Environmental Exposure History and Vulvodynia Risk: A Population-Based Study.

Abstract:
BACKGROUND
Risk factors for vulvodynia continue to be elusive. We evaluated the association between past environmental exposures and the presence of vulvodynia.

MATERIALS AND METHODS
The history of 28 lifetime environmental exposures was queried in the longitudinal population-based Woman-to-Woman Health Study on the 24-month follow-up survey. Relationships between these and vulvodynia case status were assessed using multinomial logistic regression.

RESULTS
Overall, 1585 women completed the 24-month survey, the required covariate responses, and questions required for case status assessment. Screening positive as a vulvodynia case was associated with history of exposures to home-sprayed chemicals (insecticides, fungicides, herbicides-odds ratio [OR] 2.47, 95% confidence interval [CI] 1.71-3.58, p < 0.0001), home rodent poison and mothballs (OR 1.62, 95% CI 1.25-2.09, p < 0.001), working with solvents and paints (OR 2.49, 95% CI 1.68-3.70, p < 0.0001), working as a housekeeper/maid (OR 2.07, 95% CI 1.42-3.00, p < 0.0001), working as a manicurist/hairdresser (OR 2.00, 95% CI 1.14-3.53, p < 0.05), and working at a dry cleaning facility (OR 2.13, 95% CI 1.08-4.19, p < 0.05). When classified into nine individual environmental exposure categories and all included in the same model, significant associations remained for four categories (home-sprayed chemicals, home rodent poison or mothballs, paints and solvents, and working as a housekeeper).

CONCLUSIONS
This preliminary evaluation suggests a positive association between vulvodynia and the reported history of exposures to a number of household and work-related environmental toxins. Further investigation of timing and dose of environmental exposures, relationship to clinical course, and treatment outcomes is warranted.

Reed|Barbara D|BD|
McKee|Kimberly S|KS|
Plegue|Melissa A|MA|
Park|Sung Kyun|SK|
Haefner|Hope K|HK|
Harlow|Sioban D|SD|

D000328:Adult
D000393:Air Pollutants
D004781:Environmental Exposure
D004785:Environmental Pollutants
D005260:Female
D006801:Humans
D008824:Michigan
D008875:Middle Aged
D016273:Occupational Exposure
D011159:Population Surveillance
D011446:Prospective Studies
D012307:Risk Factors
D011795:Surveys and Questionnaires
D056650:Vulvodynia
D016387:Women's Health

environmental exposures
vulvodynia
risk
population based


Overexpression of Candida albicans Secreted Aspartyl Proteinase 2 or 5 Is Not Sufficient for Exacerbation of Immunopathology in a Murine Model of Vaginitis.

Abstract: The secreted aspartyl proteinases of Candida albicans have long been implicated in virulence at the mucosal surface, including contributions to colonization and immunopathogenesis during vulvovaginal candidiasis. In an effort to disentangle hypha-associated virulence factor regulation from morphological transition, the purpose of this study was to determine if overexpression of SAP2 or SAP5 in an efg1Δ/Δ cph1Δ/Δ mutant could restore the capacity to cause immunopathology during murine vaginitis to this avirulent hypofilamentous strain. Two similar yet distinct genetic approaches were used to construct expression vectors to achieve SAP overexpression, and both genetic and functional assays confirmed elevated SAP activity in transformed strains. Similar to previous findings, intravaginal challenge of C57BL/6 mice with hypha-defective strains attained high levels of mucosal colonization but failed to induce robust vaginal immunopathology (neutrophil recruitment, interleukin-1β [IL-1β] secretion, and lactate dehydrogenase release) compared to that with the hypha-competent control. Moreover, constitutive expression of SAP2 or SAP5 in two distinct sets of such strains did not elicit immunopathological markers at levels above those observed during challenge with isogenic empty vector controls. Therefore, these results suggest that the physiological contributions of SAPs to vaginal immunopathology require hypha formation, other hypha-associated factors, or genetic interaction with EFG1 and/or CPH1 to cause symptomatic infection. Additionally, the outlined expression strategy and strain sets will be useful for decoupling other downstream morphogenetic factors from hyphal growth.

Willems|Hubertine M E|HME|
Bruner|Winter S|WS|
Barker|Katherine S|KS|
Liu|Junyan|J|
Palmer|Glen E|GE|
Peters|Brian M|BM|

Candida
vaginitis
vulvovaginal
virulence factors
SAPs
fungal
pathogenesis


Determining the effect of malondialdehyde on the IgE-binding capacity of shrimp tropomyosin upon in vitro digestion.

Abstract:
BACKGROUND
Stability in simulated gastric fluids is considered an important parameter for the estimation of food allergenicity. Moreover, proteins in food are highly susceptible to lipid oxidation during processing and preservation. In this study, the change in the IgE-binding capacity of malondialdehyde (MDA)-treated shrimp tropomyosin (TM) following in vitro digestion was investigated by SDS-PAGE and western blot.

RESULTS
Shrimp TM treated with different concentrations of MDA was slightly degraded and became increasingly resistant to pepsin digestion over time. While untreated TM was rapidly degraded, MDA-treated TM showed some resistance and was degraded by trypsin only after increasing the digestion time. Results of immunoblotting studies on IgE using sera from patients allergic to shrimp indicated that the IgE-binding capacity of TM and MDA (50 mmol L-1 )-treated TM decreased slightly after pepsin digestion and significantly decreased after trypsin digestion.

CONCLUSION
The study indicated that the resistance of TM to degradation increased after oxidation. The treatment with proteases, especially trypsin, is quite effective in decreasing the IgG/IgE-binding capacity of shrimp TM. © 2017 Society of Chemical Industry.

shrimp
tropomyosin
digestibility
simulated gastric fluid
western blot
simulated intestinal fluid


Mathematical Approaches of Branching Morphogenesis.

Abstract: Many organs require a high surface to volume ratio to properly function. Lungs and kidneys, for example, achieve this by creating highly branched tubular structures during a developmental process called branching morphogenesis. The genes that control lung and kidney branching share a similar network structure that is based on ligand-receptor reciprocal signalling interactions between the epithelium and the surrounding mesenchyme. Nevertheless, the temporal and spatial development of the branched epithelial trees differs, resulting in organs of distinct shape and size. In the embryonic lung, branching morphogenesis highly depends on FGF10 signalling, whereas GDNF is the driving morphogen in the kidney. Knockout of Fgf10 and Gdnf leads to lung and kidney agenesis, respectively. However, FGF10 plays a significant role during kidney branching and both the FGF10 and GDNF pathway converge on the transcription factors ETV4/5. Although the involved signalling proteins have been defined, the underlying mechanism that controls lung and kidney branching morphogenesis is still elusive. A wide range of modelling approaches exists that differ not only in the mathematical framework (e.g., stochastic or deterministic) but also in the spatial scale (e.g., cell or tissue level). Due to advancing imaging techniques, image-based modelling approaches have proven to be a valuable method for investigating the control of branching events with respect to organ-specific properties. Here, we review several mathematical models on lung and kidney branching morphogenesis and suggest that a ligand-receptor-based Turing model represents a potential candidate for a general but also adaptive mechanism to control branching morphogenesis during development.

branching morphogenesis
lung
kidney
FGF10
mathematical modelling


Effect of the impression margin thickness on the linear accuracy of impression and stone dies: an in vitro study.

Abstract: The space available for impression material in gingival sulcus immediately after the removal of retraction cord has been found to be 0.3-0.4 mm. However after 40 s only 0.2 mm of the retracted space is available. This is of concern when impression of multiple abutments is to be made. Hence a study was planned to determine the minimum width of the retracted sulcus necessary to obtain a good impression. Five metal dies were machined to accurately fit a stainless steel block with a square cavity in the center with spaces, 1 mm deep and of varying widths (0.11-0.3 mm) away from the block. Polyvinyl siloxane impressions were made and poured using a high strength stone. Using traveling microscope, length and widths of abutment, impression and die were measured and compared for linear accuracy and completeness of impression. Results showed 1.5-3 times greater mean distortion and larger coefficient of variance in the 0.11 mm group than in the wider sulcular groups. ANOVA test for distortion also showed statistically significant differences (P < 0.05). 75 % of impressions in 0.11 mm group were defective compared to less than 25 % of impressions in other width groups. It is not always possible to predictably obtain accurate impressions in sulcus width of 0.11 mm or lesser. Dimensionally accurate and defect free impressions were obtained in sulcus width of 0.15 mm and wider. Hence clinicians must choose retraction methods to obtain a width greater than 0.35 mm. Further immediate loading of the impression material after cord removal may improve accuracy.


Does genetic distance between parental species influence outcomes of hybridization among coral reef butterflyfishes?

Abstract: Christmas Island is located at the overlap of the Indian and Pacific Ocean marine provinces and is a hot spot for marine hybridization. Here, we evaluate the ecological framework and genetic consequences of hybridization between butterflyfishes Chaetodon guttatissimus and Chaetodon punctatofasciatus. Further, we compare our current findings to those from a previous study of hybridization between Chaetodon trifasciatus and Chaetodon lunulatus. For both species groups, habitat and dietary overlap between parental species facilitate frequent heterospecific encounters. Low abundance of potential mates promotes heterospecific pair formation and the breakdown of assortative mating. Despite similarities in ecological frameworks, the population genetic signatures of hybridization differ between the species groups. Mitochondrial and nuclear data from C. guttatissimus × C. punctatofasciatus (1% divergence at cyt b) show bidirectional maternal contributions and relatively high levels of introgression, both inside and outside the Christmas Island hybrid zone. In contrast, C. trifasciatus × C. lunulatus (5% cyt b divergence) exhibit unidirectional mitochondrial inheritance and almost no introgression. Back-crossing of hybrid C. guttatissimus × C. punctatofasciatus and parental genotypes may eventually confound species-specific signals within the hybrid zone. In contrast, hybrids of C. trifasciatus and C. lunulatus may coexist with and remain genetically distinct from the parents. Our results, and comparisons with hybridization studies in other reef fish families, indicate that genetic distance between hybridizing species may be a factor influencing outcomes of hybridization in reef fish, which is consistent with predictions from terrestrially derived hybridization theory.

Montanari|Stefano R|SR|
Hobbs|Jean-Paul A|JP|
Pratchett|Morgan S|MS|
Bay|Line K|LK|
Van Herwerden|Lynne|L|

Christmas Island
introgression
Chaetodontidae
NEWHYBRIDS
STRUCTURE
hybrid ecology


Stimulated by insight: Exploration of critical care nurses' experience of research participation in a recovery programme for intensive care survivors.

Abstract:
AIMS AND OBJECTIVES
To explore critical care nurses' experiences of research participation during a one-year recovery programme for intensive care survivors.

BACKGROUND
Nurse-led postintensive care follow-up consultations have emerged to help patients to recover and overcome problems related to critical illness and admission at the intensive care unit (ICU). Previous research exploring post-ICU follow-up programmes have shown inconclusive evidence of their effectiveness on patient-reported outcome measurements, and provider evaluation is scarce. The context of this study is the Recovery and Aftercare in Postintensive care Therapy (RAPIT) trial.

DESIGN
A qualitative descriptive telephone interview study.

