Σάββατο 10 Ιουνίου 2017

Site-saturation mutagenesis library construction and screening for specific broad-spectrum single-domain antibodies against multiple Cry1 toxins

Abstract

Potential ecological environmental and food safety risks of various Cry toxins of Bacillus thuringiensis (Bt) in transgenic food have received gradually increasing attention, which urged to establish an efficient and broad-spectrum detection technology for Cry toxins. Based on the single-domain antibody (sdAb) A8 against Bt Cry1Ab toxin screened from the humanized domain antibody library, the key amino acids of sdAb (A8) binding five kinds of Cry1 toxins were predicted using homology modeling and molecular docking technology, and the results showed that 105th asparagine, 106th arginine, 107th valine, and 114th arginine, respectively, located in heavy-chain complementarity-determining region 3 were common key amino acid sites. Subsequently, site-saturation cooperative mutagenesis of the four key sites was performed using overlap extension PCR, and multiple site-saturation mutagenesis sdAb library with the capacity of 1.2 × 105 colony-forming units (CFU) was successfully constructed. With alternating five Cry1 toxins as coating antigen, two generic sdAbs (2-C1, 2-C9) were screened out from the mutagenesis library, which could detect six kinds of Cry1 toxins at least. Through ELISA analysis, the binding activity of 2-C9 was significantly enhanced, and its OD values versus Cry1Aa, Cry1Ab, Cry1B, Cry1C, and Cry1E increased to 1.34, 1.53, 1.82, 2.39, and 2.7 times, respectively, compared with maternal antibody A8. The IC50 values of 2-C9 against Cry1Aa, Cry1Ab, Cry1B, and Cry1C were lower than that of A8, which showed that the affinity of 2-C9 against Cry1 toxins was enhanced. The results were beneficial to developing high-throughput and high-sensitive immune-detecting technology for Cry toxins.



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Lichenysin production is improved in codY null Bacillus licheniformis by addition of precursor amino acids

Abstract

Lichenysin is categorized into the family of lipopeptide biosurfactants and has a variety of applications in the petroleum industry, bioremediation, pharmaceuticals, and the food industry. Currently, large-scale production is limited due to the low yield. This study found that lichenysin production was repressed by supplementation of extracellular amino acids. The global transcriptional factor CodY was hypothesized to prevent lichenysin biosynthesis under an amino acid-rich condition in Bacillus licheniformis. Thus, the codY null strain was constructed, and lichenysin production was increased by 31.0% to 2356 mg/L with the addition of precursor amino acids, and the lichenysin production efficiency was improved by 42.8% to 98.2 mg/L• h. Correspondingly, the transcription levels of the lichenysin synthetase gene lchAA, and its corresponding regulator genes comA, degQ, and degU, were upregulated. Also, the codY deletion enhanced biosynthesis of lichenysin precursor amino acids (Gln, Ile, Leu, and Val) and reduced the formation of byproducts, acetate, acetoin, and 2,3-butanediol. This study firstly reported that lichenysin biosynthesis was negatively regulated by CodY and lichenysin production could be further improved with the precursor amino acid amendment in the codY null strain.



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Frailty, polypharmacy, and potentially inappropriate medications in old people: findings in a representative sample of the French population

Abstract

Purpose

This study analyses the relationship between medication use and frailty by considering the quantity of medications prescribed (polypharmacy) and the quality of medication prescribing (according to French criteria for Potentially Inappropriate Medications—PIMs) in people aged 65 and over.

Methods

This is a cross-sectional study based on the data from a nationally representative study about health and use of healthcare resources in France (ESPS 2012). The number of frailty criteria was assessed among exhaustion, unintentional weight loss, muscle weakness, impaired mobility, and low level of physical activity. Polypharmacy and PIMs were assessed from the data of reimbursement by the National Health Insurance over the whole year 2012. PIMs were defined according to the Laroche list plus additional criteria dealing with inappropriate prolonged use of medications. The analyses used Poisson regression models, with the number of frailty criteria as dependent variable.

Results

The study population was composed of 1003 women and 887 men, of mean age 74.7 +/− 7.4 years. Polypharmacy (5 to 9 drugs) and excessive polypharmacy (≥10 drugs) were reported in 42.9 and 27.4% of the study population, respectively, while 46.7% of the study population received at least one PIM during the year 2012. Polypharmacy and PIMs were both associated with the number of frailty criteria in models adjusted for socio-demographic and health characteristics of the participants. The prescription of anticholinergic medications was the only PIM that remained significantly associated with the number of frailty criteria after adjustment for polypharmacy.

Conclusions

Polypharmacy and use of anticholinergic medications are independently associated with frailty in old people.



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Suppressing the CRISPR/Cas adaptive immune system in bacterial infections

Abstract

Clustered regularly interspaced short palindromic repeats (CRISPR) coupled with CRISPR-associated (Cas) proteins (CRISPR/Cas) are the adaptive immune system of eubacteria and archaebacteria. This system provides protection of bacteria against invading foreign DNA, such as transposons, bacteriophages and plasmids. Three-stage processes in this system for immunity against foreign DNAs are defined as adaptation, expression and interference. Recent studies suggested a correlation between the interfering of the CRISPR/Cas locus, acquisition of antibiotic resistance and pathogenicity island. In this review article, we demonstrate and discuss the CRISPR/Cas system's roles in interference with acquisition of antibiotic resistance and pathogenicity island in some eubacteria. Totally, these systems function as the adaptive immune system of bacteria against invading foreign DNA, blocking the acquisition of antibiotic resistance and virulence factor, detecting serotypes, indirect effects of CRISPR self-targeting, associating with physiological functions, associating with infections in humans at the transmission stage, interfering with natural transformation, a tool for genome editing in genome engineering, monitoring foodborne pathogens etc. These results showed that the CRISPR/Cas system might prevent the emergence of virulence both in vitro and in vivo. Moreover, this system was shown to be a strong selective pressure for the acquisition of antibiotic resistance and virulence factor in bacterial pathogens.



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Surgical and Advanced Medical Therapy for the Treatment of Type 2 Diabetes in Class I Obese Patients: a Short-Term Outcome

Abstract

Background

Bariatric surgery, incretin-based therapy (glucagon-like peptide-1 analogues), and sodium-glucose co-transporter 2 (SGLT2) inhibitors have antidiabetic properties in morbidly obese patients. However, their comparative efficacy in treating type 2 diabetes mellitus (T2DM) in class I obese patients specifically in Indian has not been studied yet. This study evaluates and compares the efficacy and side effect of surgical and advanced medical management of T2DM in class I obese patients.

Methods

T2DM patients with body mass index ranging from 30 to 35 kg/m2 and with a median duration of 3 years and HbA1c level >7.5% were recruited for the study. Selection of treatment option that is bariatric surgery, GLP-1 analogues and SGLT2 inhibitor, was kept on patient's choice. Each group had 30 patients after 12 months of follow-up. Fasting plasma glucose (FPG), HbA1c, and lipid profile levels were assessed at baseline and after 12 months of follow-up.

Results

There was statistically significant lowering of HbA1c and FPG after 12 months in all the three groups. However, this lowering was clinically insignificant in GLP-1 and SGLT2 groups. There was also improvement in lipid profile values in all the three groups with significantly higher percentage change in bariatric surgery group when compared to other modalities.

