electronic devices to biological systems are critically important to the development of advanced biomedical implants for biological research and for clinical medicine. By comparison with simple interfaces based on arrays of passive electrodes, the active electronics in such systems provide powerful and sometimes essential levels of functionality; they also demand long-lived, perfect biofluid barriers to prevent corrosive degradation of the active materials and electrical damage to the adjacent tissues. Recent reports describe strategies that enable relevant capabilities in flexible electronic systems, but only for capacitively coupled interfaces. Here, we introduce schemes that exploit patterns of highly doped silicon nanomembranes chemically bonded to thin, thermally grown layers of SiO2 as leakage-free, chronically stable, conductively coupled interfaces. The results can naturally support high-performance, flexible silicon electronic systems capable of amplified sensing and active matrix multiplexing in biopotential recording and in stimulation via Faradaic charge injection. Systematic in vitro studies highlight key considerations in the materials science and the electrical designs for high-fidelity, chronic operation. The results provide a versatile route to biointegrated forms of flexible electronics that can incorporate the most advanced silicon device technologies with broad applications in electrical interfaces to the brain and to other organ systems.

Li|Jinghua|J|
Song|Enming|E|
Chiang|Chia-Han|CH|
Yu|Ki Jun|KJ|
Koo|Jahyun|J|
Du|Haina|H|
Zhong|Yishan|Y|
Hill|Mackenna|M|
Wang|Charles|C|
Zhang|Jize|J|
Chen|Yisong|Y|
Tian|Limei|L|
Zhong|Yiding|Y|
Fang|Guanhua|G|
Viventi|Jonathan|J|0000-0001-6054-0541
Rogers|John A|JA|

flexible electronics
bioelectronics
brain interface
neuroscience