A prelude to wearable technology for the measurement and restoration of core body temperature and heart rate in athletes suffering from hypothermia.

Abstract: An individual who is in good physical health tends to exhibit an internal core temperature of 37°C and a heart rate of 60-100 beats per minute. Increase in the temperature of the surrounding environment can serve as the basis for the onset of the condition of Hypothermia. Hypothermia acts as one of the most significant barriers being faced by winter athletes and starts initially with an increase in the heart and breathing rate. However, if the condition persists it can lead to reduction in the heart and breathing rate and ultimately results in cardiac failure. Although, jackets are commercially available, they tend to operate manually and furthermore, do not serve the primary purpose of counteracting the condition of hypothermia, particularly experienced by athletes taking part in winter sports. The objective of this study is to design a heating jacket that enables effective counteraction of the condition of Hypothermia. It enables precise measurement of the of core body temperature with the aid of a pyroelectric sensor. Along with this, a pulse rate sensor for detecting the accurate heart rate has been incorporated on the index finger. Five heating pads would get activated to attain optimal temperature, in case the core body temperature of <37°C is detected. If the condition of hypothermia advances to the moderate stage, two additional heating pads will get activated and provide extra warmth to attain normal heart rate along with core body temperature. Overall, this wearable technology serves as a definitive solution to counteract the condition of hypothermia only when the internal parameters exhibit that you actually have it. The results of the study exhibited that this prototype can be utilized for detecting and treating the condition of Hypothermia.

wearable technology
Athletes
hypothermia
pyroelectric sensor
pulse rate sensor


Shikonin induces odontoblastic differentiation of dental pulp stem cells via AKT-mTOR signaling in the presence of CD44.

Abstract: Purpose: In our previous study, we demonstrated that hyaluronan induces odontoblastic differentiation of dental pulp stem cells via interactions with CD44. However, it remains unclear whether CD44 expression by dental pulp stem cells is required for odontoblastic differentiation.Methods: We searched for a compound other than hyaluronan that induces odontoblastic differentiation of dental pulp stem cells and used western blotting to determine whether CD44 is involved in the induction of odontoblastic differentiation by the compound. We further validated the cell signaling details of the compound-induced expression of dentin sialophosphoprotein (DSPP), which is known as a marker of odontoblastic differentiation.Results: We investigated shikonin, which is one of the derivatives of naphthoquinone, the skeleton of vitamin K. Shikonin-induced expression of DSPP was inhibited by PI3K, AKT, and mTOR inhibitors. Additionally, shikonin-induced expression of DSPP was inhibited in dental pulp stem cells transfected with siRNA against CD44.Conclusions: Shikonin can stimulate dental pulp stem cells to undergo odontoblastic differentiation through a mechanism involving the AKT-mTOR signaling pathway and CD44. Although expression of CD44 is important for inducing odontoblastic differentiation of dental pulp stem cells, the relationship between the AKT-mTOR signaling pathway and CD44 expression, in the context of shikonin stimulation, has not yet been elucidated. This study suggests that shikonin may be useful for inducing odontoblastic differentiation of dental pulp stem cells, and that it may have clinical applications, including protection of the dental pulp.

Kajiura|Kunihiro|K| Umemura|Naoki|N| Ohkoshi|Emika|E| Ohta|Takahisa|T| Kondoh|Nobuo|N| Kawano|Satoshi|S|

odontoblast differentiation
Dental pulp stem cells
CD44
dentin sialophosphoprotein
mammalian target of rapamycin


Effect of Structure on Charge Distribution in the Isatin Anions in Aprotic Environment: Spectral Study.

Abstract: Five isatin anions were prepared by deprotonation of initial isatins in aprotic solvents using basic fluoride and acetate anions (F- and CH₃COO-). The F- basicity is sufficient to deprotonate isatin NH hydrogen from all the studied compounds. This process is reversible. In the presence of proton donor solvents, the anions form the corresponding isatins. The isatin hydrogen acidity depends on the overall structure of the isatin derivatives. The anions were characterized by ultraviolet-visible (UV-Vis), Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopy. Interestingly, the anions form aggregates at concentrations above 10-3 mol·dm-3. Further, the effect of cations on the UV-Vis spectra of the studied anions was studied. Charge transfer and its distribution in the anion depends on the radius and the cation electron configuration. The alkali metal cations, tetrabutylammonium (TBA⁺), Mg2+ and Ag⁺, interact with the C-2 carbonyl oxygen of the isatin anion. The interaction has a coulombic character. On the other hand, Cd2+, Zn2+, Hg2+, Co2+, and Cu⁺ cations form a coordinate bond with the isatin nitrogen.

Tisovský|Pavol|P| Šandrik|Róbert|R| Horváth|Miroslav|M| Donovalová|Jana|J| Filo|Juraj|J| Gáplovský|Martin|M| Jakusová|Klaudia|K| Cigáň|Marek|M| Sokolík|Róbert|R| Gáplovský|Anton|A|

D017550:Spectroscopy, Fourier Transform Infrared

FTIR
NMR spectroscopy
UV–Vis
azanion aggregation
counterion effect
isatin azanions


Simple and Easy to Perform Preimplantation Genetic Diagnosis for β-thalassemia Major Using Combination of Conventional and Fluorescent Polymerase Chain Reaction.

Abstract:
BACKGROUND
Thalassemias are the most common monogenic disorders in many countries throughout the world. The best practice to control the prevalence of the disease is prenatal diagnosis (PND) services. Extensive practicing of PND proved effective in reducing new cases but on the other side of this success high abortion rate is hided, which ethically unfair and for many couples, especially with a previous experience of a therapeutic abortion, or moral concerns, is not a suitable choice. Preimplantation genetic diagnosis (PGD) is a strong alternative to conventional PND. At present PGD is the only abortion free fetal diagnostic process. Considering the fact that there are more than 6000 single gene disorders affecting approximately 1 in 300 live-births, the medical need for PGD services is significant.

MATERIALS AND METHODS
In the present study development of a PGD protocol for a thalassemia trait couple using nested multiplex fluorescent polymerase chain reaction (PCR) for the combination of polymorphic linked short tandem repeat (STR) markers and thalassemia mutations is described. Restriction fragment length polymorphism used to discriminate between wild and mutated alleles.

RESULTS
In PGD clinical cycle, paternal and maternal alleles for D11S988 and D11S1338 STR markers were segregated as it was expected. PCR product for IVSII-1 mutation was subsequently digested with BtscI restriction enzyme to differentiate normal allele from the mutant allele. The mother's mutation, being a comparatively large deletion, was detectable through size differences on agarose gel.

CONCLUSION
The optimized single cell protocol developed and evaluated in this study is a feasible approach for preimplantation diagnosis of β-thalassemia in our patients.

Salehi|Rasoul|R| Khosravi|Sharifeh|S| Salehi|Mansour|M| Kheirollahi|Majid|M| Khanahmad|Hossein|H|

nested fluorescent polymerase chain reaction


The effect of platelet-rich plasma on the differentiation of synovium-derived mesenchymal stem cells.

Abstract: Platelet-rich plasma (PRP), the plasma portion of blood with a high platelet concentration, has been reported to be helpful in stem cell chondrogenesis due to large amount of growth factors it contains. Here, we examined the influence of PRP on the differentiation of synovium-derived stem cells (SDSCs) and also evaluated if PRP alone was sufficient to induce SDSCs differentiation. First, the cell proliferation in various differentiation media was analyzed using the MTT assay and it was significantly higher in groups cultured with media that contained PRP. Then, We performed Safranin-O staining and type I, II, and X collagen immunohistochemistry (chondrogenesis), von Kossa staining (osteogenesis), and Oil Red O staining (adipogenesis). The staining was most prominent in groups cultured with optimized differentiation media without PRP in all three lineages of differentiation. The mRNA expression levels of typical differentiation markers were also analyzed using reverse transcription quantitative polymerase chain reaction. Although, culture in optimized differentiation media increased the mRNA expression of the typical differentiation marker genes, they were significantly reduced when cultured in the media supplemented with PRP. PRP has negative effects on SDSC differentiation in all three differentiation lineages and PRP alone does not induce SDSC differentiation.

Lee|Joon Kyu|JK|
Lee|Sahnghoon|S|
Han|Sun Ae|SA|
Seong|Sang Cheol|SC|
Lee|Myung Chul|MC|

D020133:Reverse Transcriptase Polymerase Chain Reaction

platelet-rich plasma
mesenchymal stem cell
chondrogenesis
synovium-derived stem cell


Identification of Compounds for Butyrylcholinesterase Inhibition.

Abstract: Butyrylcholinesterase (BChE) is a nonspecific cholinesterase enzyme that hydrolyzes choline-based esters. BChE plays a critical role in maintaining normal cholinergic function like acetylcholinesterase (AChE) through hydrolyzing acetylcholine (ACh). Selective BChE inhibition has been regarded as a viable therapeutic approach in Alzheimer's disease. As of now, a limited number of selective BChE inhibitors are available. To identify BChE inhibitors rapidly and efficiently, we have screened 8998 compounds from several annotated libraries against an enzyme-based BChE inhibition assay in a quantitative high-throughput screening (qHTS) format. From the primary screening, we identified a group of 125 compounds that were further confirmed to inhibit BChE activity, including previously reported BChE inhibitors (e.g., bambuterol and rivastigmine) and potential novel BChE inhibitors (e.g., pancuronium bromide and NNC 756), representing diverse structural classes. These BChE inhibitors were also tested for their selectivity by comparing their IC50 values in BChE and AChE inhibition assays. The binding modes of these compounds were further studied using molecular docking analyses to identify the differences between the interactions of these BChE inhibitors within the active sites of AChE and BChE. Our qHTS approach allowed us to establish a robust and reliable process to screen large compound collections for potential BChE inhibitors.

butyrylcholinesterase
BChE inhibitors
qHTS
molecular docking
colorimetric BChE assay


Surfactants enhance recovery of poorly soluble drugs during microdialysis sampling: Implications for in vitro dissolution-/permeation-studies.

Abstract: Aim of this project was to investigate the applicability of a recently developed in vitro microdialysis-sampling approach in connection with a dissolution-/permeation (D/P) system, especially the impact of surfactants within the perfusion fluid. The D/P-system is based on side-by-side chambers, separated by a barrier that simulates the intestinal barrier. Here, in contrast to conventional D/P-systems, the dissolution of the drug (donor chamber concentration) is followed by microdialysis sampling. This approach appears promising, because it is expected not to disturb the dynamic interplay between drug-dissolution (-release) and drug permeation. Furthermore, it should allow quantification of the unbound (free) drug concentration. In the first step, it was assessed, if the addition of the anionic surfactant sodium dodecyl sulphate (SDS) to the perfusate of the microdialysis system affects the recovery of the (slightly) water-soluble model drug acyclovir and the poorly water soluble model drug celecoxib (CXB). SDS had no influence on acyclovir-recovery, but substantially enhanced CXB-recovery, partly due to improved extraction efficiency, partly due to inhibition of loss of CXB due to non-specific binding to surfaces and the probe. The fraction of CXB recovered from aqueous CXB-solutions by microdialysis sampling using SDS-containing perfusates correlated well with the celecoxib concentration in the samples, but was found independent of the SDS-concentrations (above critical micelle concentration). In the next step microdialysis sampling with SDS-containing perfusates was assessed for celecoxib solutions in fasted state simulated intestinal fluid (FaSSIF) and compared to that in buffer. In FaSSIF, the measured CXB-concentrations were far below the overall CXB concentration, likely representing the free celecoxib, i.e. the fraction of drug, which is not associated with taurocholate surfactant micelles. In buffer, the measured concentrations matched the overall CXB concentrations. By the use of SDS-containing perfusates microdialysis sampling enabled reliable quantification of minute amounts of free CXB, which renders its use promising for dissolution-/permeation experiments with other poorly soluble drugs.

