bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatiotemporal variation in the adult sex ratio, male aggregation, and movement of two tropical cloud forest dung beetles
Authors: Barretto Julliana , Baena Martha L , Domínguez Israel Huesca , Escobar Federico
Published: December 2021

While theory suggests that at conception the sex ratio should be balanced (1:1), this can be variable across space and time in wild populations. Currently, studies of the environmental factors that regulate adult sex ratio (ASR) in species with different life history traits are scarce. Using capture–recapture over a year, we analyzed the influence of habitat type (forest and nonforest) and season (rainy and dry) on variation in ASR, male aggregation and the trajectory movement of 2 dung beetle species with different life history traits: Deltochilum mexicanum (a hornless roller species) and Dichotomius satanas (a tunneler species with horns on its head and thorax). We found opposite tendencies. The D. mexicanum population tends to be female-biased, but the population of D. satanas tends to be predominantly male, and observed values were not related to habitat type or season. However, the 95% confidence intervals estimated were highly variable between seasons depending on habitat. On examining the monthly variation in ASR for both habitats, we found that it depends on the species. In addition, male aggregation differed between species depending on habitat type and season, and species movement patterns were closely related to their habitat preferences. Based on our results, we argue that comparative population studies of species with different life history traits are necessary to understand the variation in demographic parameters as well as its ecological and evolutionary implications in the face of spatial and climatic environmental variation.
Feasibility of remote technical support for electrophysiological ablation procedures during the current COVID-19 pandemic
Authors: Müssigbrodt Andreas , Demoniere Fabrice , Banydeen Rishika , Finoly Steeve , Mommarche Max , Inamo Jocelyn
Published: December 2021

Aims

The treatment of heart rhythm disorders has been significantly impacted by direct consequences of the current COVID-19 pandemic, as well as by restrictions aimed towards constraining viral spread.

Methods and results

Usually, catheter ablations of cardiac arrhythmias are guided by electro-anatomic mapping (EAM) systems. Technical staff with medical training, or medical staff with technical training, are needed to assist the operator. Travel restrictions due to the current COVID-19 pandemic have limited the in-person availability of technical support staff. To overcome these limitations, we explored the feasibility of a trans-atlantic remote technical support for EAM, with an internet-based communication platform, for complex electrophysiological ablation procedures.

Conclusion

Our first experience, based on nine ablation procedures of different arrhythmias, highlights the feasibility of this approach. Remote support for EAM might therefore facilitate continuous care for patients with arrhythmias during the COVID-19 pandemic, particularly in insular settings. Beyond COVID-19-related challenges, this approach will likely play a greater role in the cardiology field in years to come, due to its significant advantages.
Influence on kinesiophobia by disability, physical, and behavioural variables after a heart transplantation
Authors: Marques-Sule Elena , Söderlund Anne , Almenar Luis , Espí-López Gemma Victoria , López-Vilella Raquel , Bäck Maria
Published: December 2021

Background

From clinical experience, kinesiophobia represents a barrier to being physically active after a heart transplantation (HTx), but studies in this field are lacking. Identifying the factors associated with kinesiophobia is essential to determine preventive interventions to avoid negative consequences for health.

Aims

To study the influence of disability, physical, and behavioural variables on kinesiophobia in patients with an HTx.

Methods

A total of 117 patients with an HTx [51 women; mean age 56 (SD 12.1) years] were recruited at an outpatient clinic. These patients were asked to fill in questionnaires measuring kinesiophobia, self-reported physical activity (PA), exercise self-efficacy, motivation for PA, and disability. A multiple regression analysis was conducted to examine the statistical prediction of kinesiophobia as a dependent variable, with the questionnaires, gender and education as independent variables.

Results

The independent variables explained 70% of the variance in kinesiophobia. The prediction model was significant (F = 32.1, P < 0.001). The time from transplantation (standardised coefficient, beta; −0.17), the total exercise self-efficacy (−0.16), extrinsic motivation (−0.23), and the disability total score (0.63) were significant predictors of kinesiophobia, while the independent variables of gender, education, intrinsic motivation, and the PA total score were not significant.

Conclusions

This study highlights that a short time from transplantation, low self-efficacy, low extrinsic motivation, and a high level of disability explained high levels of kinesiophobia in patients after an HTx. These results suggest that an increased awareness of the biopsychosocial health perspective is essential in order to maximising patient outcomes after an HTx.
Ankfn1-mutant vestibular defects require loss of both ancestral and derived paralogs for penetrance in zebrafish
Authors: Ross Kevin D , Ren Jie , Zhang Ruilin , Chi Neil C , Hamilton Bruce A
Published: December 2021

How and to what degree gene duplication events create regulatory innovation, redundancy, or neofunctionalization remain important questions in animal evolution and comparative genetics. Ankfn1 genes are single copy in most invertebrates, partially duplicated in jawed vertebrates, and only the derived copy retained in most mammals. Null mutations in the single mouse homolog have vestibular and neurological abnormalities. Null mutation of the single Drosophila homolog is typically lethal with severe sensorimotor deficits in rare survivors. The functions and potential redundancy of paralogs in species with two copies are not known. Here, we define a vestibular role for Ankfn1 homologs in zebrafish based on the simultaneous disruption of each locus. Zebrafish with both paralogs disrupted showed vestibular defects and early lethality from swim bladder inflation failure. One intact copy at either locus was sufficient to prevent major phenotypes. Our results show that vertebrate Ankfn1 genes are required for vestibular-related functions, with at least partial redundancy between ancestral and derived paralogs.
Integrating recreational fishing into harvest strategies: linking data with objectives
Authors: Fowler Ashley M , Ochwada-Doyle Faith A , Dowling Natalie A , Folpp Heath , Hughes Julian M , Lowry Michael B , Lyle Jeremy M , Lynch Tim P , Miles Nathan G , Chick Rowan C
Published: December 2021

