Miracle-dz/UniFAR-FTUs huggingface dataset:
Outer Hair Cell Glutamate Signaling through Type II Spiral Ganglion Afferents Activates Neurons in the Cochlear Nucleus in Response to Nondamaging Sounds

Cochlear outer hair cells (OHCs) are known to uniquely participate in auditory processing through their electromotility, and like inner hair cells, are also capable of releasing vesicular glutamate onto spiral ganglion (SG) neurons: in this case, onto the sparse Type II SG neurons. However, unlike glutamate signaling at the inner hair cell-Type I SG neuron synapse, which is robust across a wide spectrum of sound intensities, glutamate signaling at the OHC-Type II SG neuron synapse is weaker and has been hypothesized to occur only at intense, possibly damaging sound levels. Here, we tested the ability of the OHC-Type II SG pathway to signal to the brain in response to moderate, nondamaging sound (80 dB SPL) as well as to intense sound (115 dB SPL). First, we determined the VGluTs associated with OHC signaling and then confirmed the loss of glutamatergic synaptic transmission from OHCs to Type II SG neurons in KO mice using dendritic patch-clamp recordings. Next, we generated genetic mouse lines in which vesicular glutamate release occurs selectively from OHCs, and then assessed c-Fos expression in the cochlear nucleus in response to sound. From these analyses, we show, for the first time, that glutamatergic signaling at the OHC-Type II SG neuron synapse is capable of activating cochlear nucleus neurons, even at moderate sound levels. SIGNIFICANCE STATEMENT Evidence suggests that cochlear outer hair cells (OHCs) release glutamate onto Type II spiral ganglion neurons only when exposed to loud sound, and that Type II neurons are activated by tissue damage. Knowing whether moderate level sound, without tissue damage, activates this pathway has functional implications for this fundamental auditory pathway. We first determined that OHCs rely largely on VGluT3 for synaptic glutamate release. We then used a genetically modified mouse line in which OHCs, but not inner hair cells, release vesicular glutamate to demonstrate that moderate sound exposure activates cochlear nucleus neurons via the OHC-Type II spiral ganglion pathway. Together, these data indicate that glutamate signaling at the OHC-Type II afferent synapse participates in auditory function at moderate sound levels.
Effect of Compaction and Deep Tillage on Soil Hydraulic and Aeration Properties and Wheat Yield

The effects of deep tillage and annual compaction (1996–1997) of two axle loads resulting from wheeled traffic on soil were evaluated by measuring the changes in soil physical properties (cone index, air porosity, and infiltration rate) and by measuring changes in crop yield in comparison with control plots. Results included the effects of these parameters at four depths (10 to 50 cm) on soil cone index and on soil air porosity. Infiltration rate measurements for all treatments and for control plots are also reported. Data obtained from the experimental plots in 2001 showed that infiltration rate was strongly affected by the compaction. Soil cone index and air porosity were still affected from 10 down to 50 cm by axle load. The crop (wheat) response in terms of yield was found to be affected by the two axle loads. The yield was significantly reduced in 1999 and 2000 as a result of compacting loads. Deep tillage of the compacted plots removed the compaction effect and improved yields in all treatments.
Effect of Heat-Killed Lactobacillus casei DKGF7 on a Rat Model of Irritable Bowel Syndrome

Non-viable bacteria, referred to as “paraprobiotics,” have attracted attention as potentially safer alternatives to probiotics. The aim of this study was to investigate the efficacy of heat-killed Lactobacillus casei DKGF7 on the symptomatic improvement of irritable bowel syndrome (IBS) in a rat disease model and to elucidate the underlying mechanisms that contribute to the beneficial effects of heat-killed probiotics. Seven male Wistar rats were induced with IBS by restraint stress and administered heat-killed L. casei DKGF7 for four weeks and then compared with seven rats in the control group. Stool consistency measured four weeks after initial treatment was the primary outcome measure. To investigate the mechanism of action of the heat-killed bacteria on IBS, we measured serum corticosterone levels, inflammatory cytokines in colon tissue, and expression of tight junction proteins (TJPs) in the epithelium. The treatment group showed significantly better stool consistency scores than the control group at week 4, as well as at every measured time point (all p values < 0.05). The treatment group showed lower serum corticosterone levels, lower colonic inflammatory cytokine levels, and higher expression of TJPs compared with the control group. Paraprobiotics such as heat-killed L. casei DKGF7 can improve stool consistency in a rat IBS model, which may indicate a potential therapeutic strategy for IBS treatment.
The effects of cardiac stretch on atrial fibroblasts: Analysis of the evidence and potential role in atrial fibrillation.