Koplin|Sebastian|S| Kumpugdee-Vollrath|Mont|M| Bauer-Brandl|Annette|A| Brandl|Martin|M|

Surfactant Microdialysis Dissolution Permeation Celecoxib Micelle


Inflammatory Bowel Disease in Japan-Is It Similar to or Different from Westerns?

Abstract: Ulcerative colitis and Crohn's disease, the most common types of inflammatory bowel disease, are idiopathic, intractable disease characterized by chronic inflammation in the intestine. In recent years, studies elucidating the clinical characteristics of these diseases and basic researches have suggested that the diseases are induced by the immunological abnormalities through the involvement of environmental factors with their predisposition. In Japan, significant progress of basic and epidemiological researches has been developed for these diseases and the clinical guidelines have been established. However, no fundamental treatment for these diseases has been established yet. The current number of patients in Japan continues to increase, with at least 180,000 patients suffering from ulcerative colitis and 40,000 suffering from Crohn's disease. Thus, further studies are required to understand these diseases and improve medical treatments.

inflammatory bowel disease
ulcerative colitis
Crohn's disease


The weather condition and epidemics as triggers for febrile seizure: A single-center retrospective observational study.

Abstract:
OBJECTIVE
The objective of this study was to investigate the association between the weather and epidemic condition and risk of febrile seizures (FSs) in Japan.

STUDY DESIGN
This single-center, retrospective study included 560 children (age, 6-60 months) with FSs who were transported to our center by ambulance from January 2011 through December 2018. The weather (temperature, atmospheric pressure, relative air humidity, amount of rainfall, sunshine duration, and air concentration of nitrogen dioxide [NO2] and sulfur dioxide [SO2]) and epidemic (influenza virus infection, infectious gastroenteritis, and exanthem subitum) conditions in this region were compared between the periods (days or weeks) with the transportation of children with FS to our hospital and those without such transportation.

RESULTS
In the univariate analyses, neither daily or weekly weather condition nor weekly epidemic condition was correlated to FS transportation. Furthermore, the multiple logistic regression analysis suggested that epidemic influenza virus infection (odds ratio [OR], 1.34; 95% confidence interval [CI], 1.08-1.73) and infectious gastroenteritis (OR, 1.64; 95% CI, 1.09-2.54) were the independent risk factors for FS occurrence and weather condition was not associated with FS risk.

CONCLUSIONS
Febrile seizure incidence may be increased by epidemic febrile infections but not by weather condition.

Kawakami|Isao|I| Inoue|Masataka|M| Adachi|Shunichi|S| Koga|Hiroshi|H|

Temperature
Atmospheric pressure
Humidity
Rain
Sunlight


Ecosystem services provided by bromeliad plants: A systematic review.

Abstract: The unprecedented loss of biological diversity has negative impacts on ecosystems and the associated benefits which they provide to humans. Bromeliads have high diversity throughout the Neotropics, but they have been negatively affected by habitat loss and fragmentation, climate change, invasive species, and commercialization for ornamental purpose. These plants provide direct benefits to the human society, and they also form microecosystems in which accumulated water and nutrients support the communities of aquatic and terrestrial species, thus maintaining local diversity. We performed a systematic review of the contribution of bromeliads to ecosystem services across their native geographical distribution. We showed that bromeliads provide a range of ecosystem services such as maintenance of biodiversity, community structure, nutrient cycling, and the provisioning of food and water. Moreover, bromeliads can regulate the spread of diseases, and water and carbon cycling, and they have the potential to become important sources of chemical and pharmaceutical products. The majority of this research was performed in Brazil, but future research from other Neotropical countries with a high diversity of bromeliads would fill the current knowledge gaps and increase the generality of these findings. This systematic review identified that future research should focus on provisioning, regulating, and cultural services that have been currently overlooked. This would enhance our understanding of how bromeliad diversity contributes to human welfare, and the negative consequences that loss of bromeliad plants can have on communities of other species and the healthy functioning of the entire ecosystems.

ecosystem services
bromeliad plants
neotropics
microecosystems
biodiversity
disease
climate regulation
pharmaceutical potential
water storage


Laser Acupuncture Improves Tear Film Stability in Patients with Dry Eye Disease: A Two-Center Randomized-Controlled Trial.

Abstract: To investigate the efficacy of laser acupuncture (LA) therapy in patients with dry eye disease (DED).  A two-center randomized controlled trial.  The Department of Ophthalmology, Chinese Medicine at the Kaohsiung Chang Gung Memorial Hospital, and the Sunming Eye Clinic in South Taiwan.  Fifty-nine participants ages 20 to 65 years were enrolled and randomly assigned to the experimental group (LA plus conventional treatment) or the sham control group (LA without laser output plus conventional treatment).  Subjects underwent LA treatment three times a week for 12 weeks. The subjects in the experimental group sequentially received 0.375 J of energy at each of the following acupoints: BL2, TE23, ST2, LI4, ST36, and GB37. Subjects in the control group received a sham LA treatment, without any laser output.  The primary outcome measure was ocular surface disease index (OSDI). The secondary outcome measures included tear film breakup time (TFBUT), Schirmer-I test finding, and visual analog scale (VAS) score.  At 4 and 12 weeks after the first visit, the experimental group showed significant improvement of dry eye symptoms as measured by OSDI, TFBUT, Shirmer-I test, and VAS. Compared with the control group, the OSDI (7.23, p = 0.001) and TFBUT (-1.78, p = 0.001) significantly improved in the experimental group at 12 weeks of treatment.  LA improved the symptoms and tear stability related to DED in conjunction with conventional treatment. The authors suggest that LA be considered a complementary therapy for DED when conventional treatment does not provide satisfactory effects.  ClinicalTrials.gov Identifier NCT03204903.

Hu|Wen-Long|WL| Yu|Hun-Ju|HJ| Pan|Li-Yen|LY| Wu|Pei-Chang|PC| Pan|Chih-Chin|CC| Kuo|Chun-En|CE| Tseng|Ying-Jung|YJ| Hung|Yu-Chiang|YC|

laser acupuncture
dry eye disease
Traditional Chinese Medicine


Genotyping and macrolide resistance of Mycoplasma pneumoniae identified in children with community-acquired pneumonia in Medellín, Colombia.

Abstract:
OBJECTIVES
The aim of this study was to describe the genotypes and the main characteristics of community-acquired pneumonia (CAP) caused by Mycoplasma pneumoniae in hospitalized children in Medellín and neighboring municipalities during the period 2011-2012.

METHODS
The M. pneumoniae genotype was determined by PCR and sequencing of the p1 and 23S rRNA genes from induced sputum samples and nasopharyngeal swabs (NPS). Samples were obtained from children with CAP who were hospitalized in 13 healthcare centers. In addition, a spatio-temporal analysis was performed to identify the potential risk areas and clustering of the cases over time.

RESULTS
A variant of type 2 was the dominant genotype in the induced sputum (96.1%) and NPS (89.3%) samples; the type 1 variant was identified in 3.9% and 10.7% of these samples, respectively. No strains with mutations in the 23S rRNA gene associated with macrolide resistance were found. The cases in Medellín were mainly concentrated in the northeastern areas and western districts. However, no temporal relationship was found among these cases.

CONCLUSIONS
A variant of type 2 of M. pneumoniae prevailed among children with CAP during the study period. No strains with mutations associated with macrolide resistance were found.

Copete|Angela Rocio|AR|
Aguilar|Yudy Alexandra|YA|
Rueda|Zulma Vanessa|ZV|
Vélez|Lázaro Agustín|LA|


Survival of clinical and food Acinetobacter spp. isolates exposed to different stress conditions.

Abstract: Acinetobacter baumanni is recognized as one of the most important agents of nosocomial infections. Other species such as Acinetobacter lwoffii have also been associated with such infections. These species can be found in food products, such as vegetables, fruits and meats which can be a source of transmission of these organisms to community and hospital settings. Evidence that hospitals' kitchens are a route of entry of pathogenic and antimicrobial-resistant bacteria was recently demonstrated. This study aimed to determine whether different Acinetobacter spp. isolated from human and food samples (lettuce, turkey meat, apple and pear) were resistant to stress conditions often applied in food processes, such as exposure to 60 °C, AMUKINA® and vinegar. Also the influence of food matrices on the behavior of isolates to these stress conditions was evaluated. Treatment with AMUKINA® and vinegar were effective against all clinical and food isolates. Exposure to 60 °C resulted in the reduction of the majority of isolates to values below the detection limit of the enumeration technique, however, it is important to note that most of the reductions only occurred after 30 min of exposure. One food isolate identified as A. baumanni was resistant to this thermal treatment and one clinical isolate only decreased 4 log cycles after 1 h. In general, food isolates were demonstrated to be more resistant than clinical isolates and no significant differences (p > 0.05) were found between A. baumanni and A. lwoffii species. With the exception of one food isolate that was more resistant to thermal stress in the presence of turkey meat, the food matrices investigated did not confer protection to the applied stresses. Due to the limited knowledge on this topic, we believe that this study is an important contribution to understanding the behavior of Acinetobacter spp. when exposed to treatments commonly applied to foods.

Campos|Ana|A|
Lopes|Maria Sequeira|MS|
Carvalheira|Ana|A|
Barbosa|Joana|J|
Teixeira|Paula|P|

Acinetobacter lwoffii
Vinegar
Food matrices
Thermal stress
AMUKINA(®)
Acinetobacter baumannii


Correlation between gonial angle and dynamic tongue collapse in children with snoring/sleep disordered breathing - an exploratory pilot study.

Abstract:
BACKGROUND
Drug induced sleep endoscopy (DISE) is hoped to identify reasons of failure of adenotonsillectomy (AT) in treating pediatric sleep disordered breathing (SDB). Maxillomandibular disproportion has been studied as another association which may explain alternative pathogenesis of SDB. We aimed to explore the relation between the size of the gonial angle and inclination of the epiglottis measured from cone beam CT (CBCT) and tongue base collapse based on DISE in children with SDB.

METHOD
A retrospective chart review was conducted at a tertiary pediatric center. Children (6-17 years old) assessed at a multi-disciplinary Upper Airway Clinic, diagnosed with SDB and maxillo-mandibular disproportion (MMD), and who underwent DISE were eligible. Variables obtained from the electronic medical records of the clinic and prospective database included demographics, comorbidities, surgeries performed, investigations, DISE findings and CBCT findings. The gonial angle of subjects with and without tongue base collapse (TBC) on SNP were compared.