Recreational fishing (RF) is a popular pastime resulting in substantial fish mortality in many regions. Yet inclusion of RF in fishery harvest strategies is limited, because the sector's objectives are poorly understood, as are the data required to track their performance. To address this, we reviewed RF data sources available from a region of globally high participation (New South Wales [NSW], Australia) and evaluated their utility for RF-specific performance indicators within harvest strategies. We then linked these data sources to RF objectives they may be used to monitor. A total of 21 RF data sources were identified in NSW over the past two decades, spanning all major aquatic environments and 146 fished species. Numerous data sources were available to monitor ecological objectives, providing time-series and potential reference points for key indicators such as catch-per-unit-effort. Few data sources were available for social, economic, and institutional objectives, consistent with a global paucity of these data. We found that most social objectives of RF lie outside the scope of traditional harvest strategies, although some are linked to underlying ecological performance. Harvest strategy performance for RF will depend on the relative importance of social objectives and whether these can be achieved by controlling harvest.
Head Transplantation and Immortality: When Is Life Worth Living Forever?
Authors: Parker J Clint
Published: December 2021

Head transplantation fits within the broader conceptual space occupied by transhumanists and others who seek to extend the lives of human beings indefinitely. It is reasonable to reflect on whether, under what circumstances, and in what ways human immortality would be good. In this paper, I disambiguate the ways in which immortality might be considered a human good and then argue that immortality is neither necessary nor sufficient condition for objective meaning in life. I also argue that mortality is not a necessary condition for objective meaning in life.
Heads, Bodies, Brains, and Selves: Personal Identity and the Ethics of Whole-Body Transplantation
Authors: Iltis Ana
Published: December 2021

Plans to attempt what has been called a head transplant, a body transplant, and a head-to-body transplant in human beings raise numerous ethical, social, and legal questions, including the circumstances, if any, under which it would be ethically permissible to attempt whole-body transplantation (WBT) in human beings, the possible effect of WBT on family relationships, and how families should shape WBT decisions. Our assessment of many of these questions depends partially on how we respond to sometimes centuries-old philosophical thought experiments about personal identity. As with so much in bioethics, it is impossible to escape, or at least inadvisable to try to bypass, the relevant foundational philosophical concerns.
A Dilemma for Respecting Autonomy: Bridge Technologies and the Hazards of Sequential Decision-Making
Authors: Kestigian Aidan , London Alex John
Published: December 2021

Respect for patient autonomy can apply at two levels: ensuring that patient care reflects their considered values and wishes and honoring patient preferences about how to make momentous decisions. Caregivers who seek to respect patient autonomy in the context of some end-of-life decisions face a dilemma. Because these decisions are fraught, patients may prefer to approach them sequentially, only making decisions at the time they arise. However, respecting patients’ preferences for a sequential approach can increase the likelihood that surrogates and care teams wind up in situations in which they lack information needed to ensure patients receive care that conforms to their considered values after they are no longer competent to make decisions for themselves. Sequential decision-making can thus conflict with the goal of ensuring care reflects the wishes of patients. After illustrating how this dilemma can arise in the use of life-sustaining “bridge” technologies, we argue that care teams may be warranted in requiring patients to articulate their wishes in an advance care plan before treatment begins. In some cases, care teams may even be permitted to refuse to undertake certain courses of care, unless patients articulate their wishes in an advance care plan.
Dark matter haloes in the multicomponent model. III. From dwarfs to galaxy clusters
Authors: Todoroki Keita , Medvedev Mikhail V
Published: December 2021

A possibility of DM being multicomponent has a strong implication on resolving decades-long known cosmological problems on small scale. In addition to elastic scattering, the model allows for inelastic interactions, which can be characterized by a ‘velocity kick’ parameter. The simplest 2cDM model with cross-section $0.01\lesssim \sigma /m\lt 1\, \textrm {cm}^{2}{ \rm g}^{-1}$ and the kick velocity $V_{\mathrm{ k}}\simeq 100\, \rm {km\, s}^{-1}$ have been shown to robustly resolve the missing satellites, core-cusp, and too-big-to-fail problems in N-body cosmological simulations tested on Milky Way (MW)-like haloes of a virial mass ${\sim}5 \times 10^{11}\, {\rm M_{\odot }}$ (Papers I & II). With the aim of further constraining the parameter space available for the 2cDM model, we extend our analysis to dwarf and galaxy cluster haloes with their virial mass of ∼107−108 and ${\sim}10^{13} - 10^{14}\, {\rm M_{\odot }}$, respectively. We find that σ0/m ≳ 0.1 cm2g−1 is preferentially disfavoured for both dwarfs and galaxy cluster haloes in comparison with observations, while σ0/m = 0.001 cm2g−1 causes little perceptible difference from that of the CDM counterpart for most of the cross-section’s velocity dependence studied in this work. Our main result is that within the reasonable set of parameters, the 2cDM model can successfully explain the observational trends seen in dwarf galaxy and galaxy cluster haloes, and the model leaves us an open window for other possible alternative DM models.
An Egalitarian Account of Composition and Realization
Authors: Piccinini Gualtiero
Published: December 2021

