COVIDiagnosis-Net: Deep Bayes-SqueezeNet based diagnosis of the coronavirus disease 2019 (COVID-19) from X-ray images.

Abstract: The Coronavirus Disease 2019 (COVID-19) outbreak has a tremendous impact on global health and the daily life of people still living in more than two hundred countries. The crucial action to gain the force in the fight of COVID-19 is to have powerful monitoring of the site forming infected patients. Most of the initial tests rely on detecting the genetic material of the coronavirus, and they have a poor detection rate with the time-consuming operation. In the ongoing process, radiological imaging is also preferred where chest X-rays are highlighted in the diagnosis. Early studies express the patients with an abnormality in chest X-rays pointing to the presence of the COVID-19. On this motivation, there are several studies cover the deep learning-based solutions to detect the COVID-19 using chest X-rays. A part of the existing studies use non-public datasets, others perform on complicated Artificial Intelligent (AI) structures. In our study, we demonstrate an AI-based structure to outperform the existing studies. The SqueezeNet that comes forward with its light network design is tuned for the COVID-19 diagnosis with Bayesian optimization additive. Fine-tuned hyperparameters and augmented dataset make the proposed network perform much better than existing network designs and to obtain a higher COVID-19 diagnosis accuracy.

Coronavirus Disease 2019
Bayesian Optimization
Deep Learning
Rapid Diagnosis of COVID-19
SARS-CoV-2


Current opinions on the mechanism, classification, imaging diagnosis and treatment of post-traumatic osteomyelitis.

Abstract: Post-traumatic osteomyelitis (PTO) is a worldwide problem in the field of orthopaedic trauma. So far, there is no ideal treatment or consensus-based gold standard for its management. This paper reviews the representative literature focusing on PTO, mainly from the following four aspects: (1) the pathophysiological mechanism of PTO and the interaction mechanism between bacteria and the body, including fracture stress, different components of internal fixation devices, immune response, occurrence and development mechanisms of inflammation in PTO, as well as the occurrence and development mechanisms of PTO in skeletal system; (2) clinical classification, mainly the etiological classification, histological classification, anatomical classification and the newly proposed new classifications (a brief analysis of their scope and limitations); (3) imaging diagnosis, including non-invasive examination and invasive examination (this paper discusses their advantages and disadvantages respectively, and briefly compares the sensitivity and effectiveness of the current examinations); and (4) strategies, including antibiotic administration, surgical choices and other treatment programs. Based on the above-mentioned four aspects, we try to put forward some noteworthy sections, in order to make the existing opinions more specific.

Yang|Jian|J| Yao|Jiang-Ling|JL| Wu|Zi-Quan|ZQ| Zeng|De-Lu|DL| Zheng|Lin-Yang|LY| Chen|Dong|D| Guo|Zheng-Dong|ZD| Peng|Lei|L|

Diagnosis
Treatment
Post-traumatic osteomyelitis
Osteomyelitis
Clinical classification
Bone infection
Pathology


Is Low Inferior Mesenteric Artery Ligation Worthwhile to Prevent Urinary and Sexual Dysfunction After Total Mesorectal Excision for Rectal Cancer?

Abstract:
BACKGROUND/AIM
We studied the role of high or low inferior mesenteric artery (IMA) tie on defecatory, sexual and urinary dysfunctions in patients who underwent laparoscopic TME for early rectal cancer.

PATIENTS AND METHODS
Forty-six consecutive patients undergoing curative laparoscopic resection for pT2N0M0, rectal adenocarcinoma from February 2013 to March 2019 were enrolled into this prospective randomized open label parallel trial to have a laparoscopic TME with a high (Group 1) or low IMA ligation (Group 2). Demographic data and information on symptoms and comorbidity, intra- and post-operative outcomes and defecatory, sexual and urinary functions before and after surgery according to the validated International quality of life questionnaires.

RESULTS
A significant difference in postoperative total score of FIQL scale, Jorge-Wexner incontinence score and Agachan-Wexner constipation score were observed between the high and low tie groups at 1, 6, and 12 months after surgery. ICIQ-UI short form, FSFI, and IIEF demonstrated at 1, 6 and 12 months, the scores were significantly higher for patients of Group 1 as compared to those of Group 2.

CONCLUSION
A low IMA ligation permits a better fecal continence, less abdominal pain, and less genito-urinary and sexual dysfunctions in patients submitted to TME for rectal cancer.

Fiori|Enrico|E|
Crocetti|Daniele|D|
Lamazza|Antonietta|A|
DE Felice|Francesca|F|
Sterpetti|Antonio V|AV|
Irace|Luigi|L|
Mingoli|Andrea|A|
Sapienza|Paolo|P|
DE Toma|Giorgio|G|

sexual dysfunction
rectal cancer
Urinary dysfunction
high inferior mesenteric artery tie
low inferior mesenteric artery tie


How People with Dementia and their Carers Adapt their Homes. A Qualitative Study.

Abstract: The objective was to explore the ways in which people with dementia and their carers adapt their homes, including the barriers and use of available information. Semi-structured interviews were conducted with 10 people with dementia and their informal carer. The collected data were analysed using thematic analysis. Three core themes emerged: Maintaining familiarity and coping with change, Having knowledge and finding knowledge and Meeting challenges through home adaptation. The most significant barriers to making home adaptations were lack of knowledge and maintaining familiarity. Having more information and making home modifications earlier might enable individuals with dementia to adjust to their adapted environment.

dementia
qualitative
information
home adaptation
home modification


Combining A4R and MCDA in priority setting for health.

Abstract: Multiple criteria decision analysis (MCDA) has been proposed as a method for determining the criteria to be used in health technology assessment. A standard criticism of MCDA is that it lacks attention to securing legitimacy for its decisions. The relevance condition of A4R has been criticized for its vagueness because it lacks a focus on criteria selection. Combining the two methods addresses the central criticisms of each and provides a way of addressing the problem of priority setting for health.

Legitimacy
Accountability for reasonableness
Multi criteria decision analysis
Stakeholders


Transposed-letter priming effects in reading aloud words and nonwords.

Abstract: A masked nonword prime generated by transposing adjacent inner letters in a word (e.g., jugde) facilitates the recognition of the target word (JUDGE) more than a prime in which the relevant letters are replaced by different letters (e.g., junpe). This transposed-letter (TL) priming effect has been widely interpreted as evidence that the coding of letter position is flexible, rather than precise. Although the TL priming effect has been extensively investigated in the domain of visual word recognition using the lexical decision task, very few studies have investigated this empirical phenomenon in reading aloud. In the present study, we investigated TL priming effects in reading aloud words and nonwords and found that these effects are of equal magnitude for the two types of items. We take this result as support for the view that the TL priming effect arises from noisy perception of letter order within the prime prior to the mapping of orthography to phonology.

Mousikou|Petroula|P| Kinoshita|Sachiko|S| Wu|Simon|S| Norris|Dennis|D|

Reading aloud
Transposed-letter (TL) priming effect
Computational models of reading aloud


Observation of Phototropic Responses in the Liverwort Marchantia polymorpha.

Abstract: The liverwort species, Marchantia polymorpha, shows environment-dependent morphological plasticity throughout its life cycle. Thalli, representing the predominant body form throughout most of this bryophyte's life cycle, grow with repeated dichotomous branching at the apex and develop horizontally under sufficient light intensity. Spores, after germination, produce a mass of cells, called sporelings, which then grow into thalli. Both thalli and sporelings, if grown under weak light conditions, form narrow shapes, and their apices grow toward the light source. These phototropic responses are specific to blue light and dependent on the blue-light receptor phototropin. This chapter provides several basic procedures, along with some tips, for designing and performing experiments with M. polymorpha to observe their phototropic responses, as well as methods for observing the localization of the phototropin "Mpphot" with a fluorescent protein tag.

Phototropic responses
Liverwort
Marchantia polymorpha
Sporeling
Blue light
Phototropin
Gemmaling


Peptide Amphiphile Nanostructures for Targeting of Atherosclerotic Plaque and Drug Delivery.

Abstract: Co-assembled peptide amphiphile nanofibers designed to target atherosclerotic plaque and enhance cholesterol efflux are shown to encapsulate and deliver a liver X receptor agonist to increase efflux from murine macrophages in vitro. Fluorescence microscopy reveals that the nanofibers, which display an apolipoprotein-mimetic peptide, localize at plaque sites in LDL receptor knockout mice with or without the encapsulated molecule, while nanofibers displaying a scrambled, non-targeting peptide sequence do not demonstrate comparable binding. These results show that nanofibers functionalized with apolipoprotein-mimetic peptides may be effective vehicles for intravascular targeted drug delivery to treat atherosclerosis.

So|Miranda M|MM|
Mansukhani|Neel A|NA|
Peters|Erica B|EB|
Albaghdadi|Mazen S|MS|
Wang|Zheng|Z|
Pérez|Charles M Rubert|CMR|
Kibbe|Melina R|MR|
Stupp|Samuel I|SI|

peptides
atherosclerosis
self-assembly
supramolecular chemistry


Recent developments in the management of recurrent Clostridioides difficile infection.

Abstract: Clostridioides (formerly Clostridium) difficile is responsible for a substantial burden of nosocomial infection. Recurrent C. difficile infection (rCDI) remains a concern due to its high morbidity, mortality, and cost. Despite the updated 2017 IDSA C. difficile treatment guidelines, there remains a lack of well-studied preventive control measures and treatment modalities for rCDI. There are ongoing efforts to develop novel therapies, such as new antibiotics with a lesser impact on gut microbiota and more targeted therapies, such as bacteriotherapy. This mini review highlights key rCDI management updates, preventive measures and ongoing research on novel treatment strategies including bacteriotherapy.

Mendo-Lopez|Rafael|R|
Villafuerte-Gálvez|Javier|J|
White|Nicole|N|
Mahoney|Monica V|MV|
Kelly|Ciaran P|CP|
Alonso|Carolyn D|CD|

D000900:Anti-Bacterial Agents
D019072:Antibiotic Prophylaxis
D016360:Clostridioides difficile
D003015:Clostridium Infections
D003131:Combined Modality Therapy
D019468:Disease Management
D006801:Humans
D012008:Recurrence
D016896:Treatment Outcome

Recurrence
Clostridioides difficile infection
Antibiotics
Bacteriotherapy
Prophylaxis


Manganese transporter Slc30a10 controls physiological manganese excretion and toxicity.

Abstract: Manganese (Mn), an essential metal and nutrient, is toxic in excess. Toxicity classically results from inhalational exposures in individuals who work in industrial settings. The first known disease of inherited Mn excess, identified in 2012, is caused by mutations in the metal exporter SLC30A10 and is characterized by Mn excess, dystonia, cirrhosis, and polycythemia. To investigate the role of SLC30A10 in Mn homeostasis, we first generated whole-body Slc30a10-deficient mice, which developed severe Mn excess and impaired systemic and biliary Mn excretion. Slc30a10 localized to canalicular membranes of hepatocytes, but mice with liver Slc30a10 deficiency developed minimal Mn excess despite impaired biliary Mn excretion. Slc30a10 also localized to the apical membrane of enterocytes, but mice with Slc30a10 deficiency in small intestines developed minimal Mn excess despite impaired Mn export into the lumen of the small intestines. Finally, mice with Slc30a10 deficiency in liver and small intestines developed Mn excess that was less severe than that observed in mice with whole-body Slc30a10 deficiency, suggesting that additional sites of Slc30a10 expression contribute to Mn homeostasis. Overall, these results indicated that Slc30a10 is essential for Mn excretion by hepatocytes and enterocytes and could be an effective target for pharmacological intervention to treat Mn toxicity.