RESULTS
In total 29 patients (13 male, 8 female) age 6-17 (median= 9) were eligible for the study from January 2009 - July 2016. We included 11 subjects, and 10 comparators. The mean gonial angle of the TBC group was 139.3°± 7.6°, while that of the comparison group was 129.4°±3.5 (mean difference -9.937, 95% CI of -15.454 to - 4.421, P = 0.001, power of test 0.95). Additionally, the mean inclination of the epiglottis had a mild positive correlation (r=0.32, p<0.05) with the gonial angle, in the whole cohort.

CONCLUSIONS
This pilot study suggests that TBC may be mediated by a wider gonial angle in children with SDB patients. The posterior tilt of the epiglottis on CBCT may be a surrogate sign of TBC.

Gonial angle
Drug induced sleep endoscopy
Pediatric sleep disordered breathing
Maxillo-mandibular disproportion
Adeno-tonsillectomy
Pharyngeal collapse


Mouse ES cells have a potential to differentiate into odontoblast-like cells using hanging drop method.

Abstract:
OBJECTIVES
We examined whether mouse embryonic stem (ES) cells can differentiate into odontoblast-like cells without epithelial-mesenchymal interaction.

MATERIALS AND METHODS
Cells were cultured by the 'hanging drop' method using a collagen type-I scaffold (CS) combined with bone morphogenetic protein (BMP)-4 (CS/BMP-4). Expression of odontoblast-related mRNA and protein, and cell proliferation were performed by reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence staining and WST-1 assay, respectively.

RESULTS
Cells potently expressed odontoblast-related cell marker mRNAs following induction of odontoblastic differentiation. Dentin sialophosphoprotein, a marker of mature odontoblasts, was strongly expressed in differentiated ES cells. The cells also acquired an odontoblast-like functional phenotype, as evidenced by the appearance of alkaline phosphatase activity and calcification. The cell-surface expression of α2, α6, αV and αVβ3 integrin proteins was rapidly upregulated in differentiated cells. Finally, anti-α2 integrin antibody suppressed the expression of odontoblastic markers in cells grown using this culture system, suggesting that α2 integrin expression in ES cells triggers their differentiation into odontoblast-like cells.

CONCLUSIONS
Mouse ES cells cultured by the 'hanging drop' method are able to differentiate into cells with odontoblast-specific physiological functions and cell-surface integrin protein expression.

Kawai|R|R| Ozeki|N|N| Yamaguchi|H|H| Tanaka|T|T| Nakata|K|K| Mogi|M|M| Nakamura|H|H|

collagen
odontoblast
integrin
cell differentiation
cell-matrix interactions
stem cell


Optic perineuritis: A Canadian case series and literature review.

Abstract:
BACKGROUND
Optic perineuritis (OPN) is a rare orbital inflammatory disorder that primarily involves the optic nerve sheath (ONS). This study aimed to describe the clinical features of idiopathic OPN as well as OPN secondary to other infectious and inflammatory conditions in a Canadian case series as current literature on secondary OPN in Western countries is mostly limited to case reports.

METHODS
Retrospective case series of all patients seen in a tertiary neuro-ophthalmology practice with a diagnosis of OPN from 2014 to 2020.

RESULTS
A total of 21 patients (14 women, mean age 55.8) corresponding to 29 eyes with OPN were identified. Fifteen cases were associated with inflammatory or infectious conditions and only 6 were idiopathic. All idiopathic cases were unilateral. The most common secondary causes of OPN were anti-myelin oligodendrocyte glycoprotein (MOG) antibody disease (n = 4), syphilis (n = 3), sarcoidosis (n = 3), and giant cell arteritis (n = 3). At initial presentation, best-corrected visual acuity (BCVA) was 20/20 or better in 24% (n = 7) and visual field mean deviation (VF MD) was better than -5 dB in 34% of eyes (10/29). Treatment consisted of intravenous penicillin for syphilitic OPN and high-dose corticosteroids followed by oral taper with or without immunosuppressive therapy for non-syphilitic OPN. BCVA improved in 34% (10/29) and VF MD improved in 45% (13/29) eyes.

CONCLUSION
OPN primarily occurred in association with systemic inflammatory conditions, especially in bilateral cases. Syphilis must be ruled out in all patients. Anti-MOG antibody disease is an important, newly recognized secondary cause of OPN, and serologic testing should be included in the investigation of all patients with OPN.

Xie|Jim Shenchu|JS|
Donaldson|Laura|L|
Margolin|Edward|E|

Optic perineuritis
Sarcoidosis
Giant cell arteritis
MOG-associated disease
Syphils


Teamwork in clinical reasoning - cooperative or parallel play?

Abstract: Teamwork is fundamental for high-quality clinical reasoning and diagnosis, and many different individuals are involved in the diagnostic process. However, there are substantial gaps in how these individuals work as members of teams and, often, work is done in parallel, rather than in an integrated, collaborative fashion. In order to understand how individuals work together to create knowledge in the clinical context, it is important to consider social cognitive theories, including situated cognition and distributed cognition. In this article, the authors describe existing gaps and then describe these theories as well as common structures of teams in health care and then provide ideas for future study and improvement.

clinical reasoning
diagnosis
education
medical education


The first prevalence study of primary headaches in adults in a post-conflict area of Serbia.

Abstract:
AIM
The aim of the present study was to establish annual prevalence of primary headaches, migraine, and tension-type headache among adults in a post-conflict area of Serbia.

METHODS
The data for this cross-sectional study was obtained via face-to-face interviews using questionnaires specifically designed for this purpose, in line with the available guidelines. The study sample included adults aged 18-65 years whose native language is Serbian with residence in six predominantly Serbian communities in Kosovo and Metohija. Relevant diagnoses were established according to the diagnostic criteria of the International Classification of Headache Disorders, 3rd edition.

RESULTS
The study included 1062 adults. Analyses indicated 47.7% prevalence of primary headaches. The 1-year prevalence of migraine (with aura and without aura) and tension-type headache was established at 15.2% (3.3% and 11.9%), and 32.2%, respectively. One-year prevalence of chronic headache was calculated at 3.5%, while the prevalence of medication overuse headache was slightly lower at 2.9%. Primary headaches were more prevalent among women, participants residing south of the river Ibar, married or cohabiting individuals, as well as among interviewees (persons) who reported feeling unsafe in Kosovo and Metohija. This is the first study of the prevalence of primary headache disorders in Serbia. The obtained data is comparable to the data available for other countries, especially those in the Balkan region.

Milošević|Nenad|N|
Trajković|Jasna Zidverc|JZ|
Mijajlović|Milija|M|
Milošević|Jovana|J|
Podgorac|Ana|A|
Vitošević|Zdravko|Z|
Novaković|Tatjana|T|
Pekmezović|Tatjana|T|

prevalence
Primary headaches
post-conflict area
Serbia


Neurochemical and molecular mechanisms underlying the retrieval-extinction effect.

Abstract: Extinction within the reconsolidation window, or 'retrieval-extinction', has received much research interest as a possible technique for targeting the reconsolidation of maladaptive memories with a behavioural intervention. However, it remains to be determined whether the retrieval-extinction effect-a long-term reduction in fear behaviour, which appears resistant to spontaneous recovery, renewal and reinstatement-depends specifically on destabilisation of the original memory (the 'reconsolidation-update' account) or represents facilitation of an extinction memory (the 'extinction-facilitation' account). We propose that comparing the neurotransmitter systems, receptors and intracellular signalling pathways recruited by reconsolidation, extinction and retrieval-extinction will provide a way of distinguishing between these accounts.

Retrieval-Extinction Extinction Reconsolidation Memory Behaviour


Therapeutic Potential of Neoechinulins and Their Derivatives: An Overview of the Molecular Mechanisms Behind Pharmacological Activities.

Abstract: Neoechinulins are diketopiperazine type indole alkaloids that demonstrate radical scavenging, anti-inflammatory, antiviral, anti-neurodegenerative, neurotrophic factor-like, anticancer, pro-apoptotic, and anti-apoptotic properties. An array of neoechinulins such as neoechinulins A-E, isoechinulins A-C, cryptoechunilin have been isolated from various fungal sources like Aspergillus sp., Xylaria euglossa, Eurotium cristatum, Microsporum sp., etc. Besides, neoechinulin derivatives or stereoisomers were also obtained from diverse non-fungal sources viz. Tinospora sagittata, Opuntia dillenii, Cyrtomium fortunei, Cannabis sativa, and so on. The main purpose of this review is to provide update information on neoechinulins and their analogues about the molecular mechanisms of the pharmacological action and possible future research. The recent data from this review can be used to create a basis for the discovery of new neoechinulin-based drugs and their analogues in the near future. The online databases PubMed, Science and Google scholar were researched for the selection and collection of data from the available literature on neoechinulins, their natural sources and their pharmacological properties. The published books on this topic were also analysed. In vitro and in vivo assays have established the potential of neoechinulin A as a promising anticancer and anti-neuroinflammatory lead molecule. Neoechinulin B was also identified as a potential antiviral drug against hepatitis C virus. Toxicological and clinical trials are needed in the future to improve the phyto-pharmacological profile of neoquinolines. From the analysis of the literature, we found that neoechinulins and their derivatives have special biological potential. Although some modern pharmacological analyzes have highlighted the molecular mechanisms of action and some signalling pathways, the correlation between these phytoconstituents and pharmacological activities must be validated in the future by preclinical toxicological and clinical studies.

Sharifi-Rad|Javad|J|
Bahukhandi|Amit|A|
Dhyani|Praveen|P|
Sati|Priyanka|P|
Capanoglu|Esra|E|
Docea|Anca Oana|AO|
Al-Harrasi|Ahmed|A|
Dey|Abhijit|A|
Calina|Daniela|D|

neoechinulins
alkaloid
anti-inflammatory
antiviral
anticancer
in vitro
in vivo
fungus


LRRK2 Phosphorylation: Behind the Scenes.

Abstract: Mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) are known today as the most common genetic cause of Parkinson's disease (PD). LRRK2 is a large protein that is hypothesized to regulate other proteins as a scaffold in downstream signaling pathways. This is supported by the multiple domain composition of LRRK2 with several protein-protein interaction domains combined with kinase and GTPase activity. LRRK2 is highly phosphorylated at sites that are strictly controlled by upstream regulators, including its own kinase domain. In cultured cells, most pathogenic mutants display increased autophosphorylation at S1292, but decreased phosphorylation at sites controlled by other kinases. We only begin to understand how LRRK2 phosphorylation is regulated and how this impacts its physiological and pathological function. Intriguingly, LRRK2 kinase inhibition, currently one of the most prevailing disease-modifying therapeutic strategies for PD, induces LRRK2 dephosphorylation at sites that are also dephosphorylated in pathogenic variants. In addition, LRRK2 kinase inhibition can induce LRRK2 protein degradation, which might be related to the observed inhibitor-induced adverse effects on the lung in rodents and non-human primates, as it resembles the lung pathology in LRRK2 knock-out animals. In this review, we will provide an overview of how LRRK2 phosphorylation is regulated and how this complex regulation relates to several molecular and cellular features of LRRK2.

