bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of DNA adducts derived from the tobacco carcinogens, benzo[a]pyrene and dibenzo[def,p]chrysene in human oral buccal cells
Authors: Chen Kun-Ming , Sun Yuan-Wan , Krebs Nicolle M , Sun Dongxiao , Krzeminski Jacek , Reinhart Lisa , Gowda Krishne , Amin Shantu , Mallery Susan , Richie John P , El-Bayoumy Karam
Published: June 2022

Polycyclic aromatic hydrocarbons (PAHs) are recognized as potential etiological agents in the development of oral cancer in smokers. In particular, benzo[a]pyrene (B[a]P) and dibenzo[def,p]chrysene (DB[a,l]P) are detected in cigarette smoke and the environment and can induce DNA damage, mutagenesis and carcinogenesis in the oral cavity of rodents. Consequently, DNA adducts are regarded as the most direct markers of genotoxicity and can be used as biomarkers of cancer risk. Thus, this study used LC-MS/MS analysis with isotope labeled internal standard to detect and quantify DNA adducts derived from B[a]P and DB[a,l]P in buccal cells of cigarette smokers and non-smokers. Participants in this study include 21 smokers and 16 non-smokers. Our data are the first to report that levels (mean ± SD) of BPDE-N2-dG were significantly (P < 0.001) higher in smokers (20.18 ± 8.40 adducts/108 dG) than in non-smokers (0.84 ± 1.02 adducts/108 dG). Likewise, levels of DBPDE-N6-dA in smokers (5.49 ± 3.41 adducts/108 dA) were significantly higher (P = 0.019) than non-smokers (2.76 ± 2.29 adducts/108 dA). Collectively, the results of this clinical study support that PAHs in tobacco smoke can contribute to the development of oral cancer in humans.
Altered alpha/beta desynchronization during item–context binding contributes to the associative deficit in older age
Authors: Karlsson Anna E , Sander Myriam C
Published: June 2022

It is proposed that older adults have difficulties to bind item and context and to recruit deep, elaborative processing during encoding. Senescent changes in the oscillatory foundations of these processes are currently unclear. We recorded electroencephalography during item–context memory formation in younger (n = 57) and older (n = 55) adults. At test, we assessed memory for the items and the item–context pairs and examined encoding-related activity based on how much information was recovered at retrieval (miss < item–only < pair). Item memory was comparable between age groups while pair memory was reduced in the older adults. Theta synchronization and alpha/beta desynchronization increased linearly with the amount of information available. Single-trial theta power could not predict subsequent item memory, but predicted pair memory in an age-invariant manner, in line with a mechanism supporting associative memory. In contrast, single-trial alpha/beta power predicted both item and pair memory, in line with a mechanism reflecting the depth of information processing, and predicted pair memory less well in the older than the younger adults. Thus, theta and alpha/beta oscillations contribute differently in shaping the contents of memories and reduced processing capacity contributes to episodic memory decline in older age.
Microstates imbalance is associated with a functional dysregulation of the resting-state networks in obsessive–compulsive disorder: a high-density electrical neuroimaging study using the TESS method
Authors: Thirioux Bérangère , Langbour Nicolas , Bokam Prasanth , Renaudin Léa , Wassouf Issa , Harika-Germaneau Ghina , Jaafari Nematollah
Published: June 2022

The dysfunctional patterns of microstates dynamics in obsessive–compulsive disorder (OCD) remain uncertain. Using high-density electrical neuroimaging (EEG) at rest, we explored microstates deterioration in OCD and whether abnormal microstates patterns are associated with a dysregulation of the resting-state networks interplay. We used EEG microstates analyses, TESS method for sources reconstruction, and General Linear Models to test for the effect of disease severity on neural responses. OCD patients exhibited an increased contribution and decreased duration of microstates C and D, respectively. Activity was decreased in the Salience Network (SN), associated with microstate C, but increased in the Default Mode Network (DMN) and Executive Control Network (ECN), respectively, associated with microstates E and D. The hyperactivity of the right angular gyrus in the ECN correlated with the symptoms severity. The imbalance between microstates C and D invalidates the hypothesis that this electrophysiological pattern is specific to psychosis. Demonstrating that the SN-ECN dysregulation manifests as abnormalities in microstates C and D, we confirm that the SN deterioration in OCD is accompanied by a failure of the DMN to deactivate and aberrant compensatory activation mechanisms in the ECN. These abnormalities explain typical OCD clinical features but also detachment from reality, shared with psychosis.
Maturation of large-scale brain systems over the first month of life
Authors: Nielsen Ashley N , Kaplan Sydney , Meyer Dominique , Alexopoulos Dimitrios , Kenley Jeanette K , Smyser Tara A , Wakschlag Lauren S , Norton Elizabeth S , Raghuraman Nandini , Warner Barbara B , Shimony Joshua S , Luby Joan L , Neil Jeffery J , Petersen Steven E , Barch Deanna M , Rogers Cynthia E , Sylvester Chad M , Smyser Christopher D
Published: June 2022