Conclusions

Bariatric surgery is a safe and effective procedure to treat T2DM in class I obese patients. It is also superior to advance medical treatment modalities such as GLP-1 analogues and SGLT2 inhibitors.



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The Association of SNP276G>T at Adiponectin Gene with Insulin Resistance and Circulating Adiponectin in Morbid Obese Patients After a Biliopancreatic Diversion Surgery

Abstract

Background

The effects of rs1501299 variant of ADIPO gene on weight loss after bariatric surgery have not been evaluated. We decided to investigate the role of this genetic variant on anthropometric and biochemical outcomes such as serum adiponectin levels after biliopancreatic diversion (BPD) surgery in morbidly obese patients during 3 years.

Material and Methods

A sample of 64 patients with morbid obesity without diabetes mellitus was operated. Biochemical and anthropometric evaluation were realized at basal visit and at each visit during 3 years (1, 2, and 3 years).

Results

Percent excess weight loss, body mass index, weight, waist circumference, fat mass, blood pressure, fasting glucose, LDL cholesterol, total cholesterol, and triglycerides levels improved in both genotype groups. Fasting insulin levels and HOMA-IR decreased significantly only in non-T allele carriers. The decrease of fasting insulin levels at 3 years (delta −9.2 ± 3.4 vs −2.9 ± 2.2 mUI/L; p = 0.01) and HOMA-IR (delta −1.3 ± 0.3 vs −0.8 ± 0.4 units; p = 0.03) were higher in non-T allele carriers than T carriers. Adiponectin levels increased in all times after surgery in non-T allele carriers, too. The increase of adiponectin levels at 3 years (delta 12.2 ± 3.6 vs 1.8 ± 1.2 ng/mL; p = 0.01) was higher in non-T allele carriers than T carriers.

Conclusion

Non-T allele of ADIPOQ gene variant (rs1501299) is associated with increases in adiponectin levels and better improvements of insulin and HOMA-IR after BPD massive weight loss. These parameters remained unchanged in T allele carriers



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Recurrent or symptomatic residual posterior fossa hemangioblastomas: how are they different from their primary counterparts?

Abstract

Background

Posterior fossa hemangioblastomas are WHO grade I benign lesions with a surprisingly high recurrence rate. This study determines the factors responsible for recurrence and the clinico-radiological and histopathological differences between primary (group A; n = 60) and recurrent/symptomatic residual (group B; n = 24) tumors.

Methods

Radiologically, tumors were differentiated into cystic, cystic with a mural nodule, solid-cystic/microcystic and solid. Surgery was undertaken via a midline or lateral suboccipital approach. Histopathology differentiated them into reticular, cellular or mixed subtypes.

Results

Truncal-appendicular ataxia in group A and von Hippel-Lindau (VHL) disease and raised intracranial pressure in group B were the predominant presentations. VHL patients in group B had a longer duration of symptoms (median 72 months) than those with non-VHL recurrences (median: 36 months). Multicentric mural nodules (n = 9/24, 37.50%, P = 0.0001) and bilateral cerebellar hemispheric involvement (n = 6/24, 25%, P = 0.0003) were exclusively seen in the preoperative radiology of group B tumors. Brainstem involvement was seen in the tumors of ten (16.67%) patients in group A and six (25.00%) patients in group B. One subset of patients required several resurgeries for repeated recurrences. Abnormal vascular proliferation and papillary projections into adjacent brain, and highly cellular stroma were unique histological features at recurrence. Total resection was achieved in 45 group A and 19 group B patients. The outcome based on the Karnofsky performance scale (KPS) was assessed at follow-up at 6 weeks (A: n = 60, B: n = 24): KPS0: A = 4, B = 1; KPS10–40 (dependent): A: 4, B = 5; KPS50–70 (independent for daily needs): A = 36, B = 16; KPS80–100 (fully independent): A = 16; B = 2.

Conclusions

In recurrent/residual tumors, the radiological as well as histopathological features showed a distinctive change toward a more aggressive nature. Higher incidences of multiple mural nodules, bilateral spread, remote recurrence and VHL disease at preoperative radiology; as well as proliferative angioarchitecture, an irregular brain tumor interface and highly cellular stroma at histology were found in these patients compared to their primary counterparts.



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Characterization of an Lrp/AsnC family regulator SCO3361, controlling actinorhodin production and morphological development in Streptomyces coelicolor

Abstract

Lrp/AsnC family regulators have been found in many bacteria as crucial regulators controlling diverse cellular processes. By genomic alignment, we found that SCO3361, an Lrp/AsnC family protein from Streptomyces coelicolor, shared the highest similarity to the SACE_Lrp from Saccharopolyspora erythraea. Deletion of SCO3361 led to dramatic reduction in actinorhodin (Act) production and delay in aerial mycelium formation and sporulation on solid media. Dissection of the mechanism underlying the function of SCO3361 in Act production revealed that it altered the transcription of the cluster-situated regulator gene actII-ORF4 by directly binding to its promoter. SCO3361 was an auto-regulator and simultaneously activated the transcription of its adjacent divergently transcribed gene SCO3362. SCO3361 affected aerial hyphae formation and sporulation of S. coelicolor by activating the expression of amfC, whiB, and ssgB. Phenylalanine and cysteine were identified as the effector molecules of SCO3361, with phenylalanine reducing the binding affinity, whereas cysteine increasing it. Moreover, interactional regulation between SCO3361 and SACE_Lrp was discovered for binding to each other's target gene promoter in this work. Our findings indicate that SCO3361 functions as a pleiotropic regulator controlling secondary metabolism and morphological development in S. coelicolor.



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Radiologic features of dropped head syndrome in the overall sagittal alignment of the spine

Abstract

Purpose

Dropped head syndrome (DHS) is a rare clinical entity which is defined as a chin-on-chest deformity in the standing or sitting position, resulting from sagittal imbalance of the cervical region. The purpose of the present study was to clarify the radiologic features of DHS in the overall sagittal alignment of the spine. We also investigated the changes in sagittal alignment after correction surgery for DHS.

Methods

Twenty DHS patients [1 male and 19 female, with an average age of 78.9 years (range 59–88)] with a main complaint of horizontal gaze disorder were enrolled in this study. Spino-pelvic lateral radiographs in the free-standing clavicle position were taken of all patients. Parameters such as sagittal vertical axis (SVA), C2-7 angle, clivo-axial angle (CAA), C2-7 SVA, T1 slope, thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI), sacral slope (SS), and pelvic tilt (PT) were measured, and the radiologic features of DHS in the overall sagittal alignment of the spino-pelvis were investigated. Eight patients underwent correction surgery, and the parameter changes between pre- and post-operative radiographs were also examined.

Results

DHS appeared to have two distinct types: SVA+ and SVA−. Seven of 20 cases were SVA+, and 13 were SVA−. The radiologic parameters in which we found statistically significant differences between the groups were: 80.2 ± 68 and −44.5 ± 40 (SVA), 42.1 ± 16.8 and 18.4 ± 11.4 (T1 slope), and 21.1 ± 19.2 and 44.2 ± 19.8 (LL) in SVA+ and SVA−, respectively. After surgical intervention, T1 slope and LL appeared to approach normal in the SVA− group, because compensation at downward spine was no longer necessary. In SVA+ group, although the patients gained horizontal gaze after surgery, abnormality of the sagittal alignment in the whole spine remained, because compensation in the thoracic and lumbar spine was still insufficient.