METHODS
Data were collected after completion of the RAPIT trial. Participants (n = 14) were trained intensive care nurses, who delivered the post-ICU recovery programme, representing nine out of ten sites from the RAPIT trial. Two focus group discussions were used to construct a semistructured interview guide. A thematic data analysis was performed using Braun and Clark's six-step method. This study conforms to the COREQ Research Reporting Guidelines for qualitative studies.

RESULTS
Our study indicated that nurses considered participation in research as a positive experience. The main finding "Stimulated by insight" described how nurses' engagement and professional growth was gained by reflection, patient feedback and research competencies acquired in the clinical setting. The research programmes stimulated to new knowledge, broaden their perspectives and enhanced critical reflection of ICU nursing practice.

CONCLUSIONS
The study indicates that nurses developed research competencies and enhanced their job satisfaction by using critical reflection and patient feedback. However, there is still a substantial need for support to strengthen nurses' competencies in collaboration with colleagues, managers and researchers.

RELEVANCE TO CLINICAL PRACTICE
This study can contribute to the development of recommendations supporting nurses doing research and to optimise implementation of clinical research.

nurses
ICU
engagement
reflection
competencies
job satisfaction
clinical research
patient follow-up consultations
the RAPIT study


Observation of proximities between spin-1/2 and quadrupolar nuclei in solids: Improved robustness to chemical shielding using adiabatic symmetry-based recoupling.

Abstract: We introduce a novel heteronuclear dipolar recoupling based on the R21-1 symmetry, which uses the tanh/tan (tt) shaped pulse as a basic inversion element and is denoted R21-1(tt). Using first-order average Hamiltonian theory, we show that this sequence is non-γ-encoded and that it reintroduces the |m| = 1 spatial component of the Chemical Shift Anisotropy (CSA) of the irradiated isotope and its heteronuclear dipolar interactions. Using numerical simulations and one-dimensional (1D) 27Al-{31P} through-space D-HMQC (Dipolar Heteronuclear Multiple-Quantum Correlation) experiments on VPI-5, we compare the performances of this recoupling to those of other non-γ-encoded |m| = 1 heteronuclear recoupling schemes: REDOR (Rotational-Echo DOuble Resonance), SFAM (Simultaneous Frequency and Amplitude Modulation) and R42-1(tt). Such comparison indicates that the R21-1(tt) scheme is more robust to CSA, offset and radiofrequency field inhomogeneities than the other schemes. We take advantage of the high robustness of R21-1(tt) to CSA and offset to demonstrate the possibility to correlate the signals of 207Pb isotope with those of neighboring half-integer spin quadrupolar nuclei. Such approach is demonstrated experimentally by acquiring 11B-{207Pb} D-HMQC 2D spectra of Pb4O(BO3)2 crystalline powder.

Nagashima|Hiroki|H|
Lilly Thankamony|Aany Sofia|AS|
Trébosc|Julien|J|
Montagne|Lionel|L|
Kerven|Gwendal|G|
Amoureux|Jean-Paul|JP|
Lafon|Olivier|O|

Heteronuclear dipolar recoupling
(207)Pb-(11)B correlation
Adiabatic pulse
Quadrupolar isotope


Characteristic imaging features of neurovascular involvement in primary Sneddon's syndrome: an analysis of 12 cases.

Abstract:
OBJECTIVE
Sneddon's syndrome is a cerebrocutaneous non-inflammatory progressive distal arteriopathy, characterized by livedo racemosa, stroke, and neuropsychiatric symptoms. Our aim was to highlight the characteristic neuroimaging features of Sneddon's syndrome that might be helpful to clinicians in timely diagnosis of this entity.

METHODS
Twelve patients (median age 49 years, 11 female) with primary Sneddon's syndrome, diagnosed in last 10 years, were analyzed from the perspective of magnetic resonance imaging (MRI) features. In addition, a novel pseudoangiomatosis score was defined for grading angiographic abnormalities (range: 0 to 6).

RESULTS
Median interval from the onset of neurological symptoms to diagnosis was 6 years. Presentation was with acute stroke in 5, seizures in 3, dementia/speech problems in 2, seizures plus cognitive dysfunction in 1, and chronic progressive hemiparesis in 1. All patients had a typical lesion pattern on MRI. This included multiple (median 3) cortical-subcortical supratentorial and cerebellar non-territorial infarcts, accompanied by multifocal cerebral atrophy. Of note, large territorial infarcts due to cerebral parent artery occlusion, an embolic pattern with multi-territorial involvement on diffusion-weighted imaging, small vessel disease features like severe white matter involvement or lacunar infarcts, and cerebral hemorrhage in the absence of anticoagulation were not observed. MRI lesion severity was not correlated with angiographic arteriopathy severity, clinical stage, or presentation symptoms.

CONCLUSION
Sneddon's syndrome is characterized by highly typical clinico-radiological features. Brain MRI has diagnostic value. By knowing the characteristics of the syndrome, misdiagnosis and potentially harmful treatment can be prevented in this entity that might pose a diagnostic challenge.

Arteriopathy
Hemorrhage
Cerebral embolism
Endocarditis
Vasculitis
Vasculopathy


Drain Insertion in Chronic Subdural Hematoma: An International Survey of Practice.

Abstract:
OBJECTIVE
To investigate whether, after the publication of grade I evidence that it reduces recurrence rates, the practice of drain insertion after burr-hole drainage of chronic subdural hematoma has changed. Further, we aimed to document various practice modalities concerning the insertion of a drain adopted by neurosurgeons internationally.

METHODS
We administered a survey to neurosurgeons worldwide with questions relating to the surgical treatment of chronic subdural hematoma, with an emphasis on their practices concerning the use of a drain.

RESULTS
The preferred surgical technique was burr-hole drainage (89%). Most surgeons prefer to place a drain (80%), whereas in 56% of the cases the reason for not placing a drain was brain expansion after evacuation. Subdural drains are placed by 50% and subperiosteal drains by 27% of the responders, whereas 23% place primarily a subdural drain if possible and otherwise a subperiosteal drain. Three quarters of the responders leave the drain for 48 hours and give prophylactic antibiotic treatment, mostly a single-shot dose intraoperatively (70%). Routine postoperative computed tomography is done by 59% mostly within 24-48 hours after surgery (94%). Adjunct treatment to surgery rarely is used (4%).

CONCLUSIONS
The publication of grade I evidence in favor of drain use influenced positively this practice worldwide. Some surgeons are still reluctant to insert a drain, especially when the subdural space is narrow after drainage of the hematoma. The insertion of a subperiosteal drain could be a good alternative solution. However, its outcome and efficacy must be evaluated in larger studies.

Soleman|Jehuda|J| Kamenova|Maria|M| Lutz|Katharina|K| Guzman|Raphael|R| Fandino|Javier|J| Mariani|Luigi|L|

Chronic subdural hematoma
Survey
Burr-hole drainage
Subdural drain
Subperiosteal drain
Subgaleal drain


Hepatopancreatic intoxication of lambda cyhalothrin insecticide on albino rats.

Abstract:
BACKGROUND
Despite the known adverse effects of lambda cyhalothrin insecticide, little is known about its hepatopancreatic intoxication effects. The present study was carried out to elucidate sub-chronic effect of Karat 2.5% EC formulation of lambda cyhalothrin on male albino rats.

METHODS
To explore the effects of exposure to lambda cyhalothrin on rats and its mechanism, low (1/40 of LD50, 5 mg/kg/day) and high dose (1/4 of LD50, 50 mg/kg/day) lambda cyhalothrin were applied to rats via drinking water for 3 months. Blood samples were collected monthly, and the animals were dissected for liver and pancreas's examination at the end of the experiment. Lambda cyhalothrin administration was associated with the elevation in lipid peroxidation marker, malondialdehyde (MDA), reduction in SH-protein a major marker for antioxidant, as well as basel paraoxonase (PON) in both treated groups throughout the experimental periods.

RESULTS
In addition, significant elevations in liver enzymes alanin amino transferase, (ALT), and aspartate amino transferase (AST), as well as plasma acetylcholinesterase (AChE) and glucose level. While, significant reduction in insulin level through the experimental periods. Results of histopathological and histochemical studies showed that lambda cyhalothrin exposure induces liver and pancreatic tissues damage and depletion in glycogen content was pronounced in liver of both treated groups.

CONCLUSIONS
In conclusion subchronic intoxication with lambda cyhalothrin formulation induced remarkable changes in the examined parameters.

Elhalwagy|Manal Ea|ME|
Abd-Alrahman|Sherif H|SH|
Nahas|A A|AA|
Ziada|Reem M|RM|
Mohamady|Aziza H|AH|

liver enzymes
Pyrethroids
oxidative stress
pancreatic intoxication


Comprehensive chronic laminar single-unit, multi-unit, and local field potential recording performance with planar single shank electrode arrays.

Abstract:
BACKGROUND
Intracortical electrode arrays that can record extracellular action potentials from small, targeted groups of neurons are critical for basic neuroscience research and emerging clinical applications. In general, these electrode devices suffer from reliability and variability issues, which have led to comparative studies of existing and emerging electrode designs to optimize performance. Comparisons of different chronic recording devices have been limited to single-unit (SU) activity and employed a bulk averaging approach treating brain architecture as homogeneous with respect to electrode distribution.

NEW METHOD
In this study, we optimize the methods and parameters to quantify evoked multi-unit (MU) and local field potential (LFP) recordings in eight mice visual cortices.

RESULTS
These findings quantify the large recording differences stemming from anatomical differences in depth and the layer dependent relative changes to SU and MU recording performance over 6-months. For example, performance metrics in Layer V and stratum pyramidale were initially higher than Layer II/III, but decrease more rapidly. On the other hand, Layer II/III maintained recording metrics longer. In addition, chronic changes at the level of layer IV are evaluated using visually evoked current source density.

COMPARISON WITH EXISTING METHOD(S)
The use of MU and LFP activity for evaluation and tracking biological depth provides a more comprehensive characterization of the electrophysiological performance landscape of microelectrodes.

CONCLUSIONS
A more extensive spatial and temporal insight into the chronic electrophysiological performance over time will help uncover the biological and mechanical failure mechanisms of the neural electrodes and direct future research toward the elucidation of design optimization for specific applications.

Kozai|Takashi D Y|TD|
Du|Zhanhong|Z|
Gugel|Zhannetta V|ZV|
Smith|Matthew A|MA|
Chase|Steven M|SM|
Bodily|Lance M|LM|
Caparosa|Ellen M|EM|
Friedlander|Robert M|RM|
Cui|X Tracy|XT|

Electrophysiology
Electrochemical impedance spectroscopy
Firing rate
Gamma oscillations
Microelectrode arrays
Power density spectra
Signal-to-noise
Visual cortex
Visual evoked activity


Detecting adaptive trait loci in nonmodel systems: divergence or admixture mapping?