De Wit|Tina|T|
Baekelandt|Veerle|V|
Lobbestael|Evy|E|

D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2

LRRK2
phosphorylation
kinase inhibition
Parkinson’s disease


Discovery, Development, and Evaluation of a Horn Fly-Isolated (Diptera: Muscidae) Beauveria bassiana (Hypocreales: Cordyciptaceae) Strain From Florida, USA.

Abstract: The horn fly, Haematobia irritans (L.) is an important cattle pest and traditionally has been managed using insecticides; however, many horn fly populations are insecticide-resistant in United States. Use of alternative control techniques has been limited because of the challenges of managing a fly pest on pastured cattle. After the discovery of a wild horn fly infected with Beauveria bassiana in Florida, the fungus was cultured and evaluated for efficacy against laboratory-reared horn flies. This fungal strain was selected for increased virulence by passage through laboratory-reared horn fly hosts to shorten interval from infection to fly death and subsequent conidia formation, properties important to future use of the fungus as a biological control agent against horn flies. After seven passages through horn fly hosts, fly mortality was not significantly accelerated as evaluated through LT50 values, but conidia were readily produced from these killed flies. Although further development is needed to improve fungal efficacy, this fungal strain holds promise as a biological control agent for inclusion in horn fly integrated pest management programs.

Holderman|Christopher J|CJ|
Wood|Lois A|LA|
Geden|Christopher J|CJ|
Kaufman|Phillip E|PE|

Haematobia irritans
cattle
biological control
integrated pest management
biting fly


Antifungal Extraction by the Extracorporeal Membrane Oxygenation Circuit.

Abstract: Invasive candidiasis is common and often fatal in patients supported with extracorporeal membrane oxygenation (ECMO), and treatment relies on optimal antifungal dosing. The ECMO circuit can extract drug and decrease drug exposure, placing the patient at risk of therapeutic failure. This ex vivo study determined the extraction of antifungal drugs by the ECMO circuit. Fluconazole and micafungin were studied separately in three closed-loop circuit configurations to isolate the impact of the oxygenator, hemofilter, and tubing on circuit extraction. Each circuit was primed with human blood, and flow was set to 1 L/min. Drug was dosed to achieve therapeutic concentrations. Each antifungal was added to a separate tube of blood to serve as a control. Serial blood samples were collected over 24 hours and concentrations were quantified with a validated assay. Drug recovery was calculated at each time point: (C  /C  )*100, with C  and C  the concentrations at time = t and 1 minute, respectively. After 24 hours of recirculation, mean recovery of fluconazole in the ECMO circuit (95-98%) and controls (101%) was high. In contrast, mean recovery of micafungin was dependent on the time and circuit configuration. Recovery at 4 hours was only 46% when a hemofilter was in-line but was much higher when the hemofilter was removed (91%). By 24 hours, however, micafungin recovery was low in all circuit configurations (26-43%), regardless of the presence of a hemofilter, as well as in the controls (57%). In conclusion, these results suggest that micafungin is extracted by the ECMO circuit, which may result in decreased drug exposure in vivo.

Watt|Kevin M|KM|
Cohen-Wolkowiez|Michael|M|
Williams|Duane C|DC|
Bonadonna|Desiree K|DK|
Cheifetz|Ira M|IM|
Thakker|Dhiren|D|
Benjamin|Daniel K|DK|
Brouwer|Kim L R|KLR|

antifungal extraction
extracorporeal membrane oxygenation
fluconazole
micafungin


How dislocation and professional anxiety influence readiness for change during the implementation of hospital-based home care for children newly diagnosed with diabetes - an ethnographic analysis of the logic of workplace change.

Abstract:
BACKGROUND
In 2013-14, the evidence based care model Hospital-based Home Care for children newly diagnosed with diabetes was implemented at a large paediatric diabetes care facility in the south of Sweden. The first step of the implementation was to promote readiness for change among the professionals within the diabetes team through regular meetings. The aim was to analyse the implicit facilitators and barriers evident on a cultural micro level in discussions during the course of these meetings. What conceptions, ideals and identities might complicate, or facilitate, implementation?

METHODS
A case study was conducted during the implementation process. This article draw on ethnographic observations carried out at team meetings (n = 6) during the introductory element of implementation. From a discourse theoretical perspective, the verbal negotiations during these meetings were analysed.

RESULTS
Three aspects were significant in order to understand the dislocation during this element of implementation: an epistemological disagreement that challenged the function of information within care practice; a paradoxical understanding of the time-knowledge intersection; and expressions of professional anxiety. More concretely, the professionals exhibited an unwillingness to give up the opportunity to provide structured, age-independent information; a resistance against allowing early discharge; and a professional identity formed both by altruistic concern and occupational guardiancy. The findings suggest the necessity of increased awareness of the conceptions and ideals that constitute the basis of a certain professional practice; a deeper understanding of the cultural meaning that influences care practice within a specific logic in order to predict in what way these ideals might be challenged by the implemented evidence.

CONCLUSIONS
Our main contribution is the argument that the implemented evidence in itself needs to be examined and problematized from a cultural analytical perspective before initiation in order to be able to actively counter negative connotations and resistance.

Nilsson|Gabriella|G|0000-0001-7995-6838 Hansson|Kristofer|K| Tiberg|Irén|I| Hallström|Inger|I|

D018575:Home Care Services, Hospital-Based

Professional anxiety
Evidence
Paediatric diabetes
Time-knowledge intersection
Management


Hormonal contraception and breast cancer.

Abstract: The recent Danish cohort study reported a 20% increased risk of breast cancer among current and recent hormonal contraception users. These results are largely consistent with previous studies. This study did not report on stage of disease at diagnosis, and it is not clear to what extent the apparent increased risk may be due to a small advance in the timing of diagnosis. This study did not report on the risk associated with the use of a 20-mcg ethinyl estradiol pill. They did find an increasing risk in current users of longer duration and an increased risk with use of the levonorgestrel intrauterine system-both of these potentially important findings have not been consistently found in previous studies and require further investigation. The breast cancer effects described now in multiple studies wane with time, and in the long term, hormonal contraception use has been found not to be associated with any increased total cancer risk.

Westhoff|Carolyn L|CL|
Pike|Malcolm C|MC|

Hormonal contraceptives
Breast cancer
Epidemiology
Methodology


PROMIS and legacy measures compared in a supportive care intervention for breast cancer patients and caregivers: Experience from a randomized trial.

Abstract:
OBJECTIVE
Accurate and efficient measurement of patient-reported outcomes is key in cancer symptom management trials. The newer Patient Reported Outcomes Measurement Information System (PROMIS) and previously developed measures of similar conceptual content (legacy) are available to measure symptoms and functioning. This report compares the performance of two sets of measures, PROMIS and legacy, in a recently completed trial of a supportive care intervention that enrolled breast cancer patients and their friend or family caregivers.

METHODS
Patient-caregiver dyads (N = 256) were randomized to either reflexology delivered by caregivers or usual care control. Post-intervention, PROMIS and legacy measures of symptoms and functioning were analyzed in relation to trial arm, while adjusting for baseline values. Responsiveness of the two sets of measures was assessed using effect sizes and P-values for the effect of trial arm on patients' and caregivers' symptom and functioning outcomes.

RESULTS
Similar conclusions about intervention effects were found using PROMIS and legacy measures for pain, fatigue, sleep, anxiety, physical, and social functioning. Different conclusions were obtained for patient and caregiver depression: legacy measures indicated the efficacy of reflexology, while PROMIS depression measure did not.

CONCLUSION
Evidence of similar responsiveness supports the use of either set of measures for symptoms and functioning in clinical and general populations. Differences between PROMIS and legacy measures of depression need to be considered when choosing instruments for use in trials of supportive care interventions and in clinical practice.

Sikorskii|Alla|A| Victorson|David|D| O'Connor|Patrick|P| Hankin|Vered|V| Safikhani|Abolfazl|A| Crane|Tracy|T|0000-0002-4288-134X Badger|Terry|T| Wyatt|Gwen|G|0000-0003-1608-8505

D000071066:Patient Reported Outcome Measures

PROMIS
legacy measures
measurement
cancer
symptom management


Localized Fluctuant Oscillatory Activity by Working Memory Load: A Simultaneous EEG-fMRI Study.

Abstract: Working memory (WM) is a resource-limited memory system for temporary storage and processing of brain information during the execution of cognitive tasks. Increased WM load will increase the amount and difficulty of memory information. Several studies have used electroencephalography (EEG) or functional magnetic resonance imaging (fMRI) to explore load-dependent cognition processing according to the time courses of electrophysiological activity or the spatial pattern of blood oxygen metabolic activity. However, the relationships between these two activities and the underlying neural mechanism are still unclear. In this study, using simultaneously collected EEG and fMRI data under an n-back verbal WM task, we modeled the spectral perturbation of EEG oscillation and fMRI activation through joint independent component analysis (JICA). Multi-channel oscillation features were also introduced into the JICA model for further analysis. The results showed that time-locked activity of theta and beta were modulated by memory load in the early stimuli evaluation stage, corresponding to the enhanced activation in the frontal and parietal lobe, which were involved in stimulus discrimination, information encoding and delay-period activity. In the late response selection stage, alpha and gamma activity changes dependent on the load correspond to enhanced activation in the areas of frontal, temporal and parietal lobes, which played important roles in attention, information extraction and memory retention. These findings suggest that the increases in memory load not only affect the intensity and time course of the EEG activities, but also lead to the enhanced activation of brain regions which plays different roles during different time periods of cognitive process of WM.

memory load
fMRI
oscillation
joint independent component analysis
event-related spectral perturbation


High-density polystyrene-grafted silver nanoparticles and their use in the preparation of nanocomposites with antibacterial properties.

Abstract: The achievement of uniform nanoparticles distribution in polymer matrix is still a major challenge in the design and fabrication of polymer nanocomposites with desired properties. In this paper we propose a novel approach for the preparation of homogeneous polystyrene/silver nanocomposites utilizing Nitroxide Mediated Radical Polymerization (NMRP). In the first step of the developed procedure, the polystyrene grafted silver nanoparticles (Ag@PS) with well-defined core-shell structure and exceptionally high grafting density (from 2 chains/nm2 to 5.9 chains/nm2) have been synthesized through late injection of nitroxide-coated silver nanoparticles (N-AgNPs) into a TEMPOL mediated styrene polymerization system. Afterwards, the synthesized Ag@PS have been used for the preparation of nanocomposites (PS/Ag@PS) by mixing them with narrow-dispersity polystyrenes and thermoforming at 140°C. Due to the high flexibility of polymer chains attached to silver surface through nitroxide linker, free volume effect enables interpenetration of polystyrene molecules that provides excellent mutual miscibility of Ag@PS with polymer matrix. The synthesized nanohybrids (Ag@PS) and their nanocomposites (PS/Ag@PS) exhibit effective antibacterial activity with respect to pathogenic bacteria: Pseudomonas aeruginosa (Gram-negative representative) and Staphylococcus aureus (Gram-positive representative).

Silver nanoparticles
Nanocomposites
Nitroxides
Antibacterial materials
Controlled radical polymerization
Polymer brushes


Molecular imaging in stem cell-based therapies of cardiac diseases.