Conclusions

The present study has indicated that radiologic feature of DHS in the sagittal alignment of the overall spino-pelvis can be categorized into two types: SVA+ and SVA−.



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Suksdorfin Promotes Adipocyte Differentiation and Improves Abnormalities in Glucose Metabolism via PPARγ Activation

Abstract

Although the Apiaceae herb family has been traditionally used for the management of type 2 diabetes, its molecular mechanism has not been clarified. Coumarin derivatives, which are abundant in plants of the Apiaceae family, were evaluated for their effects on adipogenesis. We found that suksdorfin significantly promoted adipocyte differentiation and enhanced production of adiponectin, an anti-diabetic adipokine. We also demonstrated that suksdorfin activates peroxisome proliferator-activated receptor gamma (PPARγ), a master regulator of adipogenesis. Furthermore, we showed metabolic disorders in obese diabetic KK-Ay mice were attenuated by suksdorfin feeding. Suksdorfin intake induced adipocyte miniaturization and increased expression levels of PPARγ target genes related to adipocyte differentiation. These results indicated that suksdorfin induces adipogenesis in white adipose tissue (WAT) via the activation of PPARγ, leading to improvement of obesity-induced metabolic disorders. Therefore, suksdorfin-mediated amelioration of WAT dysfunctions might be responsible for the anti-diabetic effects of traditional herbal medicine therapy with Apiaceae.



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Hirschsprung’s disease in twins: a systematic review and meta-analysis

Abstract

Aim of the study

Hirschsprung's disease (HSCR) is known to occur in families. The reported overall incidence of familial cases is 7.6%, with a higher incidence of 15–21% in total colonic aganglionosis and 50% in the rare total intestinal aganglionosis. HSCR is extremely rare in twins. The aim of this study was to systematically analyse the patterns of HSCR in twins published in the literature.

Methods

Electronic databases Pubmed and Medline were screened for relevant articles using the keywords "Hirschsprung's disease", "aganglionosis", "twins", "monozygotic", and "dizygotic". Examining reference lists identified further relevant papers.

Main results

Twelve studies with a total of 18 twin pairs were included in this analysis. 67% twins were discordant. HSCR was found in 24 out of 36 twin subjects (67%), of which 83% affected were male. Rectosigmoid type was reported in 71% of patients, long-segment disease in 21, and 8% presented with a total aganglionosis. Three twin pairs had at least one family member affected with HSCR.

Conclusion

HSCR was found in two-thirds of twin subjects with a male predominance. Rectosigmoid aganglionosis was the most common variant. Disease discordance was identified, where environmental insults were postulated to be predisposing factors to disease expression. Future studies investigating the disease-associated mutations in the already identified HSCR genes should provide insights into the genetic basis of HSCR in twins.



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Embryological and clinical implications of the association between anorectal malformations and spinal dysraphisms

Abstract

Purpose

To describe the association of anorectal malformation (ARM) and spinal dysraphism (SD) in terms of impact on the management of SD and embryogenetic implications.

Methods

Patients with SD associated with (A) or without (B) ARM were included. The two groups were further divided into operated on (A1/B1) or not (A2/B2) for SD. Groups A and B were compared for type of SD (embryogenetic classification) and prevalence of neurosurgery; Groups A1 vs. A2 for type of ARM (Wingspread classification); Groups A1 vs. B1 for age at neurosurgery, neurophysiology, and clinical symptoms.

Main results

One hundred twenty-one patients with SD, 83 with and 38 without ARM were consecutively treated (1999–2015). Group A was associated only with SDs developing after primary neurulation, corresponding to the period of cloacal septation and organogenesis (p = 0.0007). Untethering surgery was significantly less frequent in Group A (p < 0.0001 and p = 0.04, respectively). Higher ARMs were not associated with increased risk for neurosurgery. No other significant differences were detected.

Conclusions

In our series, ARMs were associated only with SD developing after primary neurulation, suggesting a single insult leading to both SD and the associated ARM. Neurosurgery is indicated less frequently in patients with ARM-associated SD, despite the similar preoperative clinical features.



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Sensory innervation of the anal canal and anorectal line in Hirschsprung’s disease: histological evidence from mouse models

Abstract

Aim

We used non-Hirschsprung's disease (HD) Sox10-Venus Transgenic mice (non-HDSV-mice), an endothelin receptor-B knockout mouse model of HD (HD-mice), and C57B6C3 wild controls (C-mice) to identify the correlation between the anorectal line (ARL) and successful transanal pull-through (TAPT).

Methods

In non-HDSV-mice, intestinal neural crest-derived cells can be visualized with Venus,—a green fluorescent protein—without histochemical staining. We exposed the anal canal in each non-HDSV-mouse and marked the ARL directly with red ink. Specimens of anus and rectum from HD- and C-mice were immunostained with sensory nerve markers substance P and calcitonin gene related peptide (CGRP) and Hematoxylin and Eosin.

Results

Stereoscopic microscopy confirmed a squamous-columnar epithelial junction corresponding to the red ink in non-HDSV-mice. Fluorescence microscopy showed intense Venus expression proximal to the ARL and little enteric nerve expression distally. Substance P and CGRP expression were strong in the basal layer of the anal transitional zone (ATZ) in both HD- and C-mice; i.e., distal sensory innervation was normal in HD-mice.

Conclusions

The ARL delineated a distinct demarcation in sensory innervation that is normal even in HD-mice. Thus, the initial incision during TAPT should be based on the ARL because it is readily identifiable and intimately involved with bowel function.



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Variability, stability, and resilience of fecal microbiota in dairy cows fed whole crop corn silage

Abstract

The microbiota of whole crop corn silage and feces of silage-fed dairy cows were examined. A total of 18 dairy cow feces were collected from six farms in Japan and China, and high-throughput Illumina sequencing of the V4 hypervariable region of 16S rRNA genes was performed. Lactobacillaceae were dominant in all silages, followed by Acetobacteraceae, Bacillaceae, and Enterobacteriaceae. In feces, the predominant families were Ruminococcaceae, Bacteroidaceae, Clostridiaceae, Lachnospiraceae, Rikenellaceae, and Paraprevotellaceae. Therefore, Lactobacillaceae of corn silage appeared to be eliminated in the gastrointestinal tract. Although fecal microbiota composition was similar in most samples, relative abundances of several families, such as Ruminococcaceae, Christensenellaceae, Turicibacteraceae, and Succinivibrionaceae, varied between farms and countries. In addition to the geographical location, differences in feeding management between total mixed ration feeding and separate feeding appeared to be involved in the variations. Moreover, a cow-to-cow variation for concentrate-associated families was demonstrated at the same farm; two cows showed high abundance of Succinivibrionaceae and Prevotellaceae, whereas another had a high abundance of Porphyromonadaceae. There was a negative correlation between forage-associated Ruminococcaceae and concentrate-associated Succinivibrionaceae and Prevotellaceae in 18 feces samples. Succinivibrionaceae, Prevotellaceae, p-2534-18B5, and Spirochaetaceae were regarded as highly variable taxa in this study. These findings help to improve our understanding of variation and similarity of the fecal microbiota of dairy cows with regard to individuals, farms, and countries. Microbiota of naturally fermented corn silage had no influence on the fecal microbiota of dairy cows.



