Social Support and Human Immunodeficiency Virus-Status Disclosure to Friends and Family: Implications for Human Immunodeficiency Virus-Positive Youth.

Abstract:
PURPOSE
The fear of negative reactions from friends and family members affects many human immunodeficiency virus (HIV)-positive adolescents' decisions regarding disclosure of their HIV status. The complex relationships and interplay among social support, fear of stigma, and disclosure of HIV status need to be better understood among youth living with HIV (YLHIV).

METHODS
Social support from friends and family members and HIV status disclosure were examined among 402 youth, aged 12-24 years, living with HIV.

RESULTS
In separate analyses, (1) HIV-positive youth who reported more than one close friend and (2) HIV-positive youth who reported that friends and family members continued to socialize with them after disclosure of their HIV diagnosis, had higher levels of perceived social support overall (both p < .05). Furthermore, perceived social support did not differ significantly between those participants for whom no family member knew their HIV status and those for whom at least one family member knew their status (p = .13). Race/ethnicity, sexual orientation, education level, and current living situation were not associated with family's knowledge of the participants' HIV infection status (p > .07).

CONCLUSION
This investigation adds important information concerning YLHIV, whose early disclosure experiences may influence their resilience and future coping mechanisms regarding experienced stigma, and thus influence the length of time they conceal their HIV status, their decision to disclose their status, and potentially their decisions regarding treatment. Interventions and support systems to assist YLHIV with disclosure, as well as medical care, may improve their overall quality of life.

Lee|Sonia|S|
Yamazaki|Michiyo|M|
Harris|D Robert|DR|
Harper|Gary W|GW|
Ellen|Jonathan|J|

Social support
Adolescents
HIV status disclosure
Social network


Linear growth faltering in infants is associated with Acidaminococcus sp. and community-level changes in the gut microbiota.

Abstract:
BACKGROUND
Chronic malnutrition, termed stunting, is defined as suboptimal linear growth, affects one third of children in developing countries, and leads to increased mortality and poor developmental outcomes. The causes of childhood stunting are unknown, and strategies to improve growth and related outcomes in children have only had modest impacts. Recent studies have shown that the ecosystem of microbes in the human gut, termed the microbiota, can induce changes in weight. However, the specific changes in the gut microbiota that contribute to growth remain unknown, and no studies have investigated the gut microbiota as a determinant of chronic malnutrition.

RESULTS
We performed secondary analyses of data from two well-characterized twin cohorts of children from Malawi and Bangladesh to identify bacterial genera associated with linear growth. In a case-control analysis, we used the graphical lasso to estimate covariance network models of gut microbial interactions from relative genus abundances and used network analysis methods to select genera associated with stunting severity. In longitudinal analyses, we determined associations between these selected microbes and linear growth using between-within twin regression models to adjust for confounding and introduce temporality. Reduced microbiota diversity and increased covariance network density were associated with stunting severity, while increased relative abundance of Acidaminococcus sp. was associated with future linear growth deficits.

CONCLUSIONS
We show that length growth in children is associated with community-wide changes in the gut microbiota and with the abundance of the bacterial genus, Acidaminococcus. Larger cohorts are needed to confirm these findings and to clarify the mechanisms involved.

Gough|Ethan K|EK|
Stephens|David A|DA|
Moodie|Erica E M|EE|
Prendergast|Andrew J|AJ|
Stoltzfus|Rebecca J|RJ|
Humphrey|Jean H|JH|
Manges|Amee R|AR|

Growth
Microbiota
Stunting
Networks
Intestinal
Microbiome
Statistical learning


First report of gastroenteritis by genotype G12 rotavirus in Dakar, Senegal.

Abstract: The genotype G12 rotavirus was isolated from the stool of children 5 years old or younger with acute gastroenteritis during 1 year in three Dakar hospitals. The G12 genotype was the most common (58.25%). VP4 genotyping revealed mixed genotypes (1.94%).

Dia|M L|ML|
Diop|A|A|
Sonko|M A|MA|
Bâ|M|M|
Cissé|M F|MF|

rotavirus
Senegal
Children
G12 genotype
diarrhea


Environmental impacts of income inequality: evidence from G7 economies.

Abstract: This study probes the environmental consequences of income inequality (INQ) in G7 economies from 1971 to 2015. INQ is captured by four indicators comprising GINI coefficients, Palma ratio, Theil index, and Atkinson index on per capita carbon emission as a proxy for environmental degradation using both fully modified OLS (FM-OLS) and dynamic OLS (D-OLS). The empirical data are subjected to pre-test using cross-sectional dependence (CSD) test and panel unit root and panel cointegration tests. The following results are established. First, the absence of CSD and presence of cointegration is confirmed. Second, positive effects of INQ indices are reported for the panel analyses. Third, the results of country-specific analyses are divergent and mixed among the G7 economies. For instance, positive impacts are reported for Canada, Japan, and the USA and negative for France and Germany; and insignificant impacts are evident in the case of Italy and the UK. Fourth, the effects of other covariates emerge from two directions entailing both positive and negative. While per capita GDP (LGDPPC) and trade openness (OPN) are aligned with the former a prior, per energy use (PEU) and inflation (INF) satisfied the latter. Consequently, embarking on pro-poor programs such as social welfare funds, private initiative support fund, and state intervention aimed at checkmating the excesses of the capitalists is seen as sacrosanct to solving the INQ-pco2 nexus disharmony.

Fully and dynamic ordinary least squares’ estimators


Biocatalytic Synthesis and Polymerization via ROMP of New Biobased Phenolic Monomers: A Greener Process toward Sustainable Antioxidant Polymers.

Abstract: Antioxidant norbornene-based monomers bearing biobased sterically hindered phenols (SHP)-NDF (norbornene dihydroferulate) and NDS (norbornene dihydrosinapate)-have been successfully prepared through biocatalysis from naturally occurring ferulic and sinapic acids, respectively, in presence of Candida antarctica Lipase B (Cal-B). The ring opening metathesis polymerization (ROMP) of these monomers was investigated according to ruthenium catalyst type (GI) vs. (HGII) and monomer to catalyst molar ratio ([M]/[C]). The co-polymerization of antioxidant functionalized monomer (NDF or NDS) and non-active norbornene (N) has also been performed in order to adjust the number of SHP groups present per weight unit and tune the antioxidant activity of the copolymers. The polydispersity of the resulting copolymers was readily improved by a simple acetone wash to provide antioxidant polymers with well-defined structures. After hydrogenation with p-toluenesulfonylhydrazine (p-TSH), the radical scavenging ability of the resulting saturated polymers was evaluated using α,α-diphenyl-β-picrylhydrazyl (DPPH) analysis. Results demonstrated that polymers bearing sinapic acid SHP exhibited higher antiradical activity than the polymer bearing ferulic acid SHP. In addition it was also shown that only a small SHP content was needed in the copolymers to exhibit a potent antioxidant activity.

Diot-Néant|Florian|F|
Migeot|Loïs|L|
Hollande|Louis|L|
Reano|Felix A|FA|
Domenek|Sandra|S|
Allais|Florent|F|

ROMP
antioxidants
norbornene
sinapic acid
lipase
CAL-B
DPPH
ferulic acid


Evolution of Anabaenopeptin Peptide Structural Variability in the Cyanobacterium Planktothrix.

Abstract: Cyanobacteria are frequently involved in the formation of harmful algal blooms wherein, apart from the toxic microcystins, other groups of bioactive peptides are abundant as well, such as anabaenopeptins (APs). The APs are synthesized nonribosomally as cyclic hexapeptides with various amino acids at the exocyclic position. We investigated the presence and recombination of the AP synthesis gene cluster (apnA-E) through comparing 125 strains of the bloom-forming cyanobacterium Planktothrix spp., which were isolated from numerous shallow and deep water habitats in the temperate and tropical climatic zone. Ten ecologically divergent strains were purified and genome sequenced to compare their entire apnA-E gene cluster. In order to quantify apn gene distribution patterns, all the strains were investigated by PCR amplification of 2 kbp portions of the entire apn gene cluster without interruption. Within the 11 strains assigned to P. pseudagardhii, P. mougeotii, or P. tepida (Lineage 3), neither apnA-E genes nor remnants were observed. Within the P. agardhii/P. rubescens strains from shallow waters (Lineage 1, 52 strains), strains both carrying and lacking apn genes occurred, while among the strains lacking the apnA-E genes, the presence of the 5'end flanking region indicated a gene cluster deletion. Among the strains of the more derived deep water ecotype (Lineage 2, 62 strains), apnA-E genes were always present. A high similarity of apn genes of the genus Planktothrix when compared with strains of the genus Microcystis suggested its horizontal gene transfer during the speciation of P. agardhii/P. rubescens. Genetic analysis of the first (A1-) domain of the apnA gene, encoding synthesis of the exocyclic position of the AP molecule, revealed four genotype groups that corresponded with substrate activation. Groups of genotypes were either related to Arginine only, the coproduction of Arginine and Tyrosine or Arginine and Lysine, or even the coproduction of Arginine, Tyrosine, and Lysine in the exocyclic position of the AP-molecule. The increased structural diversity resulted from the evolution of apnA A1 genotypes through a small number of positively selected point mutations that occurred repeatedly and independently from phylogenetic association.

Entfellner|Elisabeth|E| Frei|Mark|M| Christiansen|Guntram|G| Deng|Li|L| Blom|Jochen|J| Kurmayer|Rainer|R|

ecotype
horizontal gene transfer
speciation
chemotype
cyanoHABs
cyanotoxins
gene deletion
natural products


Topography of the common fibular nerve terminal division in human fetuses.

Abstract:
BACKGROUND
The progress of pediatric surgery and increasingly better diagnosis of fetal defects require detailed knowledge of human developmental anatomy. Precise knowledge of the anatomy of innervation of the lower extremities corresponds to this subject and is not only cognitive but also clinically important. The end of the common fibular nerve is superficially located in the area exposed to frequent injuries as well as in the area subject to possible surgical repair procedures.

MATERIALS AND METHODS
The analysis was carried out on 200 human foetuses aged from the 113th day to 222nd day of foetal life. The study material is a part of local fetal collection. The study incorporated the following methods: anthropological, preparational and image acquisition which was acquired with the use of high-resolution digital camera. Statistical analysis was carried out with the use of STATISTICA package.

RESULTS
Based on the research results the new typology of the examined nerve was determined. The head of the fibula was the criterion: (i) high division - above the head of the fibula (1%); (ii) intermediate division - at the height of the head of the fibula (34%); (iii) low division - below the head of the fibula (65%). The mathematical analysis did not reveal statistically significant bilateral and gender differences. Moreover the additional branch was observed in 30% of fetuses, regardless of age class. This branch occurred in 50% of cases in both sides of the fetus. This nerve was defined as the accessory fibular nerve (nervus fibularis/peroneus accessorius).

CONCLUSIONS
The created unique typology of the terminal division of common fibular nerve is an important supplement to the anatomical knowledge and at the same time, due to the peripheral and superficial location of the described structures, it has a relatively high clinical significance.

human fetuses
accessory fibular nerve
common peroneal nerve
dissection


Characterization and flocculation mechanism of a bioflocculant from hydrolyzate of rice stover.