I argue that wholes are neither identical to nor (completely) distinct from their parts. Instead, wholes are invariants under some transformations in their parts. Similarly, higher-level properties are neither identical to nor (completely) distinct from their lower-level realizers. Instead, higher-level properties are aspects of their realizers that are invariant under some transformations in their realizers. Nowhere in this picture is there any ontological hierarchy between levels of composition or realization. Neither wholes nor their parts are more fundamental. Neither is prior. Neither reduces to the other. Neither is eliminated. Ditto for higher-level properties and their lower-level realizers. Instead, wholes and their properties as well as parts and their properties are different yet invariant aspects of reality. The result is an egalitarian account of composition and realization.
Societal targeting in researcher funding: An exploratory approach
Authors: Ramos-Vielba Irene , Thomas Duncan A , Aagaard Kaare
Published: December 2021

Shaping public research to enhance its societal contribution has become a key policy concern. Against this background, how research funding may stimulate the societal orientation of scientific research—or how funding is societally targeted—has been underexplored. This article proposes an exploratory approach to characterize societal targeting in individual researcher funding, based on four key societal targeting dimensions: interdisciplinarity, transdisciplinarity, prioritized research problems and user-oriented outputs. All these targeting dimensions of funding can potentially shape both researchers’ research networks and practices towards societal goals. These dimensions can be identified in context by studying ex ante specifications of funding instruments, i.e. rules and conditions for funding provision to researchers. We illustrate the dimensions in various degrees using two real cases of national public research funding. This systematic perspective on funding instrument characteristics then can potentially improve research evaluation, by allowing assessment in more detail of which funding dimensions associate with particular kinds of research ultimately being undertaken.
Dietary strategies for the prevention of asthma in children
Authors: Venter Carina , Smith Peter K. , Arshad Hasan
Published: December 2021

Purpose of review

This review summarizes information relating to dietary intake during pregnancy, lactation and early life that may prevent childhood asthma. This review also summarizes how future studies may be improved.

Recent findings

Recent findings from observational studies suggest that eating according to certain dietary patterns during pregnancy, such as the dietary inflammatory index, Mediterranean diet and Maternal diet index, may reduce asthma and or wheeze in the child. Vitamin D supplementation with higher doses than recommended during pregnancy may be associated with reduced early transient childhood wheezing in the offspring. Higher levels of omega-3 fatty acids in breast milk may be protective against childhood asthma. Breastfeeding infants has been shown to offer many benefits to mother and child but a direct relationship between breastfeeding and the development of asthma has not been established. During childhood, infants and children may need to reduce their intake of advanced glycation end products, increase their food intake according to the traditional Mediterranean diet and increase the diversity of foods eaten.

Current evidence provides limited suggestions regarding dietary changes for preventing early transient childhood wheezing. In order to harmonize methods for future data collection and reporting, it is important to harmonize relevant definitions and other important factors. The aim of the considerations described here is to enable a better comparison of future studies and provide better guidance to patients and families.
Injecting Opioid Use Disorder Treatment in Jails and Prisons: The Potential of Extended-release Buprenorphine in the Carceral Setting
Authors: Berk Justin , del Pozo Brandon , Rich Josiah D. , Lee Joshua D.
Published: December 2021

As the opioid overdose cases rise, policy-makers and researchers should target interventions to populations at highest risk. Incarceration serves as a risk factor for opioid overdose (Gan et al. Addiction 2021) and a large portion of recent overdose deaths have had encounters in the criminal justice system.

Medications for opioid use disorder in the criminal justice system can save lives, though unique administrative barriers in jails and prisons hinder access. As facilities expand medications for opioid use disorder access (due to new legislation and court rulings across states), extended-release buprenorphine offers an opportunity to overcome these barriers including logistics of administration, diversion concern, patient stigma, and an increased bridge of treatment during re-entry to the community.

As extended-release buprenorphine has practical advantages in correctional health delivery, future research and policy discussions should investigate its optimal role in treating opiate addiction in a carceral setting.
Oxazepam Detected in Urine 79 Days After Withdrawal of Diazepam: A Case Report
Authors: Serkland Trond Trœtteberg , Dale Gro Helen , Kaldestad Ingeborg Caroline , Berg Jon Andsnes , Methlie Camilla Borthen
Published: December 2021