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Persistent coxsackievirus B4 infection induces microRNA dysregulation in human pancreatic cells

Abstract

Enterovirus infections are implicated in the development of type 1 diabetes (T1D). MicroRNAs as regulators of gene expression are involved in many physiological and pathological processes. Given that viral infections dysregulate cellular microRNAs, we investigated the impact of persistent coxsackievirus B4 infection on microRNA expression of human pancreatic cells. Next-generation sequencing was used to determine microRNA expression in PANC-1 cells persistently infected (for several weeks) with coxsackievirus B4 and uninfected control cells. Target prediction restricted to T1D risk genes was performed with miRWalk2.0. Functional annotation analysis was performed with DAVID6.7. Expression of selected microRNAs and T1D risk genes was measured by quantitative reverse-transcription polymerase chain reaction. Eighty-one microRNAs were dysregulated in persistently infected PANC-1 cells. Forty-nine of the known fifty-five T1D risk genes were predicted as putative targets of at least one of the dysregulated microRNAs. Most functional annotation terms that were enriched in these 49 putative target genes were related to the immune response or autoimmunity. mRNA levels of AFF3, BACH2, and IL7R differed significantly between persistently infected cells and uninfected cells. This is the first characterization of the microRNA expression profile changes induced by persistent coxsackievirus B4 infection in pancreatic cells. The predicted targeting of genes involved in the immune response and autoimmunity by the dysregulated microRNAs as well as the dysregulated expression of diabetes risk genes shows that persistent coxsackievirus B4 infection profoundly impacts the host cell. These data support the hypothesis of a possible link between persistent coxsackievirus B4 infection and the development of T1D.



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Expert’s comment concerning Grand Rounds case entitled “Tailor made management of thoracic scoliosis with cervical hyperextension in muscular dystrophy” by A. Angelliaume et al. (Eur Spine J; 2017: doi:10.1007/s00586-017-5113-8)



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Patient-specific image denoising for ultra-low-dose CT-guided lung biopsies

Abstract

Purpose

Low-dose CT screening of the lungs is becoming a reality, triggering many more CT-guided lung biopsies. During these biopsies, the patient is submitted to repeated guiding scans with substantial cumulated radiation dose. Extension of the dose reduction to the biopsy procedure is therefore necessary. We propose an image denoising algorithm that specifically addresses the setup of CT-guided lung biopsies. It minimizes radiation exposure while keeping the image quality appropriate for navigation to the target lesion.

Methods

A database of high-SNR CT patches is used to filter noisy pixels in a non-local means framework, while explicitly enforcing local spatial consistency in order to preserve fine image details and structures. The patch database may be created from a multi-patient set of high-SNR lung scans. Alternatively, the first scan, acquired at high-SNR right before the needle insertion, can provide a convenient patient-specific patch database.

Results

The proposed algorithm is compared to state-of-the-art denoising algorithms for a dataset of 43 real CT-guided biopsy scans. Ultra-low-dose scans were simulated by synthetic noise addition to the sinogram, equivalent to a 96% reduction in radiation dose. The feature similarity score for the proposed algorithm outperformed the compared methods for all the scans in the dataset. The benefit of the patient-specific patch database over the multi-patient one is demonstrated in terms of recovered contrast for a tiny porcine lung nodule, following denoising with both approaches.

Conclusions

The proposed method provides a promising approach to the denoising of ultra-low-dose CT-guided biopsy images.



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Closed-loop regulation of arterial pressure after acute brain death

Abstract

The purpose of this concept study was to investigate the possibility of automatic mean arterial pressure (MAP) regulation in a porcine heart-beating brain death (BD) model. Hemodynamic stability of BD donors is necessary for maintaining acceptable quality of donated organs for transplantation. Manual stabilization is challenging, due to the lack of vasomotor function in BD donors. Closed-loop stabilization therefore has the potential of increasing availability of acceptable donor organs, and serves to indicate feasibility within less demanding patient groups. A dynamic model of nitroglycerine pharmacology, suitable for controller synthesis, was identified from an experiment involving an anesthetized pig, using a gradient-based output error method. The model was used to synthesize a robust PID controller for hypertension prevention, evaluated in a second experiment, on a second, brain dead, pig. Hypotension was simultaneously prevented using closed-loop controlled infusion of noradrenaline, by means of a previously published controller. A linear model of low order, with variable (uncertain) gain, was sufficient to describe the dynamics to be controlled. The robustly tuned PID controller utilized in the second experiment kept the MAP within a user-defined range. The system was able to prevent hypertension, exceeding a reference of 100 mmHg by more than 10%, during 98% of a 12 h experiment. This early work demonstrates feasibility of the investigated modelling and control synthesis approach, for the purpose of maintaining normotension in a porcine BD model. There remains a need to characterize individual variability, in order to ensure robust performance over the expected population.



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Characteristics and diversity of endophytic bacteria in moso bamboo ( Phyllostachys eduli s) based on 16S rDNA sequencing

Abstract

To understand the diversity and distribution of endophytic bacteria in moso bamboo (Phyllostachys edulis), we used 16S rDNA sequencing to investigate the characteristics and diversity of endophytic bacteria in different moso bamboo tissues. After 454 pyrosequencing, we obtained 141,269 sequences from seven moso bamboo tissue samples. The taxonomic origins of unique sequences were identified using RDP classifier. The results showed that these sequences belonged to 26 bacterial orders, including the Actinomycetales, Rickettsiales, Burkholderiales, Enterobacteriales, and Rhizobiales. Among these, Enterobacteriales was widely found in all bamboo tissues. Endophytic bacterial communities differed between the moso bamboo shoot and pole. With continuous growth and development, the number of endophytic species in the moso bamboo pole increased gradually.



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Kinetic Monte Carlo simulation of nanoparticle film formation via nanocolloid drying

Abstract

A kinetic Monte Carlo simulation of nanoparticle film formation via nanocolloid drying is presented. The proposed two-dimensional model addresses the dynamics of nanoparticles in the vertical plane of a drying nanocolloid film. The gas–liquid interface movement due to solvent evaporation was controlled by a time-dependent chemical potential, and the resultant particle dynamics including Brownian diffusion and aggregate growth were calculated. Simulations were performed at various Peclet numbers defined based on the rate ratio of solvent evaporation and nanoparticle diffusion. At high Peclet numbers, nanoparticles accumulated at the top layer of the liquid film and eventually formed a skin layer, causing the formation of a particulate film with a densely packed structure. At low Peclet numbers, enhanced particle diffusion led to significant particle aggregation in the bulk colloid, and the resulting film structure became highly porous. The simulated results showed some typical characteristics of a drying nanocolloid that had been reported experimentally. Finally, the potential of the model as well as the remaining challenges are discussed.