Abstract: In the past 15years, despite that regenerative medicine has shown great potential for cardiovascular diseases, the outcome and safety of stem cell transplantation has shown controversial results in the published literature. Medical imaging might be useful for monitoring and quantifying transplanted cells within the heart and to serially characterize the effects of stem cell therapy of the myocardium. From the multiple available noninvasive imaging techniques, magnetic resonance imaging and nuclear imaging by positron (PET) or single photon emission computer tomography (SPECT) are the most used clinical approaches to follow the fate of transplanted stem cells in vivo. In this article, we provide a review on the role of different noninvasive imaging modalities and discuss their advantages and disadvantages. We focus on the different in-vivo labeling and reporter gene imaging strategies for stem cell tracking as well as the concept and reliability to use imaging parameters as noninvasive surrogate endpoints for the evaluation of the post-therapeutic outcome.

Imaging
Cardiovascular disease
Stem cells therapy
Magnetic resonance imaging
Nuclear imaging
Cell tracking
Endpoints of imaging


MicroRNA-1-3p inhibits the proliferation and migration of oral squamous cell carcinoma cells by targeting DKK1.

Abstract: We investigated the functional role and mechanism of miR-1-3p and DKK1 in oral squamous cell carcinoma (OSCC) cells. The level of miR-1-3p and DKK1 expression were detected in OSCC tissues and cells using reverse-transcription - quantitative PCR and Western blot. A dual luciferase reporter gene assay was applied to confirm the targeting relationship between miR-1-3p and DKK1. Functional assays, including MTT, Transwell, colony formation, and flow cytometry analysis were conducted to verify their effect on cell progressions. MTT, colony formation, and Transwell assays indicated that the proliferation, migration, and invasion of SCC-4 cells was impaired with high miR-1-3p expression but promoted with high DKK1 expression. The results from cell cycle analysis and annexin-V-PI assays for apoptosis suggested that miR-1-3p suppressed the transit of SCC-4 cells from G0/G1 to S and induced apoptosis. In summary, miR-1-3p suppressed the progression of OSCC by inhibiting DKK1 expression.

Wang|Zhenshi|Z| Wang|Jiaolong|J| Chen|Zhihua|Z| Wang|Kun|K| Shi|Lianshui|L|

D015972:Gene Expression Regulation, Neoplastic

D036341:Intercellular Signaling Peptides and Proteins

DKK1
miR-1-3p
OSCC
SCC-4 cells
CECO
cellules SCC-4


Relationship between physical performance and quality of life in Charcot-Marie-Tooth disease: a pilot study.

Abstract: Charcot-Marie-Tooth (CMT) is a rare inherited peripheral neuropathy in which quality of life (QoL) is reduced compared with the general population. This paper investigates the relationship between QoL and physical performance in people with CMT with the aim of identifying avenues for future research into rehabilitation strategies. Cross-sectional data was obtained from 10 participants (5 men, 5 women, age 46 ± 13 years, height 1.7 ± 0.1 m, body mass 77 ± 17 kg) with CMT (CMT1A n = 5; CMT-X n = 3; unknown genetic origin n = 2). Participants were evaluated for QoL, falls efficacy (FES), balance, mobility, muscle strength, and power. Physical component score (PCS) of the Short Form-36 (SF-36) was significantly and directly related to higher leg press power (r = 0.75, p = 0.02). Better FES scores were significantly related to faster habitual gait speed (r = -0.70, p = 0.02), left hip abduction, and seated row strength (r = -0.68, p = 0.03; r = -0.73, p = 0.03, respectively). Future research should aim to substantiate these preliminary findings in a larger cohort and investigate whether interventions targeting muscle strength and power can improve QoL and mobility outcomes in people with CMT.

Roberts-Clarke|Daniel|D|
Fornusek|Che|C|
Saigal|Nidhi|N|
Halaki|Mark|M|
Burns|Joshua|J|
Nicholson|Garth|G|
Fiatarone Singh|Maria|M|
Hackett|Daniel|D|

exercise
functionality
hereditary motor and sensory neuropathy
muscular power
resistance training


Molecular identification of Betacoronavirus in bats from Sardinia (Italy): first detection and phylogeny.

Abstract: Bats may be natural reservoirs for a large variety of emerging viruses, including mammalian coronaviruses (CoV). The recent emergence of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) in humans, with evidence that these viruses may have their ancestry in bats, highlights the importance of virus surveillance in bat populations. Here, we report the identification and molecular characterization of a bat β-Coronavirus, detected during a viral survey carried out on different bat species in the island of Sardinia (Italy). Cutaneous, oral swabs, and faecal samples were collected from 46 bats, belonging to 15 different species, and tested for viral presence. Coronavirus RNA was detected in faecal samples from three different species: the greater horseshoe bat (Rhinolophus ferrumequinum), the brown long-eared bat (Plecotus auritus), and the European free-tailed bat (Tadarida teniotis). Phylogenetic analyses based on RNA-dependent RNA polymerase (RdRp) sequences assigned the detected CoV to clade 2b within betacoronaviruses, clustering with SARS-like bat CoVs previously reported. These findings point to the need for continued surveillance of bat CoV circulating in Sardinian bats, and extend the current knowledge on CoV ecology with novel sequences detected in bat species not previously described as β-Coronavirus hosts.

Lecis|Roberta|R| Mucedda|Mauro|M| Pidinchedda|Ermanno|E| Pittau|Marco|M| Alberti|Alberto|A|

Bats
Sardinia
Coronavirus
Rhinolophus ferrumequinum
RNA-dependent RNA polymerase


Interest and Knowledge of HIV Pre-Exposure Prophylaxis in a Unified Jail and Prison Setting.

Abstract: Pre-exposure prophylaxis (PrEP) may be an effective approach to prevent HIV among people who are currently incarcerated or who have been recently released from incarceration. However, awareness and interest in PrEP are largely unknown in this population. This study assessed 417 incarcerated men's lifetime HIV risk engagement and gauged their interest and willingness to take PrEP. Twenty percent reported ever injecting drugs and 4% ever having sex with a man without a condom; 88% had never heard of PrEP. More White men had heard of PrEP, but higher percentages of men of color were interested in learning more about PrEP and willing to take PrEP to prevent HIV. Future interventions should focus on PrEP education and uptake among individuals who are incarcerated.

Brinkley-Rubinstein|Lauren|L|
Crowley|Christina|C|
Montgomery|Madeline C|MC|
Peterson|Meghan|M|
Zaller|Nickolas|N|
Martin|Rosemarie|R|
Clarke|Jennifer|J|
Dubey|Manisha|M|
Chan|Philip A|PA|

D007722:Health Knowledge, Attitudes, Practice

D010342:Patient Acceptance of Health Care

HIV
pre-exposure prophylaxis
PrEP
incarceration


Application of 15N tracing for estimating nitrogen cycle processes in soils of a constructed wetland.

Abstract: Integrated Constructed Wetlands (ICW) area technology for the attenuation of contaminants such as organic carbon (C), nitrogen (N), phosphorous (P) and sulphur (S) in water coming from point or diffuse sources. Currently there is a lack of knowledge on the rates of gross N transformations in soils of the ICW bed leading to losses of reactive N to the environment. In addition, the kinetics of these processes need to be studied thoroughly for the sustainable use of ICW for removal of excessive N in the treatment of waste waters. Gross N transformation processes were quantified at two soil depths (0-15 and 30-45 cm) in the bed of a surface flow ICW using a 15N tracing approach. The ICW, located in Dunhill village at Waterford in Southeastern Ireland, receives 500 person equivalent waste waters containing large quantities of organic pollutants (ca. mean annual C, N, P and S contents of 240, 60, 5 and 73 mg L-1). Soil was removed from these depths in December 2014 and incubated anaerobically in the laboratory, with either 15N labeled ammonium (NH4+) or nitrate (NO3-), differentially labeled with 14NH415NO3 and 15NH414NO3 in parallel setups, enriched to 50 atm% 15N. Results showed that at both soil depths, NO3- production rates were small, which may have resulted in lower NO3- reduction by either denitrification or dissimilatory NO3- reduction to ammonium (DNRA). However, despite being low, the DNRA rates were greater than denitrification rates. Direct transformation of organic N to NO3-, without mineralization to NH4+, was a prevalent pathway of NO3- production accounting for 28-33% of the total NO3- production. Relative contribution of this process to the total N mineralization was negligible at depth 1 (0.01%) but dominant at depth 2 (99.7%). Total NO3-production to total immobilization of NH4+ and NO3- was very small (<0.50%) suggesting that ICW soils are not a source of NO3-. Despite a large potential of N immobilization existed at both the layers, relative N immobilization to the total N conversion was higher at depth 2 (ca. 2.2) than at depth 1 (ca. 1.5). The NH4+ desorption rate at 30-45 cm was high. However, immobilization in the recalcitrant and labile organic N pools was higher. Mineralization and immobilization of NH4+ processes showed that recalcitrant organic N was the predominant source in ICW soils whereas the labile organic N was comparatively small. Source apportionment of N2O production showed that the majority of the N2O produced through denitrification (ca. 92.5%) followed by heterotrophic nitrification (ca. 5.5%), co-denitrification (ca. 1.90%) and nitrification (0.20%). These results revealed that application of a detailed 15N tracing method can provide insights on the underlying processes of ecosystem based abundances of reactive N. A key finding of this study was that both investigated ICW layers were characterised by large N immobilization which restricts production of NO3- and further gaseous N losses.

Jahangir|M M R|MMR|
Fenton|O|O|
Carolan|R|R|
Harrington|R|R|
Johnston|P|P|
Zaman|M|M|
Richards|K G|KG|
Müller|C|C|

Constructed wetland
Gross N transformation
Labile organic N
Recalcitrant organic N
(15)N tracing Model


Do not throw the baby out with the bath water: a guide for using non-significant results in practice.

Abstract: Acting on results that are not statistically significant is challenging for clinicians. Such results are often interpreted as evidence of lack of association or as useless evidence. We provide a framework for interpreting and applying non-significant results at the point of care using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Tello|Mouaffaa|M|
Zaiem|Feras|F|
Tolcher|Mary Catherine|MC|
Murad|Mohammad Hassan|MH|

D019317:Evidence-Based Medicine
D017410:Practice Guidelines as Topic

EDUCATION & TRAINING (see Medical Education & Training)


Enhanced photovoltaic performance of dye-sensitized solar cells based on NaYF4:Yb(3+), Er(3+)-incorporated nanocrystalline TiO2 electrodes.

Abstract: Near infrared to visible up-conversion of light by rare earth ion-doped phosphors (NaYF4:Yb(3+), Er(3+)) that convert multiple photons of lower energy to higher energy photons offer new possibilities for improved performance of photovoltaic devices. Here, up-conversion phosphor NaYF4:Yb(3+), Er(3+) doped nanocrystalline TiO2 films are designed and used as a electrode for dye-sensitized solar cells, and the photovoltaic performance of DSSCs based on composite electrodes are investigated. The results show the cell with NaYF4:Yb(3+), Er(3+) achieves a power conversion efficiency of 7.65% under one sun illumination (AM 1.5G, 100mWcm(-2)), which is an increase of 14% compared to the cell without NaYF4:Yb(3+), Er(3+) (6.71%). The performance improvement is attributed to the dual effects of enhanced light harvesting from extended light absorption range and increased light scattering, and lower electron transfer resistance.