The period immediately after birth is a critical developmental window, capturing rapid maturation of brain structure and a child’s earliest experiences. Large-scale brain systems are present at delivery, but how these brain systems mature during this narrow window (i.e. first weeks of life) marked by heightened neuroplasticity remains uncharted. Using multivariate pattern classification techniques and functional connectivity magnetic resonance imaging, we detected robust differences in brain systems related to age in newborns (n = 262; R2 = 0.51). Development over the first month of life occurred brain-wide, but differed and was more pronounced in brain systems previously characterized as developing early (i.e. sensorimotor networks) than in those characterized as developing late (i.e. association networks). The cingulo-opercular network was the only exception to this organizing principle, illuminating its early role in brain development. This study represents a step towards a normative brain “growth curve” that could be used to identify atypical brain maturation in infancy.
Sex differences in the taste-evoked functional connectivity network
Authors: Ponticorvo Sara , Prinster Anna , Cantone Elena , Di Salle Francesco , Esposito Fabrizio , Canna Antonietta
Published: June 2022

The central gustatory pathway encompasses multiple subcortical and cortical regions whose neural functional connectivity can be modulated by taste stimulation. While gustatory perception has been previously linked to sex, whether and how the gustatory network differently responds to basic tastes between men and women is unclear. Here, we defined the regions of the central gustatory network by a meta-analysis of 35 fMRI taste activation studies and then analyzed the taste-evoked functional connectivity between these regions in 44 subjects (19 women) in a separate 3 Tesla activation study where sweet and bitter solutions, at five concentrations each, were administered during scanning. From the meta-analysis, a network model was set up, including bilateral anterior, middle and inferior insula, thalamus, precentral gyrus, left amygdala, caudate and dorsolateral prefrontal cortex. Higher functional connectivity than in women was observed in men between the right middle insula and bilateral thalami for bitter taste. Men exhibited higher connectivity than women at low bitter concentrations and middle-high sweet concentrations between bilateral thalamus and insula. A graph-based analysis expressed similar results in terms of nodal characteristics of strength and centrality. Our findings add new insights into the mechanisms of taste processing by highlighting sex differences in the functional connectivity of the gustatory network as modulated by the perception of sweet and bitter tastes. These results shed more light on the neural origin of sex-related differences in gustatory perception and may guide future research on the pathophysiology of taste perception in humans.
Normal-Phase TLC and Gradient Reversed-Phase HPLC for the Simultaneous Determination of Enrofloxacin and Bromhexine HCl in Presence of Two of Their Official Impurities
Authors: Tantawy Mahmoud A , Abdulla Shaaban A , Mohamed Ola Y , Abou Al-Alamein Amal M
Published: June 2022

In this work, two chromatographic methods are developed and validated for the determination of enrofloxacin and bromhexine (BRM) HCl in the presence of two of their specified impurities, ciprofloxacin and BRM impurity C. The suggested chromatographic methods included the use of thin layer chromatography (TLC-densitometry) and high-performance liquid chromatography (HPLC). In case of TLC-densitometry, good separation was achieved by using mobile phase of n.butanol:acetone:water:glacial acetic acid:triethylamine (10:3:1:0.5:0.5, by volume) on silica gel stationary phase at 254-nm detection. The developed HPLC method used BDS HYPERSIL C18 column with a mobile phase of water:acetonitrile:methanol:triflouroacetic acid. A linear gradient elution of 75–10%, 20–50% and 5–40% for water, acetonitrile and methanol, respectively, was applied in 13 min at a flow rate of 1.5 mL min−1. These methods were sufficient to separate the four substances simultaneously, and they are validated as per International Conference on Harmonization guidelines.
A New Strategy for the Software-Assisted LC Separations of Ketoconazole and Its Impurities
Authors: Agrawal Roopali , Belemkar Sateesh , Bonde Chandrakant
Published: June 2022

Analytical quality by design and the use of dissimilar chromatographic systems can be employed to accelerate chromatographic separations. Herein, a software (S-Matrix)-assisted platform was used to proficiently screen, optimize and select the optimal parameters for the chromatographic separation of ketoconazole and its related impurities. This approach evaluated the various chromatographic parameters in a stepwise manner based on the statistical tools and provided an in-depth understanding of the critical parameters influencing the peak selectivities and separations. It was demonstrated that dissimilar conditions, such as different stationary phases, mobile phase pH and organic modifiers (i.e., critical method variables), can improve the peak resolution, while the critical quality attributes can provide conditions appropriate for quantification purposes via a quality target analytical method. Furthermore, an orthogonal method was established to support the primary method. The orthogonality between the two methods was defined by the correlation matrix between the two systems using the Pearson correlation coefficient and was found to be 0.12. Using the optimized method, the primary method was validated as per International Council for Harmonization in the range of 0.05–1.0% for impurities and 80.0–120.0% for ketoconazole, thereby indicating the suitability of the method for use in quality control laboratories.
Preparation of Isoquercetin From Toona sinensis by Liquid–Liquid-Refining Extraction And Consecutive Counter-Current Chromatography
Authors: Guo Shuang , Wang Shuai , Yang Yi , Yin Yuxin , Gu Dongyu
Published: June 2022