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Synthesis of silicon nanocomposite for printable photovoltaic devices on flexible substrate

Abstract

Renewed interest has been established in the preparation of silicon nanoparticles for electronic device applications. In this work, we report on the production of silicon powders using a simple ball mill and of silicon nanocomposite ink for screen-printable photovoltaic device on a flexible substrate. Bulk single crystalline silicon was milled for 25 h in the ball mill. The structural properties of the produced silicon nanoparticles were investigated using X-ray diffraction (XRD) and transmission electron microscopy. The results show that the particles remained highly crystalline, though transformed from their original single crystalline state to polycrystalline. The elemental composition using energy dispersive X-ray florescence spectroscopy (EDXRF) revealed that contamination from iron (Fe) and chromium (Cr) of the milling media and oxygen from the atmosphere were insignificant. The size distribution of the nanoparticles follows a lognormal pattern that ranges from 60 nm to about 1.2 μm and a mean particle size of about 103 nm. Electrical characterization of screen-printed PN structures of the nanocomposite formed by embedding the powder into a suitable water-soluble polymer on Kapton sheet reveals an enhanced photocurrent transport resulting from photo-induced carrier generation in the depletion region with energy greater that the Schottky barrier height at the metal-composite interface.



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Dissecating aneurysm of extracranial internal carotid artery presenting with Tapia syndrome in patient with essential thrombocythemia



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Prevalence of idiopathic scoliosis in anorexia nervosa patients: results from a cross-sectional study

Abstract

Purpose

A long debate exists about the connection between anorexia nervosa (AN) and scoliosis due to conflicting evidence. No study so far has evaluated the prevalence of scoliosis in patients with AN. The aim of the study is to evaluate the prevalence of idiopathic scoliosis in patients with AN.

Methods

Design: cross-sectional study. Study group: convenience sample of all patients matching the inclusion criteria. Control group: female participants coming from an epidemiological screening for scoliosis. Inclusion criteria: patients had a diagnosis of AN during adolescence according to the DSM-IV-TR criteria. We applied a two-level screening using a Bunnell scoliometer and a radiograph. We calculated the odds ratio compared with participants coming from a school screening.

Results

Seventy-seven females with AN were compared to 816 females screened for scoliosis. The prevalence of scoliosis in the AN group was 16.9% (OR 5.77, 95% CI 3.12–10.67) with respect to the control group. If we consider as positive only those who received a scoliosis diagnosis during adolescence, the OR would be 3.15 (95% CI 1.55–6.42).

Discussion

This is the first study performed on patients with AN showing a sixfold greater odds of presenting with scoliosis. A cause–effect relationship cannot be determined due to the design.



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Validity of humerus fracture classification in the Swedish fracture register

Abstract

Background

The ability to correctly classify fractures is of importance for choosing the appropriate treatment and for providing appropriate data for research and quality registers. In the Swedish Fracture Register (SFR) fractures of all types are registered by the attending physician, often a junior doctor. For the majority of fractures, a modified AO/OTA classification is used. This study aimed to validate the accuracy of classification of humerus fractures in the SFR and also at providing insight into inherent classification uncertainties.

Methods

One hundred and sixteen humerus fractures (among them 90 proximal) were retrieved by computer randomisation from the SFR and reassessed independently at two occasions, 6 weeks apart, by three senior orthopaedic surgeons blinded to patient information and a consensus "gold standard" classification was established. This was compared with the classifications that had been entered into the register.

Results

The agreement between gold standard classification and original classification in the SFR was kappa = 0.57 for all humerus fractures. For proximal humerus fractures kappa-coefficient for intra-observer agreement was 0.593, 0.599 and 0.752 for the three observers respectively. Taking into account the similarities between certain fracture groups, a modified calculation of agreement was performed. With this modification the intra-observer agreement was 0.910-0.974 and inter-observer agreement was 0.912.

Conclusion

The classification of humerus fractures in the Swedish Fracture Register was just as accurate as in previous studies, i.e. moderate as defined by Landis and Koch. However, when we introduced a modified analysis, that takes into account the similarities between certain fractures, the accuracy was "near perfect".



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Varied facets of rectal atresia and rectal stenosis

Abstract

Rectal atresia (RA) and rectal stenosis (RS) are rare anomalies with varied treatment options. A thorough literature review was done on reported cases/series of RA and RS. Based on evidence from cases managed over last 15 years, new insights into embryology were hypothesized. A comprehensive review was compiled with updated knowledge on diagnosis and management. RA is classified into five types I: II: III: IV: V as RS: RA with septal defect: RA with a fibrous cord between two atretic ends: RA with a gap: Multiple RA and/or RS. Current definitive surgical repair of these anomalies preserves the anal canal, dentate line, and sphincter complex. Most neonates with RA undergo sigmoid colostomy except few with RS who can rarely decompress adequately. Membranous RS and septal RA may seldom respond to dilatation or be amenable to transanal repair. Posterior sagittal anorectoplasty with an end-to-end/side repair is recommended for RA and most intramural RS. RS may be associated with a presacral mass and colonic/rectal motility disorders. The expected postoperative outcome is good if the normally developed anal sphincter complex is retained undamaged. Early recognition of the type of anomaly is necessary for appropriate management.



http://ift.tt/2rbZS6Z

Cerebellar Exposure to Cell-Free Hemoglobin Following Preterm Intraventricular Hemorrhage: Causal in Cerebellar Damage?

Abstract

Decreased cerebellar volume is associated with intraventricular hemorrhage (IVH) in very preterm infants and may be a principal component in neurodevelopmental impairment. Cerebellar deposition of blood products from the subarachnoid space has been suggested as a causal mechanism in cerebellar underdevelopment following IVH. Using the preterm rabbit pup IVH model, we evaluated the effects of IVH induced at E29 (3 days prior to term) on cerebellar development at term-equivalent postnatal day 0 (P0), term-equivalent postnatal day 2 (P2), and term-equivalent postnatal day 5 (P5). Furthermore, the presence of cell-free hemoglobin (Hb) in cerebellar tissue was characterized, and cell-free Hb was evaluated as a causal factor in the development of cerebellar damage following preterm IVH. IVH was associated with a decreased proliferative (Ki67-positive) portion of the external granular layer (EGL), delayed Purkinje cell maturation, and activated microglia in the cerebellar white matter. In pups with IVH, immunolabeling of the cerebellum at P0 demonstrated a widespread presence of cell-free Hb, primarily distributed in the white matter and the molecular layer. Intraventricular injection of the Hb scavenger haptoglobin (Hp) resulted in a corresponding distribution of immunolabeled Hp in the cerebellum and a partial reversal of the damaging effects observed following IVH. The results suggest that cell-free Hb is causally involved in cerebellar damage following IVH and that blocking cell-free Hb may have protective effects.



http://ift.tt/2rX5L5k

Degradation of Emerging Organic Contaminants in an Agricultural Soil: Decoupling Biotic and Abiotic Processes

Abstract

Although there is a growing interest in emerging organic contaminants (EOCs), most research is focused on wastewater treatment, the occurrence of EOCs, and their fate in the aquatic environment. There is limited information about their behavior in agricultural soils, where they can be introduced via irrigation with treated wastewater (TWW). In this study, the degradation in an agricultural soil of eight EOCs (bisphenol A, carbamazepine, diethyl phthalate, ethyl paraben, 5-methyl-1H-benzotriazole, primidone, Surfynol 104, and tris(2-chloroethyl) phosphate) with a broad range of physical-chemical properties was monitored for 40 days. Two types of soil treatments were performed: non-sterilization and sterilization. In the non-sterilized soil, by the end of the incubation period, degradation was greater than 70% for all the target compounds except carbamazepine, Surfynol 104, and primidone (<50%). In contrast, in the sterilized soil, the degradation of most of the compounds was less than 50%, except ethyl paraben, 5-methyl-1H-benzotriazole, and diethyl phthalate (>70%). These findings indicate that soil sterilization reduces overall degradation rates, which suggests that microbial activity plays an important role in the degradation of most of the EOCs studied in soil.