Patients suffering from substance use disorder, including for instance benzodiazepines, may have comorbidity with attention deficit hyperactivity disorder (ADHD). Centrally acting stimulants play an important role in the treatment of ADHD. Before such treatment can be initiated, withdrawal of benzodiazepines may be necessary. Urine testing is the preferred method for monitoring adherence in benzodiazepine withdrawal, but there is a lack of studies reporting detection time. Here, we report a case of a 30-year-old woman with substance use disorder and ADHD who had detectable metabolites of diazepam 79 days after withdrawal. To our knowledge, no cases with detection time equivalent to this have previously been published. This case report serves as an example that clinicians may need to consider interindividual pharmacokinetic characteristics when interpreting the results of urine drug tests, and that a positive urine test may still be consistent with abstinence from a certain drug. In the current case, a high body mass index and a genetic polymorphism gave a reasonable explanation for the prolonged detection of diazepam metabolites.
Low Dose Initiation of Buprenorphine: A Narrative Review and Practical Approach
Authors: Cohen Shawn M. , Weimer Melissa B. , Levander Ximena A. , Peckham Alyssa M. , Tetrault Jeanette M. , Morford Kenneth L.
Published: December 2021

Low dose buprenorphine initiation, is an alternative method of initiating buprenorphine in which the starting dose is very low and gradually increased to therapeutic levels over a period of days. This method takes advantage of slow displacement of the full opioid agonist from mu-opioid receptors, avoiding the need for a person with opioid use disorder to experience opioid withdrawal symptoms before initiating buprenorphine, while also minimizing the risk of precipitated opioid withdrawal. With this initiation method, full opioid agonists can be continued as buprenorphine is initiated, expanding the population to which buprenorphine can be offered. To date, the literature on low dose initiation is primarily case-based but rapidly growing. While evidence emerges, guidance for the use of low dose initiation is clearly desired and urgently needed in the context of an increasingly risky and contaminated opioid drug supply, particularly with high potency synthetic opioids, driving overdose deaths. Despite limited evidence, several principles to guide low dose initiation have been identified including: (1) choosing the appropriate clinical situation, (2) initiating at a low buprenorphine dose, (3) titrating the buprenorphine dose gradually, (4) continuing the full opioid agonist even if it is nonmedical, (5) communicating clearly with frequent monitoring, (6) pausing or delaying buprenorphine dose changes if opioid withdrawal symptoms occur, and (7) prioritizing care coordination. We review a practical approach to low dose initiation in hospital-based and outpatient settings guided by the current evidence.
Low Dose Buprenorphine Induction With Full Agonist Overlap in Hospitalized Patients With Opioid Use Disorder: A Retrospective Cohort Study
Authors: Bhatraju Elenore P. , Klein Jared W. , Hall Allana N. , Chen David R. , Iles-Shih Matthew , Tsui Judith I. , Merrill Joseph O.
Published: December 2021

Objective

To describe the outcomes of buprenorphine/naloxone low dose induction with overlap of full opioid agonists among hospitalized patients with opioid use disorder (OUD) as an alternative to standard induction strategies.

Methods

Retrospective cohort study of patients with OUD who were admitted to the hospital over a 1-year period and initiated ono buprenorphine using initial doses of 0.5 mg and gradually increased while the patient remained on full agonists. Descriptive variables included basic demographics, reason for switching to buprenorphine, baseline opioid and morphine equivalent dose. The primary outcome was a successful transition defined by the patient leaving the hospital with a buprenorphine prescription. Bivariate analysis identified factors associated with unsuccessful medication transitions. Secondary outcomes included reported withdrawal symptoms and 30 day follow up to an outpatient buprenorphine program.

Results

Sixty two patients underwent low dose with overlap induction during the study period. Fourteen patients were on methadone for OUD before hospital admission. Fifty one patients (82%) successfully left the hospital with a prescription for buprenorphine. Factors associated with lower likelihood of success included older age, transitioning due to discharge placement needs and presence of withdrawal symptoms during the transition. Overall, 66% (N = 23) of patients referred within the same health care system followed up within 30 days.

Conclusions

Low dose inductions with overlap of full opioid agonists were largely successful in transitioning hospitalized patients from full agonist opioids to buprenorphine. However, there were several factors associated with lower likelihood of success. Future work could focus on treatment of withdrawal symptoms and system-level changes ensuring patient-centered medication decisions.
Are Measures of Physical Function of the Neck Region Associated With Poor Prognosis Following a Whiplash Trauma?
Authors: Alalawi Ahmed , Mazaheri Masood , Gallina Alessio , Luque-Suarez Alejandro , Sterling Michele , Falla Deborah
Published: December 2021

Objective:

The objective of this study was to synthesize the current evidence regarding the predictive ability of measures of physical function (PF) of the neck region and perceived PF on prognosis following a whiplash injury.

Materials and Methods:

Electronic databases were searched by 2 independent reviewers up to July 2020, including MEDLINE, EMBASE, CINAHL, PsycINFO, Scopus, and Web of Science as well as gray literature. Eligible studies were selected by 2 reviewers who then extracted and assessed the quality of evidence. Observational cohort studies were included if they involved participants with acute whiplash-associated disorders (WAD), followed for at least 3 months postinjury, and included objective measures of neck PF or self-reported measures of PF as prognostic factors. Data could not be pooled and therefore were synthesized qualitatively.

Results:

Fourteen studies (13 cohorts) were included in this review. Low to very low quality of evidence indicated that initial higher pain-related disability and higher WAD grade were associated with poor outcome, while there was inconclusive evidence that neck range of motion, joint position error, activity of the superficial neck muscles, muscle strength/endurance, and perceived functional capacity are not predictive of outcome. The predictive ability of more contemporary measures of neck PF such as the smoothness of neck movement, variability of neck motion, and coactivation of neck muscles have not been assessed.