A high-speed counter-current chromatographic (HSCCC) method using ethyl acetate–water as solvent system was established to separate isoquercetin from Toona sinensis. In an HSCCC single separation, the sample sizes of ethanol extract were optimized from 203 to 1200 mg. The results showed that the yield of the target compound increased from 4 to 26 mg, and the corresponding purity decreased from 93.30 to 81.82%. To further improve the yield and purity, liquid–liquid-refining extraction was introduced to pretreat the ethanol extract and enrich the target compound. The ethanol extract was extracted with n-hexane-ethyl acetate-method-water (1:5:1:5, v/v) and ethyl acetate-water in turn to remove the low-polarity and high-polarity impurities and obtain the crude sample. Under the similar conditions, 85.25 mg of the target compound with the purity of 95.12% was separated from 240 mg of the crude sample. Subsequently, a consecutive HSCCC was developed to obtain 257 mg of the target compound from 720 mg of crude sample, which was equivalent to 14.4 g of ethanol extract. This method improved the purity of the target compound, but more importantly, the sample size can reach 12 times of the maximum sample size of the ethanol extract in a single run.
The US Coronavirus Disease 2019 (COVID-19) Surveillance Environment: An Ecological Analysis of the Relationship of Testing Adequacy in the Context of Vaccination
Authors: Choi Daesung , Nielsen Jannie , Waller Lance A , Patel Shivani A
Published: June 2022

Background

Coronavirus disease 2019 (COVID-19) testing is a critical component of public health surveillance and pandemic control, especially among the unvaccinated, as the nation resumes in-person activities. This study examined the relationships between COVID-19 testing rates, testing positivity rates, and vaccination coverage across US counties.

Methods

Data from the Health and Human Services’ Community Profile Report and 2016–2020 American Community Survey 5-Year Estimates were used. A total of 3114 US counties were analyzed from January through September 2021. Associations among the testing metrics and vaccination coverage were estimated using multiple linear regression models with fixed effects for states and adjusted for county demographics. COVID-19 testing rates (polymerase chain reaction [PCR] testing per 1000), testing positivity (percentage of all PCR tests that were positive), and vaccination coverage (percentage of county population that was fully vaccinated) were determined.

Results

Nationally, median daily COVID-19 testing rates were highest in January and September (35.5 and 34.6 tests per capita, respectively) and lowest in July (13.2 tests per capita). Monthly testing positivity was between 0.03 and 0.12 percentage points lower for each percentage points of vaccination coverage, and monthly testing rates were between 0.08 and 0.22 tests per capita higher for each percentage point of vaccination coverage.

Conclusions

The quantity of COVID-19 testing was associated with vaccination coverage, implying counties having populations with relatively lower protection against the virus are conducting less testing than counties with relatively more protection. Monitoring testing practices in relation to vaccination coverage may be used to monitor the sufficiency of COVID-19 testing based on population susceptibility to the virus.
Antibiotic Use and Stewardship Practices in a Pediatric Community-based Cohort Study in Peru: Shorter Would be Sweeter
Authors: Schiaffino Francesca , Colston Josh M , Paredes Olortegui Maribel , Rengifo Pinedo Silvia , Zamora Babilonia Marcelo , Ramal Asayag Cesar , Peñataro Yori Pablo , Kosek Margaret N
Published: June 2022

Background

There is a need to evaluate antibiotic use, duration of therapy, and stewardship in low- and middle-income countries to guide the development of appropriate stewardship programs that are global in scope and effectively decrease unnecessary antibiotic use.

Methods

We prospectively collected information on illness occurrence and antibiotic use from a cohort of 303 children. We evaluated the incidence, duration of therapy, and appropriateness of antibiotic prescriptions by 5 main antibiotic prescribers (physicians and nurses, pharmacists, nursing assistants, self-prescriptions, and neighbors or family members).

Results

Ninety percent of children received an antibiotic during follow-up, and on average, by the end of follow-up a child had spent 4.3% of their first 5 years of life on antibiotics. The most frequent prescribers were physicians/nurses (79.4%), followed by pharmacists (8.1%), self-prescriptions (6.8%), nursing assistants (3.7%), and family or neighbors (1.9%). Of the 3702 courses of antibiotics prescribed, 30.9% were done so for the occurrence of fever, 25.3% for diarrhea, 2.8% for acute lower respiratory disease, 2.7% for dysentery, and 38.2% for an undetermined illness. Courses exceeding the recommended duration were common for the principal diseases for which treatment was initiated, with 27.3% of courses exceeding the recommended length duration, representing a potential reduction in 13.2% of days on which this cohort spent on antibiotics.

Conclusions

Stewardship programs should target medical personnel for a primary care stewardship program even in a context in which antibiotics are available to the public with little or no restrictions and appropriate duration should be emphasized in this training.
Doubly robust identification for causal panel data models
Authors: Arkhangelsky Dmitry , Imbens Guido W
Published: June 2022

We study identification and estimation of causal effects in settings with panel data. Traditionally, researchers follow model-based identification strategies relying on assumptions governing the relation between the potential outcomes and the observed and unobserved confounders. We focus on a different, complementary approach to identification, where assumptions are made about the connection between the treatment assignment and the unobserved confounders. Such strategies are common in cross-section settings, but rarely used with panel data. We introduce different sets of assumptions that follow the two paths to identification and develop a double robust approach. We propose estimation methods that build on these identification strategies.
Microbial biodiversity contributes to soil carbon release: a case study on fire disturbed boreal forests
Authors: Zhou Xuan , Sun Hui , Heinonsalo Jussi , Pumpanen Jukka , Berninger Frank
Published: June 2022