Zhu|Guang|G| Wang|Hongyan|H| Zhang|Quanxin|Q| Zhang|Li|L|

Light harvesting
Light scattering
Dye sensitized solar cell
NaYF(4):Yb(3+), Er(3+)


Regulation of AMPA receptor phosphorylation by the neuropeptide PACAP38.

Abstract: Dynamic changes in synaptic strength are thought to be critical for higher brain function such as learning and memory. Alterations in synaptic strength can result from modulation of AMPA receptor (AMPAR) function and trafficking to synaptic sites. The phosphorylation state of AMPAR subunits is one mechanism by which cells regulate receptor function and trafficking. Receptor phosphorylation is in turn regulated by extracellular signals; these include neuronal activity, neuropeptides, and neuromodulators such as dopamine and norepinephrine (NE). Although numerous studies have reported that the neuropeptide pituitary adenylate cyclase activating polypeptide 38 (PACAP38) alters hippocampal CA1 synaptic strength and GluA1 synaptic localization, its effect on AMPAR phosphorylation state has not been explored. We determined that PACAP38 stimulation of hippocampal cultures increased phosphorylation of S845, and decreased phosphorylation of T840 on the GluA1 AMPAR subunit. Increases in GluA1 S845 phosphorylation primarily occurred via PAC1 and VPAC2 receptor activation, whereas a reduction in GluA1 T840 phosphorylation was largely driven by PAC1 receptor activation and to a lesser extent by VPAC1 and VPAC2 receptor activation. GluA1 S845 phosphorylation could be blocked by a PKA inhibitor, and GluA1 T840 dephosphorylation could be blocked by a protein phosphatase 1/2A (PP1/PP2A) inhibitor and was partly blocked by a NMDA receptor (NMDAR) antagonist. These results demonstrate that the neuropeptide PACAP38 inversely regulates the phosphorylation of two distinct sites on GluA1 and may play an important role modulating AMPAR function and synaptic plasticity in the brain.

Toda|Alyssa M A|AM|
Huganir|Richard L|RL|

D017868:Cyclic AMP-Dependent Protein Kinases

D051219:Pituitary Adenylate Cyclase-Activating Polypeptide

D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I

D051239:Receptors, Vasoactive Intestinal Peptide, Type II

AMPA receptor phosphorylation
PACAP38
synaptic transmission


Restricted versus Standard Maintenance Fluid Volume in Management of Transient Tachypnea of Newborn: A Clinical Trial.

Abstract:
OBJECTIVE
The incidence of Transient Tachypnea of Newborn (TTN) is higher in infants born by cesarean section than with  vaginal delivery. Treatment of transient tachypnea of newborn is supportive. The purpose of this study was to assess the effect of restricted fluid volume intake on the course of respiratory distress in patients with TTN.

METHODS
This is a quasi-experimental clinical trial of 83 neonates diagnosed with TTN admitted to a neonatal intensive care unit in south west Iran. In this study the effect of restriction of maintenance fluid volume in the course of respiratory distress in newborns with transient tachypnea was assessed.

FINDINGS
In the standard fluid volume intake group 18 (42.8%) cases needed nasal continuous positive airway pressure (NCPAP) and one (2.38%) case mechanical ventilation, and in restricted fluid volume intake group 13 (32.5%) cases needed NCPAP and two (5%) cases mechanical ventilation. 54.82% of cases were supported with oxyhood in the standard fluid volume and 62.5% in the restricted fluid volume intake group. Differences in duration of the needed NCPAP and oxygen hood between the two groups were significant. Fluid restriction had no adverse effect on the urine specific gravity or weight loss of the studied newborns.

CONCLUSION
Limited fluid administered to newborns with transient tachypnea of newborn is safe and resulted in shorter duration of respiratory support.

Dehdashtian|Masoud|M| Aramesh|Mohammad-Reza|MR| Melekian|Arash|A| Aletayeb|Mohammad-Hasan|MH| Ghaemmaghami|Anahita|A|

Fluid
Transient Tachypnea of Newborn
Newborns
Cesarean Section
Specific Gravity


Medication-Related Hospital Readmissions Within 30 Days of Discharge: Prevalence, Preventability, Type of Medication Errors and Risk Factors.

Abstract: Background: Hospital readmission rates are increasingly used as a measure of healthcare quality. Medicines are the most common therapeutic intervention but estimating the contribution of adverse drug events as a cause of readmissions is difficult. Objectives: To assess the prevalence and preventability of medication-related readmissions within 30 days after hospital discharge and to describe the risk factors, type of medication errors and types of medication involved in these preventable readmissions. Design: A cross-sectional observational study. Setting: The study took place across the cardiology, gastroenterology, internal medicine, neurology, psychiatry, pulmonology and general surgery departments in the OLVG teaching hospital, Netherlands. Participants: Patients with an unplanned readmission within 30 days after discharge from an earlier hospitalization (index hospitalization: IH) were reviewed. Measurements: The prevalence and preventability of medication-related readmissions were assessed by residents in multidisciplinary meetings. A senior internist and hospital pharmacist reassessed the prevalence and preventability of identified cases. Generalized estimating equation with logistic regression was performed to identify risk factors of potentially preventable medication-related readmissions. Results: Of 1,111 included readmissions, 181 (16%) were medication-related, of which 72 (40%) were potentially preventable. The number of medication changes at IH (Adjusted odds ratio [ORadj]: 1.14; 95% CI: 1.05-1.24) and having ≥3 hospitalizations 6 months before IH (ORadj: 2.11; 95% CI: 1.12-3.98) were risk factors of a preventable medication-related readmission. Of these preventable readmissions, 35% were due to prescribing errors, 35% by non-adherence and 30% by transition errors. Medications most frequently involved were diuretics and antidiabetics. Conclusion: This study shows that 16% of readmissions are medication-related, of which 40% are potentially preventable. If the results are confirmed in larger multicentre studies, this may indicate that more attention should be paid to medication-related harm in order to lower the overall readmission rates.

Uitvlugt|Elien B|EB|
Janssen|Marjo J A|MJA|
Siegert|Carl E H|CEH|
Kneepkens|Eva L|EL|
van den Bemt|Bart J F|BJF|
van den Bemt|Patricia M L A|PMLA|
Karapinar-Çarkit|Fatma|F|

readmission
ADEs
medication related problem
quality of care
transitions in care


Post-marketing research and its outcome for novel anticancer agents approved by both the FDA and EMA between 2005 and 2010: A cross-sectional study.

Abstract: Post-marketing research in oncology has rarely been described. We aimed to characterize post-marketing trials for a consistent set of anticancer agents over a long period. We performed a cross-sectional analysis of post-marketing trials registered at ClinicalTrials.gov through September 2014 for novel anticancer agents approved by both the US Food and Drug Administration and the European Medicines Agency between 2005 and 2010. All relevant post-marketing trials were classified according to indication, primary outcome, starting date, sponsors, and planned enrollment. Supplemental indications were retrieved from regulatory documents and publication rate was assessed by two different methods. Ten novel anticancer agents were eligible: five were indicated for hematologic malignancies and the remaining five for solid cancers (three for kidney cancer). We identified 2,345 post-marketing trials; 1,362 (58.1%) targeted an indication other than the originally approved one. We observed extreme variations among drugs in both number of post-marketing trials (range 8-530) and overall population to be enrolled per trial (1-8,381). Post-marketing trials assessed almost all types of cancers, the three most frequently studied cancers being leukemia, kidney cancer and myeloma. In all, 6.6% of post-marketing trials had a clinical endpoint as a primary outcome, and 35.9% and 54.1% had a safety or surrogate endpoint, respectively, as a primary outcome. Nine drugs obtained approval for supplemental indications. The publication rate at 10 years was 12.3 to 26.1% depending on the analysis method. In conclusion, we found that post-marketing research in oncology is highly heterogeneous and the publication rate of launched trials is low.

D014486:United States Food and Drug Administration

outcome
anticancer agents
post-marketing trials
publication rate


Effect of Triticum turgidum subsp. turanicum wheat on irritable bowel syndrome: a double-blinded randomised dietary intervention trial.

Abstract: The aim of the present study was to examine the effect of a replacement diet with organic, semi-whole-grain products derived from Triticum turgidum subsp. turanicum (ancient) wheat on irritable bowel syndrome (IBS) symptoms and inflammatory/biochemical parameters. A double-blinded randomised cross-over trial was performed using twenty participants (thirteen females and seven males, aged 18-59 years) classified as having moderate IBS. Participants received products (bread, pasta, biscuits and crackers) made either from ancient or modern wheat for 6 weeks in a random order. Symptoms due to IBS were evaluated using two questionnaires, which were compiled both at baseline and on a weekly basis during the intervention period. Blood analyses were carried out at the beginning and end of each respective intervention period. During the intervention period with ancient wheat products, patients experienced a significant decrease in the severity of IBS symptoms, such as abdominal pain (P< 0·0001), bloating (P= 0·004), satisfaction with stool consistency (P< 0·001) and tiredness (P< 0·0001). No significant difference was observed after the intervention period with modern wheat products. Similarly, patients reported significant amelioration in the severity of gastrointestinal symptoms only after the ancient wheat intervention period, as measured by the intensity of pain (P= 0·001), the frequency of pain (P< 0·0001), bloating (P< 0·0001), abdominal distension (P< 0·001) and the quality of life (P< 0·0001). Interestingly, the inflammatory profile showed a significant reduction in the circulating levels of pro-inflammatory cytokines, including IL-6, IL-17, interferon-γ, monocyte chemotactic protein-1 and vascular endothelial growth factor after the intervention period with ancient wheat products, but not after the control period. In conclusion, significant improvements in both IBS symptoms and the inflammatory profile were reported after the ingestion of ancient wheat products.

Sofi|Francesco|F|
Whittaker|Anne|A|
Gori|Anna Maria|AM|
Cesari|Francesca|F|
Surrenti|Elisabetta|E|
Abbate|Rosanna|R|
Gensini|Gian Franco|GF|
Benedettelli|Stefano|S|
Casini|Alessandro|A|

D042461:Vascular Endothelial Growth Factor A

Wheat
Irritable bowel syndrome
Diets
Cytokines
Grains


OIP5-AS1 modulates epigenetic regulator HDAC7 to enhance non-small cell lung cancer metastasis via miR-140-5p.

Abstract: Long non-coding RNAs have been reported to be involved in non-small cell lung cancer (NSCLC) progression. However, whether Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) serves a role in NSCLC remains unclear. Bioinformatics analysis of The Cancer Genome Atlas datasets showed clinical significance and relevance of OIP5-AS1 in NSCLC. Western blotting and reverse transcription-quantitative PCR revealed protein and RNA expression levels of the genes [including OIP5-AS1, microRNA (miR)-140-5p, histone deacetylase 7 (HDAC7) and vascular endothelial growth factor A (VEGFA)]. Direct associations between the genes (miR-140-5p and OIP5-AS1, or miR-140-5p and HDAC7) were confirmed using a dual-luciferase reporter assay. Lymphatic vessel formation and invasion ability were detected using a lymphatic vessel formation assay and Transwell invasion assay. OIP5-AS1 knockdown attenuated lymphatic vessel length and invasion. The role of OIP5-AS1 was reverted by miR-140-5p. HDAC7 and VEGFA are downstream effectors of miR-140-5p-mediated NSCLC metastasis. OIP5-AS1, miR-140-5p, HDAC7 and VEGFA were all dysregulated in human clinical NSCLC tumor tissues. In conclusion, the present results demonstrated a novel mechanism for OIP5-AS1-induced metastatic phenotypes of NSCLC via the miR-140-5p/HDAC7/VEGFA axis.