Abstract: This study investigated the characterization and flocculation mechanism of a bioflocculant from hydrolyzate of rice stover. Production of the bioflocculant was positively associated with cell growth and a highest value of 2.4 g L(-1) was obtained. During the kaolin suspension flocculation, charge neutralization and inter-particle bridging were proposed as the reasons for enhanced performance. Apart from this, the bioflocculant showed good performances in sludge dewatering and swine wastewater pretreatment. After conditioning by the bioflocculant, dry solids (DS) and specific resistance to filtration (SRF) of the sludge reached 18.4% and 4.8×10(12) m kg(-1), respectively, which were much better than that by conventional chemical flocculants. In the swine wastewater pretreatment, the removal efficiencies of COD, ammonium, and turbidity reached 48.3%, 43.6% and 75.8% at pH 8.0 when the bioflocculant dose was adjusted to 20 mg L(-1).

Guo|Junyuan|J| Yu|Jing|J| Xin|Xin|X| Zou|Changwu|C| Cheng|Qingfeng|Q| Yang|Huaijin|H| Nengzi|Lichao|L|

D017550:Spectroscopy, Fourier Transform Infrared

Bioflocculant
Rice stover
Sludge dewatering
Swine wastewater pretreatment


Quinoxaline and Pyrido[x,y-b]pyrazine-Based Emitters: Tuning Normal Fluorescence to Thermally Activated Delayed Fluorescence and Emitting Color over the Entire Visible-Light Range.

Abstract: Quinoxaline (Q), pyrido[2,3-b]pyrazine (PP) and pyrido[3,4-b]pyrazine (iPP) are used as electron acceptors (A) to design a series of D-π-A-type light-emitting materials with different donor (D) groups. By adjusting the molecular torsion angles through changing D from carbazole (Cz) to 10-dimethylacridine (DMAC) or 10H-phenoxazine (PXZ) for a fixed A, the luminescence is tuned from normal fluorescence to thermally activated delayed fluorescence (TADF). By gradually enhancing the intramolecular charge-transfer extent through combining different D and A, the emission color is continuously and regularly tuned from pure blue to orange-red. Organic light-emitting diodes (OLEDs) containing these compounds as doped emitters exhibit bright electroluminescence with emission colors covering the entire visible-light range. An external quantum efficiency (ηext ) of 1.2 % with excellent color coordinates of (0.16, 0.07) is obtained for the pure-blue OLED of Q-Cz. High ηext values of 12.9 (35.9) to 16.7 % (51.9 cd A-1 ) are realized in the green, yellow, and orange-red TADF OLEDs. All PP- and iPP-based TADF emitters exhibit superior efficiency stabilities to that of analogues of Q. This provides a practical strategy to tune the emission color of Q, PP, and iPP derivatives with the same molecular skeletons over the entire visible-light range.


Umbilical cord blood: Current uses for transfusion and regenerative medicine.

Abstract: The past 20 years of experience with umbilical cord blood transplantation have demonstrated that cord blood is effective in the treatment of a spectrum of diseases, including hematological malignancies, bone marrow failure, hemoglobinopathies, and inborn errors of metabolism. However, only a few number of umbilical cord blood units collected have a cell content adequate for an allogenic hematopoietic stem cell transplantation. In the meanwhile, there is an increasing interest in exploiting cord blood derivatives in different fields. In this review, we will summarize the most recent updates on clinical applications of umbilical cord blood platelet derivatives for regenerative medicine, and we will revise the literature concerning the use of umbilical cord blood for autologous or allogeneic transfusion purposes. The methodological aspect and the biological characteristics of these products also will be discussed.

Orlando|Nicoletta|N|
Pellegrino|Claudio|C|
Valentini|Caterina Giovanna|CG|
Bianchi|Maria|M|
Barbagallo|Ombretta|O|
Sparnacci|Sabrina|S|
Forni|Franca|F|
Fontana|Tecla Maria|TM|
Teofili|Luciana|L|

D001803:Blood Transfusion
D005312:Fetal Blood
D006801:Humans
D044968:Regenerative Medicine

Allogenic cord RBC
Umbilical cord blood platelet gel
Umbilical cord blood serum
Umbilical cord blood transfusion


Formalizing video documentation of the Critical View of Safety in laparoscopic cholecystectomy: a step towards artificial intelligence assistance to improve surgical safety.

Abstract:
BACKGROUND
In laparoscopic cholecystectomy (LC), achievement of the Critical View of Safety (CVS) is commonly advocated to prevent bile duct injuries (BDI). However, BDI rates remain stable, probably due to inconsistent application or a poor understanding of CVS as well as unreliable reporting. Objective video reporting could serve for quality auditing and help generate consistent datasets for deep learning models aimed at intraoperative assistance. In this study, we develop and test a method to report CVS using videos.

METHOD
LC videos performed at our institution were retrieved and the video segments starting 60 s prior to the division of cystic structures were edited. Two independent reviewers assessed CVS using an adaptation of the doublet view 6-point scale and a novel binary method in which each criterion is considered either achieved or not. Feasibility to assess CVS in the edited video clips and inter-rater agreements were evaluated.

RESULTS
CVS was attempted in 78 out of the 100 LC videos retrieved. CVS was assessable in 100% of the 60-s video clips. After mediation, CVS was achieved in 32/78(41.03%). Kappa scores of inter-rater agreements using the doublet view versus the binary assessment were as follows: 0.54 versus 0.75 for CVS achievement, 0.45 versus 0.62 for the dissection of the hepatocystic triangle, 0.36 versus 0.77 for the exposure of the lower part of the cystic plate, and 0.48 versus 0.79 for the 2 structures connected to the gallbladder.

CONCLUSIONS
The present study is the first to formalize a reproducible method for objective video reporting of CVS in LC. Minute-long video clips provide information on CVS and binary assessment yields a higher inter-rater agreement than previously used methods. These results offer an easy-to-implement strategy for objective video reporting of CVS, which could be used for quality auditing, scientific communication, and development of deep learning models for intraoperative guidance.

Mascagni|Pietro|P|0000-0001-7288-3023 Fiorillo|Claudio|C| Urade|Takeshi|T| Emre|Taha|T| Yu|Tong|T| Wakabayashi|Taiga|T| Felli|Emanuele|E| Perretta|Silvana|S| Swanstrom|Lee|L| Mutter|Didier|D| Marescaux|Jacques|J| Pessaux|Patrick|P| Costamagna|Guido|G| Padoy|Nicolas|N| Dallemagne|Bernard|B|

Critical View of Safety
Laparoscopic cholecystectomy
Surgical safety
Bile duct injury
Objective video reporting
Surgical data science


First identification in Tasmania of fish pathogens Tenacibaculum dicentrarchi and T. soleae and multiplex PCR for these organisms and T. maritimum.

Abstract: This work describes a new polymerase chain reaction (PCR) assay for rapid identification of the fish pathogens Tenacibaculum dicentrarchi, T. maritimum and T. soleae, 3 organisms which can cause tenacibaculosis in farmed salmonids. The selected primers amplified a 688 bp fragment for T. dicentrarchi, a 288 bp fragment of the T. maritimum and a 183 bp fragment of the T. soleae 16S rRNA genes. The PCR assay was shown to be both specific and sensitive with a detection limit of approximately 50 fg DNA for each species in the presence of competing DNA. The multiplex PCR allowed detection of each pathogen from pure or mixed cultures, where the different Tenacibaculum species can be difficult to distinguish phenotypically. Our results indicate that the specific primers and PCR method developed here provide sensitive and fast detection of T. dicentrarchi, T. maritimum and T. soleae alone or in combination.

Wilson|Teresa K|TK|
Douglas|Marianne|M|
Dunn|Vivianne|V|

D060885:Multiplex Polymerase Chain Reaction

Tenacibaculum · maritimum · dicentrarchi · soleae


Natural Products in the Prevention of Metabolic Diseases: Lessons Learned from the 20th KAST Frontier Scientists Workshop.

Abstract: The incidence of metabolic and chronic diseases including cancer, obesity, inflammation-related diseases sharply increased in the 21st century. Major underlying causes for these diseases are inflammation and oxidative stress. Accordingly, natural products and their bioactive components are obvious therapeutic agents for these diseases, given their antioxidant and anti-inflammatory properties. Research in this area has been significantly expanded to include chemical identification of these compounds using advanced analytical techniques, determining their mechanism of action, food fortification and supplement development, and enhancing their bioavailability and bioactivity using nanotechnology. These timely topics were discussed at the 20th Frontier Scientists Workshop sponsored by the Korean Academy of Science and Technology, held at the University of Hawaii at Manoa on 23 November 2019. Scientists from South Korea and the U.S. shared their recent research under the overarching theme of Bioactive Compounds, Nanoparticles, and Disease Prevention. This review summarizes presentations at the workshop to provide current knowledge of the role of natural products in the prevention and treatment of metabolic diseases.

natural products
cancer
obesity
inflammation-related diseases
antioxidants
nanoparticles
aging
anti-inflammation
bioactive food components


Cognitive deficits and clinical symptoms in patients with treatment-refractory obsessive-compulsive disorder: The role of slowness in information processing.

Abstract: Patients with Obsessive-Compulsive Disorder (OCD) present neuropsychological deficits across different cognitive domains, especially in executive functioning and information processing speed. Some studies have even suggested that speed deficits may underlie poor neuropsychological performance. However, this hypothesis remains unanswered in both OCD general population and OCD refractory subgroup. In addition, it is not clear whether such deficits are secondary to the clinical symptoms or may constitute a primary deficit. The aim of this study was to explore the speed of processing hypothesis in treatment-refractory OCD patients, and to clarify to what extent slowness is related to psychopathological symptoms. Both clinical and neuropsychological examination was conducted to assess 39 OCD refractory patients candidates for neurosurgery and 39 healthy matched individuals. Principal component analysis revealed a three-component structure in the neuropsychological battery being used, including a speed of processing, working memory, and conflict monitoring components. Group comparisons revealed that OCD patients performed significantly worse than healthy individuals in speed measures, but no differences were found in executive tests not influenced by time. Correlation analyses revealed a lack of association between neuropsychological and clinical measures. The results suggest that treatment-refractory OCD patients exhibit a primary deficit in information processing speed independent of clinical symptoms.

Simón-Martínez|Vanesa|V|
Laseca-Zaballa|Garazi|G|
Lubrini|Genny|G|
Periáñez|José A|JA|
Martínez Álvarez|Roberto|R|
Torres-Díaz|Cristina V|CV|
Martínez Moreno|Nuria|N|
Álvarez-Linera|Juan|J|
Ríos-Lago|Marcos|M|

D003071:Cognition
D003072:Cognition Disorders
D056344:Executive Function
D006801:Humans
D009483:Neuropsychological Tests
D009771:Obsessive-Compulsive Disorder

Clinical symptoms
Slowness
Neuropsychology
Executive function
Information processing speed
Attention
Obsessive–compulsive disorder


Neural Mechanisms of Updating under Reducible and Irreducible Uncertainty.