Discussion:

Although initial higher pain-related disability and higher WAD grade are associated with poor outcome, there is little evidence available investigating the role of neck PF on prognosis following a whiplash injury.
Molecular Changes in the Dorsal Root Ganglion during the Late Phase of Peripheral Nerve Injury–induced Pain in Rodents: A Systematic Review
Authors: Chalaki Mehrman , Cruz Luis J. , van Neerven Sabien G. A. , Verhaagen Joost , Dahan Albert , Malessy Martijn J. A.
Published: December 2021

The dorsal root ganglion is widely recognized as a potential target to treat chronic pain. A fundamental understanding of quantitative molecular and genomic changes during the late phase of pain is therefore indispensable. The authors performed a systematic literature review on injury-induced pain in rodent dorsal root ganglions at minimally 3 weeks after injury. So far, slightly more than 300 molecules were quantified on the protein or messenger RNA level, of which about 60 were in more than one study. Only nine individual sequencing studies were performed in which the most up- or downregulated genes varied due to heterogeneity in study design. Neuropeptide Y and galanin were found to be consistently upregulated on both the gene and protein levels. The current knowledge regarding molecular changes in the dorsal root ganglion during the late phase of pain is limited. General conclusions are difficult to draw, making it hard to select specific molecules as a focus for treatment.
Advances in understanding and examining lymphatic function: relevance for understanding autoimmunity
Authors: Ambler William , Santambrogio Laura , Lu Theresa T.
Published: December 2021

Purpose of review

The aim of this review is to give insights into how novel lymphatics functions may influence autoimmunity.

Recent findings

The lymphatic system connects peripheral tissues to draining lymph nodes to regulate adaptive immunity and directly interfaces with leukocytes in lymph vessels and in the lymph node. Here, we discuss recent findings showing evidence of dysfunctional lymphatics in autoimmune disease, new understanding of how afferent lymphatic regulation can modulate immunity, lymph node lymphatic heterogeneity and how these lymphatics can directly modulate lymphocyte function, how this understanding can be harnessed for new therapeutics, and new tools for the investigation of lymphatic and immune biology.

Lymphatics have an active role in the regulation of inflammation and the adaptive immune response. Here, we review recent findings in lymphatics biology in peripheral tissues and lymph nodes and emphasize the relevance for better understanding autoimmune diseases.
Pediatric pelvic fractures: an epidemiological analysis of a population-based database
Authors: DiCenso Stefano M. , Kaelber David C. , Mistovich R. Justin
Published: December 2021

Despite a high prevalence in the pediatric trauma population, there remains a lack of large population-based epidemiological studies on pediatric pelvic fractures. Using a de-identified national clinical registry, we investigated the epidemiological features of pediatric pelvic fractures. We performed a retrospective analysis of data obtained from the IBM Watson Health Explorys Platform (Armonk, NY). From all children ages 0-14, two cohorts were created, children diagnosed with a traumatic injury and children diagnosed with a fracture of the pelvis. We then calculated the overall incidence of pelvic fractures, mortality rate, and identified common associated injuries, fracture locations, and complications. 2,690 pediatric pelvic fractures were identified yielding an incidence of 9.8/100,000 children per year with a mortality rate of 0.3%. Pelvic fractures were more common among Caucasians than in African Americans and Asians, and more common in males than females. The most common types of pelvic fracture were fractures of the ilium (42%), pubis (18%), sacrum (11%), ischium (10%), and acetabulum (8%). Most common associated injuries included injury of the lower extremity (43%), intracranial injury (16%), chest injury (13%), injury of the abdomen (9%), and urogenital injury (3%). Rates of common complications associated with malunion were low back pain (10%), acquired leg length discrepancy (1%), and acquired scoliosis (0.3%). The current incidence of pediatric pelvic fracture is 9.8/100,000 children per year with a mortality rate of 0.3%. Further study utilizing large data sets may help to better understand associated injuries, risks of poor outcomes, and optimize treatment strategies.
Nocturnal urine 6-hydroxy sulfate melatonin is associated with the outcome of subjects with sepsis
Authors: Li Wenjie , Chen Jiameng , Pan Shuming , Gao Chengjin
Published: December 2021

Background

It is imperative to identify potential biomarkers for early diagnosis and intervention of severe sepsis. This study investigated the relationship between melatonin secretion and outcome of sepsis after 28-day admission.

Methods

Patients with sepsis were randomly divided into an eye mask group and a control group. Blood and urine samples were collected from day 0 to 4. Relevant clinical data and 28-day survival data were obtained. Serum melatonin and urine 6-hydroxy sulfate melatonin (6-SMT) levels were measured.

Results

The outcome of sepsis did not differ between the eye mask and control groups. Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores were significantly higher and monocyte human leukocyte antigen-DR (mHLA-DR), serum melatonin, nocturnal urine 6-SMT, and 24-hour urine 6-SMT levels were significantly lower in the nonsurvivors than in the survivors. The outcome at day 28 after admission was significantly associated with APACHE II and SOFA scores and mHLA-DR, nocturnal urine 6-SMT, and 24-hour urine 6-SMT levels. The areas under the receiver operating characteristic curve were 0.785, 0.740, 0.774, and 0.858 for APACHE II score, SOFA score, mHLA-DR expression, and nocturnal urine 6-SMT amount, respectively. The optimal thresholds for mHLA-DR and nocturnal urine 6-SMT were 30.13% and 43.60%, respectively. Nocturnal urine 6-SMT level was significantly and positively correlated with mHLA-DR expression.