Mercadante|Courtney J|CJ|
Prajapati|Milankumar|M|
Conboy|Heather L|HL|
Dash|Miriam E|ME|
Herrera|Carolina|C|
Pettiglio|Michael A|MA|
Cintron-Rivera|Layra|L|
Salesky|Madeleine A|MA|
Rao|Deepa B|DB|
Bartnikas|Thomas B|TB|

Genetic diseases
Genetics
Metabolism
Mouse models


SWAN platform: A web-based tool to support the development of industrial solid waste reuse business models.

Abstract: The SWAN platform is an integrated suite of online resources and tools for assessing industrial symbiotic opportunities based on solid industrial waste reuse. It has been developed as a digital solid waste reuse platform and is already applied in four countries (Greece, Bulgaria, Albania and Cyprus). The SWAN platform integrates a database with the spatial and technical characteristics of industrial solid waste producers and potential consumers, populated with data from these countries. It also incorporates an inventory of commercially implemented best practices on solid industrial waste reuse. The role of the SWAN platform is to facilitate the development of novel business cases. Towards this end, decision support services, based on a suitable matching algorithm, are provided to the registered users, helping them to identify and assess potential novel business models, based on solid waste reuse, either for an individual industrial unit (source/potential receiver of solid waste) or a specific region.

web-based tool
Solid waste
SWAN project
industrial symbiosis


Current Advances of Artificial Pancreas Systems: A Comprehensive Review of the Clinical Evidence.

Abstract: Since Banting and Best isolated insulin in the 1920s, dramatic progress has been made in the treatment of type 1 diabetes mellitus (T1DM). However, dose titration and timely injection to maintain optimal glycemic control are often challenging for T1DM patients and their families because they require frequent blood glucose checks. In recent years, technological advances in insulin pumps and continuous glucose monitoring systems have created paradigm shifts in T1DM care that are being extended to develop artificial pancreas systems (APSs). Numerous studies that demonstrate the superiority of glycemic control offered by APSs over those offered by conventional treatment are still being published, and rapid commercialization and use in actual practice have already begun. Given this rapid development, keeping up with the latest knowledge in an organized way is confusing for both patients and medical staff. Herein, we explore the history, clinical evidence, and current state of APSs, focusing on various development groups and the commercialization status. We also discuss APS development in groups outside the usual T1DM patients and the administration of adjunct agents, such as amylin analogues, in APSs.

Moon|Sun Joon|SJ|
Jung|Inha|I|
Park|Cheol-Young|CY|

Blood glucose self-monitoring
Diabetes mellitus, type 1
Hypoglycemia
Insulin infusion systems
Pancreas, artificial
Wearable electronic devices


Hapl-o-Mat: open-source software for HLA haplotype frequency estimation from ambiguous and heterogeneous data.

Abstract:
BACKGROUND
Knowledge of HLA haplotypes is helpful in many settings as disease association studies, population genetics, or hematopoietic stem cell transplantation. Regarding the recruitment of unrelated hematopoietic stem cell donors, HLA haplotype frequencies of specific populations are used to optimize both donor searches for individual patients and strategic donor registry planning. However, the estimation of haplotype frequencies from HLA genotyping data is challenged by the large amount of genotype data, the complex HLA nomenclature, and the heterogeneous and ambiguous nature of typing records.

RESULTS
To meet these challenges, we have developed the open-source software Hapl-o-Mat. It estimates haplotype frequencies from population data including an arbitrary number of loci using an expectation-maximization algorithm. Its key features are the processing of different HLA typing resolutions within a given population sample and the handling of ambiguities recorded via multiple allele codes or genotype list strings. Implemented in C++, Hapl-o-Mat facilitates efficient haplotype frequency estimation from large amounts of genotype data. We demonstrate its accuracy and performance on the basis of artificial and real genotype data.

CONCLUSIONS
Hapl-o-Mat is a versatile and efficient software for HLA haplotype frequency estimation. Its capability of processing various forms of HLA genotype data allows for a straightforward haplotype frequency estimation from typing records usually found in stem cell donor registries.

Open-source software
HLA
Haplotype
Population genetics
Expectation-maximization algorithm
Bioinformatics
Immunogenetics


Buccal misoprostol for treatment of fetal death at 14-28 weeks of pregnancy: a double-blind randomized controlled trial.

Abstract:
OBJECTIVE
To assess whether buccal misoprostol is effective for the treatment of intrauterine fetal death.

STUDY DESIGN
This double-blind randomized trial was conducted at five tertiary-level hospitals in the United States and Vietnam. One hundred fifty-three women with an intrauterine fetal death at 14-28 weeks of pregnancy received either 100 mcg buccal misoprostol or 200 mcg buccal misoprostol every 6 h for a maximum of 8 doses. The main outcome measure was the fetal-placental delivery rate within 48 hours of prostaglandin commencement without any additional intervention.

RESULTS
Most of the women (140/153) were recruited at the study site in Vietnam. Expulsion of both fetus and placenta within 48 hours of prostaglandin commencement without any additional interventions occurred in 61.8% (47/76) of women receiving misoprostol 100 mcg and 77.9% (60/77) of women receiving misoprostol 200 mcg. The 200 mcg dose was significantly more effective than the 100 mcg dose at expelling the fetus and placenta within 48 h [RR 0.68 (95% CI: 0.50-0.92; p=.03)]. The mean time to expulsion was significantly shorter using the 200 mcg dose (18.5±11.9 h) than the 100 mcg dose (23.9±12.5 h) (p=.02). Most women in both groups found the procedure satisfactory or very satisfactory (100 mcg: 76.7% (56/73); 200 mcg: 89.5% (68/76) [RR 0.86 (95% CI: 0.74-1.00)].

CONCLUSION
Buccal misoprostol is an effective method for medical induction of labor after intrauterine fetal demise. A 200 mcg dose is significantly more effective than 100 mcg for evacuating the uterus within 48h. The treatment is highly acceptable to women.

IMPLICATIONS
Administration of 200 mcg buccal misoprostol every six hours is an effective and acceptable method to effect the delivery of a demised fetus at 14-28 weeks that can be feasibly implemented in a wide variety of settings.

Bracken|Hillary|H|
Ngoc|Nguyen Thi Nhu|NT|
Banks|Erika|E|
Blumenthal|Paul D|PD|
Derman|Richard J|RJ|
Patel|Ashlesha|A|
Gold|Marji|M|
Winikoff|Beverly|B|
|||

Buccal misoprostol
Intrauterine fetal demise


Submental Artery Island Flap in Oral Cavity Reconstruction. An Observational, Retrospective Two-centre Study.

Abstract: Introduction  The submental flap provides an alternative technique in orofacial reconstruction, especially in situations in which free flaps are not available, or the patients are unfit. Objective  To demonstrate the oncological safety and benefits of this flap in oral cavity reconstruction. Methods  A total of 14 patients with oral cavity cancers, who underwent submental flap reconstruction from January 2016 to January 2018, were included in the study. Results  There were 11 male and 3 female patients with a mean age of 66.7 ± 14 (Min: 52/Max: 91) years old. The most common primary tumor site was the mobile tongue in 12 (85.7%) patients. All of the patients underwent ipsilateral selective neck dissection after the flap was harvested. Flap partial necrosis was observed in one patient, and total necrosis in another one. The mean follow-up was of one year. Nonlocal or regional recurrences were observed. Conclusion  Submental island flap represents a good option in oral cavity reconstruction in a restricted setting or in patients considered not fit for free flap reconstruction. Preoperative selection of clinically neck node-negative patients is essential due to the potential risk of occult metastasis.


Transperineal systematic biopsies in addition to targeted biopsies are important in the detection of clinically significant prostate cancer.

Abstract:
BACKGROUND
This study aimed to determine whether the addition of transperineal systematic biopsies (SB) to targeted biopsies (TB) improved clinically significant prostate cancer (csPC) detection rates without high increase in insignificant prostate cancer detection rates in an Australian population.

METHODS
In this retrospective review, a total of 254 patients who had a Prostate Imaging-Reporting and Data System score between 3 and 5, and a transperineal TB and SB between 2014 and 2019 from two centres were included in this study. The primary outcome of this study was to determine csPC rates on TB and SB. The secondary outcome was a comparison of the Gleason Grade Group between TB and SB. csPC was defined as an International Society of Urological Pathology Gleason Grade Group of 2 or greater.

RESULTS
SB alone detected more csPC overall compared to TB (152/254 (60%) versus 128/254 (51%), respectively). An additional 40 of 254 (16%) csPC cases were diagnosed with the addition of SB. Furthermore, the cost of diagnosing insignificant prostate cancer by SB when TB were negative was an additional 13/254 (5.1%).

CONCLUSION
A combination of TB and SB provides the best outcomes for detecting csPC and is especially warranted for patients with a higher Prostate Imaging-Reporting and Data System score on multiparametric magnetic resonance imaging.

D001315:Australia
D006801:Humans
D061705:Image-Guided Biopsy
D008279:Magnetic Resonance Imaging
D008297:Male
D011446:Prospective Studies
D011471:Prostatic Neoplasms
D012189:Retrospective Studies
D018084:Ultrasonography, Interventional

Systematic
biopsy
Targeted
Prostate
cancer
magnetic resonance imaging


Epstein-Barr virus infection after adolescence and human herpesvirus 6A as risk factors for multiple sclerosis.

Abstract:
BACKGROUND AND PURPOSE
Infections with human herpesvirus 6A (HHV-6A) and Epstein-Barr virus (EBV) have been linked to multiple sclerosis (MS) development. For EBV, late infection has been proposed as a risk factor, but serological support is lacking. The objective of this study was to investigate how age affects the EBV and HHV-6A associated risks of developing MS.

METHODS
In this nested case-control study, Swedish biobanks were accessed to find pre-symptomatically collected blood samples from 670 individuals who later developed relapsing MS and 670 matched controls. A bead-based multiplex assay was used to determine serological response against EBV and HHV-6A. Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals.

RESULTS
Seropositivity against EBV exhibited a pattern where associations switched from a decreased risk of developing MS in the group below 20 years of age to an increased risk amongst individuals aged 20-29 and 30-39 years (p for trend 0.020). The age of transition was estimated to be 18.8 years. In contrast, HHV-6A was associated with increased MS risk in all age groups (total cohort odds ratio 2.1, 95% confidence interval 1.6-2.7).

CONCLUSIONS
This study suggests EBV infection after adolescence and age independent HHV-6A infection as risk factors for MS.

Biström|M|M|0000-0003-3994-2305 Jons|D|D| Engdahl|E|E| Gustafsson|R|R| Huang|J|J| Brenner|N|N| Butt|J|J| Alonso-Magdalena|L|L| Gunnarsson|M|M| Vrethem|M|M| Bender|N|N| Waterboer|T|T| Granåsen|G|G| Olsson|T|T| Kockum|I|I| Andersen|O|O| Fogdell-Hahn|A|A| Sundström|Peter|P|

D000293:Adolescent
D016022:Case-Control Studies
D020031:Epstein-Barr Virus Infections
D004854:Herpesvirus 4, Human
D015654:Herpesvirus 6, Human
D006801:Humans
D009103:Multiple Sclerosis
D012307:Risk Factors

Epstein-Barr virus
human herpesvirus 6A
multiple sclerosis
serology
case-control studies


Standard-Volume Plasma Exchange Improves Outcomes in Patients With Acute Liver Failure: A Randomized Controlled Trial.

