bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between non-nutritive sweetener consumption and liver enzyme levels in adults: a systematic review and meta-analysis of randomized clinical trials
Authors: Golzan S Amirhossein , Movahedian Mina , Haghighat Neda , Asbaghi Omid , Hekmatdoost Azita
Published: January 2023

Context

The use of non-nutritive sweeteners (NNSs) is dramatically increasing in food commodities, and their effects on biochemical parameters have been the subject of great controversy. Liver enzymes as markers of liver injury may be helpful measures of non-alcoholic fatty liver disease (NAFLD), but the outcomes of randomized controlled trials (RCTs) suggest their associations with NNSs are contentious.

Objective

The current study was designed to provide a GRADE-assessed systematic review and meta-analysis of RCTs studying the consequences of NNS consumption on ALT, AST, and GGT concentrations (ie, the 3 main liver enzymes in adults).

Data Sources

Scopus, PubMed, and EMBASE were searched for relevant studies up to April 2021, with no time and language limitations.

Data Extraction

Two independent researchers extracted information from qualified studies, and a third researcher rechecked it.

Data Analysis

Of 3212 studies, 10 studies that enrolled a total of 854 volunteers were included. A random-effects or fixed-effects model was utilized to calculate weighted mean differences (WMDs) and 95% confidence intervals (CIs). Heterogeneity between studies was evaluated using Cochran’s Q test and quantified using the I2 statistic. The pooled results demonstrated that, compared with control groups, NNS intake led to nonsignificant reductions in ALT (WMD: −.78, 95% CI: –2.14, .57, P = .25) and GGT (WMD: –.21, 95% CI: –1.46, 1.04, P = .74). Also, a small nonsignificant increasing effect on AST level was found (WMD: .02, 95% CI: –1.26, 1.30, P = .97). NNS significantly reduced AST levels in type 2 diabetes patients when subgroup analyses were performed. Also, in trials with ≥24-week intervention or studies that utilized stevioside for intervention, a significant reducing effect on ALT level was observed.

Conclusion

The results of this study showed that NNS intake has no significant effect on liver enzyme levels in adults.

Systematic Review Registration

PROSPERO registration no. CRD42021250067.
Shade avoidance in the context of climate change
Authors: Casal Jorge J , Fankhauser Christian
Published: January 2023

When exposed to changes in the light environment caused by neighboring vegetation, shade-avoiding plants modify their growth and/or developmental patterns to access more sunlight. In Arabidopsis (Arabidopsis thaliana), neighbor cues reduce the activity of the photosensory receptors phytochrome B (phyB) and cryptochrome 1, releasing photoreceptor repression imposed on PHYTOCHROME INTERACTING FACTORs (PIFs) and leading to transcriptional reprogramming. The phyB-PIF hub is at the core of all shade-avoidance responses, whilst other photosensory receptors and transcription factors contribute in a context-specific manner. CONSTITUTIVELY PHOTOMORPHOGENIC1 is a master regulator of this hub, indirectly stabilizing PIFs and targeting negative regulators of shade avoidance for degradation. Warm temperatures reduce the activity of phyB, which operates as a temperature sensor and further increases the activities of PIF4 and PIF7 by independent temperature sensing mechanisms. The signaling network controlling shade avoidance is not buffered against climate change; rather, it integrates information about shade, temperature, salinity, drought, and likely flooding. We, therefore, predict that climate change will exacerbate shade-induced growth responses in some regions of the planet while limiting the growth potential in others.
The Back Pain Consortium (BACPAC) Research Program: Structure, Research Priorities, and Methods
Authors: Mauck Matthew C , Lotz Jeffrey , Psioda Matthew A , Carey Timothy S , Clauw Daniel J , Majumdar Sharmila , Marras William S , Vo Nam , Aylward Ayleen , Hoffmeyer Anna , Zheng Patricia , Ivanova Anastasia , McCumber Micah , Carson Christiane , Anstrom Kevin J , Bowden Anton E , Dalton Diane , Derr Leslie , Dufour Jonathan , Fields Aaron J , Fritz Julie , Hassett Afton L , Harte Steven E , Hue Trisha F , Krug Roland , Loggia Marco L , Mageswaran Prasath , McLean Samuel A , Mitchell Ulrike H , O’Neill Conor , Pedoia Valentina , Quirk David Adam , Rhon Daniel I , Rieke Viola , Shah Lubdha , Sowa Gwendolyn , Spiegel Brennan , Wasan Ajay D , Wey Hsiao-Ying (Monica) , LaVange Lisa
Published: January 2023

In 2019, the National Health Interview survey found that nearly 59% of adults reported pain some, most, or every day in the past 3 months, with 39% reporting back pain, making back pain the most prevalent source of pain, and a significant issue among adults. Often, identifying a direct, treatable cause for back pain is challenging, especially as it is often attributed to complex, multifaceted issues involving biological, psychological, and social components. Due to the difficulty in treating the true cause of chronic low back pain (cLBP), an over-reliance on opioid pain medications among cLBP patients has developed, which is associated with increased prevalence of opioid use disorder and increased risk of death. To combat the rise of opioid-related deaths, the National Institutes of Health (NIH) initiated the Helping to End Addiction Long-TermSM (HEAL) initiative, whose goal is to address the causes and treatment of opioid use disorder while also seeking to better understand, diagnose, and treat chronic pain. The NIH Back Pain Consortium (BACPAC) Research Program, a network of 14 funded entities, was launched as a part of the HEAL initiative to help address limitations surrounding the diagnosis and treatment of cLBP. This paper provides an overview of the BACPAC research program’s goals and overall structure, and describes the harmonization efforts across the consortium, define its research agenda, and develop a collaborative project which utilizes the strengths of the network. The purpose of this paper is to serve as a blueprint for other consortia tasked with the advancement of pain related science.
SAFETY IMPROVEMENT OF THE RADIOACTIVE WASTE STORAGE FACILITY IN ALBANIA
Authors: Prifti Dritan , Tushe Kozeta , Bylyku Elida , Daci Brunilda
Published: January 2023