Conclusion

Nocturnal urine 6-SMT level may be a feasible biomarker to predict the outcome of patients with sepsis. The use of a night-time eye mask has no significant effect on the outcome of sepsis.

Clinical trials

This study was registered at clinicaltrials.gov (NCT02304224).
The effects of subchronic agmatine on passive avoidance memory, anxiety-like behavior and hippocampal Akt/GSK-3β in mice
Authors: Ostovan Vahid Reza , Amiri Zeynab , Moezi Leila , Pirsalami Fatema , Esmaili Zahra , Moosavi Maryam
Published: December 2021

Agmatine, a polyamine derived from l-arginine, has been suggested to modulate memory. However, the available evidence regarding the effect of agmatine on the memory of intact animals is contradictory. This study aimed to assess the dose–response effect of subchronic agmatine on passive avoidance memory and anxiety-like parameters of elevated plus maze in adult intact mice. Furthermore, considering the roles of Akt/GSK-3β signaling pathway in memory and Alzheimer’s disease, the hippocampal contents of phosphorylated and total forms of Akt and GSK-3β proteins were determined using the western blot technique. Agmatine was administered intraperitoneally at the doses of 10, 20, 30, 40 and 80 mg/kg/daily to adult male NMRI mice for 10 days after which the behavioral assessments were performed. Upon completion of the passive avoidance test, the hippocampi were removed for western blot analysis to detect the phosphorylated and total levels of Akt and GSK-3β proteins. Results showed the biphasic effect of agmatine on passive avoidance memory; in lower doses (10, 20 and 30 mg/kg), agmatine impaired memory whereas in higher ones (40 and 80 mg/kg) improved it. Though, agmatine in none of the doses affected animals’ anxiety-like parameters in an elevated plus maze. Moreover, the memory-improving doses of agmatine augmented Akt/GSK-3β pathway. This study showed the biphasic effect of agmatine on passive avoidance memory and an augmentation of hippocampal Akt/GSK-3β signaling pathway following the memory-improving doses of this polyamine.
Blockade of the GABAB receptor suppressed alcohol self-administration in rats: an effect similar to that produced by GABAB receptor activation
Authors: Maccioni Paola , Lorrai Irene , Carai Mauro A. M. , Gessa Gian Luigi , Colombo Giancarlo
Published: December 2021

Literature data suggest that activation and blockade of the GABAB receptor may produce similar effects on several reward-related behaviours. Accordingly, the present study was designed to investigate whether treatment with the GABAB receptor antagonist, SCH 50911, reproduced the suppressing effect of the GABAB receptor agonist, baclofen, and several positive allosteric modulators of the GABAB receptor on operant oral alcohol self-administration in rats. To this end, Sardinian alcohol-preferring (sP) rats were trained to lever-respond for alcohol (15% v/v) under the fixed ratio (FR) 4 (FR4) schedule of reinforcement. Once lever-responding had stabilized, rats were exposed to test sessions preceded by treatment with SCH 50911 (0, 25, 50, and 100 mg/kg; i.p.). Two independent experiments were conducted, differing solely in the set of rats used. Selectivity of SCH 50911 effect on alcohol self-administration was assessed by evaluating the effect of SCH 50911 (0, 25, 50, and 100 mg/kg; i.p.) on self-administration of a sucrose solution (0.7% w/v) in sP rats exposed to the FR4 schedule. In both ‘alcohol’ experiments, treatment with SCH 50911 reduced lever-responding for alcohol and amount of self-administered alcohol. SCH 50911 effect was characterized by large interindividual variability, with several instances of dose-unrelated reductions, and frequent occurrence of complete suppression of lever-responding for alcohol. Similar data were collected in the ‘sucrose’ experiment. These results extend to alcohol self-administration with the notion that activation and blockade of GABAB receptor may produce unidirectional effects on reward-related behaviours; these similarities are discussed in terms of differential contribution of pre- and postsynaptic GABAB receptors.
Identification of potential druggable targets of cell cycle with small-molecule inhibitors in oral squamous cell carcinoma
Authors: Zhou Xiaoyi , Jin Wenke , Chen Yanmei , Zhu Lingjuan , Mo Anchun , Xie Qiang
Published: December 2021

Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors worldwide and there are few crucial regulators and druggable targets for early diagnosis. Therefore, the identification of biomarkers for the early diagnosis and druggable targets of OSCC is imminent. In this study, we integrated gene set enrichment analysis, differential gene expression analysis based on the negative binomial distribution, weighted correlation network analysis, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes into analyzing the OSCC cohort downloaded from The Cancer Genome Atlas, and found that cell cycle and related biologic processes are significantly enriched. Then, we constructed the core gene network of OSCC, which showed the connection of encode human Cyclin-A2 protein, encode RAD51-associated protein 1, encode human centromere-associated protein E (CENPE), encode humans centromere protein I (CENPI) and encode polo-like kinase 1 (PLK1) to several cell cycle-related genes. Survival analysis further showed that low expression of these genes was associated with a better prognosis. Furthermore, we utilized a high-throughput virtual screening to find new CENPE and PLK1 inhibitors, and one of the CENPE inhibitor DB04517 suppressed the proliferation of OSCC cells by cell cycle arrest of cell cycle. Taken together, these candidate regulators could serve as the candidate diagnostic and prognostic biomarkers for OSCC, and specific suppression of these genes may be a potential approach to prevent and treat OSCC with the candidate inhibitors.
Associations of CYP2C19 and F2R genetic polymorphisms with platelet reactivity in Chinese ischemic stroke patients receiving clopidogrel therapy
Authors: Zhang Suli , Zhu Jinhang , Li Hua , Li Fengzhen , Zhu Bin , Li Tao , Fang Shuxin , Qin Shengying
Published: December 2021