Abstract:
BACKGROUND
High volume plasma-exchange (HVPE) improves survival in patients with acute liver failure (ALF), but apprehension regarding volume overload and worsening of cerebral edema remain.

METHODS
In an open-label randomized controlled trial, 40 consecutive patients of ALF were randomized 1:1 to either standard medical treatment (SMT) or SMT with standard-volume plasma-exchange (SVPE). SVPE was performed using centrifugal apheresis [target volume of 1.5 to 2.0 plasma volumes per session] until desired response was achieved. Cerebral edema was assessed by brain imaging. Results were analyzed in an intention-to-treat analysis. Primary outcome was 21-day transplant-free survival. The levels of cytokines, damage-associated molecular patterns (DAMPs) and endotoxins were analyzed at baseline and day 5.

RESULTS
ALF patients [aged 31.5 ± 12.2 years, 60% male, 78% viral, 83% hyperacute, 70% with SIRS were included. At day 5, SVPE [mean sessions 2.15 ± 1.42, median plasma volume replaced 5.049 L] compared to SMT alone, resulted in higher lactate clearance (p = .02), amelioration of SIRS (84% vs. 26%; P = .02), reduction in ammonia levels [(221.5 ± 96.9) vs.(439 ± 385.6) μg/dl, P = .02) and SOFA scores [9.9(±3.3) vs. 14.6(±4.8); P = .001]. There were no treatment related deaths. SVPE was associated with a higher 21-day transplant free-survival [75% vs. 45%; P = .04, HR 0.30, 95%CI 0.01-0.88]. A significant decrease in levels of pro-inflammatory cytokines and an increase in anti-inflammatory cytokines along with a decrease in endotoxin and DAMPs was seen with SVPE.

CONCLUSION
In ALF patients with cerebral edema, SVPE is safe and effective and improves survival possibly by a reduction in cytokine storm and ammonia. ClinicalTrial.gov (identifier: NCT02718079).

Maiwall|Rakhi|R|
Bajpai|Meenu|M|
Singh|Akanksha|A|
Agarwal|Tanvi|T|
Kumar|Guresh|G|
Bharadwaj|Ankit|A|
Nautiyal|Nidhi|N|
Tevethia|Harsh|H|
Jagdish|Rakesh Kumar|RK|
Vijayaraghavan|Rajan|R|
Choudhury|Ashok|A|
Mathur|Rajendra Prasad|RP|
Hidam|Ashini|A|
Pati|Nirupama Trehan|NT|
Sharma|Manoj Kumar|MK|
Kumar|Anupam|A|
Sarin|Shiv Kumar|SK|

DAMPs
Endotoxin
SIRS
Lactate
Artificial Liver Support Systems
CRRT
Liver Transplant


Quality of life in long-term survivors treated for metastatic medulloblastoma with a hyperfractionated accelerated radiotherapy (HART) strategy.

Abstract:
PURPOSE
An intensive therapeutic strategy for metastatic medulloblastoma was launched in 1998 in our Institution. The aim of this study was to examine the long-term quality of life (QoL) in survivor patients at least 3 years after the end of the treatment.

METHODS
Patients were asked to complete self-administered QoL questionnaires. An index of physical impairment (IPI) was scored (range 0-100; the lower the score the better) based on clinical objective observations. Patients were divided into two groups (lower IPI group, and higher IPI group) and descriptively compared accordingly.

RESULTS
The study was completed by 25/33 eligible patients. Despite patients with a higher IPI reported worse perceived health condition, they had better emotional and psychological scores than those with a lower IPI in all QoL questionnaires.

CONCLUSION
In our sample, patients with more severe objective and perceived physical impairments reported a better psychosocial QoL, possibly because the greater attention paid to them by society and family contributes to a better adjustment in long-term survivors. On this base, it should be recommended that all survivors receive a strong support as the most impaired patients.

Veneroni|L|L|
Boschetti|L|L|
Barretta|F|F|
Clerici|C A|CA|
Simonetti|F|F|
Schiavello|E|E|
Biassoni|V|V|
Spreafico|F|F|
Gandola|L|L|
Pecori|E|E|
Diletto|B|B|
Poggi|G|G|
Gariboldi|F|F|
Sensi|R|R|
Massimino|M|M|

Quality of life
Survivors
Metastatic medulloblastoma
HART strategy


UNC-2 CaV2 Channel Localization at Presynaptic Active Zones Depends on UNC-10/RIM and SYD-2/Liprin-α in Caenorhabditis elegans.

Abstract: Presynaptic active zone proteins couple calcium influx with synaptic vesicle exocytosis. However, the control of presynaptic calcium channel localization by active zone proteins is not completely understood. In a Caenorhabditis elegans (C. elegans) forward genetic screen, we find that UNC-10/RIM (Rab3-interacting molecule) and SYD-2/Liprin-α regulate presynaptic localization of UNC-2, the CaV2 channel ortholog. We further quantitatively analyzed live animals using endogenously GFP-tagged UNC-2 and active zone components. Consistent with the interaction between RIM and CaV2 in mammals, the intensity and number of UNC-2 channel puncta at presynaptic terminals were greatly reduced in unc-10 mutant animals. To understand how SYD-2 regulates presynaptic UNC-2 channel localization, we analyzed presynaptic localization of endogenous SYD-2, UNC-10, RIMB-1/RIM-BP (RIM binding protein), and ELKS-1. Our analysis revealed that although SYD-2 is the most critical for active zone assembly, loss of SYD-2 function does not completely abolish presynaptic localization of UNC-10, RIMB-1, and ELKS-1, suggesting an existence of SYD-2-independent active zone assembly. UNC-2 localization analysis in double and triple mutants of active zone components show that SYD-2 promotes UNC-2 localization by partially controlling UNC-10 localization, and ELKS-1 and RIMB-1 also contribute to UNC-2 channel localization. In addition, we find that core active zone proteins are unequal in their abundance. Although the abundance of UNC-10 at the active zone is comparable to UNC-2, SYD-2 and ELKS-1 are twice more and RIMB-1 four times more abundant than UNC-2. Together our data show that UNC-10, SYD-2, RIMB-1, and ELKS-1 control presynaptic UNC-2 channel localization in redundant yet distinct manners.SIGNIFICANCE STATEMENT Precise control of neurotransmission is dependent on the tight coupling of the calcium influx through voltage-gated calcium channels (VGCCs) to the exocytosis machinery at the presynaptic active zones. However, how these VGCCs are tethered to the active zone is incompletely understood. To understand the mechanism of presynaptic VGCC localization, we performed a C. elegans forward genetic screen and quantitatively analyzed endogenous active zones and presynaptic VGCCs. In addition to RIM, our study finds that SYD-2/Liprin-α is critical for presynaptic localization of VGCCs. Yet, the loss of SYD-2, a core active zone scaffolding protein, does not completely abolish the presynaptic localization of the VGCC, showing that the active zone is a resilient structure assembled by redundant mechanisms.

Oh|Kelly H|KH|
Krout|Mia D|MD|
Richmond|Janet E|JE|
Kim|Hongkyun|H|0000-0002-4879-7122

D036341:Intercellular Signaling Peptides and Proteins

active zone
C. elegans
voltage-gated calcium channel


Being on active surveillance: the patient perspective.

Abstract: Prostate cancer (PCa) patients selected for active surveillance (AS) have received information on prostate cancer PCa, treatment, knew their serum prostate specific antigen (PSA), a digital rectal examination (DRE) done and could rely on their set of biopsies to be labelled as low grade, low volume disease (by adding a radiographic/ultrasonic measurement). They usually react euphoric to the selection hoping to escape invasive curative treatment and its side-effects. Unfortunately, this positive feeling waivers in front of uncertainty in the follow-up including biopsies. Improvements on prognostics are needed. The patients need reassuring information and confidence building to keep his choice to AS based on evidence and confidence.

Prostate cancer (PCa)
active surveillance (AS)
T1a
T1c
natural history
prognosis


Elimination of human cytomegalovirus DNA degradation in urine.

Abstract: Congenital cytomegalovirus infection (cCMVi) is an important cause of sensorineural hearing loss in newborns. Detection of human cytomegalovirus (HCMV) DNA in urine has been used to screen for cCMVi in newborns. However, the matrix effect of urine on HCMV DNA detection is unclear. To evaluate the matrix effect of urine on HCMV DNA detection and optimize the sample process strategy to eliminate or minimize the impact of urine on HCMV DNA detection, DNA in spiked samples was extracted using different DNA extraction methods, and urine samples that could inhibit HCMV DNA detection were mixed to evaluate the inhibitory substances, inhibitory mechanism, and elimination of the inhibitory effect. The optimal urine sample process strategy was evaluated using 42 adult female urine samples and 42 newborn urine samples spiked with HCMV. Some urine samples were found to inhibit HCMV DNA detection due to DNA degradation. The addition of ≥5 mM EDTA to the urine before extraction eliminated the inhibitory effect of urine and did not affect the detection results of urine exhibiting no inhibition. Of the 42 adult female and 42 newborn urine samples, four and two samples, respectively, could inhibit HCMV DNA detection. However, the inhibitory effects of these six urine samples were eliminated after the addition of EDTA. The collective results indicate that the addition of EDTA can completely eliminate the impact of inhibitors present in urine on HCMV DNA extraction and improve the detection of HCMV in urine.


Scalp high-frequency oscillation rates are higher in younger children.

Abstract: High-frequency oscillations in scalp EEG are promising non-invasive biomarkers of epileptogenicity. However, it is unclear how high-frequency oscillations are impacted by age in the paediatric population. We prospectively recorded whole-night scalp EEG in 30 children and adolescents with focal or generalized epilepsy. We used an automated and clinically validated high-frequency oscillation detector to determine ripple rates (80-250 Hz) in bipolar channels. Children < 7 years had higher high-frequency oscillation rates (P = 0.021) when compared with older children. The median test-retest reliability of high-frequency oscillation rates reached 100% (iqr 50) for a data interval duration of 10 min. Scalp high-frequency oscillation frequency decreased with age (r = -0.558, P = 0.002), whereas scalp high-frequency oscillation duration and amplitude were unaffected. The signal-to-noise ratio improved with age (r = 0.37, P = 0.048), and the background ripple band activity decreased with age (r = -0.463, P = 0.011). We characterize the relationship of scalp high-frequency oscillation features and age in paediatric patients. EEG intervals of  10 min duration are required for reliable measurements of high-frequency oscillation rates. This study is a further step towards establishing scalp high-frequency oscillations as a valid epileptogenicity biomarker in this vulnerable age group.

high-frequency oscillations
scalp EEG
biomarker
reliability
paediatric epilepsy


Nutritional risk and associated factors of adult in-patients at a teaching hospital in the Copperbelt province in Zambia; a hospital-based cross-sectional study.

Abstract:
Background
Nutritional risk and undernutrition are common problems among medical and surgical patients. In hospital, malnutrition is frequently under-diagnosed and untreated thereby contributing to morbidity and mortality. The purpose of this study was to determine the prevalence of nutritional risk among adult inpatients at a teaching hospital in Zambia. In addition, the study sought to establish factors associated with nutritional risk.

Methods
A hospital-based cross-sectional study comprising of 186 consecutive in-patients aged 18-64 years admitted in medical and surgical wards was conducted at a teaching hospital. Out of one hundred and ninety eight (198) patients eligible to participate, complete data were collected from 186, representing a response rate of 93.9%. The Malnutrition Universal Screening Tool was used to collect data over a period of six months. Evaluated patients were dichotomized into no risk and nutritional risk. Binary logistic regression was performed to identify variables associated with nutritional risk.