Abstract: Mapping adaptive trait loci (ATL) underlying ecological divergence is an essential step towards understanding the processes that generate phenotypic diversity. Technological advances have made it possible to sequence exomes in nonmodel systems, providing an efficient means of analysing functional genetic variants. Divergence scans of genetic markers for outlier loci, or 'divergence mapping', have been used to map locally adapted genes, but this approach is likely to be underpowered when background divergence is elevated. Genotype-phenotype association tests in admixed populations, or 'admixture mapping', may provide a useful approach for mapping locally adapted loci when neutral divergence is high. To determine the power and limits of divergence mapping, we simulated exomes containing a single ATL across two parental populations of varying neutral divergence, estimated divergence and quantified the power to identify the ATL. We found that divergence mapping had very high power when background FST is <0.2, but decreased dramatically above this level. To evaluate the utility of admixture mapping, we simulated exomes from admixed populations, then simulated phenotypes, conducted genotype-phenotype association tests and found that even two generations of random mating after admixture could provide high mapping power in scenarios where pure divergence mapping was ineffective (FST = 0.35). Moreover, admixture mapping had high power across all levels of divergence after 20 generations since admixture. Together with high-throughput exome sequencing, admixture mapping could be used to map ATL in systems such as Heliconius butterflies or Gryllus crickets when experimental design and analytical approach are chosen accordingly.

adaptation
nonmodel systems
admixture
hybridization


Photolytic insertion of albumin on activated carbon modified with ozone.

Abstract: 254nm photolyses of bovine serum albumin [BSA] in aqueous solutions, were carried out in the presence of activated carbons modified by reaction with ozone. The photolyses were monitored by fluorescence spectroscopy and UV spectrophotometry, and the products were characterized by elemental analysis, FTIR, TGA, total organic carbon analyses [TOC], and XPS. The ozonation reaction was carried out at room temperature with O3 under dry and wet conditions. The carbon characterization showed that the reaction increased the amount of epoxide and carbonyl groups on the carbon matrix. The activated carbon modified with dry O3 exhibited higher concentration of oxidized groups in its surface, smaller surface area and lower thermal stability. Characterization of the photolysis of ozonized carbons pointed to a small release of carbon organic groups during the reaction with elimination of epoxide groups and increase of carbonyl groups without change of thermal stability. Photolysis of BSA in aqueous solution occurred with fluorescence quenching due to changes of the local microenvironment and/or macromolecular conformational changes. Absorbance increase of the UV spectrum indicated a hyperchromic effect due to albumin structure modifications during photolysis. TGA analysis of the photolysed activated carbons in the presence of BSA suggested that ozonized carbon samples underwent insertion of BSA upon photolysis, in particular the sample ozonized under dry conditions. The changes observed for the FTIR and elemental analysis agreed with this conclusion, which was further supported by 13C SS-NMR, fluorescence emission and XPS.

Peralta Muniz Moreira|Regina de Fátima|RF|

Albumin
Activated carbon
Photolysis
Immobilization
Photoinsertion


Frailty is an important predictor of 30-day morbidity in patients treated for lumbar spondylolisthesis using a posterior surgical approach.

Abstract:
BACKGROUND CONTEXT
Traditionally, a nonoperative approach has been favored for elderly patients with lumbar spondylolisthesis due to a perceived higher risk of morbidity with surgery. However, most studies have used an arbitrary age cut-off to define "elderly" and this research has yielded conflicting results.

PURPOSE
The purpose of this study was to investigate the impact of frailty on morbidity after surgery for degenerative lumbar spondylolisthesis treated with a posterior approach.

STUDY DESIGN
A retrospective cohort study was performed.

PATIENT SAMPLE
The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database, with years 2010 to 2018 included in this study. Patients who received posterior lumbar spine decompression with or without single level posterior instrumented fusion for degenerative lumbar spondylolisthesis were included. Patients who received anterior and/or lateral approaches were excluded.

OUTCOME MEASURES
The primary outcome was Clavien-Dindo grade IV complication. Secondary outcomes were readmission, reoperation, and discharge to location other than home.

METHODS
Patient demographics and comorbidities were extracted. Logistic regression analysis was performed to investigate the association between outcomes and the Modified Frailty Index-5, adjusting for age, gender, body mass index, smoking status, and surgical procedure performed. A sub-analysis was done to assess the effect of frailty in three different age groups (18-45 years, 46-65 years, and >65 years) for the two surgical cohorts.

RESULTS
There were 15,658 patients in this study. The mean age was 62.5 years. Approximately 70% of the patients received decompression with fusion. Frailty was significantly associated with an increased risk of major complication, unplanned readmission, reoperation, and non-home discharge. The risk increased with increasing frailty. For patients who received decompression, frailty was associated with a higher risk of readmission and non-home discharge in patients >65 years. For patients who received decompression and fusion, frailty was associated with a higher risk of complications, readmission, and non-home discharge in patients >65 years.

CONCLUSIONS
Frailty is independently associated with a higher risk of morbidity after posterior surgery in patients with lumbar spondylolisthesis, especially in patients older than 65. These data are of significance to clinicians in planning treatment for these patients.

Chan|Vivien|V|
Witiw|Christopher D|CD|
Wilson|Jamie Rf|JR|
Wilson|Jefferson R|JR|
Coyte|Peter|P|
Fehlings|Michael G|MG|

Frailty
Morbidity
Spondylolisthesis
Elderly
Surgery
Patient outcomes


Preparation of Artificial Skin that Mimics Human Skin Surface and Mechanical Properties.

Abstract: We have developed an artificial skin that mimics the morphological and mechanical properties of human skin. The artificial skin comprises a polyurethane block possessing a microscopically rough surface. We evaluated the tactile sensations when skin-care cream was applied to the artificial skin. Many subjects perceived smooth, moist, and soft feels during the application process. Cluster analysis showed that these characteristic tactile feels are similar to those when skin-care cream is applied to real human skin. Contact angle analysis showed that an oil droplet spread smoothly on the artificial skin surface, which occurred because there were many grooves several hundred micrometers in width on the skin surface. In addition, when the skin-care cream was applied, the change in frictional force during the dynamic friction process increased. These wetting and frictional properties are important factors controlling the similarity of artificial skin to real human skin.

artificial skin
polyurethane
rough surface
texture


The FOXA2 transcription factor is frequently somatically mutated in uterine carcinosarcomas and carcinomas.

Abstract:
BACKGROUND
Uterine carcinosarcomas (UCSs) are a rare but clinically aggressive form of cancer. They are biphasic tumors consisting of both epithelial and sarcomatous components. The majority of uterine carcinosarcomas are clonal, with the carcinomatous cells undergoing metaplasia to give rise to the sarcomatous component. The objective of the current study was to identify novel somatically mutated genes in UCSs.

METHODS
We whole exome sequenced paired tumor and nontumor DNAs from 14 UCSs and orthogonally validated 464 somatic variants using Sanger sequencing. Fifteen genes that were somatically mutated in at least 2 tumor exomes were Sanger sequenced in another 39 primary UCSs.

RESULTS
Overall, among 53 UCSs in the current study, the most frequently mutated of these 15 genes were tumor protein p53 (TP53) (75.5%), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) (34.0%), protein phosphatase 2, regulatory subunit A, alpha (PPP2R1A) (18.9%), F-box and WD repeat domain containing 7 (FBXW7) (18.9%), chromodomain helicase DNA binding protein 4 (CHD4) (17.0%), and forkhead box A2 (FOXA2) (15.1%). FOXA2 has not previously been implicated in UCSs and was predominated by frameshift and nonsense mutations. One UCS with a FOXA2 frameshift mutation expressed truncated FOXA2 protein by immunoblotting. Sequencing of FOXA2 in 160 primary endometrial carcinomas revealed somatic mutations in 5.7% of serous, 22.7% of clear cell, 9% of endometrioid, and 11.1% of mixed endometrial carcinomas, the majority of which were frameshift mutations.

CONCLUSIONS
Collectively, the findings of the current study provide compelling genetic evidence that FOXA2 is a pathogenic driver gene in the etiology of primary uterine cancers, including UCSs. Cancer 2018;124:65-73. © 2017 American Cancer Society.

D058534:Class I Phosphatidylinositol 3-Kinases

D000073979:F-Box-WD Repeat-Containing Protein 7

D051542:Hepatocyte Nuclear Factor 3-beta

D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex

D018297:Neoplasms, Cystic, Mucinous, and Serous

mutation
carcinosarcoma
exome
endometrial carcinoma
uterine cancer
endometrial cancer


The complete mitochondrial genome of the tessellated leatherjacket Thamnaconus tessellatus (Tetraodontiformes: Monacanthidae).

Abstract: The long PCR and primer walking methods were applied for obtaining the complete mitochondrial genome of the tessellated leatherjacket Thamnaconus tessellatus. The complete mitochondrial genome was 16,437 bp in length and contained 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, an origin of L-strand replication and a control region. The arrangements and characteristics of these segments shared common features with other teleosts. Extended termination associated sequence domain (TAS, cTAS), central conserved sequence block domain (CSB-F, CSB-E, CSB-D) and conserved sequence block domain (CSB-1, CSB-2, CSB-3) were identified in the control region.

Wang|Zhiyang|Z| Li|Yuan|Y| Zhang|Zhaohui|Z| Lin|Longshan|L| Gao|Tianxiang|T|

D000818:Animals
D020459:Genes, rRNA
D054629:Genome, Mitochondrial
D058977:Molecular Sequence Annotation
D008969:Molecular Sequence Data
D016366:Open Reading Frames
D012343:RNA, Transfer
D017422:Sequence Analysis, DNA
D023721:Tetraodontiformes

mitochondrial genome
Thamnaconus tessellatus
Monacanthidae
Control region


Bacterial genotoxin colibactin promotes colon tumour growth by inducing a senescence-associated secretory phenotype.

Abstract:
BACKGROUND
Escherichia coli strains harbouring the pks island (pks+ E. coli) are often seen in human colorectal tumours and have a carcinogenic effect independent of inflammation in an AOM/IL-10(-/-) (azoxymethane/interleukin) mouse model.

OBJECTIVE
To investigate the mechanism sustaining pks+ E. coli-induced carcinogenesis.

METHOD
Underlying cell processes were investigated in vitro and in vivo (xenograft model) using intestinal epithelial cells infected by pks+ E. coli or by an isogenic mutant defective for pks (pks- E. coli). The results were supported by data obtained from an AOM/DSS (azoxymethane/dextran sodium sulphate) colon cancer mouse model and from human colon cancer biopsy specimens colonised by pks+ E. coli or pks- E. coli.

RESULTS
Colibactin-producing E. coli enhanced tumour growth in both xenograft and AOM/DSS models. Growth was sustained by cellular senescence (a direct consequence of small ubiquitin-like modifier (SUMO)-conjugated p53 accumulation), which was accompanied by the production of hepatocyte growth factor (HGF). The underlying mechanisms involve microRNA-20a-5p, which targets SENP1, a key protein regulating p53 deSUMOylation. These results are consistent with the expression of SENP1, microRNA-20a-5p, HGF and phosphorylation of HGF receptor found in human and mouse colon cancers colonised by pks+ E. coli.

CONCLUSION
These data reveal a new paradigm for carcinogenesis, in which colibactin-induced senescence has an important role.

Cougnoux|Antony|A| Dalmasso|Guillaume|G| Martinez|Ruben|R| Buc|Emmanuel|E| Delmas|Julien|J| Gibold|Lucie|L| Sauvanet|Pierre|P| Darcha|Claude|C| Déchelotte|Pierre|P| Bonnet|Mathilde|M| Pezet|Denis|D| Wodrich|Harald|H| Darfeuille-Michaud|Arlette|A| Bonnet|Richard|R|

E. Coli
Cell Proliferation
Colon Carcinogenesis
DNA Damage
Gene Expression


Association of Wolbachia with Gene Expression in Drosophila Testes.