Objectives

Genetic variation has been considered a major contributor to the high variability in the response to dual antiplatelet therapy in patients with acute ischemic stroke or transient ischemic attack. Recently, incidences of ischemic stroke are increasing rapidly in China. We aimed to evaluate the influence of potential determinants on the response of antiplatelet therapy and adverse events in Chinese ischemic stroke patients receiving clopidogrel-aspirin treatment.

Methods

Based on the clopidogrel drug response pathway and the coagulation and anticoagulation function, we systematically selected 34 genetic polymorphisms in 12 candidate genes. Three hundred and eight patients were divided into 2 groups according to their degree of inhibition of platelet aggregation. Multivariate analysis was then performed to assess the influence of demographic, clinical and genetic factors on platelet reactivity in Chinese ischemic stroke patients.

Results

We found that polymorphisms in CYP2C19 and F2R genes were still significantly associated with platelet reactivity in Chinese ischemic stroke patients (P = 0.037 and 0.015). The newly identified rs168753 in F2R gene may influence the efficacy to clopidogrel-aspirin therapy for ischemic stroke patients. We also found that ischemic stroke patients with low level of inhibition of platelet aggregation had higher risk of recurrent ischemic events (P = 0.001).

Conclusions

Together, these results emphasized the necessity of genotype-directed antiplatelet therapy and facilitated to minimize adverse ischemic events.
RETINAL DETACHMENT IN EYES WITH BOSTON TYPE 1 KERATOPROSTHESIS
Authors: Bonnet Clémence , Chehaibou Ismael , McCannel Colin A. , McCannel Tara A. , Prasad Pradeep S. , Kreiger Allan E. , Schwartz Steven D. , Aldave Anthony , Hubschman Jean-Pierre
Published: December 2021

Purpose:

To evaluate the mid-term outcomes of pars plana vitrectomy performed for retinal detachment (RD) repair after Boston Type 1 keratoprosthesis (KPro) implantation.

Methods:

Retrospective review of medical records of KPro implanted at the Stein Eye Institute presenting with RD and treated by pars plana vitrectomy. Functional success was defined as a postoperative visual acuity maintained within 2 Snellen lines of the corrected distance visual acuity measured before the development of the RD (baseline) and anatomical success as an attached retina after the pars plana vitrectomy. Kaplan–Meyer survival analyses were performed.

Results:

Among the 224 KPro performed, 28 (15.2%) RD were identified; of which, 21 (9.4%) were included. The mean follow-up was 42.5 ± 27.3 months. Vitreoretinal proliferation was present in 18 of 21 eyes (85.7%). Surgical techniques were adapted to the complex anterior segment anatomy of KPro eyes. Anatomical success was achieved in 18 of 21 eyes (85.7%). Functional success occurred in 17 of 21 eyes (81.0%), and 5 of 21 eyes (23.8%) reached 20/400 or better visual acuity at the final follow-up. The KPro was retained in 11 in 21 eyes (52.4%). The retention rate decreased from 94.7% at 1 year to 53.5% at 5 years. The most frequent complications were retroprosthetic membrane (47.6%) and corneal melt (23.8%).

Conclusion:

Modified pars plana vitrectomy techniques resulted in relatively good mid-term anatomical, functional, and retention rate outcomes, given the severity of RD at presentation and the numerous preoperative comorbidities of KPro eyes.
RONA Technique: A Novel ILM Peeling Method for Treatment of Large Full-Thickness Macular Holes
Authors: Nourinia Ramin , Nikzad Parisa , Abolhosseini Mohammad , Moshtaghion Seyed-Mohamadmehdi , Abtahi Seyed-Hossein
Published: December 2021

Purpose:

To present a new technique, RONA, for internal limiting membrane peeling and show its comparable success rate in closure of large full-thickness macular holes (FTMHs).

Methods:

This prospective interventional case series was implemented from January 2018 to November 2019. Consecutive cases with large FTMH with an aperture size of more than 500 μm were included. The RONA technique was used to make consecutive flaps; the central border of which remained adherent to the FTMH edge. The emphasis is that the central border of all flaps should remain adherent to the FTMH edge, letting the flaps remain there spontaneously.

Results:

Seventeen eyes of 17 patients (4 males and 13 females; age 62.3 ± 7.8 years) were included. The mean size of opening and base of FTMH were 651.1 ± 141.1 μm (range: 501–950) and 964.6 ± 383.8 μm (range: 527–2098), respectively. One week after the surgery, complete closure of all FTMHs occurred with no hole reopening until the end of 12 months. The mean best-corrected visual acuity at baseline and 12 months after surgery were 1.57 ± 0.30 and 0.75 ± 0.028 logarithm of the minimum angle of resolution, respectively, with statistically significant improvement (P < 0.001).