Abstract: Adaptive decision making depends on an agent's ability to use environmental signals to reduce uncertainty. However, because of multiple types of uncertainty, agents must take into account not only the extent to which signals violate prior expectations but also whether uncertainty can be reduced in the first place. Here we studied how human brains of both sexes respond to signals under conditions of reducible and irreducible uncertainty. We show behaviorally that subjects' value updating was sensitive to the reducibility of uncertainty, and could be quantitatively characterized by a Bayesian model where agents ignore expectancy violations that do not update beliefs or values. Using fMRI, we found that neural processes underlying belief and value updating were separable from responses to expectancy violation, and that reducibility of uncertainty in value modulated connections from belief-updating regions to value-updating regions. Together, these results provide insights into how agents use knowledge about uncertainty to make better decisions while ignoring mere expectancy violation.SIGNIFICANCE STATEMENT To make good decisions, a person must observe the environment carefully, and use these observations to reduce uncertainty about consequences of actions. Importantly, uncertainty should not be reduced purely based on how surprising the observations are, particularly because in some cases uncertainty is not reducible. Here we show that the human brain indeed reduces uncertainty adaptively by taking into account the nature of uncertainty and ignoring mere surprise. Behaviorally, we show that human subjects reduce uncertainty in a quasioptimal Bayesian manner. Using fMRI, we characterize brain regions that may be involved in uncertainty reduction, as well as the network they constitute, and dissociate them from brain regions that respond to mere surprise.

updating
decision making
fMRI
ambiguity
risk
valuation


Self-Reported Behavioral Symptoms of People with Dementia: A Pilot Study Examining Individual's Perceived Illness Experience.

Abstract:
BACKGROUND AND OBJECTIVES
Persons with dementia experience behavioral symptoms, such as agitation and repeating questions, which have been reported as one of the most burdensome and stressful aspects of providing care for dementia caregivers. However, no published studies have assessed the subjective experience of behavioral symptoms and distress from people with dementia.

RESEARCH DESIGN AND METHODS
The current pilot study examined the feasibility of people with dementia providing self-reported behaviors and behavioral-related distress. Data from a larger, on-going research study was used consisting of people with mild to moderate dementia (n = 12) residing in a long-term memory care facility.

RESULTS
Participants were able to provide reliable (∝=.91) self-reported data concerning their own behaviors and behavioral-related distress with variability among responses. The most frequently self-reported behaviors included agitation (66.7%) and complaining/criticizing things (58.3%) while the least reported behaviors were refusing to be left alone (8.3%) and yelling/swearing (8.3%). The highest behavioral distress reported was agitation (58.3%) while the least was wandering (8.3%).

DISCUSSION AND IMPLICATIONS
Understanding the subjective, perceived experience of people with dementia provides valuable information on the illness experience. Additional research is needed to examine the role and impact of self-reported behaviors and the resulting behavioral- related distress on outcomes of well-being. Subjective reports of behavioral-related distress could predict well-being, above and beyond that of traditional objective measures, creating the potential for novel non-pharmacological intervention development for people with dementia.

Minyo|Morgan J|MJ|0000-0001-6182-3172
Judge|Katherine S|KS|

Subjective experience
Well-being
Cognitive impairment
Person-centered care


Neuromuscular scoliosis complication rates from 2004 to 2015: a report from the Scoliosis Research Society Morbidity and Mortality database.

Abstract: OBJECTIVE Postoperative complications are one of the most significant concerns in surgeries of the spine, especially in higher-risk cases such as neuromuscular scoliosis. Neuromuscular scoliosis is a classification of multiple diseases affecting the neuromotor system or musculature of patients leading to severe degrees of spinal deformation, disability, and comorbidity, all likely contributing to higher rates of postoperative complications. The objective of this study was to evaluate deformity correction of patients with neuromuscular scoliosis over a 12-year period (2004-2015) by looking at changes in postsurgical complications and management. METHODS The authors queried the Scoliosis Research Society (SRS) Morbidity and Mortality (M&M) database for neuromuscular scoliosis cases from 2004 to 2015. The SRS M&M database is an international database with thousands of self-reported cases by fellowship-trained surgeons. The database has previously been validated, but reorganization in 2008 created less-robust data sets from 2008 to 2011. Consequently, the majority of analysis in this report was performed using cohorts that bookend the 12-year period (2004-2007 and 2012-2015). Of the 312 individual fields recorded per patient, demographic analysis was completed for age, sex, diagnosis, and preoperative curvature. Analysis of complications included infection, bleeding, mortality, respiratory, neurological deficit, and management practices. RESULTS From 2004 to 2015, a total of 29,019 cases of neuromuscular scoliosis were reported with 1385 complications, equating to a 6.3% complication rate when excluding the less-robust data from 2008 to 2011. This study shows a 3.5-fold decrease in overall complication rates from 2004 to 2015. A closer look at complications shows a significant decrease in wound infections (superficial and deep), respiratory complications, and implant-associated complications. The overall complication rate decreased by approximately 10% from 2004-2007 to 2012-2015. CONCLUSIONS This study demonstrates a substantial decrease in complication rates from 2004 to 2015 for patients with neuromuscular scoliosis undergoing spine surgery. Decreases in specific complications, such as surgical site infection, allow us to gauge our progress while observing how trends in management affect outcomes. Further study is needed to validate this report, but these results are encouraging, helping to reinforce efforts toward continual improvement in patient care.

Cognetti|Daniel|D|
Keeny|Heather M|HM|
Samdani|Amer F|AF|
Pahys|Joshua M|JM|
Hanson|Darrell S|DS|
Blanke|Kathy|K|
Hwang|Steven W|SW|

MRSA = methicillin-resistant Staphylococcus aureus

MSSA = methicillin-sensitive Staphylococcus aureus

NSQIP = National Surgical Quality Improvement Program


Plasticity-Enhancing Effects of Levodopa Treatment after Stroke.

Abstract: Dopaminergic treatment in combination with rehabilitative training enhances long-term recovery after stroke. However, the underlying mechanisms on structural plasticity are unknown. Here, we show an increased dopaminergic innervation of the ischemic territory during the first week after stroke induced in Wistar rats subjected to transient occlusion of the middle cerebral artery (tMCAO) for 120 min. This response was also found in rats subjected to permanent focal ischemia induced by photothrombosis (PT) and mice subjected to PT or tMCAO. Dopaminergic branches were detected in the infarct core of mice and rats in both stroke models. In addition, the Nogo A pathway was significantly downregulated in rats treated with levodopa (LD) compared to vehicle-treated animals subjected to tMCAO. Specifically, the number of Nogo A positive oligodendrocytes as well as the levels of Nogo A and the Nogo A receptor were significantly downregulated in the peri-infarct area of LD-treated animals, while the number of Oligodendrocyte transcription factor 2 positive cells increased in this region after treatment. In addition, we observed lower protein levels of Growth Associated Protein 43 in the peri-infarct area compared to sham-operated animals without treatment effect. The results provide the first evidence of the plasticity-promoting actions of dopaminergic treatment following stroke.

Talhada|Daniela|D| Marklund|Niklas|N|0000-0002-9797-5626 Wieloch|Tadeusz|T| Kuric|Enida|E| Ruscher|Karsten|K|

D020244:Infarction, Middle Cerebral Artery

D000076104:Oligodendrocyte Transcription Factor 2

Nogo A
oligodendrocyte
Nogo receptor
dopamine
neuronal plasticiticy
stroke recovery


Life History of Thalerosphyrus (Ephemeroptera: Heptageniidae) in Tropical Rivers with Reference to the Varying Altitude.

Abstract: The life history and the influence of environmental parameters on Thalerosphyrus were investigated in two first-order rivers-the Batu Hampar River and the Teroi River of Gunung Jerai, Kedah-in northern peninsular Malaysia. Based on nymphal body length, Thalerosphyrus was found to be trivoltine in both rivers, regardless of the altitudinal difference, but its population abundance was four times higher in the Teroi River, presumably related to its better survival in the lower water temperature. At least nine instars of Thalerosphyrus were detected in the field-collected nymphs. Its life cycle was completed within 2.5-3.0 months, with overlapping cohorts and continual emergence of up to 3 months. The main driving factors of the high abundance of Thalerosphyrus were the water temperature and habitat quality.

Hamid|Suhaila Ab|SA|
Rawi|Che Salmah Md|CS|
Ahmad|Abu Hassan|AH|

Thalerosphyrus
Altitude
Temperature
Development
Flat-headed Mayfly


Paediatric Medicines in Europe: The Paediatric Regulation-Is It Time for Reform?

Abstract: Objectives: In this paper, we investigated the effects of the European Paediatric Regulation (EC) N° 1901/2006 with respect to satisfying the paediatric therapeutic needs, assessed in terms of the increased number of paediatric medicinal products, new therapeutic indications in specific high-need conditions (neonates, oncology, rare disease, etc.) and increased number of paediatric clinical studies supporting the marketing authorisation. Methods: We analysed the paediatric medicinal products approved by the European Medicines Agency in the period January 2007-December 2019, by collecting the following data: year of approval, active substance, legal basis for the marketing authorisation, type of medicinal product (i.e., chemical, biological, or ATMP), orphan drug status, paediatric indication, Anatomical Therapeutic Chemical code (first-level), number and type of paediatric studies. Data were compared with similar data collected in the period 1996-2006. Results: In the period January 1996-December 2019, in a total of 1,190 medicinal products and 843 active substances, 34 and 38%, respectively, were paediatric. In the two periods, before and after the Paediatric Regulation implementation, the paediatric/total medicinal products ratio was constant while the paediatric/total active substances ratio decreased. Moreover, excluding generics and biosimilars, a total of 106 and 175 paediatric medicines were granted a new paediatric indication, dosage or age group in the two periods; out of 175, 128 paediatric medicines had an approved Paediatric Investigational Plan. The remaining 47 were approved without an approved Paediatric Investigational Plan, following the provisions of Directive 2001/83/EC and repurposing an off-patent drug. The analysis of the clinical studies revealed that drugs with a Paediatric Investigational Plan were supported by 3.5 studies/drug while drugs without a Paediatric Investigational Plan were supported by only 1.6 studies/drug. Discussion: This report confirms that the expectations of the European Paediatric Regulation (EC) N° 1901/2006 have been mainly satisfied. However, the reasons for the limited development of paediatric medicines in Europe, should be further discussed, taking advantage of recent initiatives in the regulatory field, such as the Action Plan on Paediatrics, and the open consultation on EU Pharmaceutical Strategy.

Toma|Maddalena|M|
Felisi|Mariagrazia|M|
Bonifazi|Donato|D|
Bonifazi|Fedele|F|
Giannuzzi|Viviana|V|
Reggiardo|Giorgio|G|
de Wildt|Saskia|S|
Ceci|Adriana|A|
|||

paediatric medicines
paediatric clinical studies
EU paediatric regulation
orphan paediatric medicines
paediatric age
paediatric repurposing
therapeutic areas


Endoscopic endonasal transmaxillary ligation of a feeding artery and coblation plasma technology enables en bloc resection of advanced juvenile nasopharyngeal angiofibroma without preoperative embolization.

Abstract: Juvenile nasopharyngeal angiofibroma (JNA) is a hypervascular tumor and uncontrolled hemorrhage makes its removal very difficult. Although preoperative intravascular embolization of a feeding artery is recommended, serious complications such as iatrogenic thrombosis in the brain and insufficient decrease in blood flow to the tumor are concerns. Recently, coblation plasma technology has been reported to be useful for tumor removal with minimum hemorrhage under a clear surgical field. Here we report successful removal of advanced JNA without preoperative embolization, using intraoperative ligation of the maxillary artery and coblation plasma technology. The left nasal cavity of a 23-years-old man was closed by a JNA tumor at Radkowski stage IIC, which was 65mm in size and extended from the nasal cavity to the infratemporal fossa. MRA imaging showed the maxillary artery running along the posterior wall of the maxillary sinus. Therefore, the maxillary artery was first clipped using an endoscopic modified medial maxillectomy (EMMM) approach and endoscopic endonasal en bloc resection of the tumor was then completed using coblation technology with no need for blood transfusion. This case illustrates that preoperative embolization is dispensable in JNA surgery even at Stage IIC if the maxillary artery can be ligated during surgery and a coblation device can be utilized.