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Glucocorticoid-induced leucine zipper expression is associated with response to treatment and immunoregulation in systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disorder in which cytokine balance is disturbed. Glucocorticoids (GCs) are shown to balance immune response by transcriptional regulation of glucocorticoid receptor target genes such as Glucocorticoid-induced leucine zipper (GILZ) which has been introduced as an endogenous anti-inflammatory mediator. In the present study, we assessed the expression of GILZ in association with interferon-γ (IFN-γ), interleukine-10 (IL-10), and B lymphocyte stimulator (BLyS) plasma levels in SLE patients. A total of 40 female patients (18 under treatment and 22 newly diagnosed) were recruited in this study. Real-time RT PCR was conducted to quantify the mRNA expression of GILZ. The plasma levels of IFN-γ, IL-10, and BLyS were evaluated using ELISA method. GILZ was overexpressed among under treatment SLE patients. The mRNA expression of GILZ was significantly correlated with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score. IFN-γ and BLyS were downregulated in response to therapies with negative correlations to GILZ. Moreover, IL-10 was upregulated among treated patients. The levels of IFN-γ and BLyS were correlated with the severity of disease, while IL-10 was negatively correlated with SLEDAI score. GILZ could be introduced as one of the acting molecules in mediating the regulatory effects of GCs on producing pro- and anti-inflammatory cytokines in SLE.



http://ift.tt/2sowlH2

Sex-specific association between serum uric acid and self-reported snoring in rural China: a cross-sectional study

Abstract

Purpose

Until now, information has been rare on the association of serum uric acid (SUA) with self-reported snoring. Therefore, the purpose of this study was to explore the sex-specific relationship between SUA and self-reported snoring in a general Chinese population.

Methods

A large cross-sectional study of 10,912 participants aged ≥35 years old were recruited from rural areas of Liaoning Province in China during 2012 to 2013. SUA were divided into quartiles separated for males and females. Anthropometric measurements and blood biochemical indexes were examined according to standard protocols. Sleep duration and self-reported snoring status were investigated by trained personnel using a structured questionnaire.

Results

The prevalence of self-reported snoring was 37.9% (n = 2197) among females and 47.4% (n = 2420) among males, respectively. The proportion of self-reported snoring presented a significant linear increase across the quartile of SUA level in both sexes. In multivariate logistic regression analysis adjusted for possible confounders, the odds ratio (OR) for SUA with regard to self-reported snoring was significantly higher in females. The OR of self-reported snoring associated with per 1 SD increase in SUA was 1.208 (95%CI 1.118–1.305, P<0.001). The highest quartile of SUA (>293 μmol/L) conferred an independently increased risk for self-reported snoring with OR of 1.643 (95%CI 1.384–1.950, p < 0.001) compared to the lowest quartile of SUA (<209 μmol/L). However, there were no significant relationships between SUA and self-reported snoring among males in all the models.

Conclusions

Our study showed that in rural China, SUA was positively correlated with an increased risk for self-reported snoring in females but not in males. The strong association of SUA levels with self-reported snoring in females emphasizes the necessity of stratifying the sex in investigations of self-reported snoring and encourages exploration of SUA as an effective clinical tool of self-reported snoring risk.



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Essential trace elements in amyotrophic lateral sclerosis (ALS): Results in a population of a risk area of Italy

Abstract

Sardinian (Italy) island population has a uniquely high incidence of amyotrophic lateral sclerosis (ALS). Essential trace element levels in blood, hair, and urine of ALS Sardinian patients were investigated in search of valid biomarkers to recognize and predict ALS. Six elements (Ca, Cu, Fe, Mg, Se, and Zn) were measured in 34 patients compared to 30 age- and sex-matched healthy controls by a validated method. Levels of Ca and Cu in blood and of Se and Zn in hair were significantly higher in ALS than in controls, while urinary excretion of Mg and Se was significantly decreased. The selected cut-off concentrations for these biomarkers may distinguish patients with or without ALS with sufficient sensitivity and specificity. Many positive (as Se-Cu and Se-Zn) and negative associations (as Ca-Mg and Ca-Zn) between elements suggested that multiple metals involved in multiple mechanisms have a role in the ALS degeneration.



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Increased Trimethylamine-N-Oxide (TMAO) Levels After Roux-en Y Gastric Bypass Surgery—Should We Worry About It?



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Volatile organic compounds in the breath of oral candidiasis patients: a pilot study

Abstract

Objectives

The aim of the study was to investigate whether specific volatile organic compounds (VOCs) can be detected in oral candidiasis patients using breath analysis in order to develop a point-of-care diagnostic tool.

Patients/methods

Breath samples of 10 diseased patients and 10 subjects carrying no Candida spp. were analyzed using gas chromatography and mass spectrometry. In infected patients, breath tests were performed before and after antifungal therapy.

Results

Breath testing was positive for 143 volatiles in both healthy subjects and diseased patients. Among those, specific signature volatiles known to be emitted by Candida spp. in vitro were not detected. Even though no specific signature was retrieved from the diseased patients, a pattern containing nine compounds (2-methyl-2-butanol, hexanal, longifolene, methyl acetate, 1-heptene, acetophenone, decane, 3-methyl-1-butanol, chlorbenzene) was identified, which showed characteristic changes after antifungal therapy.

Conclusions

Focusing on the identified pattern, breath analysis may be applied to confirm the absence of Candida spp. after therapy in terms of a confirmatory test supplementing clinical examination, thereby replacing microbial testing. However, microbial testing will still be needed to initially confirm clinical diagnoses, as no specific signature was found.

Clinical relevance: A breath test may help in avoiding extended antifungal administration resulting in resistance development and might be useful in the monitoring of disease recurrences in vulnerable groups.