Conclusion:

The first advantage of this efficacious technique is that there is no need to manipulate FTMH edge or underneath tissues. Another and of course, the most important advantage is that there is no need to care about flap unfolding during the exchange stage.
EFFICACY OF AIR TAMPONADE TREATMENT OF IDIOPATHIC MACULAR HOLES OF DIFFERENT DIAMETERS AND OF FOLLOW-UP INTRAVITREAL AIR TAMPONADE FOR PERSISTENT HOLES
Authors: Tao Jiwei , Chen Huan , Chen Yiqi , Yu Jiangxin , Xu Jiawen , Mao Jianbo , Lin Li , Shen Lijun
Published: December 2021

Purpose:

To evaluate the efficacy of air tamponade in idiopathic macular hole (iMH) surgery and of an additional intravitreal air injection in the treatment of persistent holes.

Methods:

Retrospective, observational case series. Sixty eyes of 60 patients with an iMH underwent phacoemulsification of cataract (when appropriate), pars plana vitrectomy, and internal limiting membrane peeling, followed by air tamponade. Eyes with persistent holes underwent an additional intravitreal air injection within 1 week after surgery. The iMH closure rate and the best-corrected visual acuity were evaluated.

Results:

In all 30 eyes with an iMH diameter <400 µm, the iMH closed after the primary surgery; however, only 17 of 30 eyes with an iMH diameter of ≥400 µm closed after the primary surgery. For the 13 eyes with persistent holes, an additional intravitreal air injection resulted in successful hole closure. There was no significant difference in the best-corrected visual acuity at the final follow-up between the closed subgroup and the initially unclosed subgroup after closure.

Conclusion:

Pars plana vitrectomy combined with air tamponade effectively cured small iMHs. For large iMHs not closed after the primary surgery, an additional intravitreal air injection resulted in hole closure and achieved a good prognosis.
ASSOCIATION OF FLOW SIGNALS WITHIN POLYPS ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY WITH TREATMENT RESPONSES AFTER COMBINATION THERAPY FOR POLYPOIDAL CHOROIDAL VASCULOPATHY
Authors: Fukuyama Hisashi , Komuku Yuki , Araki Takashi , Gomi Fumi
Published: December 2021

Purpose:

To evaluate the changes of blood circulation within the polypoidal lesions by OCT angiography in eyes with polypoidal choroidal vasculopathy after combination therapy with aflibercept and photodynamic therapy.

Methods:

A total of 46 eyes from 46 patients who underwent the combination therapy for polypoidal choroidal vasculopathy were followed for more than 6 months. OCT angiography, covering an area 6 mm2 × 6 mm2 including the macula, were performed at baseline, 2 weeks, and 3 months and 6 months post-treatment.

Results:

The subretinal fluid resolved within 3 months after treatment in 44 eyes (95.7%), and 27 eyes (58.7%) showed no recurrence, with no additional treatment. Seventeen eyes (37.0%) showed recurrence, and two eyes (4.3%) showed poor response. On OCT angiography at 2 weeks after treatment, flow signals were detected in 3 of 27 eyes (11.1%) without recurrence and in 8 of 19 eyes (42.1%) with recurrence or poor responses. A detectable flow signal at 2 weeks was significantly associated with recurrence or poor response (P = 0.032).

Conclusion:

Persistent flow signals within polyps on OCT angiography at 2 weeks after combination therapy suggest less effectiveness of the initial treatment.
CHANGES OF FIXATION STABILITY AND LOCATION AFTER EPIRETINAL MEMBRANE SURGERY
Authors: Yang Xiaohan , Wang Zengyi , Yu Yanping , Liu Lingzi , Qi Biying , Zhang Ke , Liu Wu
Published: December 2021

Purpose:

This study aimed to evaluate fixation stability and position changes after epiretinal membrane (ERM) surgery.

Methods:

This is a retrospective study that included 60 consecutive eyes with idiopathic ERM. All patients received comprehensive ophthalmic examinations preoperatively and 1, 4, and 10 months postoperatively. Main outcome measures included fixation stability and position, bivariate contour ellipse area, and preferred retinal locus.

Results:

The number of patients with stable fixation and predominantly central fixation was increased significantly after ERM surgery (61.7 vs. 73.3%, P = 0.001; 41.7 vs. 71.7%, P = 0.037). The correlation analysis showed that the preoperative factors associated with improved postoperative fixation stability were a larger bivariate contour ellipse area value (P < 0.001), poorer visual acuity (P = 0.002), advanced stage (P = 0.002), thicker central fovea thickness (P = 0.015), and a longer preferred retinal locus–fovea distance (P = 0.025). As for the improved fixation location, the associated preoperative factors were age (P = 0.003), central fovea thickness (P = 0.044), and preferred retinal locus–fovea distance (P < 0.001).

Conclusion:

Our observations point to the changes of fixation parameters in patients after ERM surgery. We found that patients with preoperative unstable, eccentric fixation and poor BCVA can significantly benefit from the surgery. This result indicates that even in patients with severe macular damage, the ERM surgery still has great benefits in recovering visual function.