Atrial fibrillation (AF) is an important clinical problem. Chronic pressure/volume overload of the atria promotes AF, particularly via enhanced extracellular matrix (ECM) accumulation manifested as tissue fibrosis. Loading of cardiac cells causes cell-stretch that is generally considered to promote fibrosis by directly activating fibroblasts, the key cell-type responsible for ECM-production. The primary purpose of this article is to review the evidence regarding direct effects of stretch on cardiac fibroblasts, specifically: (i) the similarities and differences among studies in observed effects of stretch on cardiac-fibroblast function; (ii) the signaling-pathways implicated; and (iii) the factors that affect stretch-related phenotypes. Our review summarizes the most important findings and limitations in this area and gives an overview of clinical data and animal models related to cardiac stretch, with particular emphasis on the atria. We suggest that the evidence regarding direct fibroblast activation by stretch is weak and inconsistent, in part because of variability among studies in key experimental conditions that govern the results. Further work is needed to clarify whether, in fact, stretch induces direct activation of cardiac fibroblasts and if so, to elucidate the determining factors to ensure reproducible results. If mechanical load on fibroblasts proves not to be clearly profibrotic by direct actions, other mechanisms like paracrine influences, the effects of systemic mediators and/or the direct consequences of myocardial injury or death, might account for the link between cardiac stretch and fibrosis. Clarity in this area is needed to improve our understanding of AF pathophysiology and assist in therapeutic development.
Patterns of Alcohol Use Among Transgender Patients Receiving Care at the Veterans Health Administration: Overall and Relative to Nontransgender Patients.

OBJECTIVE Alcohol use is understudied among transgender persons--persons whose sex differs from their gender identity. We compare patterns of alcohol use between Veterans Health Administration (VA) transgender and nontransgender outpatients. METHOD National VA electronic health record data were used to identify all patients' last documented Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) screen (October 1, 2009-July 31, 2017). Transgender patients were identified using diagnostic codes. Logistic regression models estimated four past-year primary outcomes: (a) alcohol use (AUDIT-C > 0); (b) unhealthy alcohol use (AUDIT-C ≥ 5); (c) high-risk alcohol use (AUDIT-C ≥ 8); and (d) heavy episodic drinking (HED; ≥6 drinks on ≥1 occasion). Two secondary diagnostic-based outcomes, alcohol use disorder (AUD) and alcohol-specific conditions, were also examined. RESULTS Among 8,872,793 patients, 8,619 (0.10%) were transgender. For transgender patients, unadjusted prevalence estimates were as follows: 52.8% for any alcohol use, 6.6% unhealthy alcohol use, 2.8% high-risk use, 10.4% HED, 8.6% AUD, and 1.3% alcohol-specific conditions. After adjustment for demographic characteristics, transgender patients had lower odds of patient-reported alcohol use but higher odds of alcohol-related diagnoses compared with nontransgender patients. Differences in alcohol-related diagnoses were attenuated after adjustment for comorbid conditions and utilization. CONCLUSIONS This is the largest study of patterns of alcohol use among transgender persons and among the first to directly compare patterns to nontransgender persons. Findings suggest nuanced associations with patterns of alcohol use and provide a base for further disparities research to explore alcohol use within the diverse transgender community. Research with self-reported measures of gender identity and sex-at-birth and structured assessment of alcohol use and disorders is needed.
Targeted DNA methylation profiling reveals epigenetic signatures in peanut allergy