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An in vitro experimental model for analysis of central control of sympathetic nerve activity

Abstract

Newborn rat brainstem-spinal cord preparations are useful for in vitro analysis of various brainstem functions including respiratory activity. When studying the central control of sympathetic nerve activity (SNA), it is important to record peripheral outputs of the SNA. We developed an in vitro preparation in which neuronal connections between the cardiovascular center in the medulla and SNA peripheral outputs are preserved. Zero- to 1-day-old rats were deeply anesthetized with isoflurane, and the brainstem and spinal cord were isolated with a partial right thoracic cage to record sympathetic nerve discharge from the right thoracic sympathetic nerve trunk (T9–T11). SNA in this preparation was strongly modulated by inspiratory activity. Single-shot electrical stimulation of the ipsilateral rostral ventrolateral medulla (RVLM) induced a transient increase of SNA. Bath application of angiotensin II induced an increase of SNA, and local ipsilateral microinjection of angiotensin II to the RVLM induced a transient increase of SNA. This preparation allows analysis of the central control of the SNA in vitro.



http://ift.tt/2sdYl0t

Acupuncture stimulation at GB34 suppresses 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced oxidative stress in the striatum of mice

Abstract

Recent studies have suggested that increased oxidative stress is a potential etiology in Parkinson's disease (PD). In this study, we investigated whether acupuncture regulates antioxidants in the striatum (ST) of a PD mouse model. Male C57BL/6 mice were administered 30 mg/kg of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intraperitoneally once a day for 5 days and given acupuncture stimulation at SI3 or GB34 (Yanglingquan) was for 12 consecutive days. Dopaminergic neuronal survival in the nigrostriatal pathway and DJ-1 expression in the ST was evaluated by immunostaining, and the activities of superoxide dismutase (SOD) and catalase (CAT) in the ST was by enzyme-linked immunosorbent assay. MPTP administration induced dopaminergic neuronal death in the nigrostriatal pathway, which was suppressed by acupuncture stimulation at GB34. MPTP administration also suppressed DJ-1 expression and SOD and CAT activities in the ST, which were restored by acupuncture stimulation at GB34. These results indicate that the neuroprotective effect of acupuncture stimulation is due to regulation of the antioxidants.



http://ift.tt/2r5dpsZ

Effect of Molecular Dissociation and Sorbent Carbonization on Bisolute Sorption of Pharmaceuticals by Biochars

Abstract

Understanding the sorption behavior of mixtures of pharmaceuticals is critical for predicting their environmental behavior and for risk assessment. Experiments on ketoprofen (KTP) and triclosan (TCS) sorption by wheat straw-derived biochars at 300 °C (WS300) and 700 °C (WS700) in single solute and bisolute systems were conducted to probe the sorption mechanisms. The results of the single solute sorption indicated that WS700 with higher degree of carbonization had higher sorption coefficient (K d) and nonlinearity than WS300. In a bisolute system, no competitive effect was observed for partition of neutral KTP and TCS in the noncarbonized phase of WS300, but they competed for the adsorptive sites on the carbonized phase of WS300 and WS700 for sorption, in which π-π interaction is proposed as the main mechanism. The competition in the bisolute system varied with degree of dissociation of KTP and TCS, and led to a lower and less nonlinear sorption compared with that in the single solute system. TCS was more competitive than KTP due to its higher hydrophobicity, and sorption inhibition of KTP was enhanced with increasing TCS concentration. Degree of both molecular dissociation and sorbent carbonization should be considered in bisolute sorption of organic pollutants by biochars.



http://ift.tt/2t5EJIm

Hormone replacement therapy and breast cancer survival: a systematic review and meta-analysis of observational studies

Abstract

Previous studies on the association between hormone replacement therapy (HRT) and breast cancer survival have yielded mixed results. We aimed to perform a meta-analysis to assess the association with all available studies. Relevant studies were identified by searching PubMed and EMBASE to April 2017. We calculated the summary hazard ratios (HRs) and 95% confidence intervals (CIs) using random-effects models. The dose–response relationship was assessed by random-effects meta-analysis and dose–response meta-regression models. Forty cohort studies and two case–control studies involving 1,756,833 participants were included. The results showed that prediagnosis HRT use was associated with decreased risk of dying from breast cancer (HR = 0.88, 95% CI 0.81–0.97) or any cause (HR = 0.79, 95% CI 0.69–0.90). Postdiagnosis HRT use also showed a beneficial effect on breast cancer survival. In the subgroup analyses, we found that patients who were current users at diagnosis or who received combined hormone therapy before diagnosis seemed to show more benefit from HRT use. In dose–response analysis, we observed a linear relationship between prediagnosis HRT and breast cancer-specific mortality and a 1-year increment in duration of exposure to HRT conferred an HR of 0.99 (95% CI 0.98–1.00) for death from breast cancer. In conclusion, the average effect of HRT use seems not harmful to breast cancer survival. Nevertheless, this effect of HRT use is needed for further assessment.



http://ift.tt/2s7nokO

Functions of intrinsic disorder in transmembrane proteins

Abstract

Intrinsic disorder is common in integral membrane proteins, particularly in the intracellular domains. Despite this observation, these domains are not always recognized as being disordered. In this review, we will discuss the biological functions of intrinsically disordered regions of membrane proteins, and address why the flexibility afforded by disorder is mechanistically important. Intrinsically disordered regions are present in many common classes of membrane proteins including ion channels and transporters; G-protein coupled receptors (GPCRs), receptor tyrosine kinases and cytokine receptors. The functions of the disordered regions are many and varied. We will discuss selected examples including: (1) Organization of receptors, kinases, phosphatases and second messenger sources into signaling complexes. (2) Modulation of the membrane-embedded domain function by ball-and-chain like mechanisms. (3) Trafficking of membrane proteins. (4) Transient membrane associations. (5) Post-translational modifications most notably phosphorylation and (6) disorder-linked isoform dependent function. We finish the review by discussing the future challenges facing the membrane protein community regarding protein disorder.



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Application of a novel 3D drill template for cervical pedicle screw tunnel design: a cadaveric study

Abstract

Purpose

To develop and validate the efficacy and accuracy of a three-dimensional (3D) computed tomography (CT) reconstructive rapid prototyping drill template for cervical pedicle screw placement.

Methods

CT thin-layer scans were obtained from 12 adult cadaveric cervical specimens and reconstructed. The ideal screw channels were chosen by analyzing the cross sections of the reconstructed 3D images. The navigation templates were designed and printed based on the optimal screw channels. The pedicle screws were placed on the cadaver specimens under template guidance, and the cadaver specimens were scanned and reconstructed. The pre- and post-operative models were compared. Entry point and exit point data of these two models were collected and compared using the Chi-square test.

Results

A total of 164 cervical pedicle screws were placed; among them, six punctured the cortical bone of the vertebral pedicle reaching an accuracy of 96.3%. Among the outside screws, all of the deviation distances were <2 mm. The Chi-square test results showed that when a deviation of 1.2 mm was used as a standard for the entry point, there was no difference between the two groups (χ 2 = 1.346, p = 0.248); when a deviation of 2.2 mm was used as a standard for the exit point, there was no difference between the two groups (χ 2 = 3.250, p = 0.061).

Conclusion

The 3D CT reconstructive rapid prototyping drill template combined with the screw tunnel design based on 3D cutting technique can help facilitate accurate cervical pedicle screw insertion.



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Selective thoracic fusion of a left decompensated main thoracic curve: proceed with caution?

Abstract

Purpose

Previous research has shown that with certain idiopathic scoliosis curve types, performing a selective thoracic fusion (STF) is associated with an increased risk of coronal decompensation post-operatively. The purpose of the current study was to determine the influence of curve correction and fusion level on post-operative balance in STF for adolescent idiopathic scoliosis patients with pre-operative coronal decompensation.

Methods

A multicenter database was queried for subjects with right Lenke 1–4C curves, pre-operative left coronal imbalance, and 2-year follow-up who underwent STF (caudal fusion level of L1 or proximal). Rates of decompensation were compared between groups with different levels of fusion. Thoracic and lumbar curve correction as well as Scoliosis Research Society-22 outcome scores were compared between groups that were post-operatively balanced or persistently decompensated.