Microbial communities often possess enormous diversity, raising questions about whether this diversity drives ecosystem functioning, especially the influence of diversity on soil decomposition and respiration. Although functional redundancy is widely observed in soil microorganisms, evidence that species occupy distinct metabolic niches has also emerged. In this paper, we found that apart from the environmental variables, increases in microbial diversity, notably bacterial diversity, lead to an increase in soil C emissions. This was demonstrated using structural equation modelling (SEM), linking soil respiration with naturally differing levels of soil physio-chemical properties, vegetation coverage, and microbial diversity after fire disturbance. Our SEMs also revealed that models including bacterial diversity explained more variation of soil CO2 emissions (about 45%) than fungal diversity (about 38%). A possible explanation of this discrepancy is that fungi are more multifunctional than bacteria and, therefore, an increase in fungal diversity does not necessarily change soil respiration. Further analysis on functional gene structure suggested that bacterial and fungal diversities mainly explain the potential decomposition of recalcitrant C compare with that of labile C. Overall, by incorporating microbial diversity and the environmental variables, the predictive power of models on soil C emission was significantly improved, indicating microbial diversity is crucial for predicting ecosystem functions.
Glyphosate-based herbicide exposure: effects on gill microbiota of rainbow trout (Oncorhynchus mykiss) and the aquatic bacterial ecosystem
Authors: Bellec Laure , Le Du-Carré Jessy , Almeras Fabrice , Durand Lucile , Cambon-Bonavita Marie-Anne , Danion Morgane , Morin Thierry
Published: June 2022

The herbicide glyphosate has been widely used in the past 40 years, under the assumption that side effects were minimal. In recent years, its impact on microbial compositions and potential indirect effects on plant, animal and human health have been strongly suspected. Glyphosate and co-formulates have been detected in various water sources, but our understanding of their potential effects on aquatic animals is still in its infancy compared with mammals. In this study, we investigated the effect of chronic exposure to an environmentally relevant concentration of glyphosate on bacterial communities of rainbow trout (Oncorhynchus mykiss). Gills, gut contents and gut epithelia were then analyzed by metabarcoding targeting the 16S rRNA gene. Our results revealed that rainbow trout has its own bacterial communities that differ from their surrounding habitats and possess microbiomes specific to these three compartments. The glyphosate-based herbicide treatment significantly affected the gill microbiome, with a decrease in diversity. Glyphosate treatments disrupted microbial taxonomic composition and some bacteria seem to be sensitive to this environmental pollutant. Lastly, co-occurrence networks showed that microbial interactions in gills tended to decrease with chemical exposure. These results demonstrate that glyphosate could affect microbiota associated with aquaculture fish.
Using champion-oriented mindset to overcome the challenges of graduate school: impact of workshop for graduate school skills on underrepresented minority retention
Authors: Marshall Andrea G , Palavicino-Maggio Caroline B , Neikirk Kit , Vue Zer , Beasley Heather K , Garza-Lopez Edgar , Murray Sandra A , Martinez Denise , Crabtree Amber , Conley Zachary C , Vang Larry , Davis Jamaine S , Powell-Roach Keesha L , Campbell Susan , Dal Angyth B , Shao Bryanna , Alexander Stefanie , Vang Nancy , Vue Neng , Vue Mein , Shuler Haysetta D , Spencer Elsie C , Morton Derrick J , Hinton Antentor
Published: June 2022

Despite efforts to increase diversity, a glaring underrepresentation of minorities (URM) persists in the fields of science, technology, engineering, and mathematics (STEM). Graduate school can be a stressful step in the STEM pipeline, especially for students previously unaware of the structure and challenges of postgraduate education. To promote successful minority participation in STEM and prepare prospective students for the impending challenges of applying for and attending graduate school, we developed a workshop based on the mentoring and fostering of a champion-oriented mindset entitled, “The Trials and Tribulations of Graduate School: How Do You Make an Impact?.” Students from the HBCU Winston-Salem State University attended the workshop, and a pre/post—a 10-point Likert scale-based survey was administered. The questions used in this seminar were newly designed by the authors as program evaluations. The results suggest that the workshop was well-received by the students and provided information that they considered helpful to help navigate the graduate school process.
Schindler's legacy: from eutrophic lakes to the phosphorus utilization strategies of cyanobacteria
Authors: Xiao Man , Burford Michele A , Wood Susanna A , Aubriot Luis , Ibelings Bas W , Prentice Matthew J , Galvanese Elena F , Harris Ted D , Hamilton David P
Published: June 2022

David Schindler and his colleagues pioneered studies in the 1970s on the role of phosphorus in stimulating cyanobacterial blooms in North American lakes. Our understanding of the nuances of phosphorus utilization by cyanobacteria has evolved since that time. We review the phosphorus utilization strategies used by cyanobacteria, such as use of organic forms, alternation between passive and active uptake, and luxury storage. While many aspects of physiological responses to phosphorus of cyanobacteria have been measured, our understanding of the critical processes that drive species diversity, adaptation and competition remains limited. We identify persistent critical knowledge gaps, particularly on the adaptation of cyanobacteria to low nutrient concentrations. We propose that traditional discipline-specific studies be adapted and expanded to encompass innovative new methodologies and take advantage of interdisciplinary opportunities among physiologists, molecular biologists, and modellers, to advance our understanding and prediction of toxic cyanobacteria, and ultimately to mitigate the occurrence of blooms.
Genomics and pathotypes of the many faces ofEscherichia coli
Authors: Geurtsen Jeroen , de Been Mark , Weerdenburg Eveline , Zomer Aldert , McNally Alan , Poolman Jan
Published: June 2022