The Albanian National Radioactive Waste Storage Facility (NRWSF) constructed in 1999 consists of an interim waste storage facility for very low level waste, low level waste, intermediate level waste and disused sealed radioactive sources (DSRS) coming from research institutions, agriculture and industrial activities and from applications in nuclear medicine in Albania. The safety assessment of this facility is performed considering its impact to workers, public and environment. In 2018, Albania started a new National project Alb 9010 titled ‘Upgrading the Radioactive Waste Storage Building According to International Standards’. The two fundamental objectives are to ensure the protection of the public, workers and the environment and to ensure retrievability of waste packages for final disposal. The project focuses on ensuring the safety of the treatment, conditioning and storage of radioactive waste and DSRS. Under this project has been done the improvement of the safety of the RWSF and upgrading of the existing building infrastructure. In the end of the project the objective is to improve the safety of the personnel in the RWSF, protection of public and environment, Upgrade the Equipment’s used in the RW Management Activities, Upgrade the existing Infrastructure of the RWSF Building and also ensure retrievability of waste packages for final disposal.
Community Violence and the Stability of Marriages and Cohabitations in Mexico
Authors: Caudillo Mónica L , Lee Jaein
Published: January 2023

This study evaluates the link between local violence and the stability of women’s first co-residential unions in Mexico by exploiting the drastic increase in homicide rates caused by the Mexican War on Drugs in December 2006. We use event history analysis and individual union histories collected by a national survey in 2009 to assess whether increasing homicide rates in the previous 2 years relates to the dissolution of marital and cohabiting unions, and to transitions to marriage among cohabitors. Cox models show that a recent spike in violence is associated with a higher risk of dissolution for first coresidential unions among less educated women. Competing-risks Cox models further show that for first cohabiting unions among the less educated, exposure to increasing violence is not only associated with a higher risk of dissolution, but also with a higher risk of transitioning to marriage. In contrast, recent spikes in violence were not significantly associated with union transitions for more educated women. This suggests that increasing local violence may be pushing disadvantaged women in coresidential unions to accelerate significant transitions in their family trajectories, by either dissolving their relationships, or getting married to their cohabiting partner, which plausibly reflects underlying differences in union quality. By evaluating the link between local criminal violence and union stability, our findings contribute to understanding how disadvantaged families cope with disruptions to their social environments.
The role of visual association cortices during response selection processes in interference-modulated response stopping
Authors: Eggert Elena , Ghin Filippo , Stock Ann-Kathrin , Mückschel Moritz , Beste Christian
Published: January 2023

Response inhibition and the ability to navigate distracting information are both integral parts of cognitive control and are imperative to adaptive behavior in everyday life. Thus far, research has only inconclusively been able to draw inferences regarding the association between response stopping and the effects of interfering information. Using a novel combination of the Simon task and a stop signal task, the current study set out to investigate the behavioral as well as the neurophysiological underpinnings of the relationship between response stopping and interference processing. We tested n = 27 healthy individuals and combined temporal EEG signal decomposition with source localization methods to delineate the precise neurophysiological dynamics and functional neuroanatomical structures associated with conflict effects on response stopping. The results showed that stopping performance was compromised by conflicts. Importantly, these behavioral effects were reflected by specific aspects of information coded in the neurophysiological signal, indicating that conflict effects during response stopping are not mediated via purely perceptual processes. Rather, it is the processing of specific, stop-relevant stimulus features in the sensory regions during response selection, which underlies the emergence of conflict effects in response stopping. The findings connect research regarding response stopping with overarching theoretical frameworks of perception–action integration.
Estimating drug-induced liver injury risk by in vitro molecular initiation response and pharmacokinetic parameters for during early drug development
Authors: Nukaga Takumi , Takemura Akinori , Endo Yuka , Uesawa Yoshihiro , Ito Kousei
Published: January 2023

Drug-induced liver injury (DILI) is a major factor influencing new drug withdrawal; therefore, an appropriate toxicity assessment at the preclinical stage is required. Previous in silico models have been established using compound information listed in large data sources, thereby limiting the DILI risk prediction for new drugs. Herein, we first constructed a model to predict DILI risk based on a molecular initiating event (MIE) predicted by quantitative structure–activity relationships, admetSAR parameters (e.g. cytochrome P450 reactivity, plasma protein binding, and water-solubility), and clinical information (maximum daily dose [MDD] and reactive metabolite [RM]) for 186 compounds. The accuracy of the models using MIE, MDD, RM, and admetSAR alone were 43.2%, 47.3%, 77.0%, and 68.9%, while the “predicted MIE + admetSAR + MDD + RM” model’s accuracy was 75.7%. The contribution of MIE to the overall prediction accuracy was little effect or rather worsening it. However, it was considered that MIE was a valuable parameter and that it contributed to detect high DILI risk compounds in the early development stage. We next examined the effect of stepwise changes in MDD on altering the DILI risk and estimating the maximum safety dose (MSD) for clinical use based on structural information, admetSAR, and MIE parameters because it is important to estimate the dose that could prevent the DILI onset in clinical conditions. Low-MSD compounds might increase the DILI risk, as these compounds were classified as “most-DILI concern” at low doses. In conclusion, MIE parameters were especially useful to check the DILI concern compounds and to prevent the underestimation of DILI risk in the early stage of drug development.
Evolutionary rate of SARS-CoV-2 increases during zoonotic infection of farmed mink
Authors: Porter Ashleigh F , Purcell Damian F J , Howden Benjamin P , Duchene Sebastian
Published: January 2023