Coblation
Juvenile nasopharyngeal angiofibroma
Endoscopic endonasal surgery


Reproducibility of corrected QT interval in pediatric genotyped long QT syndrome.

Abstract: Reproducibility of corrected QT interval (QTc), especially QTc after exercise, has not been thoroughly investigated. We reviewed charts of pediatric patients who underwent treadmill-exercise stress testing without medication multiple times within 1 year. In patients with long-QT syndrome (LQTS; n = 22), the discrepancy in QTc between two treadmill exercise stress tests using Fridericia's formula was 14 ± 12 ms at rest, 13 ± 12 ms 4 min after exercise, with a maximum of 14 ± 12 ms after exercise. There was no statistically significant difference in QTc between the two tests. Intraclass correlation coefficients (ICC) were 0.84, 0.85, and 0.85, respectively. In controls (n = 13), the discrepancy in QTc was 18 ± 12 ms at rest, 14 ± 7 ms 4 min after exercise, with a maximum of 14 ± 9 ms after exercise. There was no significant difference in QTc between the two tests. ICC were 0.78, 0.80, and 0.80, respectively. QTc calculated using Bazett's formula also showed high reproducibility. Reproducibility of QTc in children is high at rest and after exercise.

reproducibility
long QT syndrome
exercise stress test
Fridericia's formula
Bazett's formula


Behavioral and Functional Assays for Investigating Mechanisms of Noxious Cold Detection and Multimodal Sensory Processing in Drosophila Larvae.

Abstract: To investigate cellular, molecular and behavioral mechanisms of noxious cold detection, we developed cold plate behavioral assays and quantitative means for evaluating the predominant noxious cold-evoked contraction behavior. To characterize neural activity in response to noxious cold, we implemented a GCaMP6-based calcium imaging assay enabling in vivo studies of intracellular calcium dynamics in intact Drosophila larvae. We identified Drosophila class III multidendritic (md) sensory neurons as multimodal sensors of innocuous mechanical and noxious cold stimuli and to dissect the mechanistic bases of multimodal sensory processing we developed two independent functional assays. First, we developed an optogenetic dose response assay to assess whether levels of neural activation contributes to the multimodal aspects of cold sensitive sensory neurons. Second, we utilized CaMPARI, a photo-switchable calcium integrator that stably converts fluorescence from green to red in presence of high intracellular calcium and photo-converting light, to assess in vivo functional differences in neural activation levels between innocuous mechanical and noxious cold stimuli. These novel assays enable investigations of behavioral and functional roles of peripheral sensory neurons and multimodal sensory processing in Drosophila larvae.

Noxious cold
Multimodal sensory processing
Drosophila
Calcium imaging
Optogenetics
Nociception


What Did You Expect? Substance Use Expectancies Mediate the Relationships Between Dark Triad Traits, Substance Use, and Substance Preference.

Abstract: This study explores the role of substance use expectancies as mediators between the Dark Triad of personality, substance use, and substance use preferences. A sample of college students ( M = 19.38, SD = 2.63, N = 207) completed an online questionnaire that assessed the Dark Triad traits, substance use history, substance preferences, and substance use expectancies. Three specific substance use expectancies-increased confidence, tension reduction, and cognitive enhancement-were shown to either partially or fully mediate the relationships between the Dark Triad and substance use behaviors and preference for certain substances of abuse. These findings may hold clinical implications for the treatment of substance use disorders and further the understanding of factors contributing to the etiology and progression of substance abuse and substance use disorders.

Gott|Adam Jordan|AJ|
Hetzel-Riggin|Melanie D|MD|

D007722:Health Knowledge, Attitudes, Practice

substance use
substance use expectancy
mediation
Dark Triad
substance preference
drugs and alcohol


The pharmacokinetics, efficacy, safety, and ease of use of a novel portable metered-dose cannabis inhaler in patients with chronic neuropathic pain: a phase 1a study.

Abstract: Chronic neuropathic pain is often refractory to standard pharmacological treatments. Although growing evidence supports the use of inhaled cannabis for neuropathic pain, the lack of standard inhaled dosing plays a major obstacle in cannabis becoming a "main stream" pharmacological treatment for neuropathic pain. The objective of this study was to explore the pharmacokinetics, safety, tolerability, efficacy, and ease of use of a novel portable thermal-metered-dose inhaler (tMDI) for cannabis in a cohort of eight patients suffering from chronic neuropathic pain and on a stable analgesic regimen including medicinal cannabis. In a single-dose, open-label study, patients inhaled a single 15.1 ± 0.1 mg dose of cannabis using the Syqe Inhaler device. Blood samples for Δ(9)-tetrahydrocannabinol (THC) and 11-hydroxy-Δ(9)-THC were taken at baseline and up to 120 minutes. Pain intensity (0-10 VAS), adverse events, and satisfaction score were monitored following the inhalation. A uniform pharmacokinetic profile was exhibited across all participants (Δ(9)-THC plasma Cmax ± SD was 38 ± 10 ng/mL, Tmax ± SD was 3 ± 1 minutes, AUC₀→infinity ± SD was 607 ± 200 ng·min/mL). Higher plasma Cmax increase per mg Δ(9)-THC administered (12.3 ng/mL/mg THC) and lower interindividual variability of Cmax (25.3%), compared with reported alternative modes of THC delivery, were measured. A significant 45% reduction in pain intensity was noted 20 minutes post inhalation (P = .001), turning back to baseline within 90 minutes. Tolerable, lightheadedness, lasting 15-30 minutes and requiring no intervention, was the only reported adverse event. This trial suggests the potential use of the Syqe Inhaler device as a smokeless delivery system of medicinal cannabis, producing a Δ(9)-THC pharmacokinetic profile with low interindividual variation of Cmax, achieving pharmaceutical standards for inhaled drugs.

pharmacokinetics
inhalation
neuropathic pain
pain
medicinal cannabis
analgesia
vaporization
Δ9-THC


Identification and analysis of long non-coding RNAs and mRNAs in chicken macrophages infected with avian infectious bronchitis coronavirus.

Abstract:
BACKGROUND
Avian infectious bronchitis virus (IBV) is a gamma coronavirus that severely affects the poultry industry worldwide. Long non-coding RNAs (lncRNAs), a subset of non-coding RNAs with a length of more than 200 nucleotides, have been recently recognized as pivotal factors in the pathogenesis of viral infections. However, little is known about the function of lncRNAs in host cultured cells in response to IBV infection.

RESULTS
We used next-generation high throughput sequencing to reveal the expression profiles of mRNAs and lncRNAs in IBV-infected HD11 cells. Compared with the uninfected cells, we identified 153 differentially expressed (DE) mRNAs (106 up-regulated mRNAs, 47 down-regulated mRNAs) and 181 DE lncRNAs (59 up-regulated lncRNAs, 122 down-regulated lncRNAs) in IBV-infected HD11 cells. Moreover, gene ontology (GO) and pathway enrichment analyses indicated that DE mRNAs and lncRNAs were mainly involved in cellular innate immunity, amino acid metabolism, and nucleic acid metabolism. In addition, 2640 novel chicken lncRNAs were identified, and a competing endogenous RNA (ceRNAs) network centered on gga-miR-30d and miR-146a-5p was established.

CONCLUSIONS
We identified expression profiles of mRNAs and lncRNAs during IBV infection that provided new insights into the pathogenesis of IBV.


A geological perspective on the degradation and conservation of western Atlantic coral reefs.

Abstract: Continuing coral-reef degradation in the western Atlantic is resulting in loss of ecological and geologic functions of reefs. With the goal of assisting resource managers and stewards of reefs in setting and measuring progress toward realistic goals for coral-reef conservation and restoration, we examined reef degradation in this region from a geological perspective. The importance of ecosystem services provided by coral reefs-as breakwaters that dissipate wave energy and protect shorelines and as providers of habitat for innumerable species-cannot be overstated. However, the few coral species responsible for reef building in the western Atlantic during the last approximately 1.5 million years are not thriving in the 21st century. These species are highly sensitive to abrupt temperature extremes, prone to disease infection, and have low sexual reproductive potential. Their vulnerability and the low functional redundancy of branching corals have led to the low resilience of western Atlantic reef ecosystems. The decrease in live coral cover over the last 50 years highlights the need for study of relict (senescent) reefs, which, from the perspective of coastline protection and habitat structure, may be just as important to conserve as the living coral veneer. Research is needed to characterize the geological processes of bioerosion, reef cementation, and sediment transport as they relate to modern-day changes in reef elevation. For example, although parrotfish remove nuisance macroalgae, possibly promoting coral recruitment, they will not save Atlantic reefs from geological degradation. In fact, these fish are quickly nibbling away significant quantities of Holocene reef framework. The question of how different biota covering dead reefs affect framework resistance to biological and physical erosion needs to be addressed. Monitoring and managing reefs with respect to physical resilience, in addition to ecological resilience, could optimize the expenditure of resources in conserving Atlantic reefs and the services they provide.

D003247:Conservation of Natural Resources

coral reef
bioerosion
cementation
monitoring
Acropora
Caribbean
Caribe
Holocene geology
bioerosión
cementación de arrecifes
geología de Holoceno
los arrecifes de coral
monitoreo


Assessing child abuse: "We need to talk!"

Abstract:
BACKGROUND
This discussion paper adds to the recent critical debate concerning retrospective measurement of childhood abuse and adverse experiences. A series of recent articles found only modest overlap of prospective informant-based records with retrospective self-report questionnaires, with biases evident in the latter. However, this literature has omitted the use of investigator-based interviews as an alternative retrospective tool for triangulation of measurement. Validated interview approaches can ascertain accurate data using expert scoring that can be used to test both dose-effect and specificity analyses for further research and treatment purposes.

OBJECTIVE
Arguments for the retention and further promotion of intensive interview measures for retrospective assessment of childhood neglect and abuse in relation to lifetime clinical outcomes are presented, with illustrative analyses.

METHOD AND RESULTS
A network analytic approach is outlined, with six types of childhood abuse or neglect experiences scored via a well-validated interview (the Childhood Experiences of Care and Abuse). This indicates distinct pathways between types of neglect and abuse, but also from more common emotional abuse (antipathy, critical parenting) through to more pernicious psychological abuse (coercive, sadistic control) involving physical abuse or sexual abuse pathways. This is supplemented by a case vignette to illustrate the different pathways indicated.

CONCLUSIONS
The interview approach gives victims a voice with their narrative (chance to talk) needed for better understanding of the specific dynamics of child abuse and neglect and for an entry into psychotherapeutic work. We need to ensure that such methods are retained in the research and practitioner portfolio of measurement tools.

Child abuse
Retrospective
Interview measure
CECA
Lifespan
Parental neglect


Radiographic Evaluation of Mastoid Parameters for Sexual Differentiation in North Indian Population.