DNA methylation (DNAm) has been shown to play a role in mediating food allergy; however, the mechanism by which it does so is poorly understood. In this study, we used targeted next-generation bisulfite sequencing to evaluate DNAm levels in 125 targeted highly informative genomic regions containing 602 CpG sites on 70 immune-related genes to understand whether DNAm can differentiate peanut allergy (PA) versus nonallergy (NA). We found PA-associated DNAm signatures associated with 12 genes (7 potentially novel to food allergy, 3 associated with Th1/Th2, and 2 associated with innate immunity), as well as DNAm signature combinations with superior diagnostic potential compared with serum peanut–specific IgE for PA versus NA. Furthermore, we found that, following peanut protein stimulation, peripheral blood mononuclear cell (PBMCs) from PA participants showed increased production of cognate cytokines compared with NA participants. The varying responses between PA and NA participants may be associated with the interaction between the modification of DNAm and the interference of environment. Using Euclidean distance analysis, we found that the distances of methylation profile comprising 12 DNAm signatures between PA and NA pairs in monozygotic (MZ) twins were smaller than those in randomly paired genetically unrelated individuals, suggesting that PA-related DNAm signatures may be associated with genetic factors.
Different Interventions for Rehabilitation of the Edentulous Maxilla with Implant-Supported Prostheses: An Overview of Systematic Reviews.

PURPOSE To synthesize evidence derived from systematic reviews (SRs) on different interventions for rehabilitation of the edentulous maxilla with implant-supported restorations. MATERIALS AND METHODS A protocol-oriented search was established to address the PICO question: What is the current evidence regarding rehabilitation of the edentulous maxilla with different implant-supported prostheses in terms of implant and prosthesis survival? The primary outcomes were implant and prosthesis survival rates evaluated from SRs of clinical studies including adult patients with complete edentulism of the maxilla and comparing different implant-supported rehabilitation strategies. Methodologic quality of the SRs was assessed with the AMSTAR-2 tool. RESULTS The final selection process led to the inclusion of 36 SRs that were grouped as: (1) addressing maxillae with sufficient bone to place implants; (2) addressing maxillae with insufficient bone to place implants; and (3) comparing different types of prosthesis, number of implants, patient-reported outcomes, and economic evaluations. The literature describes four or more implants as suitable for full-arch fixed prostheses and implant-supported overdentures; in both cases, the overall survival rate is > 95%. Mini-implants present very high short-term failure rates (> 30%). Poor description of technical complications, adjustments, and maintenance and corresponding costs precluded a cost-effectiveness analysis. CONCLUSION No implant-supported rehabilitation of the edentulous maxilla (fixed or removable) should be supported on fewer than four implants. A one-piece full-arch fixed dental prosthesis can be supported by a minimum of two anterior axial plus two posterior distally tilted implants or by six to eight axial implants symmetrically distributed through the posterior and anterior regions of the arch. Four to six implants is the advised number to support an overdenture. The use of mini-implants in the maxilla is inadvisable.
“Just that four letter word, hope”: stroke survivors’ perspectives of participation in an intensive upper limb exercise program; a qualitative exploration

ABSTRACT Background Less than half of stroke survivors will be able to use their arm at 6 months post-stroke. Guidelines recommend the use of intensive upper limb exercise programs to optimize recovery; however, there has been limited research exploring experiences of participation in intensive programs. Aim To identify factors influencing adherence to an intensive upper limb exercise program in people with stroke. Methods Qualitative design. Semi-structured interviews were conducted with 20 stroke survivors who had participated in an intensive upper limb program. Perspectives of participation, including perceived barriers and enablers to program adherence were explored. Interviews were audio-recorded, transcribed, and imported into NVivo for analysis. Two authors mapped themes to the Capability, Opportunity, Motivation-Behavior (COM-B) behavior change model to identify barriers and enablers to adherence. Results Enablers influencing adherence included: 1) routine practice times (Motivation – automatic); 2) accountability to staff (Motivation – reflective); and 3) social support (Opportunity – social). Barriers to adherence included: 1) exercises being too difficult (Capability - physical); 2) reliance on others to help (Capability - physical); and 3) difficulty ‘fitting it in’ (Motivation – reflective). Conclusion Findings will inform recommendations for the delivery of intensive upper limb exercise programs to improve adherence and assist services to provide rehabilitation in a manner that enables self-directed practice by stroke survivors.
Magnet dislocation following magnetic resonance imaging in cochlear implant users: Diagnostic pathways and managment