Abstract: Wolbachia is a genus of intracellular symbiotic bacteria that are widely distributed in arthropods and nematodes. These maternally inherited bacteria regulate host reproductive systems in various ways to facilitate their vertical transmission. Since the identification of Wolbachia in many insects, the relationship between Wolbachia and the host has attracted great interest. Numerous studies have indicated that Wolbachia modifies a variety of biological processes in the host. Previous studies in Drosophila melanogaster (D. melanogaster) have demonstrated that Wolbachia can affect spermatid differentiation, chromosome deposition, and sperm activity in the early stages of spermatogenesis, leading to sperm dysfunction. Here, we explored the putative effect of Wolbachia in sperm maturation using transcriptomic approaches to compare gene expression in Wolbachia-infected and Wolbachia-free D. melanogaster adult testes. Our findings show that Wolbachia affects many biological processes in D. melanogaster adult testes, and most of the differentially expressed genes involved in carbohydrate metabolism, lysosomal degradation, proteolysis, lipid metabolism, and immune response were upregulated in the presence of Wolbachia. In contrast, some genes that are putatively associated with cutin and wax biosynthesis and peroxisome pathways were downregulated. We did not find any differentially expressed genes that are predicted to be related to spermatogenesis in the datasets. This work provides additional information for understanding the Wolbachia-host intracellular relationships.

Dou|Weihao|W| Miao|Yunheng|Y| Xiao|Jinhua|J| Huang|Dawei|D|

Wolbachia
Drosophila melanogaster
Spermatogenesis
Transcriptomic
Intracellular relationship


Variations in the pulmonary venous ostium in the left atrium and its clinical importance.

Abstract:
INTRODUCTION
During early embryonic development, absorption of pulmonary venous network by the left primitive atrial chamber results in opening of four pulmonary veins which drain independently into its chamber. The extent of absorption and hence, the number of pulmonary veins which open into the left atrium, may vary. As only few studies have been done, which have shown such variations, the present study was done to evaluate the possible variations in the pulmonary veins which opened into the left atrium.

MATERIALS AND METHODS
Fifty formalin fixed adult cadaveric hearts were studied for variations in the opening of the pulmonary veins into left atrium.

RESULTS
Our results showed that 68% of the hearts which were studied, showed usual pattern of 2 pulmonary veins on either side, while remaining 32 % hearts showed variations in the number of pulmonary veins which opened. Twelve percent of the hearts showed 2 left and 3 right pulmonary veins, 14% of hearts showed 2 left and 1 right veins, 4% hearts showed 1 left and 2 right veins and 2% hearts showed 1 left and 4 right pulmonary veins opening into the left atrium.

CONCLUSION
Knowledge on such variations gains significance in isolation for radiofrequency ablation as a treatment for atrial fibrillation.

L C|Prasanna|P|
R|Praveena|P|
D'Souza|A S|AS|
Bhat|Kumar M R|KM|

Radiofrequency ablation
Atrial fibrillation
Pulmonary ostia
Veins of left atrium


The Foundations of Human Cooperation in Teaching and Imitation.

Abstract: Humans exhibit extensive large-scale cooperation, of a form unprecedented in the natural world. Here I suggest that this cooperation arises in our species alone because of our uniquely potent capacities for social learning, imitation and teaching, combined with the co-evolutionary feedbacks that these capabilities have generated on the human mind. Culture took human populations down evolutionary pathways not available to non-cultural species, either by creating conditions that promoted established cooperative mechanisms, such as indirect reciprocity and mutualism, or by generating novel cooperative mechanisms not seen in other taxa, such as cultural group selection. In the process, gene-culture co-evolution seemingly generated an evolved psychology, comprising an enhanced ability and motivation to learn, teach, communicate through language, imitate and emulate, as well as predispositions to docility, social tolerance, and the sharing of goals, intentions and attention. This evolved psychology is entirely different from that observed in any other animal, or that could have evolved through conventional selection on genes alone.

cooperation
teaching
imitation
gene-culture co-evolution
language


Gaussian accelerated molecular dynamics for elucidation of drug pathways.

Abstract: Understanding pathways and mechanisms of drug binding to receptors is important for rational drug design. Remarkable advances in supercomputing and methodological developments have opened a new era for application of computer simulations in predicting drug-receptor interactions at an atomistic level. Gaussian accelerated molecular dynamics (GaMD) is a computational enhanced sampling technique that works by adding a harmonic boost potential to reduce energy barriers. GaMD enables free energy calculations without the requirement of predefined collective variables. GaMD has proven useful in biomolecular simulations, in particular, the prediction of drug-receptor interactions. Areas covered: Herein, the authors review recent GaMD simulation studies that elucidated pathways of drug binding to proteins including the G-protein-coupled receptors and HIV protease. Expert opinion: GaMD is advantageous for enhanced simulations of, amongst many biological processes, drug binding to target receptors. Compared with conventional molecular dynamics, GaMD speeds up biomolecular simulations by orders of magnitude. GaMD enables routine drug binding simulations using personal computers with GPUs or common computing clusters. GaMD and, more broadly, enhanced sampling simulations are expected to dramatically increase our capabilities to determine the mechanisms of drug binding to a wide range of receptors in the near future. This will greatly facilitate computer-aided drug design.

D003198:Computer Simulation
D017076:Computer-Aided Design
D015195:Drug Design
D016333:HIV Protease
D006801:Humans
D056004:Molecular Dynamics Simulation
D011485:Protein Binding
D043562:Receptors, G-Protein-Coupled
D013816:Thermodynamics

Gaussian accelerated molecular dynamics
drug pathways
enhanced sampling
HIV protease
computer-aided drug design
GPCRs


Cyclotide discovery in Gentianales revisited--identification and characterization of cyclic cystine-knot peptides and their phylogenetic distribution in Rubiaceae plants.

Abstract: Cyclotides are a unique class of ribosomally synthesized cysteine-rich miniproteins characterized by a head-to-tail cyclized backbone and three conserved disulfide-bonds in a knotted arrangement. Originally they were discovered in the coffee-family plant Oldenlandia affinis (Rubiaceae) and have since been identified in several species of the violet, cucurbit, pea, potato, and grass families. However, the identification of novel cyclotide-containing plant species still is a major challenge due to the lack of a rapid and accurate analytical workflow in particular for large sampling numbers. As a consequence, their phylogeny in the plant kingdom remains unclear. To gain further insight into the distribution and evolution of plant cyclotides, we analyzed ∼300 species of >40 different families, with special emphasis on plants from the order Gentianales. For this purpose, we have developed a refined screening methodology combining chemical analysis of plant extracts and bioinformatic analysis of transcript databases. Using mass spectrometry and transcriptome-mining, we identified nine novel cyclotide-containing species and their related cyclotide precursor genes in the tribe Palicoureeae. The characterization of novel peptide sequences underlines the high variability and plasticity of the cyclotide framework, and a comparison of novel precursor proteins from Carapichea ipecacuanha illustrated their typical cyclotide gene architectures. Phylogenetic analysis of their distribution within the Psychotria alliance revealed cyclotides to be restricted to Palicourea, Margaritopsis, Notopleura, Carapichea, Chassalia, and Geophila. In line with previous reports, our findings confirm cyclotides to be one of the largest peptide families within the plant kingdom and suggest that their total number may exceed tens of thousands.

Koehbach|Johannes|J|
Attah|Alfred F|AF|
Berger|Andreas|A|
Hellinger|Roland|R|
Kutchan|Toni M|TM|
Carpenter|Eric J|EJ|
Rolf|Megan|M|
Sonibare|Mubo A|MA|
Moody|Jones O|JO|
Wong|Gane Ka-Shu|GK|
Dessein|Steven|S|
Greger|Harald|H|
Gruber|Christian W|CW|

cyclotides Rubiaceae Palicoureeae Carapichea Notopleura Psychotrieae ipecac peptidomics transcriptomics


Celastrol induce apoptosis of human multiple myeloma cells involving inhibition of proteasome activity.

Abstract: Celastrol exhibits anticancer activity and has a number of potential molecular targets. Among them, the proteasome has attracted particular attention. Although celastrol inhibits multiple myeloma (MM) cell proliferation, the induction of proteasome-inhibitory activity by celastrol in MM cells at the cellular level and in tumors of mice bearing xenografts has not been confirmed. In the present study, we found that celastrol inhibited the caspase-like (β1), trypsin-like (β2) and chymotrypsin-like (β5) proteasome activities of purified human 20S proteasomes, with half-maximal inhibitory concentration (IC50) values of 7.1, 6.3, and 9.3 μmol/L, respectively. Celastrol also inhibited human MM cellular β1, β2, and β5 proteasome activities, with IC50 values of 2.3, 2.1, and 0.9 μmol/L, respectively. After MM cells were treated with celastrol, a population of apoptotic cells and a population of cells in G0/G1 were observed. Celastrol also inhibited proteasome activity and induced apoptosis in tumor tissue. Treatment of MM.1S and RPMI 8226 tumor-bearing severe combined immunodeficiency (SCID) mice with celastrol reduced the tumor volume. In conclusion, our results reveal the effects of celastrol on proteasome activity in MM cells and shed light on the underlying mechanisms of its anticancer activity, providing a basis for developing celastrol as a potential therapeutic agent for MM.

Zhong|Yue-Ling|YL| Xu|Gao-Jie|GJ| Huang|Sheng|S| Zhao|Li|L| Zeng|Yan|Y| Xiao|Xiao-Fan|XF| An|Jing-Lin|JL| Liu|Jin|J| Yang|Tai|T|

D023041:Xenograft Model Antitumor Assays

Celastrol
Apoptosis
Multiple myeloma
Proteasome


Publishing as an Indicator of Scientific Research Quality and Ethics: The Case of Law Journals from Moldova.

Abstract: This paper analyses the way articles are published in scientific journals in the field of law in the Republic of Moldova, including an experiment with a previously published article. Lack of compliance with journal publishing standards, including peer reviewing of articles, leads to the fact that virtually any article can be published. The examined journals do not perform their natural functions, but are rather used by researchers to report that they have scientific outcomes. The study allows us to consider that publishing in scientific journals is an indicator of the quality of scientific research, as well as an indicator of compliance with scientific research ethical principles. Scientific misconduct and lack of scientific meritocracy that are characteristic of some of the post-Soviet science, are very well reflected in the law field in the Republic of Moldova.

Law
Publishing standards
Peer review
Scientific misconduct
Journal functions
Moldovan journals
Predatory publishing


Adaptive radiation therapy for bladder cancer: a review of adaptive techniques used in clinical practice.