Abstract:
INTRODUCTION
Morphometric differences of several bones form the basis of sexual differentiation. The mastoid triangle has been widely used as a predictor of sexual differentiation. However, the radiographic measurements of the mastoid triangle, which form the clinical alternative of this parameter, have not been studied in the North Indian population. Therefore, we analyzed skull radiographs of live subjects to investigate the effectiveness of the radiographic mastoid triangle in sex determination.

METHODS
One hundred skull lateral radiographs (55 male and 45 female) from the digital archives of a tertiary care teaching institute in Northern India were retrospectively analyzed. The following parameters: porion-mastoidale length, mastoidale-asterion length, asterion-porion length, and area of the mastoid triangle were measured. Gender-based differences for these parameters were then calculated for any statistical significance. Further, the low value of Wilks' lambda, high values of Eigenvalues, and percentage of correct prediction accuracy denoted higher predictive value. Finally, discriminant function analysis was used to predict the relative validity of each measured parameter.

RESULT
All measured parameters were significantly higher in the male group. The porion-mastoidale length was 32.21±2.15 mm in males and 31.66±3.21 mm in females. The mastoidale-asterion length was 50.00±9.75 mm in males and 49.84±6.97 in females. The asterion-porion length was 44.11±6.82 mm in males and 39.72±5.77 mm in females. The area of the mastoid triangle was 690.74±123.35 mm2 in males and 570.57±130.0 mm2 in females. The area of the mastoid triangle has the highest relative validity (78%).

CONCLUSION
Considerable ethnic and racial differences have been observed in the radiographic morphology of the mastoid. The radiographic dimensions of the mastoid are potential predictors of sexual dimorphism. With the use of discriminant function analysis, the current study predicts the effectiveness of the area of the mastoid triangle as a reliable parameter for sexual differentiation in the Northern Indian population.

Passey|Jigyasa|J| Pandey|Suniti|S| Passey|Nishtha|N| Singh|Rahul|R| Singh|Raveena|R| Kumar|Arvind|A|

mastoid triangle
skull radiographs
sexual dimorphism
morphometry
north india


Long-term adverse effects on reproductive function in male rats exposed prenatally to the glucocorticoid betamethasone.

Abstract: Betamethasone is the drug of choice for antenatal treatment, promoting fetal lung maturation, decreasing the incidence of respiratory distress syndrome and neonatal mortality. Previous studies reported that prenatal treatment with this drug reduced testosterone levels, sperm quality and fertility in adult rats. We aimed to further evaluate the reproductive consequences of prenatal betamethasone exposure in male rats. Pregnant Wistar rats (n=13/group) were separated into two groups: control (vehicle) and betamethasone- treated (0.1mg/kg IM) and rats were injected on gestational days 12, 13, 18 and 19. Body weight, sexual behavior, reproductive organ weights, serum hormone levels, accessory glands contractility, sperm parameters, and fertility after in utero artificial insemination were evaluated. Our results showed that prenatal betamethasone exposure provoked a significant reduction in body weight at PND 01 and, at adulthood, decrease in FSH levels, sperm motility and production. Furthermore, seminal vesicle weight was decreased while testicular and ventral prostate weights were increased. Serum LH levels and the percentage of abnormal sperm were significantly increased. Although sexual behavior was not altered, a significant reduction in fertility in the adult rats exposed prenatally to betamethasone was noted. We concluded that prenatal betamethasone exposure leads to long-term reproductive impairment in male rats. These results may have important implications for humans, considering the use of this glucocorticoid in pregnant women.

Borges|Cibele Dos S|CD|
Dias|Ana Flávia M G|AF|
Silva|Patricia V|PV|
Rosa|Josiane Lima|JL|
Guerra|Marina T|MT|
Silva|Raquel F|RF|
Kiguti|Luiz Ricardo A|LR|
Pupo|André S|AS|
Kempinas|Wilma De G|WG|

D011297:Prenatal Exposure Delayed Effects

Betamethasone
Sperm quality
Fertility
Fetal programming
Sexual glands contractility


Structural and thermodynamic basis of the inhibition of Leishmania major farnesyl diphosphate synthase by nitrogen-containing bisphosphonates.

Abstract: Farnesyl diphosphate synthase (FPPS) is an essential enzyme involved in the biosynthesis of sterols (cholesterol in humans and ergosterol in yeasts, fungi and trypanosomatid parasites) as well as in protein prenylation. It is inhibited by bisphosphonates, a class of drugs used in humans to treat diverse bone-related diseases. The development of bisphosphonates as antiparasitic compounds targeting ergosterol biosynthesis has become an important route for therapeutic intervention. Here, the X-ray crystallographic structures of complexes of FPPS from Leishmania major (the causative agent of cutaneous leishmaniasis) with three bisphosphonates determined at resolutions of 1.8, 1.9 and 2.3 Å are reported. Two of the inhibitors, 1-(2-hydroxy-2,2-diphosphonoethyl)-3-phenylpyridinium (300B) and 3-butyl-1-(2,2-diphosphonoethyl)pyridinium (476A), co-crystallize with the homoallylic substrate isopentenyl diphosphate (IPP) and three Ca(2+) ions. A third inhibitor, 3-fluoro-1-(2-hydroxy-2,2-diphosphonoethyl)pyridinium (46I), was found to bind two Mg(2+) ions but not IPP. Calorimetric studies showed that binding of the inhibitors is entropically driven. Comparison of the structures of L. major FPPS (LmFPPS) and human FPPS provides new information for the design of bisphosphonates that will be more specific for inhibition of LmFPPS. The asymmetric structure of the LmFPPS-46I homodimer indicates that binding of the allylic substrate to both monomers of the dimer results in an asymmetric dimer with one open and one closed homoallylic site. It is proposed that IPP first binds to the open site, which then closes, opening the site on the other monomer, which closes after binding the second IPP, leading to the symmetric fully occupied FPPS dimer observed in other structures.

Aripirala|Srinivas|S|
Gonzalez-Pacanowska|Dolores|D|
Oldfield|Eric|E|
Kaiser|Marcel|M|
Amzel|L Mario|LM|
Gabelli|Sandra B|SB|

Leishmania major
farnesyl diphosphate synthase
FPP
IPP


Efficacy and safety of post-cesarean section incisional infiltration with lidocaine and epinephrine versus lidocaine alone in reducing postoperative pain: A randomized controlled double-blinded clinical trial.

Abstract:
OBJECTIVE
Aim was to assess the efficacy and safety of incisional infiltration of lidocaine and epinephrine vs. lidocaine only to reduce postcesarean section (C/S) pain.

MATERIAL AND METHODS
It was a prospective, randomized, controlled, double-blinded clinical trial that was conducted in two tertiary hospitals in Egypt and included 153 women undergoing C/S under general anesthesia. They were randomly divided into the following two groups: Group I (control group, number=78), in which the wound was infiltrated before skin closure with 20 mL of 2% lidocaine, and Group II (study group, number=75), in which the wound was infiltrated before skin closure with 20 mL of 2% lidocaine and epinephrine. The primary outcomes were the time to first analgesic (TFA) request (minutes) and the postoperative pain scores that were measured using a visual analogue scale (VAS). The secondary outcomes included the duration of C/S, onset of mobilization, onset of breastfeeding, duration of hospital stay, local or systemic side effects of lidocaine and epinephrine, postoperative pyrexia, and postoperative wound infection.

RESULTS
The pain score determined using VAS after 1 and 2 h was significantly decreased in Group II than in Group I. However, at 4.8 and 16 h, these results were significantly reversed in Group II than in Group I. The cumulative postoperative opioid consumption was significantly less in Group II than in Group I (50 vs. 90 mg). The onset of mobilization, onset of breastfeeding, and duration of hospital stay was significantly shorter in Group II than in Group I, whereas the TFA request was significantly longer in Group II.

CONCLUSION
Administering epinephrine with 2% lidocaine prolongs the anesthetic effect and reduces the opioid analgesic dose postoperatively required, thereby enhancing patient recovery.

Tharwat|Ahmed A|AA|
Yehia|Amr H|AH|
Wahba|Karim A|KA|
Ali|Abd-Elrhman G|AE|

lidocaine
epinephrine
Local anesthetic
cesarean section


Identification of biosynthetic intermediates for the mating hormone α2 of the plant pathogen Phytophthora.

Abstract: The heterothallic group of the plant pathogen Phytophthora can sexually reproduce between the cross-compatible mating types A1 and A2. The mating hormone α2, produced by A2 mating type and utilized to promote the sexual reproduction of the partner A1 type, is known to be biosynthesized from phytol. In this study, we identified 2 biosynthetic intermediates, 11- and 16-hydroxyphytols (1 and 2), for α2 by administering the synthetic intermediates to an A2-type strain to produce α2 and by administering phytol to A2 strains to detect the intermediates in the mycelia. The results suggest that α2 is biosynthesized by possibly 2 cytochrome P450 oxygenases via 2 hydroxyphytol intermediates (1 and 2) in A2 hyphae and secreted outside.

mating hormone
plant pathogen
Phytophthora
sexual reproduction
biosynthesis


A year in review: sleep dysfunction and psychological distress in healthcare workers during the COVID-19 pandemic.

Abstract: The Covid-19 outbreak has taken a substantial toll on the mental and physical wellbeing of healthcare workers (HCWs), impacting healthcare systems at a global scale. One year into the pandemic, the need to establish the prevalence of sleep dysfunction and psychological distress in the face of COVID-19, identify risk and protective factors and explore effective countermeasures remains of critical importance. Despite implicit limitations relating to the quality of available studies, a plethora of evidence to-date suggests that a considerable proportion of HCWs experience significant sleep disturbances (estimated to afflict every two in five HCWs) as well as mood symptoms (with more than one in five reporting high levels of depression or anxiety). Younger age, female gender, frontline status, fear or risk of infection, occupation, current or past mental health concerns, and a lower level of social support were all associated with a greater risk of disturbed sleep and adverse psychological outcomes. Furthermore, we discuss the link between sleep deprivation, susceptibility to viral infections and psychosocial wellbeing, in relevance to COVID-19 and summarize the existing evidence regarding the presence and predictors of traumatic stress/PTSD and burnout in HCWs. Finally, we highlight the role of resilience and tailored interventions in order to mitigate vulnerability and prevent long-term physical and psychological implications. Indeed, promoting psychological resilience through an enhanced social support network has proven crucial for HCWs in coping under these strenuous circumstances. Future research should aim to provide high quality information on the long-term consequences and the effectiveness of applied interventions.

Sleep dysfunction
Healthcare workers
COVID-19
Mental health
PTSD
Burnout


Application and Dosimetric Requirements for Gallium-68-labeled Somatostatin Analogues in Targeted Radionuclide Therapy for Gastroenteropancreatic Neuroendocrine Tumors.

Abstract: Neuroendocrine tumors (NETs) are associated with variable prognosis, with grade 1 and 2 NETs having more favorable outcomes than grade 3. Patients with gastroenteropancreatic (GEP)-NET need individualized interdisciplinary evaluations and treatment. New treatment options have become available with significant improvements in progression-free survival. Peptide receptor radionuclide therapy (PRRT) using (90)Y or (177)Lu-labeled somatostatin analogues (SSTa) has also shown promise in the treatment of advanced progressive NETs. (68)Ga-1,4,7,10-tetraazacyclodecane-1,4,7,10-tetraacetic acid (DOTA)-SSTa can be used as companion imaging agents to assist in radionuclide therapy selection. (68)Ga-DOTA-SSTa PET/computed tomography might also provide information for prognosis, tumor response assessment to PRRT, and internal dosimetry.