Mei|Jiazhuan|J| Liu|Guiju|G| Wang|Wenhui|W| Xiao|Peng|P| Yang|Dan|D| Bai|Hua|H| Li|Ruijun|R|


Epidemiology and Risk Factors for Outpatient-Acquired Catheter-Related Bloodstream Infections in Children Receiving Home Parenteral Nutrition.

Abstract:
BACKGROUND
Few studies have examined the epidemiology and risk factors for the development of outpatient-acquired catheter-related bloodstream infections (CRBSIs) in children receiving home parenteral nutrition. This study aimed to (1) characterize the incidence, clinical presentation, and epidemiology of CRBSIs and (2) identify risk factors for CRBSIs in children receiving home parenteral nutrition.

METHODS
A longitudinal database approved by our Institutional Review Board was created to prospectively track CRBSIs in the UCLA pediatric population from January to December 2012. Eligible patients included those < 18 years old receiving home parenteral nutrition.

RESULTS
Thirty of 60 patients (50%) were diagnosed with 66 CRBSIs, for an overall CRBSI rate of 3.6 per 1000 catheter days. Of the CRBSIs, 73% were due to single microorganisms and 27% were polymicrobial. There was a significant difference in median (range) time for blood cultures to turn positive depending on type of CRBSIs (p = 0.03), with polymicrobial infections detected at 13.4 (8.7-24.3) hours, gram-negative infections at 16.5 (9-30.8) hours, and gram-positive infections at 18.9 (8.4-37.1) hours. The most common presenting symptom was fever (82%), followed by gastrointestinal symptoms (42%) and chills (29%). The only significant multivariate risk factor for CRBSIs was presence of a feeding tube (2.3-fold increase in CRBSI risk, p = 0.04).

DISCUSSION
Outpatient-acquired CRBSIs are common in children receiving home parenteral nutrition. CRBSIs typically present with fever, but are also associated with gastrointestinal and/or respiratory symptoms. The presence of feeding tubes may predispose children on home parenteral nutrition to developing CRBSIs.

Wozniak|Laura J|LJ|
Bechtold|Hannah M|HM|
Reyen|Laurie E|LE|
Chan|Alvin P|AP|
Marcus|Elizabeth A|EA|
Vargas|Jorge H|JH|

catheter-related bloodstream infection
parenteral nutrition
pediatrics
central venous catheter
home nutrition support
sepsis


A Magnetic-Balanced Inductive Link for the Simultaneous Uplink Data and Power Telemetry.

Abstract: When using the conventional two-coil inductive link for the simultaneous wireless power and data transmissions in implantable biomedical sensor devices, the strong power carrier could overwhelm the uplink data signal and even saturate the external uplink receiver. To address this problem, we propose a new magnetic-balanced inductive link for our implantable glaucoma treatment device. In this inductive link, an extra coil is specially added for the uplink receiving. The strong power carrier interference is minimized to approach zero by balanced canceling of the magnetic field of the external power coil. The implant coil is shared by the wireless power harvesting and the uplink data transmitting. Two carriers (i.e., 2-MHz power carrier and 500-kHz uplink carrier) are used for the wireless power transmission and the uplink data transmission separately. In the experiments, the prototype of this link achieves as high as 65.72 dB improvement of the signal-to-interference ratio (SIR) compared with the conventional two-coil inductive link. Benefiting from the significant improvement of SIR, the implant transmitter costs only 0.2 mW of power carrying 50 kbps of binary phase shift keying data and gets a bit error rate of 1 × 10 - 7 , even though the coupling coefficient is as low as 0.005. At the same time, 5 mW is delivered to the load with maximum power transfer efficiency of 58.8%. This magnetic-balanced inductive link is useful for small-sized biomedical sensor devices, which require transmitting data and power simultaneously under ultra-weak coupling.

Gong|Chen|C| Liu|Dake|D| Miao|Zhidong|Z| Li|Min|M|

simultaneous data and power transmissions


Clinical manifestation of early phase left ventricular rupture complicating acute myocardial infarction in the primary PCI era.

Abstract:
OBJECTIVE
Before reperfusion therapy was introduced, the incidence of ventricular septal and left ventricular free wall rupture complicating acute myocardial infarction (AMI) was 1-3%. Primary percutaneous coronary intervention (PCI) was expected to reduce the incidence of such mechanical complications.

METHODS
We retrospectively analysed 1290 AMI patients referred to our institute from January 2005 to January 2011. Primary PCI was done in 1002 cases of the study patients (77.7%).

RESULTS
Ventricular septal rupture (VSR) occurred in 19 cases (1.5%) and left ventricular free wall rupture (LVFR) in 17 cases (1.3%). Mean observation periods from onset to VSR and LVFR were 2.6 days. We demonstrated that risk factors for LV rupture were advanced age, female sex, absence of history of angina or myocardial infarction, lack of previous PCI, and absence of previous hypertension. Coronary angiography revealed that the culprit lesions of the left anterior descending artery or single vessel disease were the risk factors for LV rupture. Furthermore, in the present observation, 9 patients (47.4%) with VSR and 8 patients (47.1%) with LVFR developed LV rupture within 24h after symptoms onset (early rupture). The early rupture demonstrated extremely poor outcome compared with late rupture (in-hospital mortality was 88.2% in early rupture and 63.1% in late rupture).

CONCLUSION
Even in the patients' cohort with higher prevalence of primary PCI, LV rupture cases were not decreased in contrast to our expectations. More attention should be paid to early LV rupture cases within 24 h from symptom onset in those cases.

Nozoe|Masatusugu|M| Sakamoto|Tomohiro|T| Taguchi|Eiji|E| Miyamoto|Shinzou|S| Fukunaga|Takashi|T| Nakao|Koichi|K|

Left ventricular rupture
Acute myocardial infarction
Percutaneous coronary intervention


Automated data-adaptive analytics for electronic healthcare data to study causal treatment effects.

Abstract:
Background
Decision makers in health care increasingly rely on nonrandomized database analyses to assess the effectiveness, safety, and value of medical products. Health care data scientists use data-adaptive approaches that automatically optimize confounding control to study causal treatment effects. This article summarizes relevant experiences and extensions.

Methods
The literature was reviewed on the uses of high-dimensional propensity score (HDPS) and related approaches for health care database analyses, including methodological articles on their performance and improvement. Articles were grouped into applications, comparative performance studies, and statistical simulation experiments.

Results
The HDPS algorithm has been referenced frequently with a variety of clinical applications and data sources from around the world. The appeal of HDPS for database research rests in 1) its superior performance in situations of unobserved confounding through proxy adjustment, 2) its predictable efficiency in extracting confounding information from a given data source, 3) its ability to automate estimation of causal treatment effects to the extent achievable in a given data source, and 4) its independence of data source and coding system. Extensions of the HDPS approach have focused on improving variable selection when exposure is sparse, using free text information and time-varying confounding adjustment.

Conclusion
Semiautomated and optimized confounding adjustment in health care database analyses has proven successful across a wide range of settings. Machine-learning extensions further automate its use in estimating causal treatment effects across a range of data scenarios.

automation
propensity scores
health care databases
confounding adjustment
artificial intelligence
causal conclusions
confounding (epidemiology)
high-dimensional data
machine learning
real-world data


Psychological Trauma in the Context of Familial Relationships: A Concept Analysis.

Abstract: Many forms of psychological trauma are known to develop interpersonally within important relationships, particularly familial. Within the varying theoretical constructs of psychological traumas, and distinct from the processes of diagnosis, there is a need to refine the scope and definitions of psychological traumas that occur within important familial relationships to ensure a cohesive evidence base and fidelity of the concept in application to practice. This review used a philosophical inquiry methodology of concept analysis to identify the definitions, antecedents, characteristics, and consequences of the varying conceptualizations of psychological trauma occurring within important relationships. Interactions between concepts of interpersonal trauma, relational trauma, betrayal trauma, attachment trauma, developmental trauma, complex trauma, cumulative trauma, and intergenerational trauma are presented. Understanding of the discrete forms and pathways of transmission of psychological trauma between individuals, including transgenerationally within families, creates opportunities for prevention and early intervention within trauma-focused practice. This review found that concepts of psychological trauma occurring within familial relationships are not exclusive of each other but overlap in their encompassment of events and circumstances as well as the effect on individuals of events in the short term and long term. These traumas develop and are transmitted in the space between people, both purposefully and incidentally, and have particularly profound effects when they involve a dependent infant or child. Linguistic and conceptual clarity is paramount for trauma research and practice.

D005195:Family Relations
D000080037:Historical Trauma
D006801:Humans
D000067073:Psychological Trauma

intergenerational transmission of trauma


Associations between plasma levels of omega-3 fatty acids and subsequent allergic diseases.

Abstract:
BACKGROUND
Some metabolites of omega-3 fatty acids, such as Maresin have been reported as inflammation converging substances and are suspected to be related to various inflammatory diseases. However, limited number of clinical researches on the association between omega-3 fatty acid as blood levels and inflammatory diseases were published.

METHODS
We conducted a retrospective cohort study at St. Luke's International Hospital from January 2007 to December 2017. We included all adult patients who had measured plasma fatty acids levels as a part of clinical practice. We excluded patients who had a prior medical history of any allergic diseases. Our primary outcomes were the development of any allergic diseases. The outcomes were compared with Cox proportional hazard model between patients quartered by baseline plasma levels of n-3 PUFAs, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) adjusting for potential confounders.

RESULTS
A total of 1506 patients were included. The mean age was 63.3 (SD: 12.5) years and 1066 (70.8%) were male. The mean EPA levels were 84.09 (SD: 58.67) μg/ml and DHA levels were 139.61 (SD: 60.47) μg/ml. Neither EPA nor DHA levels were significantly associated with the development of allergic disease (log-rank test; p = 0.933, p = 0.908, respectively) in bivariable analyses, or multivariable analyses (hazard ratios [HRs]: 0.90-0.97 for EPA; and HRs: 0.89-0.90 for DHA).

CONCLUSIONS
The EPA and DHA levels were related to C-reactive protein (CRP) of inflammation maker, but non-significant associated with development allergic diseases.

Omega-3 fatty acids
Allergic disease
EPA
DHA


Cerebral gustatory activation in response to free fatty acids using gustatory evoked potentials in humans.