Abstract: Significant changes in the shape, size and position of the bladder during radiotherapy (RT) treatment for bladder cancer have been correlated with high local failure rates; typically due to geographical misses. To account for this, large margins are added around the target volumes in conventional RT; however, this increases the volume of healthy tissue irradiation. The availability of cone beam computed tomography (CBCT) has not only allowed in-room volumetric imaging of the bladder, but also the development of adaptive radiotherapy (ART) for modification of plans to patient-specific changes. The aim of this review is to: (1) identify and explain the different ART techniques being used in clinical practice and (2) compare and contrast these different ART techniques to conventional RT in terms of target coverage and dose to healthy tissue: A literature search was conducted using EMBASE, MEDLINE and Scopus with the key words 'bladder, adaptive, radiotherapy/radiation therapy'. 11 studies were obtained that compared different adaptive RT techniques to conventional RT in terms of target volume coverage and healthy tissue sparing. All studies showed superior target volume coverage and/or healthy tissue sparing in adaptive RT compared to conventional RT. Cross-study comparison between different adaptive techniques could not be made due to the difference in protocols used in different studies. However, one study found daily re-optimisation of plans to be superior to plan of the day technique. The use of adaptive RT for bladder cancer is promising. Further study is required to assess adaptive RT versus conventional RT in terms of local control and long-term toxicity.

Adaptive
radiation therapy
bladder
conventional
cone beam computed tomography


In vitro phagocytosis of opsonized latex beads by HD11 cells as a method to assess the general opsonization potential of chicken serum.

Abstract: Opsonins, an important arm of the innate immune system, are various soluble proteins, which play a critical role in destruction of invading pathogens directly or via engulfment of pathogens through the intermediate of phagocytosis. The diversity of opsonin profiles is under genetic influence and may be associated with variation in disease resistance. The aim of this study was to set up an assay to determine serum opsonophagocytic potential (OPp) for chicken sera by flow cytometry and to evaluate the assay using samples from different chicken lines. Two chicken lines selected for high and low concentrations of mannose-binding lectin, a known opsonin, in serum were used to establish the method. Furthermore, the presumed "robust" Hellevad chickens and two other commercial chicken lines (Hisex and Bovans) were tested to evaluate OPp as a parameter reflecting general immune competence. The results showed that Hellevad and Bovans chickens had higher OPp than Hisex chickens. There were no correlations between concentrations of total IgY or mannose-binding lectin and OPp. However, a strong positive correlation was observed between vaccine-induced infectious bronchitis virus titres and OPp. Moreover, inverse relationships were observed between concentrations of total serum IgM as well as natural antibody levels, and OPp. In conclusion, in vitro opsonophagocytosis assessment and determination of OPp may be of relevance when addressing general innate immunocompetence. RESEARCH HIGHLIGHTS A flow cytometry method was developed to assess poultry serum opsonophagocytosis potential. This method is based on serum-opsonin-coated polystyrene beads and HD11 cell phagocytosis. Serum samples from different commercial chicken lines were compared. Opsonophagocytic potential may be included in assay panels for general immune competence of poultry.

Naghizadeh|Mohammed|M|
Wattrang|Eva|E|
Kjærup|Rikke B|RB|
Bakke|Maja|M|
Shih|Sandra|S|
Dalgaard|Tina S|TS|

flow cytometry
opsonophagocytosis
immunocompetence
Serum opsonins
poultry robustness


Protein Paucimannosylation Is an Enriched N-Glycosylation Signature of Human Cancers.

Abstract: While aberrant protein glycosylation is a recognized characteristic of human cancers, advances in glycoanalytics continue to discover new associations between glycoproteins and tumorigenesis. This glycomics-centric study investigates a possible link between protein paucimannosylation, an under-studied class of human N-glycosylation [Man1-3 GlcNAc2 Fuc0-1 ], and cancer. The paucimannosidic glycans (PMGs) of 34 cancer cell lines and 133 tissue samples spanning 11 cancer types and matching non-cancerous specimens are profiled from 467 published and unpublished PGC-LC-MS/MS N-glycome datasets collected over a decade. PMGs, particularly Man2-3 GlcNAc2 Fuc1 , are prominent features of 29 cancer cell lines, but the PMG level varies dramatically across and within the cancer types (1.0-50.2%). Analyses of paired (tumor/non-tumor) and stage-stratified tissues demonstrate that PMGs are significantly enriched in tumor tissues from several cancer types including liver cancer (p = 0.0033) and colorectal cancer (p = 0.0017) and is elevated as a result of prostate cancer and chronic lymphocytic leukaemia progression (p < 0.05). Surface expression of paucimannosidic epitopes is demonstrated on human glioblastoma cells using immunofluorescence while biosynthetic involvement of N-acetyl-β-hexosaminidase is indicated by quantitative proteomics. This intriguing association between protein paucimannosylation and human cancers warrants further exploration to detail the biosynthesis, cellular location(s), protein carriers, and functions of paucimannosylation in tumorigenesis and metastasis.

protein paucimannosylation
cancer
paucimannosidic glycan
glycan
glycomics


Weakly nucleophilic potassium aryltrifluoroborates in palladium-catalyzed Suzuki-Miyaura reactions: relative reactivity of K[4-RC6F4BF3] and the role of silver-assistance in acceleration of transmetallation.

Abstract: Small differences in the reactivity of weakly nucleophilic potassium aryltrifluoroborates are revealed in the silver-assisted Pd-catalyzed cross-coupling of K[4-RC6F4BF3] (R = H, Bu, MeO, EtO, PrO, iPrO, BuO, t-BuO, CH2=CHCH2O, PhCH2O, PhCH2CH2O, PhO, F, pyrazol-1-yl, pyrrol-1-yl, and indol-1-yl) with ArX (4-BrC6H4CH3, 4-IC6H4F and 3-IC6H4F). An assumed role of silver(I) compounds Ag m Y (Y = O, NO3, SO4, BF4, F) consists in polarization of the Pd-X bond in neutral complex ArPdL n X with the generation of the related transition state or formation of [ArPdL n ][XAg m Y] with a highly electrophilic cation and subsequent transmetallation with the weakly nucleophilic borate. Efficiency of Ag m Y as a polarizing agent decreases in order Ag2O > AgNO3 ≈ Ag2SO4 > Ag[BF4] > AgF. No clear correlation between the reactivity of K[4-RC6F4BF3] and substituent electron parameters, σI and σR°, of the aryl group 4-RC6F4 was found.

Bardin|Vadim V|VV|
Shabalin|Anton Yu|AY|
Adonin|Nicolay Yu|NY|

Suzuki–Miyaura reaction
potassium polyfluoroaryltrifluoroborate
silver(I) acceleration


Deletion of Methionine Sulfoxide Reductase A Does Not Affect Atherothrombosis but Promotes Neointimal Hyperplasia and Extracellular Signal-Regulated Kinase 1/2 Signaling.

Abstract:
OBJECTIVE
Emerging evidence suggests that methionine oxidation can directly affect protein function and may be linked to cardiovascular disease. The objective of this study was to define the role of the methionine sulfoxide reductase A (MsrA) in models of vascular disease and identify its signaling pathways.

APPROACH AND RESULTS
MsrA was readily identified in all layers of the vascular wall in human and murine arteries. Deletion of the MsrA gene did not affect atherosclerotic lesion area in apolipoprotein E-deficient mice and had no significant effect on susceptibility to experimental thrombosis after photochemical injury. In contrast, the neointimal area after vascular injury caused by complete ligation of the common carotid artery was significantly greater in MsrA-deficient than in control mice. In aortic vascular smooth muscle cells lacking MsrA, cell proliferation was significantly increased because of accelerated G1/S transition. In parallel, cyclin D1 protein and cdk4/cyclin D1 complex formation and activity were increased in MsrA-deficient vascular smooth muscle cell, leading to enhanced retinoblastoma protein phosphorylation and transcription of E2F. Finally, MsrA-deficient vascular smooth muscle cell exhibited greater activation of extracellular signal-regulated kinase 1/2 that was caused by increased activity of the Ras/Raf/mitogen-activated protein kinase signaling pathway.

CONCLUSIONS
Our findings implicate MsrA as a negative regulator of vascular smooth muscle cell proliferation and neointimal hyperplasia after vascular injury through control of the Ras/Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase 1/2 signaling pathway.

Klutho|Paula J|PJ|
Pennington|Steven M|SM|
Scott|Jason A|JA|
Wilson|Katina M|KM|
Gu|Sean X|SX|
Doddapattar|Prakash|P|
Xie|Litao|L|
Venema|Ashlee N|AN|
Zhu|Linda J|LJ|
Chauhan|Anil K|AK|
Lentz|Steven R|SR|
Grumbach|Isabella M|IM|

D019950:Mitogen-Activated Protein Kinase 1

D048052:Mitogen-Activated Protein Kinase 3

methionine sulfoxide reductase
proliferation
ERK pathway
neointima
oxidation-reduction


Accuracy and reliability of landmark-based, surface-based and voxel-based 3D cone-beam computed tomography superimposition methods.

Abstract:
OBJECTIVES
To evaluate and compare the accuracy and reliability of 3 different methods of three-dimensional cone-beam computed tomography scans (3D CBCTs) superimpositions: landmark-based, surface-based and voxel-based.

MATERIALS AND METHODS
Pre- and post-orthodontic treatment CBCTs (T1 and T2) of 20 subjects with a mean age of 11 years were obtained. Seven points on the zygomatic arch and supraorbital region were selected to perform landmark-based superimposition. Surface-based and voxel-based superimpositions were performed using the anterior cranial base as a reference. Each superimposition method of T1 and T2 scans was repeated twice to assess the reliability. Accuracy of each technique was tested by superimposing duplicated sets of T1 scans. A total of 11 landmarks on the anterior cranial base, maxilla and mandible were located, and deviations of these landmarks on superimposed data were quantified to assess reliability and accuracy of all superimpositions.

RESULTS
There were no significant differences from zero when duplicated sets of T1 scans were superimposed using surface-based and voxel-based methods. Statistical significant differences were detected in several parameters when evaluating the accuracy of the landmark superimposition. Superimposition of T1 and T2 scans for testing the reliability revealed intraclass correlation coefficients greater than 0.90 for all measurements except for ACP-x and PNS-y of landmark-based method as well as ANS-x of voxel-based method.

CONCLUSIONS
Surface-based and voxel-based superimposition methods using the anterior cranial base as a reference structure were accurate and reliable in detecting changes in landmark positions when superimposing. Landmark-based superimposition method was reliable but less accurate than the other methods.

accuracy
reliability
superimposition methods
anterior cranial base


Polished silver solid amalgam electrode and cationic surfactant as tool in electroanalytical determination of methomyl pesticide.

Abstract: The polished silver solid amalgam electrode (p-AgSAE) combined with square wave voltammetry (SWV) was used in the development of an analytical procedure to Methomyl determination in natural water samples. The experimental and voltammetric parameters were optimized and the use of cationic surfactant cetyltrimethyl ammonium bromide promoted a considerable change in the kinetic and mechanism of the Methomyl reaction. Was observed the presence one-single reduction peak, related to a totally irreversible two-electrons transfer, followed by chemical reaction involving two protons. Analytical parameters (linearity range, analytical curve equations, correlation coefficient, detection and quantification limits, recovery efficiency, and relative standard deviation for intraday and interday experiments) were evaluated indicating that the proposed voltammetric procedure is suitable for determination of Methomyl. The application of the proposed procedure in natural water analysis indicated high robustness with only simple filtration, without pre-concentration steps, good stability and suitable sensitivity to determination of Methomyl in natural water samples.

Silva|Caio César Gonçalves|CCG|
De Souza|Djenaine|D|

Polished silver solid amalgam electrode
Cationic surfactant
Methomyl
Square wave voltammetry
Natural water samples
Endocrine disrupter


Heterogeneity of Collagen VI Microfibrils: STRUCTURAL ANALYSIS OF NON-COLLAGENOUS REGIONS.