To investigate genetic signatures of adaptation to the mink host, we characterised the evolutionary rate heterogeneity in mink-associated severe acute respiratory syndrome coronaviruses (SARS-CoV-2). In 2020, the first detected anthropozoonotic spillover event of SARS-CoV-2 occurred in mink farms throughout Europe and North America. Both spill-back of mink-associated lineages into the human population and the spread into the surrounding wildlife were reported, highlighting the potential formation of a zoonotic reservoir. Our findings suggest that the evolutionary rate of SARS-CoV-2 underwent an episodic increase upon introduction into the mink host before returning to the normal range observed in humans. Furthermore, SARS-CoV-2 lineages could have circulated in the mink population for a month before detection, and during this period, evolutionary rate estimates were between 3 × 10–3 and 1.05 × 10–2 (95 per cent HPD, with a mean rate of 6.59 × 10–3) a four- to thirteen-fold increase compared to that in humans. As there is evidence for unique mutational patterns within mink-associated lineages, we explored the emergence of four mink-specific Spike protein amino acid substitutions Y453F, S1147L, F486L, and Q314K. We found that mutation Y453F emerged early in multiple mink outbreaks and that mutations F486L and Q314K may co-occur. We suggest that SARS-CoV-2 undergoes a brief, but considerable, increase in evolutionary rate in response to greater selective pressures during species jumps, which may lead to the occurrence of mink-specific mutations. These findings emphasise the necessity of ongoing surveillance of zoonotic SARS-CoV-2 infections in the future.
What Science Leaves Unsaid
Authors: Gorman Geraldine , Stephenson Shirley
Published: January 2023

At a time when new and veteran nurses are fleeing the profession and the term resilience is as worn out as the workers it is meant to inspire, scholars and educators must excavate the intuitive and creative core of nursing. Science addresses facts but lacks language for nuance. This article asserts that nursing, which lags behind medicine in appreciating the value of its stories, must recognize the essential diversity the humanities bring to our understanding of the human condition. As workforce deficits, moral distress, and vicarious trauma proliferate, a consilience between the art and science of nursing and a reminder of their ability to potentiate one another are overdue.
Pustular Lichenoid Eruptions Induced by Immune Checkpoint Inhibitors: Two Case Reports and a Review of the Literature
Authors: Emonet Charlotte , Tétart Florence , Bauvin Olivia , Cellier Lucie , Courville Philippe , Mignard Claire , Janela-Lapert Raphaël , Lefebvre Alexis , Lachkar Samy , Lechevalier Diane , Lagarce Laurence , Carvalho Priscille , Tedbirt Billal
Published: January 2023

Immune checkpoint inhibitors (ICIs) have become the standard treatment for many types of cancer. After several years of using these therapies, many adverse events related to ICIs have been observed. Dermatologic toxicities such as nonspecific morbilliform rash, vitiligo, Stevens-Johnson syndrome/toxic epidermal necrolysis, and more rarely, lichenoid eruptions have been described in the literature. We report 2 cases of pustular lichenoid eruptions, 1 in a patient with nonsmall cell lung carcinoma and 1 in a patient with metastatic melanoma, induced by pembrolizumab and nivolumab, respectively. The 2 patients were treated with topical corticosteroids, and complete healing of lesions was slowly obtained. Due to the severity of the cutaneous eruptions, pembrolizumab and nivolumab were discontinued. We identified 6 cases of pustular lichenoid eruptions induced by ICIs in the published literature and in the French Pharmacovigilance Database and reviewed their main clinical features and courses.
Examining the influence of built environment on sleep disruption
Authors: Parks Jaclyn , Baghela Millie , Bhatti Parveen
Published: January 2023

Background:

Modifying aspects of the built environment may be an effective strategy for population-level improvements to sleep. However, few comprehensive evaluations of built environment and sleep have been completed.

Methods:

We conducted a cross-sectional study among participants of the British Columbia Generations Project (BCGP) who self-reported sleep duration (n = 28,385). Geospatial measures of light-at-night (LAN), greenness, air pollution (PM2.5, NO2, SO2), and road proximity were linked to participant baseline residential postal codes. Logistic regression models, adjusted for age and sex, were used to estimate the association between these factors and self-reported sleep duration (<7 vs. ≥7 hours).

Results:

Interquartile range (IQR) increases in LAN intensity, greenness, and SO2 were associated with 1.04-fold increased (95% CI = 1.02, 1.07), 0.95-fold decreased (95% CI = 0.91, 0.98), and 1.07-fold increased (95% CI = 1.03, 1.11) odds, respectively, of reporting insufficient sleep (i.e., <7 hours per night). Living <100 m from a main roadway was associated with a 1.09-fold greater odds of insufficient sleep (95% CI = 1.02, 1.17). Results were unchanged when examining all factors together within a single regression model. In stratified analyses, associations with SO2 were stronger among those with lower reported annual household incomes and those living in more urban areas.