Results
The mean age of adult in-patients was 40.72 ± 14.4 years. Majority of the patients were male (61.8%), while 38.2% were female. Results indicate that 59.7% of hospitalized patients were at nutritional risk. Vomiting, weakness, appetite decrease, dysphagia and weight loss were significantly associated (p = 0.019, p = 0.008, p < 0.001, p = 0.007, and p < 0.001 respectively) with nutritional risk. However, weight loss and appetite decrease were the most significant factors associated with nutritional risk (OR = 50.16, 95% CI = 5.75-36.70, p < 0.001 and OR = 28.06, 95% CI =1.49-8.12, p = < 0.001 respectively).

Conclusion
Findings of our study suggest that close to 60% of adult inpatients at the teaching hospital were at nutritional risk. Nutritional risk is an issue of major concern at the teaching hospital and is associated with a number of variables. Identification of nutritional risk using Malnutrition Universal Screening Tool among adult inpatients is feasible in resource-poor settings like ours.

Miyoba|Nixon|N|0000-0003-2309-492X Musowoya|Joseph|J| Mwanza|Emily|E| Malama|Angel|A| Murambiwa|Nyati|N| Ogada|Irene|I| Njobvu|Macriveness|M| Liswaniso|Doris|D|

Nutritional risk
Teaching hospital
Undernutrition
Malnutrition
Adult inpatients


Real-World Assessments of mySugr Mobile Health App.

Abstract: Mobile health (mHealth) solutions such as diabetes self-management apps improve glycated hemoglobin, particularly those that provide a feedback loop between patient and health care provider. mHealth apps that incorporate behaviorally designed interventions can improve patient access to diabetes self-management education and ongoing support. The mySugr mobile app was designed to support patients in their diabetes self-management. Most studies of mHealth apps were conducted under controlled conditions and did not elucidate the nuances of patient perceptions and utilization of these apps in everyday life. In this article, we discuss findings from real-world observations of changes in glycemic control and patient satisfaction associated with the use of the mySugr mHealth app.

App mHealth Diabetes Coaching. HbA Smartphone


Preferences and Perceived Value of WIC Foods Among WIC Caregivers

Abstract:
OBJECTIVE
To evaluate preferences for and values of Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) foods and packages and understand what factors may influence these preferences and values.

DESIGN
Using a mixed-methods approach, surveys and individual in-depth interviews were conducted to measure and understand preferences for specific WIC foods and how much WIC food packages are worth to participants.

SETTING
Eight WIC clinics across Illinois.

PARTICIPANTS
Caregivers of infants enrolled in WIC for at least 3-6 months.

PHENOMENON OF INTEREST
Preferences for WIC foods, WIC food package values, and factors that influence these categories.

ANALYSIS
Frequencies were gathered to analyze survey data and interview transcripts were analyzed using constant comparative analysis to identify emergent themes.

RESULTS
Survey (n = 150) and interview (n = 31) participants valued the food packages in WIC but they valued the infant packages more. The cash value fruit and vegetable voucher increased the perceived value of the program for many participants. Restrictions on food choice preferences (eg, type of milk) detracted value from the program.

CONCLUSIONS AND IMPLICATIONS
This study shows that providing more choice in the program could improve satisfaction with WIC overall. More research is warranted with a more representative sample to assess whether expanded food choice would improve value of and preference for WIC foods.

Weber|Summer|S| Uesugi|Keriann|K| Greene|Haley|H| Bess|Stephanie|S| Reese|LaShon|L| Odoms-Young|Angela|A|

D007722:Health Knowledge, Attitudes, Practice

WIC
food preferences
low income
retention


Enhanced retinal pigment epithelium (RPE) regeneration using curcumin/alginate hydrogels: In vitro evaluation.

Abstract: The retinal pigment epithelium (RPE) plays a significant role in retaining structural integrity of eye. Factors such as reduction in cell regeneration due to aging and physical injury pose a major hurdle in RPE regeneration. In this study, we exploited the use of alginate (AGT) incorporated with Curcumin (CCI) forming a hydrogel based system CCI/AGT. The fabricated hydrogel could anchor RPE cell in it. In vitro cell analysis revealed that the CCI/AGT hydrogel shows good biocompatibility, enhanced cell growth ability and higher ECM formation compared to the pure AGT hydrogel. In particular, the presence of CCI in the hydrogels enhances the cells proliferation of the 23% respect to the pure alginate. Also the expression of crucial genes for retina functions and matrix production were positively affected by CCI presence, with an increment of 45% for RPE65, 32% for CRALBP and 26% for Collagen type 1. In vitro tests demonstrated the potential application of CCI/AGT hydrogels for transplantation under the sub-retinal space acting as a cell delivery vehicle and also their capability to provide an appropriate environment for RPE regeneration. These results suggest that CCI/AGT hydrogel could be translated into a potential surgical graft for biological implantation of retinal tissue engineering.

Park|Jong Ho|JH|
Shin|Eun Yeong|EY|
Shin|Myeong Eun|ME|
Choi|Min Joung|MJ|
Carlomagno|Cristiano|C|
Song|Jeong Eun|JE|
Khang|Gilson|G|

D017550:Spectroscopy, Fourier Transform Infrared

Curcumin
Alginate hydrogel
Retinal pigment epithelium regeneration


Ovarian-like differentiation in eutopic and ectopic endometrioses with aberrant FSH receptor, INSL3 and GATA4/6 expression.

Abstract: Endometriosis, the hormone-dependent extrauterine dissemination of endometrial tissue outside the uterus, affects 5-15% of women of reproductive age. Pathogenesis remains poorly understood as well as the estrogen production by endometriotic tissue yielding autocrine growth. Estrogens (E2) are normally produced by the ovaries. We investigated whether aberrant "ovarian-like" differentiation occurred in endometriosis. 69 women, with (n = 38) and without (n = 31) histologically proven endometriosis were recruited. Comparative RT-qPCR was performed on 20 genes in paired eutopic and ectopic lesions, together with immunohistochemistry. Functional studies were performed in primary cultures of epithelial endometriotic cells (EEC). A broaden ovarian-like differentiation was found in half eutopic and all ectopic endometriosis with aberrant expression of transcripts and protein for the transcription factors GATA4 and GATA6 triggering ovarian differentiation, for the FSH receptor (FSHR) and the ovarian hormone INSL3. Like in ovaries the FSHR induced aromatase, the key enzyme in E2 production, and vascular factors in EEC. The LH receptor (LHR) was also aberrantly expressed in a subset of ectopic endometriosis (21%) and induced strongly androgen-synthesizing enzymes and INSL3 in EEC, as in ovaries, as well as endometriotic cell growth. The ERK pathway mediates signaling by both hormones. A positive feedback loop occurred through FSHR and LHR-dependent induction of GATA4/6 in EEC, as in ovaries, enhancing the production of the steroidogenic cascade. This work highlights a novel pathophysiological mechanism with a broadly ovarian pattern of differentiation in half eutopic and all ectopic endometriosis. This study provides new tools that might improve the diagnosis of endometriosis in the future.

Fouquet|Baptiste|B| Santulli|Pietro|P| Noel|Jean-Christophe|JC| Misrahi|Micheline|M|

CYP11A1, Cytochrome P450 Family 11 Subfamily A Member 1

CYP17, Cytochrome P450 Family 17 Subfamily A Member 1

CYP19A1, Cytochrome P450 Family 19 Subfamily A Member 1

EGVEGF, Endocrine Gland-derived vascular endothelial growth factor

FSHR, Follicle Stimulating Hormone Receptor

PTGS2, Prostaglandin-Endoperoxide Synthase 2

RT-qPCR, Reverse Transcription quantitative Polymerase Chain Reaction

VEGF, Vascular Endothelial Growth Factor


Vaccine administration and the development of immune thrombocytopenic purpura in children.

Abstract: The most important reasons cited by the opponents of vaccines are concerns about vaccine safety. Unlike issues such as autism for which no indisputable documentation of direct relationship with vaccine use is available, immune thrombocytopenic purpura (ITP) is an adverse event that can really follow vaccine administration, and may limit vaccine use because little is known about which vaccines it may follow, its real incidence and severity, the risk of chronic disease, or the possibility of recurrences after new doses of the same vaccine. The main aim of this review is to clarify the real importance of thrombocytopenia as an adverse event and discuss how it may interfere with recommended vaccination schedules. The available data clearly indicate that ITP is very rare and the only vaccine for which there is a demonstrated cause-effect relationship is the measles, mumps and rubella (MMR) vaccine that can occur in 1 to 3 children every 100,000 vaccine doses. However, also in this case, the incidence of ITP is significantly lower than that observed during the natural diseases that the vaccine prevents. Consequently, ITP cannot be considered a problem limiting vaccine use except in the case of children suffering from chronic ITP who have to receive MMR vaccine. In these subjects, the risk-benefit ratio of the vaccine should be weighed against the risk of measles in the community.

Cecinati|Valerio|V| Principi|Nicola|N| Brescia|Letizia|L| Giordano|Paola|P| Esposito|Susanna|S|

vaccine
immune thrombocytopenic purpura
vaccine safety
adverse events
MMR
platelets


Quantitative effects of atmospheric diffusion on surface aerosol extinction in the Pearl River Delta region.

Abstract: Aerosol pollution is closely related to meteorological conditions. In order to accurately evaluate the effectiveness of emission reduction policies, it is very important to separate meteorological effects from emissions in long-term PM changes. In this study, we used surface extinction coefficient (SEC) of aerosol particles as an indicator to estimate the long-term trend of PM pollutant conditions, and proposed a parameter surface ventilation index (SVI) to describe the atmospheric diffusion. A novel method was introduced to quantify the effect of atmospheric diffusion and emissions on SEC from an inter-annual scale, and its applicability and limitations was discussed. The results showed that annual mean SEC exhibited an increasing trend with a rate of 15.6 Mm-1∙year-1 from 2000 to 2007 and a decreasing trend with a rate of 14.4 Mm-1∙year-1 from 2008 to 2018. The annual frequency distribution of SVI obeyed a lognormal distribution. The SVI value mainly concentrated between 300 and 3600 m2.s-1, SEC was negatively correlated with SVI in this range. In most cases, SEC variations were mainly dominated by emissions, and SEC variations at clean sites were more influenced by atmospheric diffusion than that at polluted sites. Emissions remained high during 2003-2007, then gradually decreased during 2008-2014 and finally accelerated decrease during 2015-2018, indicating that control policies have effectively mitigated PM pollution since 2008. In generally, this method can provide valuable information for policy makers to evaluate the emission control measures for air pollution mitigation and prevention.

Gan|Quan|Q| Tan|Haobo|H| Shen|Jin|J| Weng|Jiafeng|J| Li|Minghua|M| Chan|Pakwai|P| Zhao|Jun|J| Hong|Yingying|Y| Li|Tingyuan|T| Chen|Chen|C|

Quantitative effects
Atmospheric diffusion
Surface extinction coefficient
Surface ventilation index


Pediatric forearm fractures with in situ intramedullary implants.

Abstract:
PURPOSE
The purpose of this investigation is to present our institutional experience with fractures of the pediatric forearm with in situ intramedullary nails.

METHODS
Six patients treated at our institution for forearm fracture with in situ intramedullary implants between 2004 and 2013 were reviewed. Patient demographics, injury and radiographic characteristics, method of treatment, time to union, and complications were collected from the medical record.