Abstract: Collagen VI, a collagen with uncharacteristically large N- and C-terminal non-collagenous regions, forms a distinct microfibrillar network in most connective tissues. It was long considered to consist of three genetically distinct α chains (α1, α2, and α3). Intracellularly, heterotrimeric molecules associate to form dimers and tetramers, which are then secreted and assembled to microfibrils. The identification of three novel long collagen VI α chains, α4, α5, and α6, led to the question if and how these may substitute for the long α3 chain in collagen VI assembly. Here, we studied structural features of the novel long chains and analyzed the assembly of these into tetramers and microfibrils. N- and C-terminal globular regions of collagen VI were recombinantly expressed and studied by small angle x-ray scattering (SAXS). Ab initio models of the N-terminal globular regions of the α4, α5, and α6 chains showed a C-shaped structure similar to that found for the α3 chain. Single particle EM nanostructure of the N-terminal globular region of the α4 chain confirmed the C-shaped structure revealed by SAXS. Immuno-EM of collagen VI extracted from tissue revealed that like the α3 chain the novel long chains assemble to homotetramers that are incorporated into mixed microfibrils. Moreover, SAXS models of the C-terminal globular regions of the α1, α2, α4, and α6 chains were generated. Interestingly, the α1, α2, and α4 C-terminal globular regions dimerize. These self-interactions may play a role in tetramer formation.

Maaß|Tobias|T|
Bayley|Christopher P|CP|
Mörgelin|Matthias|M|
Lettmann|Sandra|S|
Bonaldo|Paolo|P|
Paulsson|Mats|M|
Baldock|Clair|C|
Wagener|Raimund|R|

D000595:Amino Acid Sequence
D000818:Animals
D024141:Collagen Type IV
D057809:HEK293 Cells
D006801:Humans
D051379:Mice
D008969:Molecular Sequence Data
D017510:Protein Folding
D055503:Protein Multimerization
D017434:Protein Structure, Tertiary

collagen
microfibrils
VWA domain
electron microscopy (EM)
extracellular matrix
single particle analysis
small-angle x-ray scattering (SAXS)


Quick generation of Raman spectroscopy based in-process glucose control to influence biopharmaceutical protein product quality during mammalian cell culture.

Abstract: Mitigating risks to biotherapeutic protein production processes and products has driven the development of targeted process analytical technology (PAT); however implementing PAT during development without significantly increasing program timelines can be difficult. The development of a monoclonal antibody expressed in a Chinese hamster ovary (CHO) cell line via fed-batch processing presented an opportunity to demonstrate capabilities of altering percent glycated protein product. Glycation is caused by pseudo-first order, non-enzymatic reaction of a reducing sugar with an amino group. Glucose is the highest concentration reducing sugar in the chemically defined media (CDM), thus a strategy controlling glucose in the production bioreactor was developed utilizing Raman spectroscopy for feedback control. Raman regions for glucose were determined by spiking studies in water and CDM. Calibration spectra were collected during 8 bench scale batches designed to capture a wide glucose concentration space. Finally, a PLS model capable of translating Raman spectra to glucose concentration was built using the calibration spectra and spiking study regions. Bolus feeding in mammalian cell culture results in wide glucose concentration ranges. Here we describe the development of process automation enabling glucose setpoint control. Glucose-free nutrient feed was fed daily, however glucose stock solution was fed as needed according to online Raman measurements. Two feedback control conditions were executed where glucose was controlled at constant low concentration or decreased stepwise throughout. Glycation was reduced from ∼9% to 4% using a low target concentration but was not reduced in the stepwise condition as compared to the historical bolus glucose feeding regimen.

Berry|Brandon N|BN|
Dobrowsky|Terrence M|TM|
Timson|Rebecca C|RC|
Kshirsagar|Rashmi|R|
Ryll|Thomas|T|
Wiltberger|Kelly|K|

Raman spectroscopy
product quality
CHO
glycation
cell culture fedbatch production


Second Re-irradiation: Clinical Examples of Worthwhile Treatment.

Abstract:
INTRODUCTION
Improved treatment approaches have resulted in longer survival of patients with certain types of incurable cancer, without eliminating the need for symptom palliation and supportive measures. In this context, re-irradiation is an increasingly important option. Little data exists about a second or repeat re-irradiation.

METHODS
From a single institution database, patients who received a second re-irradiation with cumulative equivalent doses (equivalent dose in 2-Gy fractions (EQD2) for late effects, alpha/beta-value 3 Gy) of more than 90 Gy and survived for more than six months were identified. Illustrative clinical examples were provided.

RESULTS
The examples describe the treatment of sacral bone metastases, recurrent rectal cancer, and pelvic lymph node metastases. The maximum cumulative EQD2 was 142 Gy. Symptomatic responses were obtained without clinically relevant side effects.

CONCLUSION
These three cases illustrate that a second re-irradiation has the potential to provide worthwhile palliative effects without causing overt late toxicity during the remaining life time. In patients who tolerated previous radiotherapy well, further re-irradiation may contribute to the ever-increasing armamentarium of options that increase the survival of patients with incurable cancer and try to prolong the time period where independent living is possible.

re-irradiation
cancer
bone metastases
toxicity
palliative radiotherapy


Percutaneous cavitary lavage in the diagnosis of pulmonary cavities.

Abstract:
OBJECTIVE
To investigate diagnostic significance of percutaneous cavitary lavage (PCL) in differential diagnosis of benign and malignant pulmonary cavitary lesions.

METHODS
An alternative diagnostic method called PCL was performed on 16 patients having peripherally located pulmonary cavitary lesions with thin walls which were not suitable for tissue biopsy and whose diagnosis could not be made by sputum examination and bronchoscopic procedures. A 22-gauge needle was inserted into the cavity under computed tomography (CT) guidance. Saline was injected through the needle and then aspirated. The specimen was examined cytologically and microbiologically.

RESULTS
PCL could make a correct diagnosis in 12 of 16 patients (75%). In three patients (18.7%) appropriate specimen could not be taken. Diagnostic sensitivity and specificity of PCL for malignant-benign differentiation was 80% and 100%, respectively. The accuracy of PCL for this differentiation was 92.3%. There was only one complication, a small pneumothorax resolved without any intervention.

CONCLUSIONS
PCL is an alternative method in the differential diagnosis of thin walled pulmonary cavitary lesions especially for patients whose diagnosis could not be made by sputum and bronchoscopic procedures and who are not suitable for cutting needle biopsy.

Belet|Umit|U|
Findik|Serhat|S|
Ozmen|Zafer|Z|
Atici|Atilla Guven|AG|
Akan|Huseyin|H|

Diagnosis
bronchoalveolar lavage fluid
therapeutic irrigation


Is There any Survival Benefit of Maintenance Chemotherapy Following Adjuvant Chemotherapy in Patients with Resected Pancreatic Cancer Patients with Post-Surgery Elevated CA 19-9?

Abstract:
Background
Pancreatectomy offers only potential for cure but is only possible in a minority of patients. Even in those patients who receive adjuvant chemotherapy, majority of them succumb to death due to metastases. Radiation Therapy Oncology Group 9704 showed that post-surgery CA 19-9 levels are an important predictor of survival. European study group for pancreatic cancer-3 showed that completion of all 6 cycles of adjuvant chemotherapy was an independent prognostic factor. Any survival benefit of an intensified chemotherapy strategy has not been demonstrated in patients with persistently elevated CA 19-9 following surgery. The object of this study was to investigate any benefit of maintenance chemotherapy following adjuvant in these patients.

Methods
Twenty patients with R0 surgery of pancreatic cancer who received adjuvant chemotherapy with post-surgery elevated CA 19-9 but no radiographic evidence of cancer was identified from 2005-2017. Either biopsy or positron emission tomography scan determined recurrence of cancer. Efficacy endpoints including overall survival and disease-free survival were assessed.

Results
Maintenance and additional chemotherapeutic agents included 5-FU, capecitabine, platinum agents, irinotecan and nab-paclitaxel. CA 19-9 normalized in 3 patients while 22 persisted to be elevated or had further increase in the marker. Two patients underwent metastatectomy. Median disease-free survival was 14.5m (9-18), OS 29m (19-96) and OS rates were 80%, 50% at 1 and 2 years respectively.

Conclusions
We believe that the longer overall survival of our patients with elevated CA 19-9 post-surgery was due to maintenance and additional chemotherapy following planned 6-months of adjuvant therapy, close monitoring with monthly CA 19-9 and 3-monthly computed tomography scans. Our study also underlines importance of collecting pre-surgery CA 19-9 and complete staging including chest. Prospective study aiming to evaluate role of maintenance or intensified chemotherapy or targeted agents are indicated.

Saif|Muhammad Wasif|MW|
Smith|Melissa H|MH|
Goodman|Martin D|MD|
Salem|Ronald R|RR|

Adjuvant Chemotherapy
Capecitabine
Clinical Study
Pancreatic Neoplasms
Risk Factors


Lipid peroxidation affects red blood cells membrane properties in patients with systemic lupus erythematosus.

Abstract: Systemic lupus erythematosus (SLE) is an autoimmune, chronic inflammatory, non-organ specific disease with an important morbimortality affecting several organs and systems. Oxidative stress is a well documented mechanism of red blood cells (RBC) mechanical impairment. Free radicals could produced, through lipid peroxidation, physical and chemical alterations in the cellular membrane properties modifying its composition, packing and lipid distribution on the membrane erythrocyte. The aim of the present work is to study the lipid peroxidation in the RBC membrane in SLE patients (n = 42) affecting so far the lipid membrane fluidity and erythrocyte deformability in comparison with healthy controls (n = 52). Malonildialdehyde (MDA) is a subrogate assessing lipidic peroxidation, rigidity index estimating erythrocyte deformability and the anisotropy coefficient estimating lipid membrane fluidity were used. Our results show that MDA values are increased, while erythrocyte deformability and membrane fluidity are significantly decreased in erythrocyte membrane from SLE patients in comparison with normal controls. The association of thiobarbituric acid reactive substances (TBARS) with membrane lipid fluidity and erythrocyte deformability confirms that the damage of membrane properties is produced by lipid peroxidation.

Spengler|M I|MI|
Svetaz|M J|MJ|
Leroux|M B|MB|
Bertoluzzo|S M|SM|
Parente|F M|FM|
Bosch|P|P|

lipid peroxidation
Systemic lupus erythematosus
lipid membrane fluidity
erythrocyte deformability


UAV IoT Framework Views and Challenges: Towards Protecting Drones as "Things".

Abstract: Unmanned aerial vehicles (UAVs) have enormous potential in enabling new applications in various areas, ranging from military, security, medicine, and surveillance to traffic-monitoring applications. Lately, there has been heavy investment in the development of UAVs and multi-UAVs systems that can collaborate and complete missions more efficiently and economically. Emerging technologies such as 4G/5G networks have significant potential on UAVs equipped with cameras, sensors, and GPS receivers in delivering Internet of Things (IoT) services from great heights, creating an airborne domain of the IoT. However, there are many issues to be resolved before the effective use of UAVs can be made, including security, privacy, and management. As such, in this paper we review new UAV application areas enabled by the IoT and 5G technologies, analyze the sensor requirements, and overview solutions for fleet management over aerial-networking, privacy, and security challenges. Finally, we propose a framework that supports and enables these technologies on UAVs. The introduced framework provisions a holistic IoT architecture that enables the protection of UAVs as "flying" things in a collaborative networked environment.