Conclusions:

BCGP’s rich data enabled a comprehensive evaluation of the built environment, revealing multiple factors as potentially modifiable determinants of sleep disruption. In addition to longitudinal evaluations, future studies should pay careful attention to the role of social disparities in sleep health.
Unilateral acute macular edema with serous macular detachment after bilateral phacoemulsification
Authors: Burridge Samuel , Kazakos Dimitris , Asaria Riaz
Published: January 2023

Two cases of unilateral macular edema with serous macular detachment occurring 1 day after uneventful bilateral phacoemulsification procedures are reported. Both patients underwent sequential bilateral phacoemulsification for refractive lens exchange. On postoperative day 1, corrected distance visual acuity (CDVA) was recorded between 6/24 and 6/48 in the affected eyes of cases 1 and 2, respectively. In both cases, optical coherence tomography showed serous macular detachment with significant intraretinal fluid accumulation. Central foveal thickness (CFT) was recorded as 583 μm in case 1 and 822 μm in case 2. In case 1, the fluid was completely resorbed by postoperative day 3 with no additional treatment. Final CDVA and CFT in case 1 were 6/6 and 292 μm, respectively. Resolution of edema was more prolonged in case 2 and occurred by postoperative day 8, after the addition of nepafenac 0.1% on day 2. Final CDVA and CFT in case 2 were 6/6 and 299 μm, respectively.
The technological future of percutaneous nephrolithotomy: a Young Academic Urologists Endourology and Urolithiasis Working Group update
Authors: Hameed B.M. Zeeshan , Shah Milap , Pietropaolo Amelia , De Coninck Vincent , Naik Nithesh , Skolarikos Andreas , Somani Bhaskar K.
Published: January 2023

Purpose of review

With advancements in surgical technology along with procedural techniques, this article throws light on the latest developments and applications of artificial intelligence (AI), extended reality, 3D (three-dimensional) printing and robotics in percutaneous nephrolithotomy (PCNL).

Recent findings

This review highlights the applications of AI in PCNL over the past 2 years. Mostly studies have been reported on development of machine learning (ML) based predicting models and identification of stone composition using deep learning convolutional neural network (DL-CNN). But owing to the complexity of the models and lack of generalizability, it is still not incorporated in the routine clinical practice. Extended reality based simulation and training models have enabled trainees to enhance their skills and shorten the learning curve. Similar advantages have been reported with the use of 3D printed models when used to train young and novice endourologists to improve their skills in percutaneous access (PCA). Applications of robotics in PCNL look promising but are still in nascent stages.

Future research on PCNL should focus more on generalizability and adaptability of technological advancements in terms of training and improvement of patient outcomes.
They're Dying. Now What? The Impact of a 2-Hour End-of-Life Educational Intervention on Bedside Nurse Self-efficacy, Knowledge, and Clinical Practice
Authors: Sabolish Rachel M. , Pennartz Lauren E. , Caldwell Hollie K.
Published: January 2023

The palliative care team identified a lack of knowledge and confidence for nurses providing end-of-life care in a hospital. The team completed a quality improvement project establishing significant improvement in knowledge and self-efficacy after a 2-hour educational intervention. The next step was to study the impact on practice. Clinical management of pain, dyspnea, secretions, and agitation was compared for a 3-month period before and after intervention. Thirty-six patients were identified in the preintervention group, and 46 patients were in the postintervention group. A 2-sample proportion Z test (α = .05, 2-tailed) showed no statistical significance in the number of doses of opioids administered between preintervention and postintervention groups; however, the number of patients in the postintervention group that received an opioid orally was significantly greater (z = −2.098, P = .0357). A significantly lower proportion of the postintervention group received benzodiazepines (z = −4.334, P < .00001). The postintervention group had a statistically significant lower proportion of anticholinergics administered (z = −4.189, P < .00001). Significantly more patients in the postintervention group had oxygen titrated (z = −3.196, P = .0014) and were on room air at the time of death (z = −3.891, P = .0001). A 2-hour training led to statistically significant changes in the use of evidence-based interventions.
Ovarian RASoma With Mesonephric-like Adenocarcinoma and Mixed Mullerian Components: A Case Report With Molecular Analysis Demonstrating Multidirectional Mullerian Differentiation
Authors: Stolnicu Simona , Bartalis Rolland-Jozsef , Ye Qiqi , Da Cruz Paula Arnaud , Weigelt Britta , Soslow Robert A.
Published: January 2023

Gynecologic carcinomas with RAS mutations may show a wide spectrum of histologic types, including mixed types. We present the case of a 63-yr-old patient diagnosed with an ovarian tumor harboring a mesonephric-like adenocarcinoma in a background of mixed mesonephric-like, mucinous, and endometrioid components. Molecular analysis revealed that all 3 components shared the same clonal KRAS mutation (p.G12A) and chromosome 1q gain. Based on shifts in clonality, copy number gains, and acquisition of an additional mutation, our data suggest that the mucinous component likely constituted the substrate from which the mesonephric-like and endometrioid components arose.
Ganglioneuroblastoma Presenting as Obstructive Sleep Apnea in a 5-Year-Old Boy
Authors: Wallace Aaron , Kaufmann Gabe , Agrawal Nishant , Baroody Fuad
Published: January 2023

The authors present an interesting case of ganglioneuroblastoma, a tumor of the sympathetic chain, presenting as severe obstructive sleep apnea in a healthy 5-year-old boy. The patient’s initial polysomnogram demonstrated an apnea-hypopnea index (AHI) of 86 events/hour. He underwent an adenotonsillectomy at an outside hospital and his repeat AHI was still 62. The patient was nonobese and nonsyndromic appearing, which made his incredibly high AHI perplexing. He underwent sleep endoscopy and direct laryngoscopy for further evaluation, which demonstrated a large mass in the left posterior pharynx. He then underwent surgical excision with a resolution of his obstructive sleep apnea.
Immune Response to COVID-19 mRNA Vaccination in Previous Nonresponder Kidney Transplant Recipients After Short-term Withdrawal of Mycophenolic Acid 1 and 3 Months After an Additional Vaccine Dose
Authors: Kühn Tessa , Speer Claudius , Morath Christian , Bartenschlager Marie , Kim Heeyoung , Beimler Jörg , Buylaert Mirabel , Nusshag Christian , Kälble Florian , Reineke Marvin , Töllner Maximilian , Klein Katrin , Blank Antje , Parthé Sylvia , Schnitzler Paul , Zeier Martin , Süsal Caner , Bartenschlager Ralf , Tran Thuong Hien , Schaier Matthias , Benning Louise
Published: January 2023

Background.