Abstract: There is some evidence of specific oro-detection of FFAs in rodents and humans. The aim of this study was to record gustatory evoked potentials (GEPs) in response to FFA solutions and to compare GEPs in response to linoleic acid solution with GEPs obtained after stimulation with sweet and salty tastants. Eighteen healthy men were randomly stimulated with fatty (linoleic acid), sweet (sucrose), and salty (NaCl) solutions at two concentrations in the first experiment. Control recordings (n = 14) were obtained during stimulation by a paraffin oil mixture without FFA or by water. In the second experiment, 28 men were randomly stimulated with five FFA solutions and a paraffin emulsion. GEPs were recorded with electroencephalographic electrodes at Cz, Fz, and Pz. GEPs were observed in response to FFA in all participants. GEP characteristics did not differ according to the quality and the concentration of the solutions in the first experiment and according to the FFA in the second experiment. This study describes for the first time GEPs in response to FFA and demonstrates that the presence of FFA in the mouth triggers an activation of the gustatory cortex. These data reinforce the concept that fat taste could be the sixth primary taste.

Mouillot|Thomas|T| Szleper|Emilie|E| Vagne|Gaspard|G| Barthet|Sophie|S| Litime|Djihed|D| Brindisi|Marie-Claude|MC| Leloup|Corinne|C| Penicaud|Luc|L| Nicklaus|Sophie|S| Brondel|Laurent|L| Jacquin-Piques|Agnès|A|

fatty taste
long-chain fatty acids
medium-chain fatty acids
short-chain fatty acids


Small molecules enhance neurogenic differentiation of dental-derived adult stem cells.

Abstract:
OBJECTIVE
Dental-derived stem cells originate from the embryonic neural crest, and exhibit high neurogenic potential. This study aimed to investigate whether a cocktail of eight small molecules (Valproic acid, CHIR99021, Repsox, Forskolin, SP600125, GO6983, Y-27632 and Dorsomorphin) can enhance the in vitro neurogenic differentiation of dental pulp stem cells (DPSCs), stem cells from apical papilla (SCAPs) and gingival mesenchymal stem cells (GMSCs), as a preliminary step towards clinical applications.

MATERIALS AND METHODS
Neural induction was carried out with a small molecule cocktail based two-step culture protocol, over a total duration of 14 days. At the 8 and 14 day timepoints, the cells were analyzed for expression of neural markers with immunocytochemistry, qRT-PCR and Western Blot. The Fluo 4-AM calcium flux assay was also performed after a further 14 days of neural maturation.

RESULTS
More pronounced morphological changes characteristic of the neural lineage (i.e. neuritogenesis) were observed in all three cell types treated with small molecules, as compared to the untreated controls. This was corroborated by the immunocytochemistry, qRT-PCR and western blot data, which showed upregulated expression of several early and mature neural markers in all three cell types treated with small molecules, versus the corresponding untreated controls. Finally, the Fluo-4 AM calcium flux assay showed consistently higher calcium transient (F/Fo) peaks for the small molecule-treated versus untreated control groups.

CONCLUSIONS
Small molecules can enhance the neurogenic differentiation of DPSCs, SCAPs and GMSCs, which offer much potential for therapeutic applications.

Heng|Boon Chin|BC|
Jiang|Shan|S|
Yi|Baicheng|B|
Gong|Ting|T|
Lim|Lee Wei|LW|
Zhang|Chengfei|C|

Differentiation
Stem cells
DPSCs
SCAPs
GMSCs
Neurogenesis


Kindlin 2 promotes breast cancer invasion via epigenetic silencing of the microRNA200 gene family.

Abstract: Kindlin 2, as a focal adhesion protein, controls integrin activation and regulates Wnt signaling in an integrin-binding independent manner. However, the association of Kindlin 2 with cancer-related microRNAs is unknown. Here, we report that Kindlin 2 markedly downregulates the expression of miR-200 family by inducing CpG island hypermethylation. Mechanistically, Kindlin 2 forms a complex with DNMT3A in the cell nucleus and the two proteins co-occupy the promoter of miRNA-200b. Functionally, repression of miR-200b is required for Kindlin 2-induced breast cancer cell invasion and tumor formation. Our data indicate that Kindlin 2 plays a novel role in epigenetic repression of miR-200 family, a mechanism that promotes breast cancer invasion.

Yu|Yu|Y| Wu|Junzhou|J| Guan|Lizhao|L| Qi|Lihua|L| Tang|Yan|Y| Ma|Bo|B| Zhan|Jun|J| Wang|Yunling|Y| Fang|Weigang|W| Zhang|Hongquan|H|

Kindlins
breast cancer
DNA methyltransferase
MicroRNA-200 family


The role of structural and process quality of family planning Care in Modern Contraceptive use in Indonesia: a multilevel analysis.

Abstract:
INTRODUCTION
Despite contraceptive behaviors are influenced by multiple and multilevel variables, studies on modern contraceptive use in Indonesia has concentrated on single-level and mostly individual and household variables, and less interest has been devoted to multilevel analysis that accounts for community and SDP characteristics that may affect woman's decision to use modern FP method. This study aimed to assess the role of structural and process quality of family planning care in modern contraceptive use among women in reproductive ages in Indonesia.

METHODS
This study analyzed data from the 2016 PMA2020 survey of 10,210 women in 372 enumeration areas in Indonesia. The data were analyzed using categorical principal component analysis and multilevel mixed-effects logistic regression.

RESULTS
The key variables for structural quality were number of contraceptive provided, SDP supports CHWs, available water and electricity, and skilled FP personnel, while the main factors for process quality were privacy of clients and provision of post-abortion service. There were significant differences across communities in how study variables associated with modern FP adoption. The finding shows the evidence of significant roles of structural and process quality FP care in modern contraceptive use. Moreover, women with high autonomy in FP decision, those who had free national/district health insurance, and those living in a community with higher proportion of women visited by CHW, had higher odds of modern contraceptive usage. Yet, women who live in a community with higher mean ideal number of children or greater proportion of women citing personal/husband/religion opposition to FP, had lower odds of modern contraceptive use than their counterparts.

CONCLUSION
Study findings suggest improvement in structural and process quality of FP care will yield substantial growths in modern contraceptive use. Moreover, FP workers should also address adverse cultural/traditional customs in community and should target communities where the demand for modern FP was degraded by opposing social beliefs and norms. There was significant variation across communities in how individual, household, community, and SDP factors affect modern FP practice, hence, context should be taken into consideration in the development of FP intervention and promotion programs.

Nurjaeni|Nurjaeni|N| Sawangdee|Yothin|Y| Pattaravanich|Umaporn|U| Holumyong|Charamporn|C| Chamratrithirong|Aphichat|A|

Quality
Family planning
Contraceptive
Indonesia
Multilevel
SDP
PMA2020


DNA Topoisomerases in Unicellular Pathogens: Structure, Function, and Druggability.

Abstract: All organisms, including unicellular pathogens, compulsorily possess DNA topoisomerases for successful nucleic acid metabolism. But particular subtypes of topoisomerases exist, in all prokaryotes and in some unicellular eukaryotes, that are absent in higher eukaryotes. Moreover, topoisomerases from pathogenic members of a niche possess some unique molecular architecture and functionalities completely distinct from their nonpathogenic colleagues. This review will highlight the unique attributes associated with the structures and functions of topoisomerases from the unicellular pathogens, with special reference to bacteria and protozoan parasites. It will also summarise the progress made in the domain pertaining to the druggability of these topoisomerases, upon which a future platform for therapeutic development can be successfully constructed.

Chowdhury|Somenath Roy|SR|
Majumder|Hemanta K|HK|

topoisomerases pathogens bacteria gyrases kinetoplastids mutation


Antibiotic resistance in patients with chronic ear discharge awaiting surgery in Nepal.

Abstract:
SETTING
Biratnagar Eye Hospital, Biratnagar, Nepal, which offers ear surgery for chronic suppurative otitis media (CSOM).

OBJECTIVE
In patients with CSOM awaiting surgery, to determine the 1) sociodemographic characteristics 2) bacterial isolates and their antibiotic resistance patterns and 3) characteristics of those refused surgery, including antibiotic resistance.

DESIGN
A cohort study using hospital data, January 2018-January 2020.

RESULTS
Of 117 patients with CSOM and awaiting surgery, 64% were in the 18-35 years age group, and 79% were cross-border from India. Of 118 bacterial isolates, 80% had Pseudomonas aeruginosa and 16% had Staphylococcus aureus. All isolates showed multidrug resistance to nine of the 12 antibiotics tested. The lowest antibiotic resistance in P. aeruginosa was for vancomycin (29%) and moxifloxacin (36%), and for S. aureus, this was vancomycin (9%) and amikacin (17%). Fourteen (12%) patients underwent surgery: myringoplasty (n = 7, 50%), cortical mastoidectomy with tympanostomy (n = 4, 29%) and modified radical mastoidectomy (n = 3, 21%). Those infected with P. aeruginosa and with resistance to over six antibiotics were significantly more likely to be refused for surgery.

CONCLUSION
Patients awaiting ear surgery were predominantly infected with multidrug-resistant P. aeruginosa and were consequently refused surgery. This study can help inform efforts for improving surgical uptake and introducing cross-border antimicrobial resistance surveillance.

Karn|R R|RR|
Acharya|R|R|
Rajbanshi|A K|AK|
Singh|S K|SK|
Thakur|S K|SK|
Shah|S K|SK|
Singh|A K|AK|
Shah|R|R|
Upadhya Kafle|S|S|
Bhattachan|M|M|
Abrahamyan|A|A|
Shewade|H D|HD|
Zachariah|R|R|

SORT IT
Sustainable Development Goals
health systems
operational research, surveillance


Bi-allelic alterations in DNA repair genes underpin homologous recombination DNA repair defects in breast cancer.

Abstract: Homologous recombination (HR) DNA repair-deficient (HRD) breast cancers have been shown to be sensitive to DNA repair targeted therapies. Burgeoning evidence suggests that sporadic breast cancers, lacking germline BRCA1/BRCA2 mutations, may also be HRD. We developed a functional ex vivo RAD51-based test to identify HRD primary breast cancers. An integrated approach examining methylation, gene expression, and whole-exome sequencing was employed to ascertain the aetiology of HRD. Functional HRD breast cancers displayed genomic features of lack of competent HR, including large-scale state transitions and specific mutational signatures. Somatic and/or germline genetic alterations resulting in bi-allelic loss-of-function of HR genes underpinned functional HRD in 89% of cases, and were observed in only one of the 15 HR-proficient samples tested. These findings indicate the importance of a comprehensive genetic assessment of bi-allelic alterations in the HR pathway to deliver a precision medicine-based approach to select patients for therapies targeting tumour-specific DNA repair defects. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

D000328:Adult
D000368:Aged
D000369:Aged, 80 and over
D019313:BRCA1 Protein
D024682:BRCA2 Protein
D001943:Breast Neoplasms
D018567:Breast Neoplasms, Male
D049914:DNA Repair-Deficiency Disorders
D005260:Female
D018095:Germ-Line Mutation
D059765:Homologous Recombination
D006801:Humans
D019656:Loss of Heterozygosity
D008297:Male
D008875:Middle Aged
D009154:Mutation
D051135:Rad51 Recombinase
D059767:Recombinational DNA Repair
D055815:Young Adult

DNA repair
mutation
BRCAness
RAD51
homologous recombination-deficient