Escherichia coli is the most researched microbial organism in the world. Its varied impact on human health, consisting of commensalism, gastrointestinal disease, or extraintestinal pathologies, has generated a separation of the species into at least eleven pathotypes (also known as pathovars). These are broadly split into two groups, intestinal pathogenic E. coli (InPEC) and extraintestinal pathogenic E. coli (ExPEC). However, components of E. coli’s infinite open accessory genome are horizontally transferred with substantial frequency, creating pathogenic hybrid strains that defy a clear pathotype designation. Here, we take a birds-eye view of the E. coli species, characterizing it from historical, clinical, and genetic perspectives. We examine the wide spectrum of human disease caused by E. coli, the genome content of the bacterium, and its propensity to acquire, exchange, and maintain antibiotic resistance genes and virulence traits. Our portrayal of the species also discusses elements that have shaped its overall population structure and summarizes the current state of vaccine development targeted at the most frequent E. coli pathovars. In our conclusions, we advocate streamlining efforts for clinical reporting of ExPEC, and emphasize the pathogenic potential that exists throughout the entire species.
Intraoperative conversion from video-assisted thoracoscopic lobectomy to thoracotomy for non-small-cell lung cancer: Does it have an impact on long-term survival?
Authors: Ren Zhi-Zhen , Deng Han-Yu , Huang Weijia , Zhou Qinghua
Published: June 2022

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether intraoperative conversions to thoracotomy have an impact on long-term survival for patients with non-small-cell lung cancer who underwent video-assisted thoracoscopic lobectomy initially. A total of 461 papers were found using the reported search, of which 6 retrospective cohort studies represented the best evidence to answer the clinical question. The authors, date of publication, journal, country of the authors, patient group, study type, relevant outcomes and results of these papers were tabulated. Five cohort studies clarified that conversion did not compromise long-term survival, whereas 1 cohort study reported worse long-term outcomes after conversion to thoracotomy. However, the limited samples, different characteristics between groups and selection bias due to inherent design made it difficult to make a conclusion. Based on the current evidence, we concluded that intraoperative conversion from video-assisted thoracoscopic surgery (VATS) to thoracotomy for non-small-cell lung cancer might not impact long-term survival compared to a successful VATS lobectomy. In-hospital mortality might not be prejudiced, whereas longer hospitalizations were observed. However, whether conversion would adversely affect postoperative complication rates remained unclear because of the conflicting results. Moreover, 3 studies reported no statistical differences in short- and long-term survival between emergency and non-emergency conversions. Therefore, we suggest that thoracic surgeons should not hesitate to convert VATS into thoracotomy in the case of blood vessel injury or difficult hilum.
Single-stage repair for ascending aortic aneurysm, artery stenosis and occlusion of neck vessels caused by Takayasu arteritis
Authors: Nakai Yosuke , Nishikawa Yusuke , Saito Takayuki , Suda Hisao
Published: June 2022

Takayasu arteritis results in a variety of vascular symptoms, and there are some cases in which progressive vascular lesions require surgical intervention. We present a case with ascending aortic aneurysm, right common carotid artery stenosis, left common carotid artery occlusion and left subclavian artery stenosis caused by Takayasu arteritis that was successfully treated with total arch replacement and ascending aorta to right internal carotid artery bypass.
Alpha-2 Adrenoreceptor Antagonist Yohimbine Potentiates Consolidation of Conditioned Fear
Authors: Sperl Matthias F J , Panitz Christian , Skoluda Nadine , Nater Urs M , Pizzagalli Diego A , Hermann Christiane , Mueller Erik M
Published: June 2022

Background

Hyperconsolidation of aversive associations and poor extinction learning have been hypothesized to be crucial in the acquisition of pathological fear. Previous animal and human research points to the potential role of the catecholaminergic system, particularly noradrenaline and dopamine, in acquiring emotional memories. Here, we investigated in a between-participants design with 3 groups whether the noradrenergic alpha-2 adrenoreceptor antagonist yohimbine and the dopaminergic D2-receptor antagonist sulpiride modulate long-term fear conditioning and extinction in humans.

Methods

Fifty-five healthy male students were recruited. The final sample consisted of n = 51 participants who were explicitly aware of the contingencies between conditioned stimuli (CS) and unconditioned stimuli after fear acquisition. The participants were then randomly assigned to 1 of the 3 groups and received either yohimbine (10 mg, n = 17), sulpiride (200 mg, n = 16), or placebo (n = 18) between fear acquisition and extinction. Recall of conditioned (non-extinguished CS+ vs CS−) and extinguished fear (extinguished CS+ vs CS−) was assessed 1 day later, and a 64-channel electroencephalogram was recorded.

Results

The yohimbine group showed increased salivary alpha-amylase activity, confirming a successful manipulation of central noradrenergic release. Elevated fear-conditioned bradycardia and larger differential amplitudes of the N170 and late positive potential components in the event-related brain potential indicated that yohimbine treatment (compared with a placebo and sulpiride) enhanced fear recall during day 2.