CAR T Cell-Based Immunotherapy for the Treatment of Glioblastoma.

Abstract: Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary brain tumor in adults. Current treatment options typically consist of surgery followed by chemotherapy or more frequently radiotherapy, however, median patient survival remains at just over 1 year. Therefore, the need for novel curative therapies for GBM is vital. Characterization of GBM cells has contributed to identify several molecules as targets for immunotherapy-based treatments such as EGFR/EGFRvIII, IL13Rα2, B7-H3, and CSPG4. Cytotoxic T lymphocytes collected from a patient can be genetically modified to express a chimeric antigen receptor (CAR) specific for an identified tumor antigen (TA). These CAR T cells can then be re-administered to the patient to identify and eliminate cancer cells. The impressive clinical responses to TA-specific CAR T cell-based therapies in patients with hematological malignancies have generated a lot of interest in the application of this strategy with solid tumors including GBM. Several clinical trials are evaluating TA-specific CAR T cells to treat GBM. Unfortunately, the efficacy of CAR T cells against solid tumors has been limited due to several factors. These include the immunosuppressive tumor microenvironment, inadequate trafficking and infiltration of CAR T cells and their lack of persistence and activity. In particular, GBM has specific limitations to overcome including acquired resistance to therapy, limited diffusion across the blood brain barrier and risks of central nervous system toxicity. Here we review current CAR T cell-based approaches for the treatment of GBM and summarize the mechanisms being explored in pre-clinical, as well as clinical studies to improve their anti-tumor activity.

Maggs|Luke|L|
Cattaneo|Giulia|G|
Dal|Ali Emre|AE|
Moghaddam|Ali Sanjari|AS|
Ferrone|Soldano|S|

immunotherapy
glioblastoma
tumor antigen
CAR T cell
clinical trial
preclinical


Microanatomical study of the human pancreatic made on necroptic pieces.

Abstract: The pancreas is a bulky gland, with mixed secretion, exocrine and endocrine, attached to the duodenum, participating through its secretions in carbohydrates digestion and metabolism. For a long time, it was considered a mysterious organ, with an inaccessible, examining and exploring due to its deep retroperitoneal position. We intend to make a comparative analysis of pancreatic microanatomy, between the examination of the necroptic-collected pieces and the ex vivo pieces, intraoperatively, with the patient's prior consent. We aimed to deepen the qualitative micro anatomic study on the pancreas parts of dissection, and quantitative study of the vessels micro anatomic normal pancreatic body. The methods and techniques used were the anatomical study through dissection and intraoperative and qualitative micro anatomic study by making blades of pathological sample products taken from patients: extemporaneous and microscope examination.

pancreas
micro anatomic study
micro vascularization


Modification of Apremilast from Pills to Aerosol a Future Concept.

Abstract:
BACKGROUND
Inhaled drugs have been available in the market for several years and for several diseases. Drugs for chronic obstructive pulmonary disease, cystic fibrosis, and diabetes have been used for several years. In the field of drug modification, these drugs range from tablets to aerosol.

METHODS
Milling as used to break down the tablets to powder and nebulisers are used to produce aerosol droplets. A mastersizer was used to measure the mass median aerodynamic diameter of the aerosol droplets.

RESULTS
Apremilast produced mmad diameters (2.43 μm) without any statistical difference between the different jet-nebulizers. The residual cup B contributed to greater mmad diameters as the 95% interval of mean values, based on those the ANOVA mean square clearly indicated, followed by cups C and F. The previous interval plot is much better clarified when the interaction means between drug and residual cap are plotted. The residual cups B, C and F produce mmad between (2.0-3.2).

CONCLUSION
In the current research study we demonstrated our methodology to create apremilast powder and produce apremilast aerosol droplets with different nebulisers and residual cups.

D029424:Pulmonary Disease, Chronic Obstructive

apremilast
nebulisers
mastersizer
jet-nebulisers
psoriasis
ultrasound nebulisers


Myoclonic Absence Seizures in Dravet Syndrome.

Abstract:
BACKGROUND
Dravet syndrome is a developmental and epileptic encephalopathy that occurs as a result of SCN1A mutations in more than 80% of affected individuals. The core clinical features of Dravet syndrome include febrile and afebrile seizures beginning before 12 months; multiple seizure types, usually medically refractory, including hemiclonic, generalized tonic-clonic, focal impaired awareness, myoclonic, and absence seizures; status epilepticus; and normal early development with plateau or regression by age two years. Myoclonic absence seizures have not previously been described.

PATIENT DESCRIPTION
This 20-year-old man had infantile-onset epilepsy with the classical clinical features of Dravet syndrome and a de novo A1326P SCN1A mutation. By five years of age, photosensitive myoclonic absence seizures had become his dominant seizure type, occurring up to 20 times per day.

RESULTS
The seizures were refractory to multiple antiepileptic medications and a vagus nerve stimulator.

CONCLUSIONS
Although photosensitivity is well recognized in Dravet syndrome, myoclonic absence seizures have not been previously reported. This rare seizure type may be underreported in Dravet syndrome, as the myoclonic features may be subtle and can be missed if thorough history taking and video recordings are not available.

Myers|Kenneth A|KA|
Scheffer|Ingrid E|IE|

D062550:NAV1.1 Voltage-Gated Sodium Channel

myoclonic absence seizures
absence seizures
Dravet syndrome
epileptic encephalopathy
SCN1A


Microbial electrolysis desalination and chemical-production cell for CO2 sequestration.

Abstract: Mineral carbonation can be used for CO2 sequestration, but the reaction rate is slow. In order to accelerate mineral carbonation, acid generated in a microbial electrolysis desalination and chemical-production cell (MEDCC) was examined to dissolve natural minerals rich in magnesium/calcium silicates (serpentine), and the alkali generated by the same process was used to absorb CO2 and precipitate magnesium/calcium carbonates. The concentrations of Mg(2+) and Ca(2+) dissolved from serpentine increased 20 and 145 times by using the acid solution. Under optimal conditions, 24 mg of CO2 was absorbed into the alkaline solution and 13 mg of CO2 was precipitated as magnesium/calcium carbonates over a fed-batch cycle (24h). Additionally, the MEDCC removed 94% of the COD (initially 822 mg/L) and achieved 22% desalination (initially 35 g/L NaCl). These results demonstrate the viability of this process for effective CO2 sequestration using renewable organic matter and natural minerals.

D057919:Biological Oxygen Demand Analysis

Microbial electrolysis
Desalination
Mineral carbonation
Serpentine
CO(2) sequestration


Development of an inter-professional screening instrument for cancer patients' education process.

Abstract:
AIM
The aim of this paper is to describe the development of an inter-professional screening instrument for cancer patients' cognitive resources, knowledge expectations and inter-professional collaboration within patient education.

DESIGN AND METHODS
Four empirical datasets during 2012-2014 were analyzed in order to identify main categories, subcategories and items for inter-professional screening instrument.

FINDINGS
Our inter-professional screening instrument integrates the critical moments of cancer patient education and the knowledge expectation types obtained from patient datasets to assessment of patients' cognitive resources, knowledge expectations and comprehension; and intra; and inter-professional.

Vaartio-Rajalin|Heli|H| Huumonen|Tuula|T| Iire|Liisa|L| Jekunen|Antti|A| Leino-Kilpi|Helena|H| Minn|Heikki|H| Paloniemi|Jenni|J| Zabalegui|Adelaida|A|

Inter-professional collaboration
Patient education
Cancer care


Pattern, variability, and hemispheric differences of the subparietal sulcus on multiplanar reconstructed MR images.

Abstract:
PURPOSE
The aim of this study was to analyze variations in the morphological features of the subparietal sulcus (SPS) and to investigate interhemispheric and gender differences in these variations using multiplanar reconstructed (MPR) magnetic resonance (MR) images.

METHODS
Two hundred subjects with normal cranial MR imaging, including high-resolution T1-weighted volumetric data, were enrolled in the study. The sagittal or oblique sagittal MPR images created from high-resolution T1-weighted data were analyzed for the following morphological features: the SPS patterns, the continuity of the SPS with the cingulate sulcus and parieto-occipital sulcus (POS), and the presence of upwardly directed SPS branches reaching to the hemispheric surface. Interindividual variability of the morphologic features, hemispheric asymmetry, and gender differences were investigated.

RESULTS
Considerable variations were found in the morphological features of the SPS. The H-pattern, no connection with the cingulate sulcus or the POS, and one upwardly directed branch reaching the hemispheric surface were most commonly observed morphologic features of the SPS in 45.2, 41.8, and 48 % of the all hemispheres, respectively. Furthermore, the connection of the SPS only with the cingulate sulcus and the presence of two upwardly directed branches reaching the hemispheric surface showed the significant leftward asymmetry (P < 0.05).

CONCLUSIONS
Our study demonstrated the extensive morphological variability of the SPS and the hemispheric asymmetry for some morphological features. Knowledge of these variations and their hemispheric asymmetry may be helpful for surgical approaches in neurosurgery and structure-function correlations in functional neuroimaging studies involving the posteromedial hemisphere.

Kacar|Emre|E|
Nas|Omer Fatih|OF|
Okeer|Emre|E|
Hakyemez|Bahattin|B|

Subparietal sulcus
Multiplanar reconstruction
Variation
Asymmetry
MRI
Sulcal morphology


Primary Generalized Glucocorticoid Resistance and Hypersensitivity Syndromes: A 2021 Update.

Abstract: Glucocorticoids are the final products of the neuroendocrine hypothalamic-pituitary-adrenal axis, and play an important role in the stress response to re-establish homeostasis when it is threatened, or perceived as threatened. These steroid hormones have pleiotropic actions through binding to their cognate receptor, the human glucocorticoid receptor, which functions as a ligand-bound transcription factor inducing or repressing the expression of a large number of target genes. To achieve homeostasis, glucocorticoid signaling should have an optimal effect on all tissues. Indeed, any inappropriate glucocorticoid effect in terms of quantity or quality has been associated with pathologic conditions, which are characterized by short-term or long-lasting detrimental effects. Two such conditions, the primary generalized glucocorticoid resistance and hypersensitivity syndromes, are discussed in this review article. Undoubtedly, the tremendous progress of structural, molecular, and cellular biology, in association with the continued progress of biotechnology, has led to a better and more in-depth understanding of these rare endocrinologic conditions, as well as more effective therapeutic management.

glucocorticoid resistance
glucocorticoids
glucocorticoid receptor
NR3C1 gene mutations
glucocorticoid hypersensitivity


Early career nurses with fewer supportive peers for safe patient handling are likely to quit.

Abstract: This prospective study observed turnover during 1 year at a community hospital in Oregon (n = 39). The study tested whether nurses who at baseline nominated fewer peers as sources of safe patient handling support were more likely to quit than nurses with more supportive peers. Six nurses with tenure under 2 years left their positions. Nurses who quit reported half as many co-workers as sources of support relative to nurses who remained employed, and each additional peer nomination reduced the risk of turnover by 15%. Further research should establish the contribution of peer safety support reducing turnover among recent hires.