The impaired immune response to coronavirus disease 2019 (COVID-19) vaccination in kidney transplant recipients (KTRs) leads to an urgent need for adapted immunization strategies.

Methods.

Sixty-nine KTRs without seroconversion after ≥3 COVID-19 vaccinations were enrolled, and humoral response was determined after an additional full-dose mRNA-1273 vaccination by measuring severe acute respiratory syndrome coronavirus 2–specific antibodies and neutralizing antibody activity against the Delta and Omicron variants 1 and 3 mo postvaccination. T-cell response was analyzed 3 mo postvaccination by assessing interferon-γ release. Mycophenolic acid (MPA) was withdrawn in 41 KTRs 1 wk before until 4 wk after vaccination to evaluate effects on immunogenicity. Graft function, changes in donor-specific anti-HLA antibodies, and donor-derived cell-free DNA were monitored in KTRs undergoing MPA withdrawal.

Results.

Humoral response to vaccination was significantly stronger in KTRs undergoing MPA withdrawal 1 mo postvaccination; however, overall waning humoral immunity was noted in all KTRs 3 mo after vaccination. Higher anti-S1 immunoglobulin G levels correlated with better neutralizing antibody activity against the Delta and Omicron variants, whereas no significant association was detected between T-cell response and neutralizing antibody activity. No rejection occurred during study, and graft function remained stable in KTRs undergoing MPA withdrawal. In 22 KTRs with Omicron variant breakthrough infections, neutralizing antibody activity was better against severe acute respiratory syndrome coronavirus 2 wild-type and the Delta variants than against the Omicron variant.

Conclusions.

MPA withdrawal to improve vaccine responsiveness should be critically evaluated because withdrawing MPA may be associated with enhanced alloimmune response, and the initial effect of enhanced seroconversion rates in KTRs with MPA withdrawal disappears 3 mo after vaccination.
Relationship between the triglyceride-glucose index and the SYNTAX score 2 in patients with non-ST elevation myocardial infarction
Authors: Baydar Onur , Kilic Alparslan , Gursoy Erol
Published: January 2023

Objective

We evaluated if admissiontriglyceride-glucose index (TyG index) correlated with the anatomical synergy between percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) score 2 in non-ST elevation myocardial infarction (NSTEMI), nondiabetic patients.

Methods

SYNTAX score 2 (SSII) was retrospectively evaluated in 260 nondiabetic patients hospitalized with NSTEMI who underwent coronary angiography. The TyG index was calculated using the following equation: log [fasting triglycerides (mg/dl) × fasting glucose (mg/dl)/2]. We stratified patients according to tertiles of SSII (≤21.5, 21.5–30.6, and ≥30.6). These score ranges were defined as SSII low, SSII mid, and SSII high, respectively.

Results

The average age of the patients was 57.2 ± 10.9 years; 135 patients (52.2%) were males. The average TyG index was 8.68 ± 0.12, and SSII was 18.9 ± 9.9. A moderate correlation was found between TyG index and SSII (r = 0.347; P < 0.001) and TyG index was independent risk factors for SSII high [odds ratio (OR), 6.0; 95% CI, 2.7–17.0; P < 0.001].

Conclusion

In nondiabetic patients with NSTEMI, TyG index correlated with the SSII.
Nasopharyngeal Staphylococcus aureus colonization among HIV-infected children in Addis Ababa, Ethiopia: Antimicrobial susceptibility pattern and association with Streptococcus pneumoniae colonization
Authors: Gebre Henok Alemu , Wami Ashenafi Alemu , Kebede Eyerusalem Solomon , Yidnekachew Melaku , Gebre Meseret , Negash Abel Abera
Published: January 2023

Background

Staphylococcus aureus and Streptococcus pneumoniae are common inhabitants of the nasopharynx of children. HIV-infected children have higher risk of invasive diseases caused by these pathogens. With widespread use of pneumococcal conjugate vaccines and the emergence of methicillin-resistant S aureus, the interaction between S. aureus and S. pneumoniae is of a particular significance. We sought to determine the magnitude of colonization by methicillin-sensitive and -resistant S. aureus and colonization by S. pneumoniae; associated risk factors and antimicrobial susceptibility pattern among HIV-Infected children in Addis Ababa, Ethiopia.

Method

A prospective observational study was conducted in 183 HIV-infected children at ALERT hospital Addis Ababa, Ethiopia from September 2016 to August 2018. S. aureus and S. pneumoniae were identified using standard bacteriological techniques, antimicrobial susceptibility testing was performed on S. aureus and screening for methicillin resistance was carried out by amplifying the mecA gene. Risk factors were analyzed by using binary logistic regression.