Taïeb|David|D|
Garrigue|Philippe|P|
Bardiès|Manuel|M|
Abdullah|Ahmad Esmaeel|AE|
Pacak|Karel|K|

D014408:Biomarkers, Tumor
D004067:Digestive System Neoplasms
D005710:Gallium Radioisotopes
D006801:Humans
D007553:Isotope Labeling
D064847:Multimodal Imaging
D018358:Neuroendocrine Tumors
D049268:Positron-Emission Tomography
D011379:Prognosis
D011874:Radiometry
D019275:Radiopharmaceuticals
D061089:Radiotherapy, Image-Guided
D017481:Receptors, Somatostatin
D013004:Somatostatin
D014057:Tomography, X-Ray Computed
D016896:Treatment Outcome

Somatostatin
Gastroenteropancreatic
Neuroendocrine
PET
Gallium radioisotopes


Effects of probiotics on gut microbiota: mechanisms of intestinal immunomodulation and neuromodulation.

Abstract: Recent explorations of the human gut microbiota suggest that perturbations of microbial communities may increase predisposition to different disease phenotypes. Dietary nutrients may be converted into metabolites by intestinal microbes that serve as biologically active molecules affecting regulatory functions in the host. Probiotics may restore the composition of the gut microbiome and introduce beneficial functions to gut microbial communities, resulting in amelioration or prevention of gut inflammation and other intestinal or systemic disease phenotypes. This review describes how diet and intestinal luminal conversion by gut microbes play a role in shaping the structure and function of intestinal microbial communities. Proposed mechanisms of probiosis include alterations of composition and function of the human gut microbiome, and corresponding effects on immunity and neurobiology.

probiotics
gut microbiota
immunomodulation
diet
Lactobacillus
nervous system


Efficacy of pemetrexed and carboplatin with or without bevacizumab in lung adenocarcinoma patients with EGFR non-T790M mutations after progression on first-line EGFR-tyrosine kinase inhibitors.

Abstract:
BACKGROUND
The purpose of this study was to compare the effects of pemetrexed and carboplatin plus bevacizumab (PC + B) versus pemetrexed and carboplatin (PC) in lung adenocarcinoma patients with EGFR non-T790M mutations after progression on first-line EGFR-tyrosine kinase inhibitors (TKIs).

METHODS
Patients with EGFR-positive lung adenocarcinoma who had received second-line PC with or without bevacizumab harboring EGFR non-T790M mutations after progression on first-line EGFR-TKIs between April 2015 and 2017 at Tianjin Medical University Cancer Institute and Hospital were enrolled in the study. The primary endpoint was progression-free survival and secondary endpoints were overall survival, objective response rate, disease control rate, and safety.

RESULTS
A total of 85 patients were eligible for the study: 55 and 30 cases were enrolled in the PC and PC + B groups, respectively. The median progression-free survival was prolonged with PC + B compared to PC (median 8.2 vs. 5.1 months; P = 0.037). The objective response rate was improved with PC + B compared to PC (46.7% vs. 25.5%; P = 0.047) and overall survival prolonged with PC + B compared to PC (median 26.3 vs. 19.2 months; P = 0.012). Safety was similar to previous studies of bevacizumab in non-small cell lung cancer: one patient experienced grade 3 hypertension and proteinuria but did not require the discontinuation of therapy.

CONCLUSION
The addition of bevacizumab to PC was superior to PC alone as second-line therapy in patients with advanced non-T90M EGFR-positive lung adenocarcinoma. However, this result needs to be confirmed by prospective clinical trials.

Jiang|Zhansheng|Z| Zhang|Yu|Y| Yang|Yinli|Y| Yue|Zhensong|Z| Pan|Zhanyu|Z|

D000971:Antineoplastic Combined Chemotherapy Protocols

pemetrexed
bevacizumab
lung adenocarcinoma
Epidermal growth factor receptor (EGFR)
T790M


Behavioral activation can normalize neural hypoactivation in subthreshold depression during a monetary incentive delay task.

Abstract:
BACKGROUND
Late adolescents are under increased risk of developing depressive symptoms. Behavioral activation is an effective treatment for subthreshold depression, which can prevent the development of subthreshold depression into a major depressive disorder. However, the neural mechanisms underlying the efficacy of behavioral activation have not been clearly understood. We investigated neural responses during reward processing by individuals with subthreshold depression to clarify the neural mechanisms of behavioral activation.

METHODS
Late adolescent university students with subthreshold depression (n=15, age 18-19 years) as indicated by a high score on the Beck's Depression Inventory-ll (BDI-ll) and 15 age-matched controls with a low BDI-ll score participated in functional magnetic resonance imaging scanning conducted during a monetary incentive delay task on two occasions. The Individuals in the subthreshold depression group received five, weekly behavioral activation sessions between the two scanning sessions. Moreover, they did not receive any medication until the study was completed.

RESULTS
Behavioral activation significantly reduced depressive symptoms. Moreover, compared to the changes in brain functions in the control group, the behavioral activation group showed functional changes during loss anticipation in brain structures that mediates cognitive and emotional regulation, including the left ventrolateral prefrontal cortex and angular gyrus.

LIMITATIONS
Replication of the study with a larger sample size is required to increase the generalizability of these results.

CONCLUSIONS
Behavioral activation results in improved functioning of the fronto-parietal region during loss anticipation. These results increase our understanding of the mechanisms underlying specific psychotherapies.

Mori|Asako|A| Okamoto|Yasumasa|Y| Okada|Go|G| Takagaki|Koki|K| Jinnin|Ran|R| Takamura|Masahiro|M| Kobayakawa|Makoto|M| Yamawaki|Shigeto|S|

Behavioral activation
Depression
Monetary incentive delay task
Magnetic resonance imaging
Prefrontal cortex


Implementation of quality by design toward processing of food products.

Abstract: Quality by design (QbD) is a systematic approach that begins with predefined objectives and emphasizes product and process understanding and process control. It is an approach based on principles of sound science and quality risk management. As the food processing industry continues to embrace the idea of in-line, online, and/or at-line sensors and real-time characterization for process monitoring and control, the existing gaps with regard to our ability to monitor multiple parameters/variables associated with the manufacturing process will be alleviated over time. Investments made for development of tools and approaches that facilitate high-throughput analytical and process development, process analytical technology, design of experiments, risk analysis, knowledge management, and enhancement of process/product understanding would pave way for operational and economic benefits later in the commercialization process and across other product pipelines. This article aims to achieve two major objectives. First, to review the progress that has been made in the recent years on the topic of QbD implementation in processing of food products and second, present a case study that illustrates benefits of such QbD implementation.

D003296:Cooking
D004042:Dietary Fats, Unsaturated
D004867:Equipment Design
D005511:Food Handling
D011786:Quality Control

quality by design
QbD
Food processing
process analytical technology
PAT


Long non-coding RNAs in recurrent ovarian cancer: Theranostic perspectives.

Abstract: Nearly 70% of ovarian cancer (OC) patients experience recurrence within the first 2 years after initial treatment. Emerging evidence indicates that long non-coding RNAs (lncRNAs) play a pivotal role in the pathogenesis of OC progression, resistance to therapy and recurrent OC (ROC). Transcriptome profiling studies have reported differential expression patterns of lncRNAs in OC which are related to increased cell invasion, metastasis and drug resistance. In this review, we highlighted the roles of lncRNAs in OC progression and outlined the potential molecular mechanisms by which lncRNAs impact on ROC. Recent advances using lncRNAs as potential biomarkers for screening, detection, prediction, response to therapy and as therapeutic targets are discussed.

Bhardwaj|Vipul|V|
Tan|Yan Qin|YQ|
Wu|Ming Ming|MM|
Ma|Lan|L|
Zhu|Tao|T|
Lobie|Peter E|PE|
Pandey|Vijay|V|

D015972:Gene Expression Regulation, Neoplastic

Recurrence
LncRNA
ROC
Metastasis
Drug resistance
Cancer biomarker


A self-enforcing HOXA11/Stat3 feedback loop promotes stemness properties and peritoneal metastasis in gastric cancer cells.

Abstract: Rationale: Peritoneal metastasis is one of the most common and life-threatening metastases in gastric cancer patients. The disseminated gastric cancer cells forming peritoneal metastasis exhibit a variety of characteristics that contrast with those of adjacent epithelial cell of gastric mucosa and even primary gastric cancer cells. We hypothesized that the gene expression profiles of peritoneal foci could reveal the identities of genes that might function as metastatic activator. Methods: In this study, we show, using in vitro, in vivo, in silico and gastric cancer tissues studies in humans and mice, that Homoebox A11 (HOXA11) potently promote peritoneal metastasis of gastric cancer cells. Results: Its mechanism of action involves alternation of cancer stemness and subsequently enhancement of the adhesion, migration and invasion and anti-apoptosis. This is achieved, mainly, through formation of a positive feedback loop between HOXA11 and Stat3, which is involved in the stimulation of Stat3 signaling pathway. Conclusions: These observations uncover a novel peritoneal metastatic activator and demonstrate the association between HOXA11, Stat3 and cancer stemness of gastric cancer cells, thereby revealing a previously undescribed mechanism of peritoneal metastasis.

Wang|Chao|C| Shi|Min|M| Ji|Jun|J| Cai|Qu|Q| Jiang|Jinling|J| Zhang|Huan|H| Zhu|Zhenggang|Z| Zhang|Jun|J|


Getting Along in Assisted Living: Quality of Relationships Between Family Members and Staff.

Abstract:
BACKGROUND AND OBJECTIVES
Assisted living facilities (ALFs) have quickly expanded as an alternative to nursing homes. Research on nursing homes has revealed problems in relationships between family members and staff. However, little is known about these relationships within ALFs. The purpose of the current study was to examine the prevalence of conflict and positive and negative interactions from the perspective of both family members and staff and to examine the effects of positive and negative aspects of the relationship on salient staff and family outcomes in ALFs.

RESEARCH DESIGN AND METHODS
Data were collected from 252 family members and 472 staff members across 20 ALFs who participated in the Partners in Care in Assisted Living study. Participants completed measures including interpersonal conflict, depressive symptoms, perception of treatment, and stress related to caregiving.

RESULTS
Conflict among family and staff members was found to be relatively low. For staff, interpersonal conflict and treatment by family members significantly predicted burnout and depressive symptoms. For families, only female gender significantly predicted burden. Subgroup analyses, however, indicated that the effect of interpersonal conflict was significantly associated with perceived caregiver burden among family members whose relative had dementia.

DISCUSSION AND IMPLICATIONS
Despite the relatively harmonious relationships among family-staff in ALFs, sources of conflict and negative interactions were identified, revealing the importance of collaborative relationships and the influence these relationships have on both family and staff outcomes. These findings can inform intervention efforts to improve family-staff interactions within ALFs.

Falzarano|Francesca|F|
Reid|M Carrington|MC|
Schultz|Leslie|L|
Meador|Rhoda H|RH|
Pillemer|Karl|K|

Assisted living
Conflict
Communication
Family–staff relationships


Xanthophyllomyces dendrorhous, a Versatile Platform for the Production of Carotenoids and Other Acetyl-CoA-Derived Compounds.