Objectives Although modern cochlear implants (CIs) are approved for magnetic resonance imaging (MRIs) adverse events still occur with unacceptable frequency. Methods: In this retrospective study, magnet displacement due to MRIs was analysed. Relevant factors e.g. symptoms during MRI, diagnostics, surgical intervention following the diagnosis and possible subsequent damage were assessed. Results 16 patients were enclosed. All patients complained about pain while the scan was conducted. Computed tomography (CT) scans of the temporal bone or X-rays of the skull were performed to confirm diagnosis. Artefacts on CT scans delayed immediate diagnosis in some cases. Discussion Despite various studies demonstrating the range of adverse events related to CIs following MRI, little information is available on diagnosis and radiologic recognition of magnet dislocation. In patients complaining about pain following an MRI scan an X-ray of the head should be performed immediately. Most adverse events occur in radiological centres without expertise in cochlear implants. Conclusion Comprehensive training of patients, surgeons and radiologists is the most efficient tool to prevent damage to the CI and the patient. X-ray of the skull is suggested to be used as the method of choice in imaging.
Diagnostic criteria for early hip osteoarthritis: first steps, based on the CHECK study

Abstract Objectives Although there is a general focus on early diagnosis and treatment of hip OA, there are no validated diagnostic criteria for early-stage hip OA. The current study aimed to take the first steps in developing diagnostic criteria for early-stage hip OA, using factors obtained through history taking, physical examination, radiography and blood testing at the first consultation in individuals presenting with hip pain, suspicious for hip OA, in primary care. Methods Data of the 543 individuals with 735 symptomatic hips at baseline who had any follow-up data available from the prospective CHECK cohort study were used. A group of 26 clinical experts [general practitioners (GPs), rheumatologists and orthopaedic surgeons] evaluated standardized clinical assessment forms of all subjects on the presence of clinically relevant hip OA 5–10 years after baseline. Using the expert-based diagnoses as reference standard, a backward selection method was used to create predictive models based on pre-defined baseline factors from history taking, physical examination, radiography and blood testing. Results Prevalence of clinically relevant hip OA during follow-up was 22%. Created models contained four to eight baseline factors (mainly WOMAC pain items, painful/restricted movements and radiographic features) and obtained area under the curve between 0.62 (0.002) and 0.71 (0.002). Conclusion Based on clinical and radiographic features of hip OA obtained at first consultation at a GP for pain/stiffness of the hip, the prediction of clinically relevant hip OA within 5–10 years was ‘poor’ to ‘fair’.
Characterization and Comparative Analysis of Complete Mitogenomes of Three Cacatua Parrots (Psittaciformes: Cacatuidae)

Cacatua alba, Cacatua galerita, and Cacatua goffiniana are parrots of the family Cacatuidae. Wild populations of these species are declining with C. alba listed by the International Union for the Conservation of Nature and Natural Resources (IUCN) as Endangered. In this study, complete mitogenomes were sequenced for a comparative analysis among the Cacatua species, and a detailed analysis of the control region. Mitogenome lengths of C. alba, C. galerita, and C. goffiniana were 18,894, 18,900, and 19,084 bp, respectively. They included 13 protein coding genes, two ribosomal RNA genes, 24 transfer RNA genes, three degenerated genes, and two control regions. Ten conserved motifs were found in three domains within each of the two control regions. For an evolution of duplicated control regions of Cacatua, domain I and the 3′ end of domain III experienced an independent evolution, while domain II and most of the regions of domain III was subjected to a concerted evolution. Based on a phylogenetic analysis of 37 mitochondrial genes, the genus Cacatua formed a well-supported, monophyletic, crown group within the Cacatuidae. Molecular dating results showed that Cacatua diverged from other genera of Cacatuinae in the middle of Miocene.
Suppression of sprouting in stored potatoes by volatile organic compounds

A number of readily available volatile compounds have been tested, at concentrations of not greater than 100 μg/l in air, as inhibitors of sprouting of stored potatoes. Some of these compounds were found to be as effective, on a small scale, as the nonyl alcohol used commercially. No compounds of exceptional merit were found.
Plasma Concentrations of Extracellular Vesicles Are Decreased in Patients with Post-Infarct Cardiac Remodelling