Results

The prevalence of nasopharyngeal S. aureus, MRSA and S. pneumoniae colonization were 27.3%, 2.7% and 43.2% respectively. Multivariable analysis indicated an inverse association between S. aureus and S. pneumoniae nasopharyngeal colonization (aOR, 0.49; CI, (0.24, 0.99); p= 0.046). The highest level of resistance in both methicillin sensitive S. aureus (MSSA) and MRSA was observed against tetracycline.

Conclusions

We found an inverse association between S. aureus and S. pneumoniae colonization among HIV-infected children. Continued assessment of the impact of pneumococcal conjugate vaccines and anti-retroviral therapy on nasopharyngeal bacterial ecology is warranted.
Detection of IgM, IgG, IgA and neutralizing antibody responses to SARS-CoV-2 infection and mRNA vaccination
Authors: Fleischmann Charles J. , Bulman Christina A. , Yun Cassandra , Lynch Kara L. , Wu Alan H. B. , Whitman Jeffrey D.
Published: January 2023

Introduction. One correlate of immunity for coronavirus disease 2019 (COVID-19) is the laboratory detection of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. These tests are widely implemented for clinical, public health, or research uses.

Hypothesis/Gap Statement. Antibody responses by all classes of immunoglobulins may form from infection and vaccination, but few studies have performed direct head-to-head comparisons between these groups.

Aim. The objective of this study was to evaluate the serological responses in natural SARS-CoV-2 infection and mRNA-based vaccination across multiple immunoglobulin classes and a surrogate neutralizing antibody (NAb) assay.

Methodology. A suite of enzyme-linked immunosorbent assays (ELISAs) was used to qualitatively assess IgA, IgM and IgG positivity and neutralizing per cent signal inhibition of sera from RT-PCR-confirmed SARS-CoV-2-infected patients, COVID-19-immunized individuals ≥2 weeks after a second dose of mRNA vaccine and a set of pre-pandemic negative samples.

Results. For confirmed SARS-CoV-2 infections, seroconversion of IgA, IgM, IgG and NAb increased by week after symptom onset, with positivity reaching 100 % after the third week for every immunoglobulin class. Vaccinated individuals demonstrated 100 % IgG positivity and high per cent signal inhibition by NAb, comparable to natural infection. High specificity, ranging from 96.7–98.9 %, was observed for each assay from a set of pre-pandemic COVID-19-negative samples.

Conclusion. We make use of a comprehensive and readily adoptable suite of serological assays to provide data on the humoral immune response to SARS-CoV-2 infection and vaccination. We found that infection and vaccination both elicit robust IgG, IgM, IgA and neutralizing antibody responses.
Emergence and clonal spread of KPC-2-producing clinical Klebsiella aerogenes isolates in a hospital from northwest Argentina
Authors: Vargas Juan Martín , Moreno Mochi Maria Paula , Nuñez Juan Manuel , Mochi Silvana , Cáceres Mariel , Del Campo Rosa , Jure María Angela
Published: January 2023

Introduction.

Klebsiella aerogenes

is a nosocomial pathogen associated with drug resistance and healthcare-associated infections.

Gap Statement.

K. aerogenes

is associated with hospital-acquired infections with the ability to acquire mechanisms of resistance to reserve antimicrobials; its clinical behaviour has been poorly documented.

Objective. We proposed to investigate an outbreak of carbapenem-resistant

K. aerogenes

in a hospital that persisted for 4 months.

Methods. The primary aim was to evaluate the molecular characteristics and the clonal relationships among the isolates. We characterized isolates by polymerase chain reaction (PCR) and pulsed-field gel electrophoresis (PFGE). The information was integrated with clinical and epidemiological data.

Results. Fourteen strains were disseminated in an intensive care unit and different wards at the hospital. The overall mortality was 42.8 %, and mortality attributed to infection was 21.4 %; strains showed high rates of resistance to most of the antimicrobials tested and carried bla
KPC-2, bla
SHV-2 and bla
CTXM-15 genes. PFGE analysis indicated 2 PFGE groups; 12/14 isolates were associated with subgroup A and were likely to be primarily responsible for the ﬁrst isolation and subsequent dissemination. The outbreak characteristics data showed prolonged hospitalization and previous use of antibiotics as potential risk factors.

Conclusion. We consider that it is essential to perform phenotypic and genotypic identification of early genetic resistance mechanisms in

K. aerogenes

isolates, not only from infection sites but also from colonization, to prevent the spread of these multidrug-resistant (MDR) isolates.
Man vs Microbes – The Race of the Century
Authors: Anderson Ericka , Nair Bipin , Nizet Victor , Kumar Geetha
Published: January 2023

The complexity of the antimicrobial resistance (AMR) crisis and its global impact on healthcare invokes an urgent need to understand the underlying forces and to conceive and implement innovative solutions. Beyond focusing on a traditional pathogen-centric approach to antibiotic discovery yielding diminishing returns, future therapeutic interventions can expand to focus more comprehensively on host-pathogen interactions. In this manner, increasing the resiliency of our innate immune system or attenuating the virulence mechanisms of the pathogens can be explored to improve therapeutic outcomes. Key pathogen survival strategies such as tolerance, persistence, aggregation, and biofilm formation can be considered and interrupted to sensitize pathogens for more efficient immune clearance. Understanding the evolution and emergence of so-called ‘super clones’ that drive AMR spread with rapid clonotyping assays may guide more precise antibiotic regimens. Innovative alternatives to classical antibiotics such as bacteriophage therapy, novel engineered peptide antibiotics, ionophores, nanomedicines, and repurposing drugs from other domains of medicine to boost innate immunity are beginning to be successfully implemented to combat AMR. Policy changes supporting shorter durations of antibiotic treatment, greater antibiotic stewardship, and increased surveillance measures can enhance patient safety and enable implementation of the next generation of targeted prevention and control programmes at a global level.
Long Covid symptoms and diagnosis in primary care: a cohort study using structured and unstructured data in The Health Improvement Network primary care database
Authors: Shah Anoop D. , Subramanian Anuradhaa , Lewis Jadene , Dhalla Samir , Ford Elizabeth , Haroon Shamil , Kuan Valerie , Nirantharakumar Krishnarajah
Published: January 2023

BACKGROUND

Long Covid is a widely recognised consequence of COVID-19 infection, but little is known about the burden of symptoms that patients present with in primary care, as these are typically recorded only in free text clinical notes. Our objectives were to compare symptoms in patients with and without a history of COVID-19, and investigate symptoms associated with a Long Covid diagnosis.