RESULTS
485 patients with forearm fractures were treated with intramedullary implants and six patients presented with a fracture with in situ implants (1.2 %). Fractures in all six patients resulted from a second traumatic event after radiographic healing but before implant removal at a mean of 13.0 months from the initial procedure. One patient had an adequately aligned fracture and was treated with casting without reduction. The remaining five patients (83 %) returned to the operating room for treatment. Two patients underwent rod removal and placement of new intramedullary implants, and two patients were treated with rod removal and plating without attempt at closed reduction. One patient underwent closed reduction in the operating room with successful re-bending of the radial implant and replacement of the ulna implant. All patients went on to uncomplicated radiographic union at a mean 3.6 months.

CONCLUSIONS
The incidence of fracture of pediatric forearm with in situ intramedullary implants is low. This rare complication can be treated by several different methods, including revision TENS placement, revision to plate fixation, or in situ bending of rods, with the expectation for successful uncomplicated union.

Kelly|Brian A|BA|
Shore|Benjamin J|BJ|
Bae|Donald S|DS|
Hedequist|Daniel J|DJ|
Glotzbecker|Michael P|MP|

Pediatric
Forearm
Fracture
In situ
Implants


ZnO Q-dots as a potent therapeutic nanomedicine for in vitro cytotoxicity evaluation of mouth KB44, breast MCF7, colon HT29 and HeLa cancer cell lines, mouse ear swelling tests in vivo and its side effects using the animal model.

Abstract: Nanoformulations derived from fine porous ZnO quantum dot nanoparticles (QD NPs) can offer strong potential medical applications; especially in cancer therapy. ZnO QD NPs was synthesized by sol-gel hydrothermal process, fast cold quenching and further smart surface functionalization methods to obtain ultrasmall size (1-4 nm) NPs. ZnO nanopolymer, a wetting agent, PEG co-solvent and water/oil emulsion stabilizer were considered in our nanofluid formulation. The resulting nanofluid was characterized by SEM, FTIR, photoluminescence, band gap energy, zeta potential and UV-Vis spectroscopy. The cytotoxic effects on the growth of four cancer cell lines were evaluated by MTT assay. The IC50 (µg/ml) values of 30, 41, 40 and 35 for KB44, MCF-7, HT29 and HeLa cells, respectively, after 48 h of nanoformulation treatment suggested the cytotoxic effect of this nanoformulation on these cell lines in a concentration-dependent manner (p < .05). ZnO nanofluid destroyed cancer cell lines more efficiently than the normal HFF-2 (IC50 = 105 µg/ml). The reduction in cell viability in response to ZnO nanofluid treatment induced apoptosis in the cultured cells. Skin sensitization test plus antibacterial activity were also measured. Side effect tests on 70 white mice in vivo resulted in only 3-4 abnormal situations in hepatic tissue section possibly due to the idiosyncratic drug reactions.

Fakhroueian|Zahra|Z|
Vahabpour|Rouhollah|R|
Assmar|Mehdi|M|
Massiha|Alireza|A|
Zahedi|Afshin|A|
Esmaeilzadeh|Pegah|P|
Katouzian|Fatemeh|F|
Rezaei|Sara|S|
Keyhanvar|Peyman|P|
Mozafari Dehshiri|Alireza|A|

cytotoxicity
cancer cell lines
antibacterial activity
Smart nanosurface
anticancer
energetic quantum-dot surface
multi-proposed drug
nano-bio-interface
site effects of ZnO nanofluid


Hypogonadism and Testosterone Therapy: Associations With Cardiovascular Risk.

Abstract: Testosterone replacement therapy (TRT) use is increasing, primarily in men with symptomatic hypogonadism. There are many benefits associated with TRT use, including improved sexual function, improved bone mineral density, and increased free fat mass and strength. As TRT use increases, its role on cardiovascular health must be explored. While previous evidence identified no adverse cardiovascular risks associated with TRT use, more recent studies suggest that there may be an associated risk, especially in elderly men and younger men with cardiac disease. Care must be taken with TRT use in these groups of men by careful monitoring for cardiac dysfunction. While testosterone therapy has many benefits and may generally be well tolerated, those prescribing the therapy must be cognizant of the potential adverse cardiovascular risks and advise men on the potential risks versus benefits.

Maganty|Avinash|A|
Osterberg|E Charles|EC|
Ramasamy|Ranjith|R|

cardiovascular risk
testosterone replacement therapy (TRT)


Clinically relevant drug interactions with multikinase inhibitors: a review.

Abstract: Multikinase inhibitors (MKIs), including the tyrosine kinase inhibitors (TKIs), have rapidly become an established factor in daily (hemato)-oncology practice. Although the oral route of administration offers improved flexibility and convenience for the patient, challenges arise in the use of MKIs. As MKIs are prescribed extensively, patients are at increased risk for (severe) drug-drug interactions (DDIs). As a result of these DDIs, plasma pharmacokinetics of MKIs may vary significantly, thereby leading to high interpatient variability and subsequent risk for increased toxicity or a diminished therapeutic outcome. Most clinically relevant DDIs with MKIs concern altered absorption and metabolism. The absorption of MKIs may be decreased by concomitant use of gastric acid-suppressive agents (e.g. proton pump inhibitors) as many kinase inhibitors show pH-dependent solubility. In addition, DDIs concerning drug (uptake and efflux) transporters may be of significant clinical relevance during MKI therapy. Furthermore, since many MKIs are substrates for cytochrome P450 isoenzymes (CYPs), induction or inhibition with strong CYP inhibitors or inducers may lead to significant alterations in MKI exposure. In conclusion, DDIs are of major concern during MKI therapy and need to be monitored closely in clinical practice. Based on the current knowledge and available literature, practical recommendations for management of these DDIs in clinical practice are presented in this review.

Hussaarts|Koen G A M|KGAM|
Veerman|G D Marijn|GDM|
Jansman|Frank G A|FGA|
van Gelder|Teun|T|
Mathijssen|Ron H J|RHJ|
van Leeuwen|Roelof W F|RWF|

multikinase inhibitor
metabolism
cytochrome P450 enzyme
drug transporters
drug–drug interaction
gastric acid suppression


Ambulatory pulmonary artery pressure monitoring in advanced heart failure patients.

Abstract: Heart failure (HF) is an emerging epidemic associate with significant morbidity, mortality, and health care expenditure. Although there were major advances in pharmacologic and device based therapies for the management of HF, mortality of this condition remains high. Accurate monitoring of HF patients for exacerbations is very important to reduce recurrent hospitalizations and its associated complications. With the failure of clinical signs, tele-monitoring, and laboratory bio-markers to function as early markers of HF exacerbations, more sophisticated techniques were sought to accurately predict the circulatory status in HF patients in order to execute timely pharmacological intervention to reduce frequent hospitalizations. CardioMEMSTM (St. Jude Medical, Inc., Saint Paul, Minnesota) is an implantable, wireless pulmonary arterial pressure (PAP) monitoring system which transmits the patient's continuous PAPs to the treating health care provider in the ambulatory setting. PAP-guided medical therapy modification has been shown to significantly reduce HF-related hospitalization and overall mortality. In advanced stages of HF, wireless access to hemodynamic information correlated with earlier left ventricular assist device implantation and shorter time to heart transplantation.

Yandrapalli|Srikanth|S|
Raza|Anoshia|A|
Tariq|Sohaib|S|
Aronow|Wilbert S|WS|

Pulmonary arterial pressure monitoring
Heart failure
Left ventricular assist device
CardioMEMS
Remote heart failure monitoring


Wood Smoke Extract Promotes Extracellular Matrix Remodeling in Normal Human Lung Fibroblasts.

Abstract: Wood smoke (WS) contains many harmful compounds, including polycyclic aromatic hydrocarbons (PAHs). WS induces inflammation in the airways and lungs and can lead to the development of various acute and chronic respiratory diseases. Pulmonary fibroblasts are the main cells involved in the remodeling of the extracellular matrix (ECM) during the WS-induced inflammatory response. Although fibroblasts remain in a low proliferation state under physiological conditions, they actively participate in ECM remodeling during the inflammatory response in pathophysiological states. Consequently, we used normal human lung fibroblasts (NHLFs) to assess the potential effects of the PAHs-containing wood smoke extract (WSE) on the growth rate, total collagen synthesis, and the expression levels of collagen I and III, matrix metalloproteinase (MMP)-1, MMP-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, and the transforming growth factor (TGF)-β1. We also assessed MMPs activity. The results showed that WSE induced a trimodal behavior in the growth rate curves in NHLFs; the growth rate increased with 0.5-1 % WSE and decreased with 2.5% WSE, without causing cell damage; 5-20% WSE inhibited the growth and induced cell damage. After 3 hours of exposure, 2.5% WSE induced an increase in total collagen synthesis and upregulation of TGF-β1, collagen I and III, MMP-1, TIMP-1, and TIMP-2 expression. However, MMP-2 expression was downregulated and MMP-9 was not expressed. The gelatinase activity of MMP-2 was also increased. These results suggest that WSE affects the ECM remodeling in NHLFs and indicate the potential involvement of PAHs in this process.

wood smoke extract
extracellular matrix
fibroblasts
matrix metalloproteinases
tissue inhibitors of metalloproteinases


Pharmacokinetics of oral versus intravenous ibuprofen for closure of patent ductus arteriosus: A pilot randomised controlled study.

Abstract:
AIM
This pilot study aimed to compare the pharmacokinetic profiles of oral (PO) and intravenous (IV) ibuprofen for treatment of patent ductus arteriosus (PDA) in preterm neonates.

METHODS
In a single-centre, parallel, randomised open-label trial, neonates ≤35 weeks, weight <1800 g with haemodynamically significant PDA during the first week of life were recruited between June 2017 and February 2019 and randomised to receive either PO or IV ibuprofen at standard dosage of 10, 5 and 5 mg/kg every 24 h for three consecutive days. Plasma concentrations of ibuprofen were quantified using a validated high-performance liquid chromatography method and pharmacokinetic parameters were calculated. Treatment outcomes were recorded.

RESULTS
Eleven neonates participated in the trial, six and five patients receiving PO and IV ibuprofen, respectively. Pharmacokinetic analysis reveals similar ibuprofen exposure levels in treatment groups. Median dose- and weight-normalised Cmax values of PO and IV groups were 2.12 and 2.53 g/mL respectively (P = 0.082) and median AUC0-24 levels were comparable (PO: 34.6 g*h/mL vs. IV: 50.7.6 g*h/mL, P = 0.25).

CONCLUSION
This exploratory study demonstrates comparable pharmacokinetics of PO and IV formulations of ibuprofen in preterm neonates. Larger prospective studies are required to validate these findings.

pharmacokinetics
ibuprofen
patent ductus arteriosus
neonate
oral ibuprofen


The prevalence, characteristics, and impact of work-related musculoskeletal disorders among physical therapists in the Kingdom of Saudi Arabia - a cross-sectional study.

Abstract:
BACKGROUND
Physical therapists are known to be susceptible to work-related musculoskeletal disorders (WMSDs), but the prevalence of WMSDs in Saudi Arabia has not been documented. This study aimed to establish the prevalence, characteristics, and risk factors of WMSDs among physical therapists in Saudi Arabia.

MATERIAL AND METHODS
A cross-sectional study was conducted among 113 physical therapists in Saudi Arabia using a 6-component questionnaire. Descriptive statistics, incidence, percentages, and χ2 test were used for data analysis.