Conclusions

These results suggest that yohimbine potentiates cardiac and central electrophysiological signatures of fear memory consolidation. They thereby elucidate the key role of noradrenaline in strengthening the consolidation of conditioned fear associations, which may be a key mechanism in the etiology of fear-related disorders.
Invasive Meningococcal Disease Among People Experiencing Homelessness—United States, 2016–2019
Authors: Rudmann Keegan C , Brown Nicole E , Rubis Amy B , Burns Meagan , Ramsey April , De Las Nueces Denise , Martin Tasha , Barnes Meghan , Davizon Emily Spence , Retchless Adam C , Potts Caelin , Wang Xin , Hariri Susan , McNamara Lucy A
Published: June 2022

Background

Recently, several invasive meningococcal disease (IMD) outbreaks caused by Neisseria meningitidis have occurred among people experiencing homelessness (PEH). However, overall IMD risk among PEH is not well described. We compared incidence and characteristics of IMD among PEH and persons not known to be experiencing homelessness (non-PEH) in the United States.

Methods

We analyzed 2016–2019 IMD data from the National Notifiable Diseases Surveillance System and enhanced meningococcal disease surveillance. Incidence was calculated using US census data and point-in-time counts from the US Department of Housing and Urban Development.

Results

Of cases from states participating in enhanced surveillance during 2016–2019 (n = 1409), 45 cases (3.2%) occurred among PEH. Annual incidence was higher among PEH (2.12 cases/100 000) than non-PEH (0.11 cases/100 000; relative risk, 19.8; 95% confidence interval [CI], 14.8–26.7). Excluding outbreak-associated cases (PEH n = 18, 40%; non-PEH n = 98, 7.2%), incidence among PEH remained elevated compared to incidence in non-PEH (relative risk, 12.8; 95% CI, 8.8–18.8). Serogroup C was identified in 68.2% of PEH cases compared to 26.4% in non-PEH (P < .0001).

Conclusions

PEH are at increased risk for IMD. Further assessment is needed to determine the feasibility and potential impact of meningococcal vaccination for PEH in the United States.
Risk of Severe Coronavirus Disease 2019 Disease in Individuals With Down Syndrome: A Matched Cohort Study From a Large, Integrated Health Care System
Authors: Ku Jennifer H , Levin Myron J , Luo Yi , Florea Ana , Lin I Chun , Tian Yun , Tseng Hung Fu
Published: June 2022

Background

Down syndrome (DS) is associated with an increased risk of infections attributed to immune defects. Whether individuals with DS are at an increased risk of severe coronavirus disease 2019 (COVID-19) remains unclear.

Methods

In a matched cohort study, we evaluated the risk of COVID-19 infection and severe COVID-19 disease in individuals with DS and their matched counterparts in a pre-COVID-19 vaccination period at Kaiser Permanente Southern California. Multivariable Cox proportion hazard regression was used to investigate associations between DS and risk of COVID-19 infection and severe COVID-19 disease.

Results

Our cohort included 2541 individuals with DS and 10 164 without DS matched on age, sex, and race/ethnicity (51.6% female, 53.3% Hispanic, median age 25 years [interquartile range, 14–38]). Although the rate of COVID-19 infection in individuals with DS was 32% lower than their matched counterparts (adjusted hazard ratio [aHR], 0.68; 95% confidence interval [CI], .56–.83), the rate of severe COVID-19 disease was 6-fold higher (aHR, 6.14; 95% CI, 1.87–20.16).

Conclusions

Although the risk of COVID-19 infection is lower, the risk of severe disease is higher in individuals with DS compared with their matched counterparts. Better infection monitoring, early treatment, and promotion of vaccine for COVID-19 are warranted for DS populations.
The Clinical and Genomic Epidemiology of Rhinovirus in Homeless Shelters—King County, Washington
Authors: Chow Eric J , Casto Amanda M , Roychoudhury Pavitra , Han Peter D , Xie Hong , Pfau Brian , Nguyen Tien V , Sereewit Jaydee , Rogers Julia H , Cox Sarah N , Wolf Caitlin R , Rolfes Melissa A , Mosites Emily , Uyeki Timothy M , Greninger Alexander L , Hughes James P , Shim M Mia , Sugg Nancy , Duchin Jeffrey S , Starita Lea M , Englund Janet A , Chu Helen Y
Published: June 2022

Background

Rhinovirus (RV) is a common cause of respiratory illness in all people, including those experiencing homelessness. RV epidemiology in homeless shelters is unknown.

Methods

We analyzed data from a cross-sectional homeless shelter study in King County, Washington, October 2019–May 2021. Shelter residents or guardians aged ≥3 months reporting acute respiratory illness completed questionnaires and submitted nasal swabs. After 1 April 2020, enrollment expanded to residents and staff regardless of symptoms. Samples were tested by multiplex RT-PCR for respiratory viruses. A subset of RV-positive samples was sequenced.

Results

There were 1066 RV-positive samples with RV present every month of the study period. RV was the most common virus before and during the coronavirus disease 2019 (COVID-19) pandemic (43% and 77% of virus-positive samples, respectively). Participants from family shelters had the highest prevalence of RV. Among 131 sequenced samples, 33 RV serotypes were identified with each serotype detected for ≤4 months.

Conclusions

RV infections persisted through community mitigation measures and were most prevalent in shelters housing families. Sequencing showed a diversity of circulating RV serotypes, each detected over short periods of time. Community-based surveillance in congregate settings is important to characterize respiratory viral infections during and after the COVID-19 pandemic.