METHODS

We used primary care electronic health record data from The Health Improvement Network (THIN), a Cegedim database. We included adults registered with participating practices in England, Scotland or Wales. We extracted information about 89 symptoms and ‘Long Covid’ diagnoses from free text using natural language processing. We calculated hazard ratios (adjusted for age, sex, baseline medical conditions and prior symptoms) for each symptom from 12 weeks after the COVID-19 diagnosis.

FINDINGS

We compared 11,015 patients with confirmed COVID-19 and 18,098 unexposed controls. Only 20% of symptom records were coded, with 80% in free text. A wide range of symptoms were associated with COVID-19 at least 12 weeks post-infection, with strongest associations for fatigue (adjusted hazard ratio (aHR) 3.99, 95% confidence interval (CI) 3.59, 4.44), shortness of breath (aHR 3.14, 95% CI 2.88, 3.42), palpitations (aHR 2.75, 95% CI 2.28, 3.32), and phlegm (aHR 2.88, 95% CI 2.30, 3.61). However, a limited subset of symptoms were recorded within 7 days prior to a Long Covid diagnosis in more than 20% of cases: shortness of breath, chest pain, pain, fatigue, cough, and anxiety / depression.

CONCLUSION

Numerous symptoms are reported to primary care at least 12 weeks after COVID-19 infection, but only a subset are commonly associated with a GP diagnosis of Long Covid.
Ultrasound evaluation of vagus nerve cross-sectional area in a community-dwelling elderly Japanese cohort
Authors: Oura Kazumasa , Akasaka Hiroshi , Ishizuka Naoki , Sato Yuriko , Kudo Masahiro , Yamaguchi Takashi , Oura Mao Yamaguchi , Itabashi Ryo , Maeda Tetsuya
Published: January 2023

Objectives

Although the vagus nerve (VN) is easily observed by ultrasonography, few studies have evaluated the cross-sectional area (CSA) of the VN in healthy older individuals from East Asia. In this study, we aimed to report reference values for the CSA of the VN in community-dwelling elderly Japanese individuals and to identify any associated medical history and/or lifestyle factors.

Methods

The present study included 336 participants aged ≥ 65 years from a prospective cohort study conducted in Yahaba, Japan from October 2021 to February 2022. The CSA of the VN was measured bilaterally at the level of the thyroid gland by ultrasonography. Univariate and multivariable linear regression analyses were conducted to identify the associations between clinical and background factors and the CSA of the VN on each side.

Results

In our cohort, the median CSA of the VN was 1.3 mm2(interquartile range [IQR] 1.1– 1.6) on the right side and 1.2 mm2(IQR 1.0–1.4) on the left side. Multivariable linear regression analysis showed that history of head injury (β = -0.15,p< .01), history of convulsion (β = 0.19,p< .01), and BMI (β = 0.30,p< .01) were independently associated with the CSA of the VN on the left side. In contrast, there were no independent associations between any of the assessed variables and the CSA on the right side.

Conclusion

We have reported reference VN CSA values for community-dwelling elderly Japanese individuals. In addition, we showed that the CSA of the VN on the left side was positively associated with a history of convulsive seizure and BMI and inversely associated with a history of head injury.
Adipokine levels and their association with clinical disease severity in patients with dengue
Authors: Kuruppu Heshan , Wickramanayake W.P Rivindu H. , Jeewandara Chandima , Peranantharajah Deneshan , Colambage Hashini S. , Perera Lahiru , Gomes Laksiri , Wijewickrama Ananda , Ogg Graham S , Malavige Gathsaurie Neelika
Published: January 2023

Adipokines have not been studied in acute dengue, despite their emerging role in inducing and regulating inflammation. Therefore, we sought to identify adipokine levels in patients with varying severities of acute dengue to understand their role in disease pathogenesis. We determined the levels of leptin, resistin, omentin, adiponectin, as well as IFNβ, and NS1 using quantitative ELISA in patients with dengue fever (DF=49) and dengue haemorrhagic fever (DHF=22) at admission (febrile phase) and at the time of discharge (recovery phase). The viral loads and serotypes of all samples were quantified using quantitative real-time RT-PCR.