RESULTS
The response rate was 68.8%. The reported 12-month incidence of WMSDs was 83.8%. The low back (63.7%) was the most common site of these disorders, followed by the neck (59.2%), while the hip/thigh (4.4%) was the least involved body part. Incidence was related to gender: females were more affected than males (neck, shoulders, low back); age: younger therapists were more affected than older ones (shoulders, low back); working sector: government sector workers were more affected than those employed in other sectors (neck); and specialty: orthopedic specialists were the most frequently affected, followed by those specializing in neurology (thumbs, upper back, knees, ankle/foot). Most of the physical therapists had >5 periods of neck, shoulder, and low-back WMSDs. The most important risk factor for WMSDs was treating more patients in a day (47.7%). The most frequently adopted handling strategy identified to combat WMSDS was modifying the patient's position (62.8%).

CONCLUSIONS
Overall, WMSDs among physical therapists in Saudi Arabia are common, with the low back and the neck constituting the most frequently affected body regions. Professional experience and the awareness of ergonomics principles can help prevent the early development of WMSDs among physical therapists. Med Pr. 2021;72(4):363-73.

Kakaraparthi|Venkata Nagaraj|VN|
Vishwanathan|Karthik|K|
Gadhavi|Bhavana|B|
Reddy|Ravi Shankar|RS|
Samuel|Paul Silvian|PS|
Alshahrani|Mastour Saeed|MS|
Kakaraparthi|Lalitha|L|
Gannamaneni|Vamsi Krishna|VK|
Tedla|Jaya Shanker|JS|

prevalence
musculoskeletal disorders
Saudi Arabia
ergonomics
physical therapy
workload


Cardiorenal Syndrome: Diagnosis and Management.

Abstract: Cardiorenal syndrome (CRS) has not been well characterized in veterinary medicine, yet an accurate appreciation of the kidney and the cardiovascular system and their interactions may have practical clinical implications. A consensus for cardiovascular-renal axis disorders of dogs and cats was recently attempted. The outcome of patients with CRS is likely to improve with the increasing awareness and ability to identify and understand the pathophysiologic characteristics of CRS. The utilization of existing and emerging organ-specific biomarkers with greater sensitivities than conventional diagnostics forecast new opportunities to diagnose and manage cardiac disease.

Cardiorenal syndrome
Cardiovascular-renal axis disorders
Biomarkers
Chronic kidney disease
Heart failure


Prevalence of Locomotive Organ Impairment and Associated Factors among Middle-Aged and Older People in Nan Province, Thailand.

Abstract: While locomotive organ impairment among older people is attracting worldwide attention, this issue has not yet been widely investigated in Thailand. This study aimed to measure locomotive organ impairment prevalence and identify the determinants of locomotive function decline among middle-aged and older people in Nan Province, Thailand. This cross-sectional study included anthropometric measurements, a two-step test to investigate locomotive function, and a structured questionnaire to obtain socio-demographic and related information. Logistic regression analysis and multiple regression analysis were used to identify the determinants of locomotive organ impairment. The study participants were aged 50-87 years old (n = 165), and 71.5% of them had begun experiencing declining locomotive function; < 6 years of school education (adjusted odds ratio: 4.46), body mass index ≥25 kg/m2 (AOR: 3.06), comorbidities (AOR: 2.55), and continuous walking for <15 min (AOR: 2.51) were identified as factors associated with locomotive organ impairment. Moreover, age, knee pain, anxiety about falling in daily life, and difficulty with simple tasks were identified as factors significantly associated with exacerbated locomotive organ impairment (p < 0.05). Appropriate interventions such as guidance or follow-up and recommendations for exercises are needed to prevent locomotive organ impairment and improve treatment.

Niwayama|Marie|M| Sakisaka|Kayako|K| Wongwatcharapaiboon|Pongthep|P| Rattanachun|Valika|V| Miyata|Satoshi|S| Takahashi|Kenzo|K|

Thailand
cross-sectional study
aging
exercise
motion
obesity


Cross-Cultural Adaptation and Validation of the Lower Extremity Measure Into German.

Abstract:
INTRODUCTION
The Lower Extremity Measure (LEM) was developed to provide a specific instrument to detect changes in physical function in patients with hip fracture. Of 29 questions, 3 have a valid "not applicable" answer option. The goal of this study was to validate the LEM in German and to determine the added value to the physical functioning (pf) subscale of the Short Form 36 (SF-36).

MATERIALS AND METHODS
The LEM was translated according to published guidelines and administered to patients with hip fracture (31 A1-A3 and 31 B1-B3) shortly after surgery (baseline), at 3 months (3M), and for reliability testing at 3 months plus 1 week (3M+). The reproducibility, internal consistency, floor and ceiling effects, construct validity, and responsiveness of the German LEM were assessed.

RESULTS
A total of 106 patients completed the LEM and SF-36 (mean age 75.5; 67% women) at baseline (mean of 4.9 days after operation), and 88 completed both questionnaires at both the 3M and 3M+ assessments. At each assessment time point, between 6% and 23% of the patients answered 7 questions as "not applicable." Reproducibility and internal consistency were high (intraclass correlation coefficient = 0.93; Cronbach's α = .96). No floor effect (0%) and a minor ceiling effect (7.87%) were found for the total LEM score. The strongest correlation was found between the LEM and the SF-36 subscale pf (Spearman ρ = .93). Responsiveness was similar for the SF-36 pf subscale and the LEM when using effect size (SF-36 pf 0.71 vs LEM 0.72) and better for the LEM when using standardized response mean (SF-36 pf 0.65 vs LEM 0.76).

DISCUSSION
The German LEM is a reliable, valid, and responsive measure for the self-assessment of patients after hip fracture surgery. As a number of questions are not applicable to elderly patients, the added value of this lengthy questionnaire in these often frail, sometimes cognitively impaired patients is still open for debate.

Goldhahn|Sabine|S|
Käch|Kurt|K|
Frei|Hans Curd|HC|
Rudin|Mark|M|
Leimbacher|Melanie|M|
Platz|Andreas|A|

validation
hip fracture
fragility fractures
geriatric trauma
patient-reported outcome


Transcriptomic Characterization of the Human Habenula Highlights Drug Metabolism and the Neuroimmune System.

Abstract: Due to size and accessibility, most information about the habenula is derived from rodent studies. To better understand the molecular signature of the habenula we characterized the genes that have high expression in the habenula. We compared anatomical expression profiles of three normal adult human brains and four fetal brains. We used gene set enrichment analyses to determine if genes annotated to specific molecular functions, cellular components, and biological processes are enriched in the habenula. We also tested gene sets related to depression and addiction to determine if they uniquely involve the habenula. As expected, we observed high habenular expression of GPR151, nicotinic cholinergic receptors, and cilia-associated genes (medial division). Genes identified in genetic studies of smoking and associated with nicotine response were enriched in the habenula. Genes associated with major depressive disorder did not have enriched expression in the habenula but genes negatively correlated with hedonic well-being were, providing a link to anhedonia. We observed enrichment of genes associated with diseases that are comorbid with addictions (hematopoiesis, thrombosis, liver cirrhosis, pneumonia, and pulmonary fibrosis) and depression (rheumatoid arthritis, multiple sclerosis, and kidney disease). These inflammatory diseases mark a neuroimmune signature that is supported by genes associated with mast cells, acute inflammatory response, and leukocyte migration. We also found enrichment of cytochrome p450 genes suggesting the habenula is uniquely sensitive to endogenous and xenobiotic compounds. Our results suggest the habenula receives negative reward signals from immune and drug processing molecules. This is consistent with the habenular role in the "anti-reward" system and suggests it may be a key bridge between autoimmune disorders, drug use, and psychiatric diseases.

transcriptomics
habenula
drug metabolism
neuroimmune
depression
addiction
mast cell
cannabis


Among the severely mentally ill, who responds to ziprasidone?

Abstract: So far, demographic variables have not consistently been found to predict clinical response to antipsychotics. This study examines some differences in response to ziprasidone, which has been shown to be effective, with a better metabolic side effect profile, but was little used in New York State Hospitals. The aim was to study state hospital patients switched to ziprasidone. The results led to questions about different responses in different groups. Subjects from state hospitals who needed a change of antipsychotic participated in this openlabel 8 week trial of up to 240 mg ziprasidone. Analyses included comparisons of the very different results from two sites. Of the 36 study subjects, 12 terminated early. The 17 outpatients from Buffalo, who were older and on lower doses of antipsychotics pre-study, improved significantly. The 19 inpatients from the Bronx, overall younger and on higher pre-study doses, barely changed. Improvements in PANSS total score were significantly associated with older age, greater baseline severity, and lower doses of antipsychotics pre-study. The subjects improved on metabolic parameters. The results suggest that ziprasidone may be just as effective as previous antipsychotics taken by these severely mentally ill patients, and with fewer metabolic side effects.

Bark|Nigel|N| Lawson|Nicholas|N| Trigoboff|Eileen|E| Varadi|Rodica|R| Grace|Jeffery|J| Olympia|Josie|J| Sindhu|Nighat|N| Watson|Tom|T| El-Defrawi|Mohamed|M| Roy|Punyabrata|P|

ziprasidone
demographics
antipsychotic
metabolic side effects
age
schizophrenia


Expressions of aquaporin family in human luteinized granulosa cells and their correlations with IVF outcomes.

Abstract:
STUDY QUESTION
Are mRNAs for specific aquaporins (AQPs) expressed in human luteinized granulosa cells (GCs) and are their expression levels correlated with in vitro fertilization (IVF) outcomes?

SUMMARY ANSWER
The mRNAs of AQP1-7, 9, 11, and 12 were expressed in human luteinized GCs; the level of AQP1 mRNA was negatively associated with retrieved oocyte number and the level of AQP7 mRNA was positively associated with fertilization rate.

WHAT IS KNOWN ALREADY
mRNAs of AQP1-4 and AQP9 have been detected in human GCs.

STUDY DESIGN, SIZE, DURATION
Prospective observational study involving 111 women undergoing a stimulated IVF cycle.

PARTICIPANTS/MATERIALS, SETTING, METHODS
In a preliminary experiment on 27 women, the mRNA expression of AQP0-12 in GCs was explored by RT-PCR. In the main experiment, luteinized GCs were obtained from 111 women at the time of oocyte retrieval of whom 102 had an embryo replacement. Real-time quantitative RT-PCR (qRT-PCR) was performed to quantify the mRNA level of AQP1-7, 9, 11, and 12. The mRNA for luteinizing hormone receptor (LHR) and steroidogenic acute regulatory protein (StAR) were also quantified by qRT-PCR.

MAIN RESULTS AND THE ROLE OF CHANCE
mRNAs for AQP0, 8 and 10 were not detected in the preliminary experiment. In samples from 111 women, retrieved oocyte number was negatively associated with the mRNA levels of AQP1, 4, 6, and 11 and LHR (r = -0.311, r = -0.233, r = -0.203, r = -0.194, and r = -0.202, respectively, P < 0.05 for each), however, after adjustment for woman's age and serum anti-Müllerian hormone (AMH) levels, only correlation with AQP1 was found (r = -0.299, P < 0.05). BMI was negatively associated (after adjustment for age) with the mRNA level of AQP7 (r = -0.259, P < 0.05). Fertilization rate was positively associated with the mRNA level of AQP7 (r = 0.269, P < 0.05). The number or quality of embryos or clinical pregnancy was not associated with the mRNA levels of any of ten AQP subtypes. The mRNA levels for the ten AQP subtypes were correlated positively with LHR expression but negatively with StAR expression. Amongst high responders (oocyte number ≥14), the mRNA levels of AQP11 (1.4 ± 0.7 versus 1.7 ± 0.6) and LHR (1.3 ± 0.7 versus 1.7 ± 0.7) were significantly lower in the group with PCOS than in the non-PCOS group.