Clinical Trials Registration

NCT04141917.
Factors associated with having home care physicians as an integrated source of medications for chronic conditions among homebound patients
Authors: Lee Jason Jiunshiou , Hu Hsiao-Yun , Lin Shu-Yi , Huang Chao-Ming , Huang Sheng-Jean , Huang Nicole
Published: June 2022

Background

Inappropriate management of medications is a major threat to homebound patients with chronic conditions. Despite many efforts in improving medication reconciliation in ambulatory and inpatient settings, little research has focused on home care settings. In 2016, Taiwan initiated the Integrated Home Health Care programme, which was intended to reduce potentially inappropriate medication management and risks of uncontrolled polypharmacy through the integration of different medication sources for chronic conditions among homebound patients. This study investigated factors associated with having home care physicians as an integrated source of medications for chronic conditions among homebound patients.

Method

This retrospective cohort study enrolled 3142 community-dwelling homebound patients from Taipei City Hospital. Homebound patients’ adherence to using home care physicians as an integrated source of chronic condition medications was defined as having all prescriptions for their chronic conditions prescribed by a single home care physician for at least 6 months. Both patient and home care physician characteristics were analysed. Multivariable logistic regression was applied.

Results

Of the 3142 patients with chronic conditions, 1002 (31.9%) had consistently obtained all medications for their chronic illnesses from their home care physicians for 6 months and 2140 (68.1%) had not. The most common chronic diseases among homebound patients were hypertension, diabetes mellitus, dementia, cerebrovascular disease and constipation. Oldest-old patients with poor functional status, fewer daily medications, no co-payment exemption and no recent inpatient experience were more likely to adhere to this medication integration system. In addition, patients whose outpatient physicians were also their home care physicians were more likely to adhere to the system.

Conclusions

The finding suggests that building trust and enhancing communication among homebound patients, caregivers and home care physicians are critical. Patient and provider variations highlight the need for further improvement and policy modification for medication reconciliation and management in home care settings. The improvement in medication management and care integration in home care settings may reduce misuse and polypharmacy and improve homebound patients’ safety.
Implementation of an antimicrobial stewardship programme in three regional hospitals in the south-east of Liberia: lessons learned
Authors: Alabi Abraham S , Picka Stephen W , Sirleaf Reubvera , Ntirenganya Pacifique R , Ayebare Arnold , Correa Nidia , Anyango Sarah , Ekwen Gerald , Agu Emmanuel , Cook Rebecca , Yarngrorble John , Sanoe Ibrahim , Dugulu Henry , Wiefue Emmanuel , Gahn-Smith Diana , Kateh Francis N , Hallie Ezekiel F , Sidonie Christiane G , Aboderin Aaron O , Vassellee David , Bishop Damien , Lohmann Daniel , Naumann-Hustedt Manja , Dörlemann Alois , Schaumburg Frieder
Published: June 2022

Background

Antimicrobial stewardship (AMS) programmes can improve the use of antimicrobial agents. However, there is limited experience in the implementation of such programmes in low- and middle-income countries (LMICs).

Objectives

To assess the effect of AMS measures in south-east Liberia on the quality of antimicrobial use in three regional hospitals.

Methods

A bundle of three measures (local treatment guideline, training and regular AMS ward rounds) was implemented and quality indicators of antimicrobial use (i.e. correct compounds, dosage and duration) were assessed in a case series before and after AMS ward rounds. Primary endpoints were (i) adherence to the local treatment guideline; (ii) completeness of the microbiological diagnostics (according to the treatment guideline); and (iii) clinical outcome. The secondary endpoint was reduction in ceftriaxone use.

Results

The majority of patients had skin and soft tissue infections (n = 108) followed by surgical site infections (n = 72), pneumonia (n = 64), urinary tract infection (n = 48) and meningitis (n = 18). After the AMS ward rounds, adherence to the local guideline improved for the selection of antimicrobial agents (from 34.5% to 61.0%, P < 0.0005), dosage (from 15.2% to 36.5%, P < 0.0005) and duration (from 13.2% to 31.0%, P < 0.0005). In total, 79.7% of patients (247/310) had samples sent for microbiological analysis. Overall, 92.3% of patients improved on Day 3 (286/310). The proportion of patients receiving ceftriaxone was significantly reduced after the AMS ward rounds from 51.3% to 14.2% (P < 0.0005).

Conclusions

AMS measures can improve the quality of antimicrobial use in LMICs. However, long-term engagement is necessary to make AMS programmes in LMICs sustainable.
Effect of ergot alkaloids and a mycotoxin deactivating product on in vitro ruminal fermentation using the Rumen simulation technique (RUSITEC)
Authors: Sarich Jenna M , Stanford Kim , Schwartzkopf-Genswein Karen S , Gruninger Robert J , McAllister Tim A , Meale Sarah J , Blakley Barry R , Penner Gregory B , Ribeiro Gabriel O
Published: June 2022