Simple Summary A heart attack may lead to the remodelling of the cardiac muscle, which negatively affects patient’s prognosis. At present, the mechanisms of cardiac remodelling remain unclear. In patients with heart attack, many body cells become activated and release small particles, called extracellular vesicles, which can either aggravate cardiac injury, or contribute to healing of heart muscle. In our study, we hypothesized that the concentrations of these small particles in plasma allow to determine which patients will experience remodelling of the cardiac muscle after the heart attach. We found that concentrations of extracellular vesicles from endothelial cells, erythrocytes and platelets, measured directly the heart attack, were lower in patients who developed cardiac remodelling 6 months later, compared to patients who had no remodelling. Vesicles from endothelial cells and erythrocytes allowed to determine remodelling independently of other clinical features. Hence, decreased concentrations of these vesicles may on one hand be a sign of inappropriate cardiac repair mechanisms, and on the other hand may allow to identify patients, who will develop cardiac remodelling after the heart attack. Abstract Background, the mechanisms underlying left ventricular remodelling (LVR) after acute myocardial infarction (AMI) remain obscure. In the course of AMI, blood cells and endothelial cells release extracellular vesicles (EVs). We hypothesized that changes in EV concentrations after AMI may underlie LVR. Methods, plasma concentrations of EVs from endothelial cells (CD146+), erythrocytes (CD235a+), leukocytes (CD45+), platelets (CD61+), activated platelets (P-selectin+), and EVs exposing phosphatidylserine after AMI were determined by flow cytometry in 55 patients with the first AMI. LVR was defined as an increase in left ventricular end-diastolic volume by 20% at 6 months after AMI, compared to baseline. Results, baseline concentrations of EVs from endothelial cells, erythrocytes and platelets were lower in patients who developed LVR (p ≤ 0.02 for all). Concentrations of EVs from endothelial cells and erythrocytes were independent LVR predictors (OR 8.2, CI 1.3–54.2 and OR 17.8, CI 2.3–138.6, respectively) in multivariate analysis. Combining the three EV subtypes allowed to predict LVR with 83% sensitivity and 87% specificity. Conclusions, decreased plasma concentrations of EVs from endothelial cells, erythrocytes and platelets predict LVR after AMI. Since EV release EVs contributes to cellular homeostasis by waste removal, decreased concentrations of EVs may indicate dysfunctional cardiac homeostasis after AMI, thus promoting LVR.
Medical Assistance in Dying for Patients with Borderline Personality Disorder: Considerations and Concerns

There is an ongoing debate in Canadian medical, legal, and ethical circles regarding the provision of medical assistance in dying (MAiD) for patients with mental illness. We will establish as background that if MAiD became available for psychiatric disorders, patients with borderline personality disorder (BPD) will be among those requesting the service. Therefore, we evaluate relevant concerns regarding MAiD provision to this patient population. This article’s purpose is 2-fold: first, to highlight considerations within the debate of whether MAiD can be appropriate for mental illness such as BPD. Second, to guide the assessment of patients with BPD for eligibility should MAiD for mental illness become available in Canada.
Skin Immunomodulation during Regeneration: Emerging New Targets

Adipose-Derived Stem Cells (ADSC) are present within the hypodermis and are also expected to play a pivotal role in wound healing, immunomodulation, and rejuvenation activities. They orchestrate, through their exosome, the mechanisms associated to cell differentiation, proliferation, and cell migration by upregulating genes implicated in different functions including skin barrier, immunomodulation, cell proliferation, and epidermal regeneration. ADSCs directly interact with their microenvironment and specifically the immune cells, including macrophages and T and B cells, resulting in differential inflammatory and anti-inflammatory mechanisms impacting, in return, ADSCs microenvironment and thus skin function. These useful features of ADSCs are involved in tissue repair, where the required cell proliferation, angiogenesis, and anti-inflammatory responses should occur rapidly in damaged sites. Different pathways involved have been reported such as Growth Differentiation Factor-11 (GDF11), Tumor Growth Factor (TGF)-β, Metalloproteinase (MMP), microRNA, and inflammatory cytokines that might serve as specific biomarkers of their immunomodulating capacity. In this review, we try to highlight ADSCs’ network and explore the potential indicators of their immunomodulatory effect in skin regeneration and aging. Assessment of these biomarkers might be useful and should be considered when designing new clinical therapies using ADSCs or their specific exosomes focusing on their immunomodulation activity.