Abstract: Xanthophyllomyces dendrorhous (with Phaffia rhodozyma as its anamorphic state) is a basidiomycetous, moderately psychrophilic, red yeast belonging to the Cystofilobasidiales. Its red pigmentation is caused by the accumulation of astaxanthin, which is a unique feature among fungi. The present chapter reviews astaxanthin biosynthesis and acetyl-CoA metabolism in X. dendrorhous and describes the construction of a versatile platform for the production of carotenoids, such as astaxanthin, and other acetyl-CoA-derived compounds including fatty acids by using this fungus.

Sandmann|Gerhard|G| Pollmann|Hendrik|H| Gassel|Sören|S| Breitenbach|Jürgen|J|

Xanthophyllomyces dendrorhous
Basidiomycete
Astaxanthin
Carotenoid biosynthesis
Poly-unsaturated fatty acids


Duchenne and Becker muscular dystrophy carriers: Evidence of cardiomyopathy by exercise and cardiac MRI testing.

Abstract:
BACKGROUND
Varied detection methods have resulted in conflicting reports on the prevalence of cardiac disease in Duchenne and Becker muscular dystrophy carriers (MDC).

METHODS
We performed a prospective cohort study of 77 genetically-confirmed MDC mothers, 22 non-carrier mothers, and 25 controls. All participants underwent Cardiopulmonary Exercise Testing (CPET) and Cardiac Magnetic Resonance imaging (CMR).

RESULTS
25% of carriers had ventricular ectopy in recovery of exercise (RecVE) as compared to 1 non-carrier and no controls (p = .003). No difference in age or maximal oxygen consumption was noted. 11 carriers had abnormal (<55%) left ventricular ejection fraction by CMR. Evidence of late gadolinium enhancement (LGE) was noted in 48% of MDC, 1 non-carrier patient and no control subjects (p < .0001). Subset analysis of LGE+ and LGE- subjects revealed differences in age (44.1 v 38.6 yrs.; p = .005), presence of RecVE, (38.9% v 10.5%, p = .004), and high serum creatine kinase (CK) (> 289 U/l; 52.8% v 31.6%, p = .065).

CONCLUSION
We describe the prevalence of disease using CPET and CMR in genetically-proven MDC. 49% of carriers had fibrosis, opposed to 5% of non-carriers, highlighting the importance of genetic testing in this population. Despite cardiomyopathy, functional assessment by treadmill was normal, illustrating the discrepancy in cardiac and skeletal muscle impacts. Age, RecVE and serum CK appear to have an important role in predicting cardiomyopathy. Serum CK levels suggest that a systemic higher global disease severity and not tissue heterogeneity may be the etiology for greater cardiac disease and relatively spared skeletal muscle disease in this population. Clinical Trial Registration https://clinicaltrials.gov/ct2/show/NCT02972580?term=mendell&cond=Duchenne+Muscular+Dystrophy&rank=5; ClinicalTrials.gov Identifier: NCT02972580.

Mah|May Ling|ML|
Cripe|Linda|L|
Slawinski|Michelle K|MK|
Al-Zaidy|Samiah A|SA|
Camino|Eric|E|
Lehman|Kelly J|KJ|
Jackson|Jamie L|JL|
Iammarino|Megan|M|
Miller|Natalie|N|
Mendell|Jerry R|JR|
Hor|Kan N|KN|

D019028:Magnetic Resonance Imaging, Cine

Cardiomyopathy
Cardiac magnetic resonance imaging
Ventricular ectopy
Late gadolinium enhancement
Duchenne carrier
Peak oxygen uptake
T1 mapping


A Phenotyping Platform to Characterize Healthy Individuals Across Four Stages of Life - The Enable Study.

Abstract: Introduction: Nutritional habits and requirements are changing over the lifespan, but the dynamics of nutritional issues and the diet-health relationship in the major stages of the human life cycle are not sufficiently understood. A human phenotyping research platform for nutrition studies was established to recruit and phenotype selected population groups across different stages of life. The project is the backbone of the highly interdisciplinary enable competence cluster of nutrition research aiming to identify dietary determinants of a healthy life throughout the lifespan and to develop healthier and tasty convenience foods with high consumer acceptance. Methods: The phenotyping program included anthropometry, body composition analysis, assessment of energy metabolism, health and functional status, multisensory perception, metabolic phenotyping, lifestyle, sociodemography, chronobiology, and assessment of dietary intake including food preferences and aversions. Results: In total, 503 healthy volunteers at four defined phases of life including 3-5-year old children (n = 44), young adults aged 18-25 years (n = 94), adults aged 40-65 years ("middle agers," n = 205), and older adults aged 75-85 years (n = 160) were recruited and comprehensively phenotyped. Plasma, serum, buffy coat, urine, feces and saliva samples were collected and stored at -80°C. Significant differences in anthropometric and metabolic parameters between the four groups were found. A major finding was the decrease in fat-free mass and the concomitant increase in % body fat in both sexes across the adult lifespan. Conclusions: The dataset will provide novel information on differences in diet-related parameters over the lifespan and is available for targeted analyses. We expect that this novel platform approach will have implications for the development of innovative food products tailored to promote healthy eating throughout life. Trial registration: DRKS, DRKS00009797. Registered on 20 January 2016, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&_ID=DRKS00009797.

Brandl|Beate|B| Skurk|Thomas|T| Rennekamp|Rachel|R| Hannink|Anne|A| Kiesswetter|Eva|E| Freiherr|Jessica|J| Ihsen|Susanne|S| Roosen|Jutta|J| Klingenspor|Martin|M| Haller|Dirk|D| Krautwurst|Dietmar|D| Hofmann|Thomas|T| Linseisen|Jakob|J| Volkert|Dorothee|D| Hauner|Hans|H|

nutrition
metabolic phenotyping
biosamples
cohort
enable-cluster


Double Plant Homeodomain Fingers 2 (DPF2) Promotes the Immune Escape of Influenza Virus by Suppressing Beta Interferon Production.

Abstract: The high mutation rates of the influenza virus genome facilitate the generation of viral escape mutants, rendering vaccines and drugs against influenza virus-encoded targets potentially ineffective. Therefore, we identified host cell determinants dispensable for the host but crucial for virus replication, with the goal of preventing viral escape and finding effective antivirals. To identify these host factors, we screened 2,732 human genes using RNA interference and focused on one of the identified host factors, the double plant homeodomain fingers 2 (DPF2/REQ) gene, for this study. We found that knockdown of DPF2 in cells infected with influenza virus resulted in decreased expression of viral proteins and RNA. Furthermore, production of progeny virus was reduced by two logs in the multiple-cycle growth kinetics assay. We also found that DPF2 was involved in the replication of seasonal influenza A and B viruses. Because DPF2 plays a crucial role in the noncanonical NF-κB pathway, which negatively regulates type I interferon (IFN) induction, we examined the relationship between DPF2 and IFN responses during viral infection. The results showed that knockdown of DPF2 resulted in increased expression of IFN-β and induced phosphorylation of STAT1 in infected cells. In addition, high levels of several cytokines/chemokines (interleukin-8 [IL-8], IP-10, and IL-6) and antiviral proteins (MxA and ISG56) were produced by DPF2 knockdown cells. In conclusion, we identified a novel host factor, DPF2, that is required for influenza virus to evade the host immune response and that may serve as a potential antiviral target.IMPORTANCE Influenza virus is responsible for seasonal epidemics and occasional pandemics and is an ongoing threat to public health worldwide. Influenza virus relies heavily on cellular factors to complete its life cycle. Here we identified a novel host factor, DPF2, which is involved in influenza virus infection. Our results showed that DPF2 plays a crucial role in the replication and propagation of influenza virus. DPF2 functions in the noncanonical NF-κB pathway, which negatively regulates type I IFN induction. Thus, we investigated the relationship between the IFN response and DPF2 in influenza virus infection. Upon influenza virus infection, DPF2 dysregulated IFN-β induction and expression of cytokines/chemokines and antiviral proteins. This study provides evidence that influenza virus utilizes DPF2 to escape host innate immunity.

Shin|Dongjo|D|
Lee|Jihye|J|
Park|Ji Hoon|JH|
Min|Ji-Young|JY|

D048868:Adaptor Proteins, Signal Transducing

DPF2
immune escape
influenza virus
interferon


What Difference Does It Make? A Comparison of Health State Preferences Elicited From the General Population and From People With Multiple Sclerosis.

Abstract:
BACKGROUND
A major debate in the quality-adjusted life-year (QALY) literature concerns whose preferences should be used to estimate health state values (HSVs) and to calculate QALYs.

OBJECTIVES
This study explores differences between public and patient values for multiple sclerosis (MS) health states, described using an MS-specific classification system (Multiple Sclerosis Impact Scale-8 Dimensions [MSIS-8D]).

METHODS
The MSIS-8D is an existing preference-based measure of health-related quality of life in MS, which has 2 tariffs of HSVs, based on the preferences of a representative sample of the UK general population (n = 1702) and of people with MS living in the United Kingdom (n = 1635), elicited using the time trade-off technique. Here, we explore differences between HSVs by sample type, using descriptive statistics and multivariate regression methods.

RESULTS
Overall, the survey of people with MS produced significantly higher HSVs; estimated values ranged from 0.079 to 0.883 for the general population survey and from 0.138 to 0.894 for the MS survey. Differences in HSVs were more pronounced for severe health states. The difference between patient and public values varied across the dimensions of the MSIS-8D. People with MS placed greater importance on cognition than the general population, leading to lower HSVs when impairment was at a worse level; the reverse was true for the daily activities, fatigue, and depression dimensions.

CONCLUSIONS
We identified significant differences in HSVs by sample type. Using patient rather than public values may influence the results of economic evaluations, depending on the dimensions of health-related quality of life affected by the intervention being assessed, and may therefore have important consequences for reimbursement decisions.

D000203:Activities of Daily Living
D000293:Adolescent
D000328:Adult
D000368:Aged
D016022:Case-Control Studies
D017281:Cost of Illness
D005260:Female
D006304:Health Status
D006305:Health Status Indicators
D006801:Humans
D008297:Male
D008603:Mental Health
D008875:Middle Aged
D009103:Multiple Sclerosis
D057240:Patient Preference
D011639:Public Opinion
D011788:Quality of Life
D019057:Quality-Adjusted Life Years
D012720:Severity of Illness Index
D013997:Time Factors
D006113:United Kingdom
D055815:Young Adult

preference elicitation
multiple sclerosis
patient preferences
public preferences
utility assessment


Independent birth of a novel TRIMCyp in Tupaia belangeri with a divergent function from its paralog TRIM5.