Results

121 patients were identified with average thoracic and lumbar curves of 53° and 41°. Mean pre- and post-operative decompensations were 2.4 ± 1.0 and 1.8 ± 1.1 cm, respectively. Eighteen patients were fused short, 62 to, and 41 were fused past the stable vertebra. Ten patients were fused short, 32 to, and 78 were fused past the neutral vertebra. Incidence of post-operative decompensation was 41%. No differences in post-operative decompensation relative to the stable or neutral vertebra were noted (p = 0.66, p = 0.74). Post-operatively, those patients who were balanced had similar thoracic curve correction (58%) to those decompensated (54%, p = 0.11); however, patients balanced post-operatively had greater SLCC (45 vs 40%, p = 0.04). No differences in SRS-22 outcome scores were noted between groups (p > 0.05).

Conclusions

There was a high rate of post-operative decompensation in patients with pre-operative coronal decompensation undergoing STF. Fusion to or past the stable or neutral vertebra did not affect the risk of persistent decompensation. Attempts to improve SLCC could reduce post-operative decompensation.



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The mechanisms underlying the variety of preoperative directionalities of shoulder tilting in adolescent idiopathic scoliosis patients with double thoracic curve

Abstract

Purpose

Preoperative directionality of shoulder tilting seems to be independent of the radiographic features of proximal thoracic (PT) curve in adolescent idiopathic scoliosis (AIS) patients. To date, no study had investigated the mechanisms underlying the variety of preoperative directionalities of shoulder tilting in AIS patients. The purpose of this study was to evaluate the differences of radiographic features between Lenke type 2 (double thoracic curve) AIS patients with different preoperative directionalities of shoulder tilting.

Methods

A total of 130 Lenke type 2 AIS patients were included in this study and were divided into two groups according to the value of radiographic shoulder height (RSH). There were 78 cases (71 females and 7 males) with RSH less than 0 cm in Group A and 52 cases (44 females and 8 males) with RSH equal to or more than 0 cm in Group B. Preoperative standing anteroposterior X-ray films of the spine were obtained in all these subjects and were analyzed with respect to the following parameters: T1 tilt, PT Cobb angle, main thoracic (MT) Cobb angle, the apical level of PT curve, the apical level of MT curve, and RSH. These parameters were compared between these two groups and the correlations between RSH and the other parameters were analyzed in all of these subjects.

Results

No significant difference was found between these two groups with respect to PT Cobb angle or the apical level of PT curve (P > 0.05). The apical level of MT curve was significantly more proximal in Group A compared with Group B (P < 0.05). The MT Cobb angle was significantly larger in Group A compared with Group B (P < 0.05). Both the T1 tilt and the PT Cobb angle/MT Cobb angle ratio in Group A were significantly smaller than those in Group B (P < 0.05). The RSH was positively associated with T1 tilt, the apical level of MT curve, and the PT Cobb angle/MT Cobb angle ratio, but was negatively associated with MT Cobb angle (P < 0.05).

Conclusion

The directionality of shoulder tilting is diverse in Lenke type 2 AIS patients. The preoperative directionality of shoulder mainly depends on the profile of MT curve rather than that of PT curve. The RSH should be carefully evaluated before making a surgical plan in these patients.



http://ift.tt/2sogRmz

Osimertinib reactivated immune-related colitis after treatment with anti-PD1 antibody for non-small cell lung cancer

Summary

We reported a case of relapsing immune-related colitis (initially caused by nivolumab) following osimertinib therapy for lung adenocarcinoma. A 45-year-old female who had never smoked was diagnosed with adenocarcinoma of the lung and underwent surgical resection. Four years after surgical resection, she was diagnosed with recurrent disease and was eventually treated with nivolumab as third-line therapy. One month after the completion of nivolumab therapy, the patient reported abdominal pain and frequent diarrhea. We diagnosed immune-related colitis and started oral prednisolone. However, the steroid therapy was ineffective, so the patient was administered infliximab and an increased dose of prednisolone. Her symptoms subsequently resolved, and her mucosal lesions improved. Six months after the last administration of nivolumab, osimertinib was initiated as fourth-line therapy, but 3 days later, the patient developed blood in the stool and frequent diarrhea. Osimertinib treatment was discontinued, given the possibility that it had reactivated the patient's immune-related colitis. We subsequently re-administered oral prednisolone (2 mg/kg/day), and the colitis resolved within a few weeks.



http://ift.tt/2rfYaN1

Perioperative outcomes of robot-assisted laparoscopic partial cystectomy

Abstract

Reports of surgical outcomes after robotic partial cystectomy are limited. The objective of this study is to review surgical outcomes after robotic partial cystectomy at a large tertiary referral center and compare outcomes with patients undergoing open partial cystectomy. Patients undergoing robotic partial cystectomy between 2003 and 2014 were identified. Patients were matched 2:1 based on gender, age, and Charlson Comorbidity Score with patients undergoing open partial cystectomy during the same time period. Patient charts were reviewed for surgical outcomes. Conditional logistic regression adjusted for matching was used to compare outcomes. At our institution, 11 patients underwent robotic partial cystectomy between 2003 and 2014. Median operative time was significantly longer in the robotic group, 214 (IQR 93, 230) minutes, than the open group, 93 (IQR 58, 143) minutes (p = 0.01). There was no difference in median estimated blood loss (p = 0.1). No patient required transfusion. There were no intraoperative complications. Median hospital stay was significantly shorter in the robotic partial cystectomy group, 1 (IQR 1, 2) day, than the open partial cystectomy group, 2 (IQR 2, 4) days (p = 0.01). Median duration of catheterization and complications within 30 days of surgery were not statistically different between the two groups. Median follow-up was 15.5 (IQR 8.6, 19.7) months for the robotic partial cystectomy group and 40.7 (IQR 6.5, 69.4) months for the open partial cystectomy group. Robotic partial cystectomy is safe, effective, and is associated with minimal morbidity when performed in properly selected patients for benign and malignant indications. When compared with open partial cystectomy, robotic partial cystectomy is associated with a longer operative time, but results in a shorter postoperative hospital stay.



http://ift.tt/2s7oRrn

Frostbite, Injury, and Trauma in the Extremities

Abstract

Purpose of Review

The objective of the study is to review the current methods of evaluating and managing both frostbite injury and non-thermal extremity vascular trauma, with an emphasis on endovascular techniques.

Recent Findings

The traditional management of frostbite has a well-established role for the rapid rewarming of injured tissues. This literature review highlights the evolution of the various management techniques with a specific focus on the more recent role of intra-vascular catheter-directed thrombolytic therapy. Non-thermal extremity trauma with resulting vascular injury requires prompt diagnosis that relies heavily on both the physical examination and the appropriate imaging.

Summary

Frostbite injury manifests as a progressive insult with distinct pathophysiologic phases during which imaging can guide appropriate care. Traditional medical management, in combination with intra-vascular catheter-directed thrombolytic regimens, can restore blood flow to poorly or non-perfused digits, thereby ultimately reducing the risk of delayed amputation. Non-thermal trauma to the extremities can result in a variety of vascular injuries. Interventional radiology plays a key role in diagnosis and an expanding role using transcatheter therapies in order to provide efficacious and optimal management of patients with vascular injury.



http://ift.tt/2t534Oj

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