Health and Safety
Job Satisfaction
Occupational Health
Recruitment and Retention
Teamwork
Workforce Issues


Basal and insulin-regulated VLDL1 and VLDL2 kinetics in men with type 2 diabetes.

Abstract:
AIMS/HYPOTHESIS
Hypertriacylglycerolaemia is a hallmark of diabetic dyslipidaemia with increased concentrations of triacylglycerol (TG)-rich VLDL1 particles. However, whether VLDL1 secretion or removal is abnormal in type 2 diabetes remains unclear. The aim of this study was to compare basal and insulin-mediated VLDL1- and VLDL2-TG kinetics in men with type 2 diabetes and healthy men using a novel direct VLDL1- and VLDL2-TG labelling method.

METHODS
Twelve men with type 2 diabetes and 12 healthy men matched for age and BMI were recruited. VLDL1- and VLDL2-TG turnover were measured during a 4 h basal period and a 3.5 h hyperinsulinaemic clamp period using a primed-constant infusion of ex vivo labelled VLDL1-TG and VLDL2-TG.

RESULTS
Basal VLDL1-TG and VLDL2-TG secretion rates were similar in men with diabetes and healthy men. During hyperinsulinaemia, VLDL1-TG secretion rates were suppressed significantly in both groups, whereas no suppression of VLDL2-TG secretion rate was observed. VLDL1-TG to VLDL2-TG transfer rate was not significantly different from zero in both groups, while VLDL1-TG fatty acid oxidation rate was substantial, with a contribution to total energy expenditure of approximately 15% during postabsorptive conditions. VLDL1 and VLDL2 particle size (TG/apolipoprotein B [apoB] ratio) and apoB-100 concentration were unaltered by hyperinsulinaemia in men with type 2 diabetes, but significantly reduced in healthy men.

CONCLUSIONS/INTERPRETATION
Insulin inhibits VLDL1-TG secretion rate similarly in age- and BMI-matched men with type 2 diabetes and healthy men, while VLDL2-TG secretion is unaltered by hyperinsulinaemia. However, VLDL1- and VLDL2-apoB levels are not lowered by hyperinsulinaemia in men with type 2 diabetes, which is indicative of a diminished hepatic response to insulin.

TRIAL REGISTRATION
ClinicalTrials.gov NCT01564550.

Johansen|Rakel F|RF|
Søndergaard|Esben|E|
Sørensen|Lars Peter|LP|
Jurik|Anne Grethe|AG|
Christiansen|Jens S|JS|
Nielsen|Søren|S|

VLDL1
VLDL2
Kinetics
Type 2 diabetes
Dyslipidaemia
Healthy men
Hyperinsulinaemic clamp
Insulin resistance


Prospective study assessing three-dimensional changes of mucosal healing following soft tissue augmentation using free gingival grafts.

Abstract:
BACKGROUND
The present study aimed to assess the three-dimensional changes following soft tissue augmentation using free gingival grafts (FGG) at implant sites over a 3-month follow-up period.

METHODS
This study included 12 patients exhibiting deficient keratinized tissue (KT) width (i.e., <2 mm) at the vestibular aspect of 19 implants who underwent soft tissue augmentation using FGG at second stage surgery following implant placement. Twelve implants were considered for the statistical analysis (n = 12). The region of interest (ROI) was intraorally scanned before surgery (S0), immediately post-surgery (S1), 30 (S2) and 90 (S3) days after augmentation. Digital scanned files were used for quantification of FGG surface area (SA) and converted to standard tessellation language (STL) format for superimposition and evaluation of thickness changes between the corresponding time points. FGG shrinkage (%) in terms of SA and thickness was calculated between the assessed time points.

RESULTS
Mean FGG SA amounted to 91 (95% CI: 63 to 119), 76.2 (95% CI: 45 to 106), and 61.3 (95% CI: 41 to 81) mm2 at S1, S2, and S3, respectively. Mean FGG SA shrinkage rate was 16.3% (95% CI: 3 to 29) from S1 to S2 and 33% (95% CI: 19 to 46) from S1 to S3. Mean thickness gain from baseline (S0) to S1, S2, and S3 was 1.31 (95% CI: 1.2 to 1.4), 0.82 (95% CI: 0.5 to 1.12), and 0.37 (0.21 to 0.5) mm, respectively. FGG thickness shrinkage was of 38% (95% CI: 17.6 to 58) from S1 to S2 and 71.8% (95% CI: 60 to 84) from S1 to S3. Dimensional changes from S1 to S3 were statistically significant, P <0.017. Soft tissue healing was uneventful in all patients.

CONCLUSIONS
The present three-dimensional assessment suggests that FGG undergo significant dimensional changes in SA and thickness over a 3-month healing period.

Parvini|Puria|P|
Galarraga-Vinueza|Maria Elisa|ME|
Obreja|Karina|K|
Magini|Ricardo de Sousa|RS|
Sader|Robert|R|
Schwarz|Frank|F|

D015921:Dental Implants
D005881:Gingiva
D006801:Humans
D019647:Oral Surgical Procedures
D011446:Prospective Studies
D014945:Wound Healing

free gingival graft
shrinkage
dental implants
keratinized mucosa
three-dimensional analysis


The cyclin-dependent kinase 4/6 inhibitor, abemaciclib, exerts dose-dependent cytostatic and cytocidal effects and induces autophagy in multiple myeloma cells.

Abstract: The D-type cyclin (CCND)-cyclin-dependent kinase 4/6 (CDK4/6) complex has been implicated in multiple myeloma development. We investigated the biological activity of CDK4/6 inhibitor abemaciclib on cell growth and survival in three myeloma cell lines, KMS-12-PE, RPMI 8226, and IM-9. Abemaciclib inhibited myeloma cell growth in a dose-dependent manner in all cell lines, with significant differences seen at a concentration of 320 nM. Treatment with 1 μM abemaciclib increased the fraction of cells in the G0/G1 phase and decreased the fraction in the S-G2/M phases. Further, treatment with abemaciclib at a concentration of 3.2 μM or more showed apparent cytocidal activity accompanied with cytoplasmic vacuolization against myeloma cells. Importantly, abemaciclib induced autophagy in a dose-dependent manner in all three cell lines. These results indicate that the CCND-CDK4/6 complex is closely tied to myeloma cell growth and survival.

Iriyama|Noriyoshi|N| Hino|Hirotsugu|H| Moriya|Shota|S| Hiramoto|Masaki|M| Hatta|Yoshihiro|Y| Takei|Masami|M| Miyazawa|Keisuke|K|

Abemaciclib
autophagy
multiple myeloma
cell death


Presentation and outcomes of "wake-up strokes" in a large randomized stroke trial: analysis of data from the International Stroke Trial.

Abstract:
BACKGROUND
Recent studies comparing the outcomes of wake-up stroke (WUS) and stroke while awake (SWA) patients reveal better outcomes among SWA patients, attributable in part to their higher rates of thrombolysis. Patients with WUS are largely excluded from therapy. Earlier analyses, conducted before the approval of alteplase for acute stroke, show the true divergence of natural histories between these 2 groups.

METHODS
We analyzed 17,398 patients with ischemic stroke from the International Stroke Trial and compared both presentations and outcomes between the WUS and SWA groups. Severity was assessed by level of consciousness, Oxfordshire Community Stroke Project (OCSP) stroke classification, number of neurologic deficits, and predicted probability of dependency or death. Outcomes were assessed at day 14 and at 6 months. Outcome assessments were controlled for potential confounders.

RESULTS
WUS represented 29.6% of all ischemic strokes. More severe OSCP stroke type (total anterior circulation syndrome) was less common in WUS. Although more patients with WUS were alert at presentation with a lower predicted probability of dependency, the 14-day mortality rates and rates of poor outcome at 6 months were similar between the 2 groups.

CONCLUSIONS
WUS patients comprise one quarter to one third of ischemic stroke patients. Despite their more benign presentations, they deteriorate to outcome rates similar to SWA. Although they are typically excluded from time-dependent acute interventions, patients with WUS may benefit from acute intervention to prevent this worsening natural history.

outcomes
wake-up stroke
Natural history
severity


Histidine(7.36(305)) in the conserved peptide receptor activation domain of the gonadotropin releasing hormone receptor couples peptide binding and receptor activation.

Abstract: Transmembrane helix seven residues of G protein-coupled receptors (GPCRs) couple agonist binding to a conserved receptor activation mechanism. Amino-terminal residues of the GnRH peptide determine agonist activity. We investigated GnRH interactions with the His(7.36(305)) residue of the GnRH receptor, using functional and computational analysis of modified GnRH receptors and peptides. Non-polar His(7.36(305)) substitutions decreased receptor affinity for GnRH four- to forty-fold, whereas GnRH signaling potency was more decreased (~150-fold). Uncharged polar His(7.36(305)) substitutions decreased GnRH potency, but not affinity. [2-Nal(3)]-GnRH retained high affinity at receptors with non-polar His(7.36(305)) substitutions, supporting a role for His(7.36(305)) in recognizing Trp(3) of GnRH. Compared with GnRH, [2-Nal(3)]-GnRH potency was lower at the wild type GnRH receptor, but unchanged or higher at mutant receptors. Results suggest that His(7.36(305)) of the GnRH receptor forms two distinct interactions that determine binding to Trp(3) and couple agonist binding to the conserved transmembrane domain network that activates GPCRs.

Mayevu|Nkateko M I|NM|
Choe|Han|H|
Abagyan|Ruben|R|
Seong|Jae Young|JY|
Millar|Robert P|RP|
Katz|Arieh A|AA|
Flanagan|Colleen A|CA|

D054730:Protein Interaction Domains and Motifs

Hormone receptor
G protein-coupled receptor (GPCR)
GnRH
Peptide hormone
Peptide interaction
Receptor structure-function


Complications of interosseous infusion resulting in a diagnostic dilemma.

Abstract: Successful revival of a patient with cardiac arrest need vigilant effort on behalf of whole team but sometimes missing a small thing can create disaster. Here we present a case of 58 years old obese lady who was revived from a cardiac arrest secondary to septic shock. Obstruction due to proximal ureteric stone was relieved with JJ stent insertion. She required renal replacement therapy and invasive ventilation. Fever and inflammatory blood markers improved and she woke up after 6 days in intensive care unit (ICU). She developed another episode of sepsis but this time it was her shoulder that was hurting. Initially it was thought to be an iatrogenic skeletal injury during aggressive cardiopulmonary resuscitation (CPR) but radiographs came out to be normal. Magnetic resonance imaging (MRI) created more confusion by showing septic arthritis with proximal humeral osteomyelitis and gas formation. MRI suggested that it might be the sequelae of an intraosseous line insertion. All documented records were silent regarding the intraosseous line insertion. Resuscitation team was contacted and inquired. They confirmed the insertion of intraosseous line insertion during initial resuscitation which was removed after securing peripheral vascular access and before transferring the patient to ICU but they forgot to document. Her shoulder joint was washed out and debrided arthroscopically. She made a safe recovery without any other problem.

Khan|Mohammad Noah Hasan|MNH|
Jamal|Abdul Basit|AB|
Anjum|Syed Neshat|SN|

Septic shock
Resuscitation
CPR
Septic arthritis
Humeral osteomyelitis
Intraosseous line
Documentation error