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Animal : An International Journal of... Apr 2024Early experiences can have long-term impacts on stress adaptability. This paper is the last of three in a series on early experiences and stress in pigs, and reports on...
Early experiences can have long-term impacts on stress adaptability. This paper is the last of three in a series on early experiences and stress in pigs, and reports on the effects of early human contact and housing on the ability of pigs to cope with their general environment. Using a 2 × 2 factorial design, 48 litters of pigs were reared in either a farrowing crate (FC) or a loose farrowing pen (LP; PigSAFE pen) which was larger, more physically complex and allowed the sow to move freely. Piglets were provided with either routine contact from stockpeople (C), or routine contact plus regular opportunities for positive human contact (+HC) involving 5 min of scratching, patting and stroking imposed to the litter 5 days/week from 0 to 4 weeks of age. At 4 weeks of age (preweaning), C piglets that were reared in FC had considerably lower concentrations of serum brain-derived neurotrophic factor (BDNF) than piglets from the other treatment combinations. Compared to C pigs, +HC pigs had fewer injuries at 4 weeks of age. There were no clear effects of human contact on BDNF concentrations or injuries after weaning, or on basal cortisol or immunoglobulin-A concentrations, behavioural time budgets, tear staining, growth, or piglet survival. Compared to FC piglets, LP piglets showed more play behaviour and interactions with the dam and less repetitive nosing towards pen mates during lactation. There was no evidence that early housing affected pigs' behavioural time budgets or physiology after weaning. Tear staining severity was greater in LP piglets at 4 weeks of age, but this may have been associated with the higher growth rates of LP piglets preweaning. There was no effect of lactation housing on growth after weaning. Preweaning piglet mortality was higher in the loose system. The findings on BDNF concentrations, injuries and play behaviour suggest improved welfare during the treatment period in +HC and LP piglets compared to C and FC piglets, respectively. These results together with those from the other papers in this series indicate that positive human interaction early in life promotes stress adaptability in pigs. Furthermore, while the farrowing crate environment deprives piglets of opportunities for play behaviour and sow interaction, there was no evidence that rearing in crates negatively affected pig welfare or stress resilience after weaning. Whether these findings are specific to the two housing systems studied here, or can be generalised to other housing designs, warrants further research.
PubMed: 38772077
DOI: 10.1016/j.animal.2024.101166 -
Acute Medicine & Surgery 2024Traumatic pneumocephalus is commonly encountered after basal skull fractures and rarely associated with blunt chest trauma. Here, we report a case of pneumocephalus...
BACKGROUND
Traumatic pneumocephalus is commonly encountered after basal skull fractures and rarely associated with blunt chest trauma. Here, we report a case of pneumocephalus caused by traumatic pneumothorax and brachial plexus avulsion.
CASE PRESENTATION
A 20-year-old male was admitted to our hospital following a motorcycle accident with complete paralysis of the right upper limb. 2 days later, follow-up computed tomography revealed a slight right pneumothorax, pneumomediastinum around the neck, and intracranial air without skull fracture. Air migrates into the subarachnoid space through a dural tear caused by a brachial plexus avulsion. The pneumocephalus immediately improved after the insertion of a chest drain.
CONCLUSION
Pneumothorax combined with brachial plexus avulsion could lead to pneumocephalus. Immediate chest drainage might be the best way to stop the migration of air; however, care should be taken to not worsen cerebrospinal fluid leakage.
PubMed: 38765777
DOI: 10.1002/ams2.956 -
Journal of Clinical Medicine Apr 2024We evaluate the relationship between corneal nerve structure and function in a veteran population. 83 veterans (mean age: 55 ± 5 years) seen at the Miami Veterans...