The rumen simulation technique (RUSITEC) was used to investigate the effect of ergot alkaloids (EA) and a mycotoxin deactivating product (Biomin AA; MDP) on nutrient digestion, ruminal fermentation parameters, total gas, methane, and microbial nitrogen production. Ruminal fermentation vessels received a feedlot finishing diet of 90:10 concentrate:barley silage (DM basis). Using a randomized complete block design, treatments were assigned (n = 4 vessels/treatment) within two RUSITEC apparatuses in a 2 × 2 factorial arrangement. Treatments included: (1) control (CON) diet (no EA and no MDP); (2) CON diet + 1 g/d MDP; (3) CON diet + 20 mg/kg EA; and (4) CON diet + 20 mg/kg EA + 1 g/d MDP. The study was conducted over 14 d with 7 d of adaptation and 7 d of sample collection. Data were analyzed in SAS using PROC MIXED including fixed effects of EA, MDP, and the EA×MDP interaction. Random effects included RUSITEC apparatus and cow rumen inoculum (n = 4). Ergot alkaloids decreased dry matter (DMD) (P = 0.01; 87.9 vs. 87.2%) and organic matter disappearance (OMD) (P = 0.02; 88.8 vs. 88.4%). Inclusion of MDP increased OMD (P = 0.01; 88.3 vs. 88.9%). Neutral detergent fiber disappearance (NDFD) was improved with MDP; however, an EA×MDP interaction was observed with MDP increasing (P < 0.001) NDFD more with EA diet compared to CON. Acetate proportion decreased (P = 0.01) and isovalerate increased (P = 0.03) with EA. Consequently, acetate:propionate was reduced (P = 0.03) with EA. Inclusion of MDP increased total volatile fatty acid (VFA) production (P < 0.001), and proportions of acetate (P = 0.03) and propionate (P = 0.03), and decreased valerate (P < 0.001), isovalerate (P = 0.04), and caproate (P = 0.002). Treatments did not affect (P ≥ 0.17) ammonia, total gas, or methane production (mg/d or mg/g of organic matter fermented). The inclusion of MDP reduced (P < 0.001) microbial nitrogen (MN) production in the effluent and increased (P = 0.01) feed particle-bound MN. Consequently, total MN decreased (P = 0.001) with MDP. In all treatments, the dominant microbial phyla were Firmicutes, Bacteroidota, and Proteobacteria, and the major microbial genus was Prevotella. Inclusion of MDP further increased the abundance of Bacteroidota (P = 0.04) as it increased both Prevotella (P = 0.04) and Prevotellaceae_UCG-003 (P = 0.001). In conclusion, EA reduced OMD and acetate production due to impaired rumen function, these responses were successfully reversed by the addition of MDP.
Determination of Patient Adherence for Duloxetine in Urine
Authors: Mulder Haley A , McIntire Greg L , Wallace Frank N , Poklis Justin L
Published: June 2022

Duloxetine, known by its brand name, CymbaltaTM, is a selective serotonin and norepinephrine reuptake inhibitor used to treat major depressive disorders. Determination of patient compliance for duloxetine is typically determined through medication possession ratio (MPR) or plasma concentrations. The purpose of this paper was to characterize normal urinary duloxetine concentrations in patients prescribed duloxetine to monitor patient adherence. Patient data collected from routine screens for duloxetine concentrations in urine were included in this study. Inclusion criteria consisted of patients who were prescribed duloxetine and (i) tested positive for duloxetine, (ii) tested negative for illicit substances and (iii) included creatinine, age and duloxetine dose administered. Of the 5,592 patient urines screened, 2,004 of the results fit into the inclusion criteria. Positive urine concentrations of duloxetine ranged from 50 to 2,722 ng/mL. Duloxetine urine concentrations were normalized to creatinine and dose further characterized by sex, age, body mass index (BMI) and dose in milligrams. Sample distribution included urines collected from 1,487 females and 517 males. The age range of the specimen donors was between 15 and 90 years old with an average age of 52. BMI levels ranged from 13.9 (underweight) to 88.1 (obese), with the average BMI being 33.5. The most common dose of duloxetine prescribed was a daily, oral dose of 60 mg. Analysis of the normalized, transformed creatinine concentrations showed that there was a significant statistical difference (P < 0.05) in the urinary duloxetine concentrations by sex and by dose (mg). Female patients further showed a statistical difference in urinary duloxetine concentration in age groups 18–64 and 64 and older. By characterizing urinary duloxetine concentrations in patients prescribed the medication, normalized distributions of data ranges have been established. These data ranges for urinary duloxetine concentrations can be used to determine patient compliance with duloxetine in routine, clinical samples.
Pilot study of an artificial intelligence-based deep learning algorithm to predict time to castration-resistant prostate cancer for metastatic hormone-naïve prostate cancer
Authors: Nakata Wataru , Mori Hideo , Tsujimura Goh , Tsujimoto Yuichi , Gotoh Takayoshi , Tsujihata Masao
Published: June 2022

The object in this study is to develop an artificial intelligence-based deep learning algorithm for prediction of time to castration-resistant prostate cancer by combined androgen blockade therapy in metastatic hormone-naïve prostate cancer. We included 180 metastatic hormone-naïve prostate cancer patients who initially received combined androgen blockade. We first evaluated whether time to castration-resistant prostate cancer was a significant prognostic factor. Then, using the patients’ needle-biopsy specimen images, we developed and validated our deep learning algorithm. The results are shown below. First, we confirmed that time to castration-resistant prostate cancer correlated with overall survival (P < 0.001). Next, we selected two groups by time to castration-resistant prostate cancer of >24 months (n = 18) and <6 months (n = 6) and developed a deep learning algorithm by artificial intelligence-based machine deep learning. In 16 other metastatic hormone-naïve prostate cancer patients used as an external validation set, we confirmed the prediction accuracy remained significant (P < 0.05). In conclusion, our obtained deep learning algorithm has high predictive ability for the effectiveness of combined androgen blockade.