LIMITATIONS, REASONS FOR CAUTION
A relative small number of subjects in PCOS group is the main limitation of our study. P-values were not corrected for multiple comparisons.

WIDER IMPLICATION OF THE FINDINGS
AQP1 may be one of the factors that modulate individual ovarian response to exogenous gonadotrophin. The mRNA level of AQP7 was positively associated with fertilization rate, which is a surrogate marker of oocyte competence, thus expression of AQP7 could be a marker for adequate folliculogenesis and healthy oocytes.

STUDY FUNDING/COMPETING INTERESTS
This work was supported by grant no. A120043 from the Korea Health Care Technology R&D Project, Ministry of Health and Welfare, Korea. None of the authors has any conflict of interest to declare.

Lee|Hee Jun|HJ|
Jee|Byung Chul|BC|
Kim|Seul Ki|SK|
Kim|Hoon|H|
Lee|Jung Ryeol|JR|
Suh|Chang Suk|CS|
Kim|Seok Hyun|SH|

D018507:Gene Expression Regulation, Developmental

aquaporins
granulosa cell
in vitro fertilization
polycystic ovary syndrome


Basophil activation test in children with autoimmune chronic spontaneous urticaria: Is it ready for clinical practice?

Abstract:
INTRODUCTION
Chronic spontaneous urticaria (CSU) is characterized by recurrent itchy wheals, angioedema or both, that persist for longer than six weeks. In children, up to 40% of chronic spontaneous urticaria is due to mast cells and basophils-activating autoantibodies, mostly directed against the IgE high-affinity receptor subunit (FcεRI). Indirect basophil activation test (BAT) has been proposed in the diagnosis of autoimmune urticaria.

MATERIALS AND METHODS
Sera from sixteen patients, aged from 2 to 15 yrs, with CSU were evaluated through indirect BAT by flow cytometry using a commercial kit (Flow CAST®, BUHLMANN Laboratories, Schonenbuch, Switzerland) according to the manufacturer's instructions.

RESULTS
Indirect BAT test gave a much better diagnosis in our cohort than the gold standard ASST. Six children (37.5%) showed a positive indirect BAT while we could perform ASST in only 3 patients with just one patients showing a positive ASST. The specificity of BAT positive results was confirmed by the absence of significant difference between the BAT results obtained from negative controls vs negative sera of the patient (p = 0.65) on the basophil donors, indicating that the serum is not activating basophil per se.

CONCLUSIONS
This pilot study suggests the utility of BAT to identify the subtype of autoimmune CSU in children in clinical practice.

D'Auria|Enza|E|
De Amici|Mara|M|
Licari|Amelia|A|
Caimmi|Silvia|S|
Mantegazza|Cecilia|C|
Zuccotti|GianVincenzo|G|
Marseglia|Gianluigi|G|

Basophil activation test
Chronic spontaneous urticaria
IgE high-affinity receptor subunit
Autoimmune chronic urticaria
Autologous serum skin test


Wound closure in epidermolysis bullosa: data from the vehicle arm of the phase 3 ESSENCE Study.

Abstract:
BACKGROUND
Chronic wounds are a fundamental issue for patients with epidermolysis bullosa (EB). Herein, we assess the natural history of wound closure in patients with EB who were randomly assigned to the vehicle-control arm of the multicenter, randomized, double-blind, phase 3 ESSENCE (NCT02384460) trial.

METHODS
ESSENCE was designed to assess the efficacy and safety of a topical cream formulation of 6% allantoin (SD-101 6%) vs vehicle (SD-101 0%) in patients ≥1 month old who had a diagnosis of EB (simplex, recessive dystrophic, or intermediate junctional) and a target wound 10-50 cm2 present for ≥21 days. Time to complete target wound closure and the proportion of patients with target wound closure over time were analyzed overall and by parameters including patient age and baseline body surface area index (BSAi) of total wound burden (< 5% and ≥ 5%). Changes in BSAi of lesional skin, pain, and itching were also assessed.

RESULTS
The vehicle-control arm included 87 patients. Mean (standard deviation [SD]) time to target wound closure within 3 months was 53.6 (28.6) days, with a range of 14 to 142 days. The proportion of patients with target wound closure increased over time from 7.1% at day 14 to 53.6% at month 3. Mean (SD) changes from baseline in BSAi of total wound burden and BSAi of lesional skin at month 3 were -2.3% (6.3) and -5.0% (13.5) of total body coverage, respectively. Reductions in pain and itching were observed at day 7 and maintained for 3 months. Faster healing times and a greater proportion of patients with wound closure were observed in patients aged 1 month to < 2 years; those with wounds < 30 days old, and in those with BSAi of total body wound burden < 5%.

CONCLUSIONS
Treatment response observed in the vehicle-control arm of the ESSENCE study was unexpectedly high and may have been due to unforeseen benefits of vehicle or enhanced wound care provided by the clinical trial staff. These observations will help inform the study design of future trials in patients with EB.

TRIAL REGISTRATION
ClinicalTrials.gov , NCT02384460 ; Date of registration: February 13, 2015; First participant enrollment: March 11, 2015.

Murrell|Dedee F|DF|
Paller|Amy S|AS|
Bodemer|Christine|C|
Browning|John|J|
Nikolic|Milos|M|
Barth|Jay A|JA|
Lagast|Hjalmar|H|
Krusinska|Eva|E|
Reha|Allen|A|
|||

D004311:Double-Blind Method
D004820:Epidermolysis Bullosa
D006801:Humans
D007231:Infant, Newborn
D014945:Wound Healing

Wound closure
Epidermolysis bullosa
Natural history


AOFAS Position Statement Regarding Patient-Reported Outcome Measures.

Abstract: Outcome measures evaluate various aspects of patient health, and when appropriately utilized can provide valuable information in both clinical practice and research settings. The orthopedic community has placed increasing emphasis on patient-reported outcome measures, recognizing their value for understanding patients' perspectives of treatment outcomes. Patient-reported outcomes are information directly reported by patients regarding their perceptions of health, quality of life, or functional status without interpretation by healthcare providers. The American Orthopaedic Foot & Ankle Society (AOFAS) supports the use of validated patient-reported outcome (PRO) instruments to assess patient general health, functional status, and outcomes of treatment. It is not possible to recommend a single instrument to collect quality orthopedic data as the selection is dependent on the population being examined and the question being asked. We support the use of the PROMIS Physical Function Computerized Adaptive Test (PF CAT) or Lower Extremity Computerized Adaptive Test (LE CAT), which can be assessed with other domains such as Pain Interference. In addition, a disease-specific measure can be used when available.

Kitaoka|Harold B|HB|
Meeker|James E|JE|
Phisitkul|Phinit|P|
Adams|Samuel B|SB|
Kaplan|Jonathan R|JR|
Wagner|Emilio|E|

D000071066:Patient Reported Outcome Measures

patient-reported outcomes
ankle
PRO
PROMIS
computer adaptive testing


Probiotics: Myths or facts about their role in allergy prevention.

Abstract:
BACKGROUND
The hygiene hypothesis proposed by Strachan in the 1980s clearly emphasized the role of microorganisms in atopy prevention.

OBJECTIVES
The study objective was to assess the preventive role of probiotics in patients with allergic rhinitis, bronchial asthma, atopic dermatitis, and/or food allergy.

MATERIAL AND METHODS
The methods used in the study were the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaires for 6-7- and 13-14-year-olds and the European Community Respiratory Health Survey II (ECRHS II) questionnaire targeted for the 20-44 age group. The study was conducted as part of the cross-sectional Epidemiology of Allergic Diseases in Poland study conducted in 9 Polish regions (8 urban: Warszawa, Lublin, Białystok, Gdańsk, Poznań, Wrocław, Katowice, Kraków, and the rural regions of Zamojski and Krasnostawski counties). The study material was a group of patients diagnosed with food allergy (n = 407), atopic dermatitis (n = 311), allergic rhinitis (n = 1.353), bronchial asthma (n = 505), and healthy volunteers (n = 2,403).

RESULTS
Genetic factors play an important role in the allergy development. A family history positive for chronic skin disorders increased the risk of atopic dermatitis and food allergies (OR = 1.456, CI = 1.14-1.85, p = 0.002; and OR = 1.378, CI = 1.05-1.81, p = 0.02, respectively). The consumption of products containing live bacterial cultures showed no preventive effects in any of the evaluated disorders in early childhood. Conversely, over the age of 14 years, probiotic formulations exhibit health-promoting effects and may lower the risk of allergic diseases.

CONCLUSIONS
The use of probiotics in the Polish population showed no protective effect in the first years of life. The changes in dietary habits introduced during late adolescence demonstrated significantly greater preventive effects of live bacterial cultures against the development of allergic diseases.

Krzych-Fałta|Edyta|E| Furmańczyk|Konrad|K| Tomaszewska|Aneta|A| Olejniczak|Dominik|D| Samoliński|Bolesław|B| Samolińska-Zawisza|Urszula|U|


The Impact of Electrographic Seizures on Developing Hippocampal Dendrites Is Calcineurin Dependent.

Abstract: Neurobehavioral abnormalities are commonly associated with intractable childhood epilepsy. Studies from numerous labs have demonstrated cognitive and socialization deficits in rats and mice that have experienced early-life seizures. However, the cellular and molecular mechanisms underlying these effects are unknown. Previously, experiments have shown that recurrent seizures in infancy suppress the growth of hippocampal dendrites at the same time they impair learning and memory. Experiments in slice cultures have also demonstrated dendrite growth suppression. Here, we crossed calcineurin B1 (CaNB1) floxed and Thy1GFP-M mice to produce mice that were homozygous for the both the floxed CaNB1 and the Thy1GFP-M transgene. Littermates that were homozygous for wild-type CaNB1 and Thy1GFP-M served as controls. Hippocampal slice cultures from these mice were transfected with an AAV/hSyn-mCherry-Cre virus to eliminate CaNB1 from neurons. Immunohistochemical results showed that CaNB1 was eliminated from at least 90% of the transfected CA1 pyramidal cells. Moreover, the CaN-dependent nuclear translocation of the CREB transcription coactivator, CREB-regulated transcriptional coactivator 1 (CRTC1), was blocked in transfected neurons. Cell attach patch recordings combined with live multiphoton imaging demonstrated that the loss of CaNB1 did not prevent neurons from fully participating in electrographic seizure activity. Finally, dendrite reconstruction showed that the elimination of CaNB1 prevented seizure-induced decreases in both dendrite length and branch number. Results suggest that CaN plays a key role in seizure-induced dendrite growth suppression and may contribute to the neurobehavioral comorbidities of childhood epilepsy.

Nishimura|Masataka|M|
Casanova|J R|JR|
Swann|John W|JW|

D048868:Adaptor Proteins, Signal Transducing

D047908:Intracellular Signaling Peptides and Proteins

development
epilepsy
FK506
fCaNB1
hippocampus
viral transfections


Statistical framework for detection of genetically modified organisms based on Next Generation Sequencing.