Abstract: The origin of novel genes and their evolutionary fates are long-standing questions in evolutionary biology. These questions become more complicated for genes conserved across various lineages, such as TRIM5, an antiretroviral restriction factor and a retrovirus capsid sensor in immune signaling. TRIM5 has been subjected to numerous pathogenic challenges and undergone dynamic evolution, making it an excellent example for studying gene diversification. Previous studies among several species showed that TRIM5 gained genetic and functional novelty in a lineage-specific manner, either through gene duplication or a cyclophilin A retrotransposing into the TRIM5 locus, creating the gene fusion known as TRIM5-Cyclophilin A (TRIMCyp). To date, the general pattern of TRIM5 across the mammalian lineage remains elusive. In this study, we surveyed 36 mammalian genomes to verify a potentially novel TRIM5 pattern that uniquely seems to have occurred in tree shrews (Tupaia belangeri), and found that both gene duplication and retrotransposition worked jointly to form a specific TRIM5/TRIMCyp cluster not found among other mammals. Evolutionary analyses showed that tree shrew TRIMCyp (tsTRIMCyp) originated independently in comparison with previously reported TRIMCyps and underwent strong positive selection, whereas no signal of positive selection was detected for other tree shrew TRIM5 (tsTRIM5) genes. Functional assay results suggest a functional divergence between tsTRIMCyp and its closest paralog TRIM5-4, likely reflecting different fates under diverse evolutionary forces. These findings present a rare example of novel gene origination resulting from a combination of gene duplication, retrotransposition, and exon shuffling processes, providing a new paradigm to study genetic innovations and evolutionary fates of duplicated genes.

Mu|Dan|D| Yang|Hui|H| Zhu|Jia-Wu|JW| Liu|Feng-Liang|FL| Tian|Ren-Rong|RR| Zheng|Hong-Yi|HY| Han|Jian-Bao|JB| Shi|Peng|P| Zheng|Yong-Tang|YT|

D000595:Amino Acid Sequence
D000818:Animals
D001483:Base Sequence
D002352:Carrier Proteins
D021984:Cyclophilin A
D019143:Evolution, Molecular
D005091:Exons
D016368:Frameshift Mutation
D020440:Gene Duplication
D015870:Gene Expression
D007438:Introns
D008969:Molecular Sequence Data
D050506:Mutant Chimeric Proteins
D018626:Retroelements
D012641:Selection, Genetic
D016415:Sequence Alignment
D014417:Tupaia
D016335:Zinc Fingers

TRIMCyp
gene duplication
tree shrew
retrotransposition
positive selection
functional divergence
TRIM5α


Association between filum terminale internum length and pain in Cavalier King Charles spaniels with and without syringomyelia.

Abstract:
BACKGROUND
Lumbar syringomyelia (SM), lumbosacral pain, and more caudal spinal cord termination are reported in Cavalier King Charles spaniels (CKCS). Data are lacking on the clinical relevance of alterations in their spinal cord terminal structures.

OBJECTIVES
To compare spinal cord termination level and filum terminale internum length (FTIL) with presence of lumbar SM and clinical signs in CKCS.

ANIMALS
Forty-eight CKCS.

METHODS
In this prospective study, pain was quantified using owner and clinician assessments. Vertebral level of spinal cord and dural sac termination, presence of SM, and FTIL were determined from sagittal magnetic resonance imaging (MRI) sequences. Kappa and intraclass correlation (ICC) analyses determined interobserver reliability. The MRI findings were compared to owner and clinician-reported pain quantification.

RESULTS
Interobserver reliability was good for spinal cord and dural sac termination (kappa = 0.61 and 0.64, respectively) and excellent for FTIL (ICC: 92% agreement). The spinal cord terminated at 6th lumbar vertebra in 1, 7th lumbar vertebra in 31, and the sacrum in 15 dogs, and termination level was associated with lumbar SM (P = .002) but not clinical signs. Mean FTIL was 2.9 ± 1.08 mm; it was associated with owner-reported pain (P = .033) and spinal palpation scores (P = .023). Painful CKCS without SM had shorter FTIL compared to normal CKCS and painful CKCS with SM (P = .02).

CONCLUSIONS
Painful CKCS without SM have decreased distance between the termination of the spinal cord and dural sac, suggesting a shorter FTIL. More caudal spinal cord termination is associated with development of lumbar SM.

dural sac
Chiari-like malformation
conus medullaris
morphometry
tethered cord


More than meets the eye: Expanding and reviewing the clinical and mutational spectrum of brittle cornea syndrome.

Abstract: Brittle cornea syndrome (BCS) is a rare autosomal recessive disorder characterized by corneal thinning and fragility, leading to corneal rupture, the main hallmark of this disorder. Non-ocular symptoms include not only hearing loss but also signs of connective tissue fragility, placing it in the Ehlers-Danlos syndrome (EDS) spectrum. It is caused by biallelic pathogenic variants in ZNF469 or PRDM5, which presumably encode transcription factors for extracellular matrix components. We report the clinical and molecular features of nine novel BCS families, four of which harbor variants in ZNF469 and five in PRDM5. We also performed a genotype- and phenotype-oriented literature overview of all (n = 85) reported patients with ZNF469 (n = 53) and PRDM5 (n = 32) variants. Musculoskeletal findings may be the main reason for referral and often raise suspicion of another heritable connective tissue disorder, such as kyphoscoliotic EDS, osteogenesis imperfecta, or Marfan syndrome, especially when a corneal rupture has not yet occurred. Our findings highlight the multisystemic nature of BCS and validate its inclusion in the EDS classification. Importantly, gene panels for heritable connective tissue disorders should include ZNF469 and PRDM5 to allow for timely diagnosis and appropriate preventive measures for this rare condition.


Interdisciplinary approach for the management of bilaterally impacted maxillary canines.

Abstract: Interdisciplinary approach for the management of malocclusion provides a holistic approach of patient management. Prudent treatment planning is necessary to achieve the various treatment goals. This case report describes the orthodontic management of a 16-year-old adolescent female patient with bilateral labially impacted maxillary canines. The problems associated with impacted maxillary canines and the biomechanical interventions used for this patient are discussed. The treatment protocol involved surgical intervention, followed by sequential traction of the impacted teeth. An interdisciplinary approach to treatment with different mechanical strategies led to the achievement of the desired esthetic, functional, and occlusal treatment goals.

Sukh|Ram|R|
Singh|Gyan P|GP|
Tandon|Pradeep|P|

interdisciplinary
sequential traction
Flap designs
impacted canine
orthodontic intervention


Premium versus entry-level hearing aids: using group concept mapping to investigate the drivers of preference.

Abstract:
OBJECTIVES
To investigate the difference in outcome measures and drivers of user preference between premium and entry-level hearing aids using group concept mapping.

DESIGN
A single-blind crossover trial was conducted. Aided behavioural outcomes measured were loudness rating, speech/consonant recognition, and speech quality. Preference between hearing aids was measured with a 7-point Likert scale. Group concept mapping was utilised to investigate preference results. Participants generated statements based on what influenced their preferences. These were sorted into categories with underlying themes. Participants rated each statement on a 5-point Likert scale of importance.

STUDY SAMPLE
Twenty-three adult participants (mean: 62.4 years; range: 24-78) with mild to moderately severe bilateral SNHL (PTA500-4000 Hz > 20 dB HL).

RESULTS
A total of 83 unique statements and nine distinct clusters, with underlying themes driving preference, were generated. Clusters that differed significantly in importance between entry-level and premium hearing aid choosers were: Having access to smartphone application-based user-controlled settings, the ability to stream calls and music, and convenience features such as accessory compatibility.

CONCLUSION
This study has identified non-signal-processing factors which significantly influenced preference for a premium hearing aid over an entry-level hearing aid, indicating the importance of these features as drivers of user preference.

Saleh|Hasan K|HK|
Folkeard|Paula|P|
Van Eeckhoutte|Maaike|M|
Scollie|Susan|S|

Hearing aids
concept mapping
drivers of preference
hearing aid product profile
hearing aid technology levels
hearing aid user preference
non-signal-processing features


Efficacy of antimicrobial photodynamic therapy in the management of chronic periodontitis: a randomized controlled clinical trial.

Abstract:
AIM
To evaluate the potential of antimicrobial photodynamic therapy (aPDT) as an adjunct to scaling and root planing (SRP) in the treatment of chronic periodontitis.

MATERIAL AND METHODS
In a single-centred randomized and controlled clinical trial, 90 patients (51 females and 39 males) with untreated chronic periodontitis were randomly assigned to receive SRP with aPDT (test group) or SRP alone (control group). Clinical parameters and halitosis were recorded for 6 months after treatment by a periodontist who was blinded to the procedure.

RESULTS
Inter-group and intra-group statistical analyses were performed. Significant difference between the two groups with respect to each variable was assessed using non-parametric Rank Order ancova. Probing pocket depth and clinical attachment levels showed statistically significant reduction in the test group on evaluation at 3 months and 6 months as compared to the control group (p < 0.05). A statistically significant improvement in gingival index and gingival bleeding index was seen for the test group after 2 weeks and 1 month of aPDT (p < 0.01), whereas the improvement in gingival index and gingival bleeding index at 3 months and in plaque index at 2 weeks after aPDT was less (p < 0.05). Also, a significant difference was detected for the test group at 1 month in terms of halitosis (p < 0.05), which did not persist for long.

CONCLUSIONS
Antimicrobial photodynamic therapy acts as a beneficial adjunct to SRP in non-surgical treatment and management of chronic periodontitis in short-term. Further studies are required to assess the long-term effectiveness of aPDT.

Betsy|Joseph|J|
Prasanth|Chandra S|CS|
Baiju|Kamalasanan V|KV|
Prasanthila|Janam|J|
Subhash|Narayanan|N|

D000328:Adult
D055113:Chronic Periodontitis
D003131:Combined Modality Therapy
D003774:Dental Plaque Index
D012534:Dental Scaling
D005260:Female
D005500:Follow-Up Studies
D005889:Gingival Recession
D006209:Halitosis
D006801:Humans
D054023:Lasers, Semiconductor
D008297:Male
D008751:Methylene Blue
D017622:Periodontal Attachment Loss
D010512:Periodontal Index
D010514:Periodontal Pocket
D010778:Photochemotherapy
D017319:Photosensitizing Agents
D016745:Root Planing

photodynamic therapy
halitosis
adjunctive periodontal treatment
methylene blue
periodontal disease
randomized controlled trial


Angiographic lumen changes associated with oversized intracranial stent implantation for aneurysm treatment.

Abstract:
BACKGROUND
The effect of oversized intracranial stent implantation, and potential excessive neointimal hyperplasia from the chronic outward radial force, has not been reported. We sought to compare the angiographic narrowing associated with implantation of oversized stents.

METHODS
We reviewed an aneurysm database and identified patients treated with stent-assisted embolization involving a vessel size transition. Demographics and lesion characteristics were extracted. The relationship between lumen diameter and stent oversizing was compared.

RESULTS
Twenty vessels were identified in 18 patients, providing 80 paired data points. Mean follow-up time was 8 months (SD 6). The average oversizing in the smaller diameter parent vessel landing-zone was 1.75 mm. Mean change in lumen size from pre-stent implantation was not significantly different for any of the four sites. There was a significant difference in change of lumen size at the stent tines when compared with the respective mid-stent segment for both the proximal (P = 0.02) and distal (P = 0.0004) landing zones.

CONCLUSIONS
A small significant lumen loss occurs at stent tines when compared to midstent struts. However, there is no overall significant stenosis from highly oversized stents. Persistent luminal gain from the oversized stent radial force likely predominates over any neointimal hyperplasia.

Lazzaro|Marc A|MA|
Teleb|Mohamed S|MS|
Zaidat|Osama O|OO|

stenting
Neointimal hyperplasia
stenosis
angiography