Resistin levels (p =0.04) and omentin (p=0.006) levels were significantly higher in patients who developed DHF. Omentin levels in the febrile phase also correlated with the AST (Spearman’s r=0.38, p=0.001) and ALT levels (Spearman’s r=0.24, p=0.04); as well as serum leptin levels with both AST (Spearman’s r=0.27, p=0.02) and ALT (Spearman’s r=0.28, p=0.02). Serum adiponectin levels in the febrile phase did not correlate with any of the other adipokines or with liver enzymes, but inversely correlated with CRP levels (Spearman’s r=-0.31, p=0.008). Although not significant (p=0.14) serum IFNβ levels were lower in the febrile phase in those who progressed to develop DHF (median 0, IQR 0 to 39.4 pg/ml), compared to those who had DF (median 37.1, IQR 0 to 65.6 pg.ml). The data suggest that adipokines are likely to play a role in the pathogenesis of dengue, which should be further explored for the potential to be used as prognostic markers and as therapeutic targets.
A simplification of the Kaiser Permanente inpatient risk adjustment methodology accurately predicted in-hospital mortality: A retrospective cohort study
Authors: Roberts Surain B , Colacci Michael , Razak Fahad , Verma Amol A
Published: January 2023

Objective

We simplified and evaluated the Kaiser Permanente inpatient risk adjustment methodology (KP method) to predict in-hospital mortality, using open-source tools to measure comorbidity and diagnosis groups, and removing troponin, which is difficult to standardize across clinical assays.

Study Design and Setting

Retrospective cohort study of adult general medical inpatients at 7 hospitals in Ontario, Canada.

Results

In 206,155 unique hospitalizations with 6.9% in-hospital mortality, the simplified KP method accurately predicted the risk of mortality. Bias-corrected c-statistics were 0.874 (95%CI 0.872-0.877) with troponin and 0.873 (95%CI 0.871-0.876) without troponin, and calibration was excellent for both approaches. Discrimination and calibration were similar with and without troponin for patients with heart failure and acute myocardial infarction. The Laboratory-based Acute Physiology Score (LAPS, a component of the KP method) predicted inpatient mortality on its own with and without troponin with bias-corrected c-statistics of 0.687 (95%CI 0.682-0.692) and 0.680 (95%CI 0.675-0.685), respectively. LAPS was well calibrated, except at very high scores.

Conclusion

A simplification of the KP method accurately predicted in-hospital mortality risk in an external general medicine cohort. Without troponin, and using common open-source tools, the KP method can be implemented for risk adjustment in a wider range of settings.
Acute effects of subanesthetic ketamine on cerebrovascular hemodynamics in humans: A TD-fNIRS neuroimaging study
Authors: Castillo Adelaida , Dubois Julien , Field Ryan M. , Fishburn Frank , Gundran Andrew , Ho Wilson C. , Jawhar Sami , Kates-Harbeck Julian , Aghajan Zahra M. , Miller Naomi , Perdue Katherine L. , Phillips Jake , Ryan Wesley C. , Shafiei Mahdi , Scholkmann Felix , Taylor Moriah
Published: January 2023

Quantifying neural activity in natural conditions (i.e. conditions comparable to the standard clinical patient experience) during the administration of psychedelics may further our scientific understanding of the effects and mechanisms of action. This data may facilitate the discovery of novel biomarkers enabling more personalized treatments and improved patient outcomes. In this single-blind, placebo-controlled study with a non-randomized design, we use time-domain functional near-infrared spectroscopy (TD-fNIRS) to measure acute brain dynamics after intramuscular subanesthetic ketamine (0.75 mg/kg) and placebo (saline) administration in healthy participants (n= 15, 8 females, 7 males, age 32.4 ± 7.5 years) in a clinical setting. We found that the ketamine administration caused an altered state of consciousness and changes in systemic physiology (e.g. increase in pulse rate and electrodermal activity). Furthermore, ketamine led to a brain-wide reduction in the fractional amplitude of low frequency fluctuations (fALFF), and a decrease in the global brain connectivity of the prefrontal region. Lastly, we provide preliminary evidence that a combination of neural and physiological metrics may serve as predictors of subjective mystical experiences and reductions in depressive symptomatology. Overall, our studies demonstrated the successful application of fNIRS neuroimaging to study the physiological effects of the psychoactive substance ketamine and can be regarded as an important step toward larger scale clinical fNIRS studies that can quantify the impact of psychedelics on the brain in standard clinical settings.
Effort-reward imbalance at work, glycated hemoglobin and prediabetes prevalence in a prospective cohort
Authors: Riopel C , Trudel X , Milot A , Laurin D , Gilbert-Ouimet M , Brisson C
Published: January 2023

Contex

Prospective studies and meta-analyses suggest that psychosocial stressors at work from the effort-reward imbalance model are associated with an increased risk of type 2 diabetes mellitus (T2DM). Prediabetes is an intermediate disorder on the glucose metabolism continuum. It increases the risk of developing T2DM, while also being separately associated with increased mortality. Evidence about the effect of effort-reward imbalance at work on prediabetes is scarce.

Objective

The objective was to evaluate, in women and men, the association between effort-reward imbalance at work, glycated hemoglobin (HbA1c) concentration and the prevalence of prediabetes in a prospective cohort study.

Methods

This study was conducted among 1,354 white-collar workers followed for an average of 16 years. Effort-reward imbalance at work (ERI) was measured at baseline (1999-2001) using a validated instrument. HbA1c was assessed at follow-up (2015-18). Several covariates were considered including sociodemographics, anthropometric, and lifestyle risk factors. Differences in mean HbA1c concentration were estimated with linear models. Prediabetes prevalence ratios (PRs) were computed using Poisson regressions models.

Results

In women, those exposed to effort-reward imbalance at work had a higher prevalence of prediabetes (adjusted PR=1.52, 95% confidence interval: 1.01-2.29). There was no difference in HbA1c concentration among those exposed and those unexposed to an effort-reward imbalance at work.

Conclusion

Among women, effort-reward imbalance at work was associated with the prevalence of prediabetes. Preventive workplace interventions aiming to reduce the prevalence of effort-reward imbalance at work may be effective to reduce the prevalence of prediabetes among women.