Abstract: Because the number and diversity of genetically modified (GM) crops has significantly increased, their analysis based on real-time PCR (qPCR) methods is becoming increasingly complex and laborious. While several pioneers already investigated Next Generation Sequencing (NGS) as an alternative to qPCR, its practical use has not been assessed for routine analysis. In this study a statistical framework was developed to predict the number of NGS reads needed to detect transgene sequences, to prove their integration into the host genome and to identify the specific transgene event in a sample with known composition. This framework was validated by applying it to experimental data from food matrices composed of pure GM rice, processed GM rice (noodles) or a 10% GM/non-GM rice mixture, revealing some influential factors. Finally, feasibility of NGS for routine analysis of GM crops was investigated by applying the framework to samples commonly encountered in routine analysis of GM crops.

Willems|Sander|S|
Fraiture|Marie-Alice|MA|
Deforce|Dieter|D|
De Keersmaecker|Sigrid C J|SC|
De Loose|Marc|M|
Ruttink|Tom|T|
Herman|Philippe|P|
Van Nieuwerburgh|Filip|F|
Roosens|Nancy|N|

D060888:Real-Time Polymerase Chain Reaction

Statistical framework
NGS
GM rice
Bioinformatics
GMO detection
Processed food


Investigation of force, contact area and dwell time in finger-tapping tasks on membrane touch interface.

Abstract: This study aimed to determine the touch characteristics during tapping tasks on membrane touch interface and investigate the effects of posture and gender on touch characteristics variables. One hundred participants tapped digits displayed on a membrane touch interface on sitting and standing positions using all fingers of the dominant hand. Touch characteristics measures included average force, contact area and dwell time. Across fingers and postures, males exerted larger force and contact area than females, but similar dwell time. Across genders and postures, thumb exerted the largest force and the force of the other four fingers showed no significant difference. The contact area of the thumb was the largest, whereas that of the little finger was the smallest; the dwell time of the thumb was the longest, whereas that of the middle finger was the shortest. Relationships among finger sizes, gender, posture and touch characteristics were proposed. The findings helped direct membrane touch interface design for digital and numerical control products from hardware and software perspectives. Practitioner Summary: This study measured force, contact area and dwell time in tapping tasks on membrane touch interface and examined effects of gender and posture on force, contact area and dwell time. The findings will direct membrane touch interface design for digital and numerical control products from hardware and software perspectives. Abbreviations: M: mean; SD: standard deviation; ISO: International Organization for Standardization; LCD: liquid crystal display; ANOVA: analysis of variance; ANSI: American National Standards Institute; HFES: Human Factors and Ergonomics Society.

force
contact area
dwell time
touch characteristics
Finger tapping


Comparisons of Two-level Discectomy and Fusion with Cage Alone versus Single-level Corpectomy and Fusion with Plate in the Treatment of Cervical Degenerative Disc Disease.

Abstract:
OBJECTIVE
To compare the radiologic parameters and clinical outcomes of two-level anterior cervical discectomy and fusion (ACDF) with cage alone versus single-level anterior cervical corpectomy and fusion (ACCF) with plate in the treatment of two-level contiguous cervical degenerative disc disease.

METHODS
Of all 38 consecutive patients who were included in this study, 22 patients underwent on a two-level contiguous ACDF with cage alone (ACDF-CA group), 16 patients underwent a single-level ACCF with plate (ACCF-P group). We compared following parameters between these two groups; perioperative parameters (hospital stays, blood loss and operation duration), clinical parameters (Japanese Orthopedic Association scores and Odom's criteria) and radiologic parameters segmental height ratio (SHR), segmental lordotic angle (SLA), global lordotic angle (GLA) and fusion rate).

RESULTS
The amount of operative blood loss in the ACCF-P group was higher than in the ACDF-CA group with statistical significance (p<0.05). Clinical outcomes and fusion rates were similar between groups. The postoperative SHRs in both groups were higher than that of preoperative period with statistical significance; however, these values significantly decreased at the last follow up period. The SLA increased during the immediate postoperative period, and then mild decreased. The values of GLA in both groups did show variable differences according to each time frame.

CONCLUSION
The results of ACDF-CA were comparable with ACCF-P with regard to clinical and radiologic outcomes in contiguous two-level cervical fusion. A two-level ACDF-CA as a treatment modality for two-level contiguous cervical disc disease may be a worthwhile method as an alternative to single-level ACCF-P.

Ha|Bok Young|BY|
Sim|Hong Bo|HB|
Lyo|In Uk|IU|
Park|Eun Suk|ES|
Kwon|Soon Chan|SC|
Park|Jun Bum|JB|

Cage
Plate
Cervical spine
Spinal fusion
Spondylosis


lncRNA HAND2-AS1 is downregulated in osteoarthritis and regulates IL-6 expression in chondrocytes.

Abstract:
BACKGROUND
Osteoarthritis (OA) is a leading cause of disability. The incidence of OA is progressively rising due to the diminishing levels of physical activity and ever-expanding aging population. However, the mainstay for OA treatment only can improve symptoms without delay the progression of this severe disease. This study aimed to explore the biological role and clinical function of lncRNA HAND2-AS1 in OA.

METHODS
Blood samples and synovial fluid were collected from OA patients and normal subjects. HAND2-AS1 expression was detected by qRT-PCR and IL-6 expression was detected by ELISA. The plasma levels of HAND2-AS1 were also detected in different ages, stages, and gender of OA patients and controls. Furthermore, the ROC curve was used to analyze whether HAND2-AS1 can distinguish OA patients from normal subjects. Also, Pearson correlation coefficient analysis was used to analyze the correlation between lncRNA HAND2-AS1 and IL-6. In addition, Western blot was used to detect the IL-6 level upon HAND2-AS1 over-expression in chondrocytes and qRT-PCR was used to detect the HAND2-AS1 level after endogenous IL-6 treatment.

RESULTS
HAND2-AS1 and IL-6 were dysregulated in plasma and synovial fluid of OA patients. The expression of HAND2-AS1 in plasma of OA patients was decreased with aging and progression. Furthermore, HAND2-AS1 downregulation effectively distinguished OA patients from the healthy controls. Over-expression of HAND2-AS1 inhibited IL-6 expression in chondrocytes, while treatment with exogenous IL-6 did not affect HAND2-AS1 expression.

CONCLUSION
HAND2-AS1 effectively distinguished OA patients from the healthy controls and regulates IL-6 expression in human chondrocytes.

TRIAL REGISTRATION
ChiCTR, ChiCTR2000038635 . Registered 11 February 2019.

D051792:Basic Helix-Loop-Helix Transcription Factors

lncRNA HAND2-AS1
Osteoarthritis
Chondrocytes
Synovial fluid
Interleukin 6


Mesenteric cysts, lymphatic leak, and cerebral cavernous malformation in a proband with KRIT1-related disease.

Abstract: Cerebral cavernous malformations (CCMs) of the central nervous system arise sporadically or secondary to genomic variation. Established genetic etiologies include deleterious variants in KRIT1 (CCM1), malcavernin (CCM2), and PDCD10 (CCM3). KRIT1-related disease has not been described in conjunction with lymphatic defects, although lymphatic defects with abnormal endothelial cell junctions have been observed in mice deficient in HEG1-KRIT1 signaling. We report a proband with CCMs, multiple chylous mesenteric cysts, and chylous ascites with leaky lymphatic vasculature. Clinical short-read exome sequencing detected a disease-associated KRIT1 variant (NM_194456.1:c.[1927C>T];[=], p.(Gln643*)). We postulate an expansion of KRIT1-related disease to include lymphatic malformations and lymphatic endothelial dysfunction.

cerebral cavernous malformation
KRIT1
chylous mesenteric cysts
lymphatic malformation
endothelial dysfunction
lymphatic dysfunction


Cost-effectiveness analysis of implantable cardiac devices in patients with systolic heart failure: a US perspective using real world data.

Abstract: Aims: Heart failure with reduced ejection fraction (HFrEF) has a substantial impact on costs and patients' quality-of-life. This study aimed to estimate the cost-effectiveness of implantable cardioverter defibrillators (ICD), cardiac resynchronization therapy pacemakers (CRT-P), cardiac resynchronization therapy defibrillators (CRT-D), and optimal pharmacologic therapy (OPT) in patients with HFrEF, from a US payer perspective.Materials and methods: The analyses were conducted by adapting the UK-based cost-effectiveness analyses (CEA) to the US payer perspective by incorporating real world evidence (RWE) on baseline hospitalization risk and Medicare-specific costs. The CEA was based on regression equations estimated from data from 13 randomized clinical trials (n = 12,638). Risk equations were used to predict all-cause mortality, hospitalization rates, health-related quality-of-life, and device-specific treatment effects (vs. OPT). These equations included the following prognostic characteristics: age, QRS duration, New York Heart Association (NYHA) class, ischemic etiology, and left bundle branch block (LBBB). Baseline hospitalization rates were calibrated based on RWE from Truven Health Analytics MarketScan data (2009-2014). A US payer perspective, lifetime time horizon, and 3% discount rates for costs and outcomes were used. Benefits were expressed as quality-adjusted life-years (QALYs). Incremental cost-effectiveness analysis was conducted for 24 sub-groups based on LBBB status, QRS duration, and NYHA class.Results: Results of the analyses show that CRT-D was the most cost-effective treatment at a $100,000/QALY threshold in 14 of the 16 sub-groups for which it is indicated. Results were most sensitive to changes in estimates of hospitalization costs.Limitations: Study limitations include small sample sizes for NYHA I and IV sub-groups and lack of data availability for duration of treatment effect.Conclusions: CRT-D has higher greater cost-effectiveness across more sub-groups in the indicated patient populations against as compared to OPT, ICD, and CRT-P, from a US payer perspective.

D058409:Cardiac Resynchronization Therapy Devices

cost-effectiveness
implantable cardiac devices
Heart failure
US
C10
C50
Medicare


Prospective direct comparison of antihypertensive effect and safety between high-dose amlodipine or indapamide in hypertensive patients uncontrolled by standard doses of angiotensin receptor blockers and amlodipine.

Abstract:
OBJECTIVE
When hypertension is uncontrolled by routine treatment with an angiotensin II receptor blocker (ARB) and the calcium channel blocker amlodipine (5 mg), the dose of amlodipine can be increased or a diuretic can be added. We investigated the more effective option in a prospective multicenter open-label study.

METHODS
Hypertensive patients were recruited if the target blood pressure (BP) in The Japanese Society of Hypertension 2009 guideline could not be achieved with standard-dose ARB therapy and amlodipine (5 mg).

PATIENTS
Patients were divided into three groups. Group-1 was switched to a combination of irbesartan (100 mg) and amlodipine (10 mg). Group-2A was changed to a combination of irbesartan (100 mg), amlodipine (5 mg), and indapamide, while Group-2B received a standard-dose ARB and amlodipine (5 mg) plus indapamide. Patients were assigned by their attending physicians and were followed for 6 months. The primary endpoint was the antihypertensive effect of each regimen.

RESULTS
Group-1 contained 85 patients, Group-2A had 49 patients, and Group-2B had 4 patients. We only analyzed Group-1 and Group-2A due to the small size of Group-2B. In both groups, systolic BP and diastolic BP were significantly decreased up to 6 months (all p < 0.001). Reduction of systolic BP was greater in Group-1 than Group-2A after 1 month and 6 months (both p < 0.05). Uric acid was increased in Group-2A after 3 months, but not at 6 months.

CONCLUSION
Although both regimens were effective for reducing BP, increasing amlodipine to 10 mg daily controlled hypertension without elevation of serum uric acid.

Okamura|Keisuke|K| Shirai|Kazuyuki|K| Totake|Nao|N| Okuda|Tetsu|T| Urata|Hidenori|H|

hypertension
Angiotensin II receptor blocker
calcium channel blocker
combination drug
multicenter study