We evaluate the relationship between corneal nerve structure and function in a veteran population. 83 veterans (mean age: 55 ± 5 years) seen at the Miami Veterans Affairs (VA) eye clinic were included in this study. Each individual filled out questionnaires to evaluate ocular symptoms (5-Item Dry Eye Questionnaire, DEQ5; Ocular Surface Disease Index, OSDI) and ocular pain (Numerical Rating Scale, NRS; Neuropathic Pain Symptom Inventory modified for the Eye, NPSI-Eye). The individuals also underwent an ocular surface examination that captured functional nerve tests including corneal sensation, corneal staining, and the Schirmer test for tear production. Corneal sub-basal nerve analysis was conducted using in vivo confocal microscopy (IVCM) images with corneal nerve density, length, area, width, and fractal dimension captured. IVCM and functional corneal metrics from the right eye were examined using correlational and linear regression analysis. Most corneal structural metrics were not related to functional metrics, except for weak correlations between various IVCM metrics and tear production. In addition, corneal nerve fiber area was positively related to corneal sensation (r = 0.3, = 0.01). On linear regression analyses, only the corneal fractal dimension remained significantly related to tear production (β = -0.26, = 0.02) and only the corneal nerve fiber area remained significantly related to corneal sensation (β = 0.3, = 0.01). Most corneal nerve structural metrics did not relate to functional metrics in our veteran population, apart from a few weak correlations between structural metrics and tear production. This suggests that using corneal nerve anatomy alone may be insufficient for predicting corneal function.
PubMed: 38731042
DOI: 10.3390/jcm13092513 -
Nature Communications Apr 2024Tears have emerged as a promising alternative to blood for diagnosing diabetes. Despite increasing attempts to measure tear glucose using smart contact lenses, the...
Tears have emerged as a promising alternative to blood for diagnosing diabetes. Despite increasing attempts to measure tear glucose using smart contact lenses, the controversy surrounding the correlation between tear glucose and blood glucose still limits the clinical usage of tears. Herein, we present an in-depth investigation of the correlation between tear glucose and blood glucose using a wireless and soft smart contact lens for continuous monitoring of tear glucose. This smart contact lens is capable of quantitatively monitoring the tear glucose levels in basal tears excluding the effect of reflex tears which might weaken the relationship with blood glucose. Furthermore, this smart contact lens can provide an unprecedented level of continuous tear glucose data acquisition at sub-minute intervals. These advantages allow the precise estimation of lag time, enabling the establishment of the concept called 'personalized lag time'. This demonstration considers individual differences and is successfully applied to both non-diabetic and diabetic humans, as well as in animal models, resulting in a high correlation.
Topics: Animals; Humans; Glucose; Blood Glucose; Contact Lenses, Hydrophilic; Tears; Diabetes Mellitus
PubMed: 38565532
DOI: 10.1038/s41467-024-47123-9 -
Scientific Reports Apr 2024The conserved miR-183/96/182 cluster (miR-183C) is expressed in both corneal resident myeloid cells (CRMCs) and sensory nerves (CSN) and modulates corneal...
The conserved miR-183/96/182 cluster (miR-183C) is expressed in both corneal resident myeloid cells (CRMCs) and sensory nerves (CSN) and modulates corneal immune/inflammatory responses. To uncover cell type-specific roles of miR-183C in CRMC and CSN and their contributions to corneal physiology, myeloid-specific miR-183C conditional knockout (MS-CKO), and sensory nerve-specific CKO (SNS-CKO) mice were produced and characterized in comparison to the conventional miR-183C KO. Immunofluorescence and confocal microscopy of flatmount corneas, corneal sensitivity, and tear volume assays were performed in young adult naïve mice; 3' RNA sequencing (Seq) and proteomics in the trigeminal ganglion (TG), cornea and CRMCs. Our results showed that, similar to conventional KO mice, the numbers of CRMCs were increased in both MS-CKO and SNS-CKO vs age- and sex-matched WT control littermates, suggesting intrinsic and extrinsic regulations of miR-183C on CRMCs. The number of CRMCs was increased in male vs female MS-CKO mice, suggesting sex-dependent regulation of miR-183C on CRMCs. In the miR-183C KO and SNS-CKO, but not the MS-CKO mice, CSN density was decreased in the epithelial layer of the cornea, but not the stromal layer. Functionally, corneal sensitivity and basal tear volume were reduced in the KO and SNS-CKO, but not the MS-CKO mice. Tear volume in males is consistently higher than female WT mice. Bioinformatic analyses of the transcriptomes revealed a series of cell-type specific target genes of miR-183C in TG sensory neurons and CRMCs. Our data elucidate that miR-183C imposes intrinsic and extrinsic regulation on the establishment and function of CSN and CRMCs by cell-specific target genes. miR-183C modulates corneal sensitivity and tear production through its regulation of corneal sensory innervation.
Topics: Mice; Male; Female; Animals; Cornea; Trigeminal Ganglion; Nervous System Physiological Phenomena; MicroRNAs; Myeloid Cells
PubMed: 38561433
DOI: 10.1038/s41598-024-58403-1 -
Frontiers in Medicine 2024Dry eye causes corneal inflammation, epitheliopathy and sensorineural changes. This study evaluates the hypothesis that dry eye alters the percentages and...
BACKGROUND
Dry eye causes corneal inflammation, epitheliopathy and sensorineural changes. This study evaluates the hypothesis that dry eye alters the percentages and transcriptional profiles of immune cell populations in the cornea.
METHODS
Desiccating stress (DS) induced dry eye was created by pharmacologic suppression of tear secretion and exposure to drafty low humidity environment. Expression profiling of corneal immune cells was performed by single-cell RNA sequencing (scRNA-seq). Cell differentiation trajectories and cell fate were modeled through RNA velocity analysis. Confocal microscopy was used to immunodetect corneal immune cells. Irritation response to topical neurostimulants was assessed.
RESULTS
Twelve corneal immune cell populations based on their transcriptional profiles were identified at baseline and consist of monocytes, resident (rMP) and MMP12/13 high macrophages, dendritic cells (cDC2), neutrophils, mast cells, pre T/B cells, and innate (γDT, ILC2, NK) and conventional T and B lymphocytes. T cells and resident macrophages (rMP) were the largest populations in the normal cornea comprising 18.6 and 18.2 percent, respectively. rMP increased to 55.2% of cells after 5 days of DS. Significant changes in expression of 1,365 genes (adj < 0.0001) were noted in rMP with increases in cytokines and chemokines (), inflammatory markers (), the TAM receptor (), and decreases in complement and MHCII genes. A differentiation trajectory from monocytes to terminal state rMP was found. Phagocytosis, C-type lectin receptor signaling, NF-kappa B signaling and Toll-like receptor signaling were among the pathways with enhanced activity in these cells. The percentage of MRC1 rMPs increased in the cornea and they were observed in the basal epithelium adjacent to epithelial nerve plexus. Concentration of the chemokine CXCL1 increased in the cornea and it heightened irritation/pain responses to topically applied hypertonic saline.
CONCLUSION
These findings indicate that DS recruits monocytes that differentiate to macrophages with increased expression of inflammation associated genes. The proximity of these macrophages to cornea nerves and their expression of neurosensitizers suggests they contribute to the corneal sensorineural changes in dry eye.
PubMed: 38560382
DOI: 10.3389/fmed.2024.1362336 -
Cells Mar 2024Diabetes mellitus (DM) is one of the most prevalent diseases globally, and its prevalence is rapidly increasing. Most patients with a long-term history of DM present...
Diabetes mellitus (DM) is one of the most prevalent diseases globally, and its prevalence is rapidly increasing. Most patients with a long-term history of DM present with some degree of keratopathy (DK). Despite its high incidence, the underlying inflammatory mechanism of DK has not been elucidated yet. For further insights into the underlying immunopathologic processes, we utilized streptozotocin-induced mice to model type 1 DM (T1D) and B6.Cg-Lepob/J mice to model type 2 DM (T2D). We evaluated the animals for the development of clinical manifestations of DK. Four weeks post-induction, the total frequencies of corneal CD45CD11bLy-6G myeloid cells, with enhanced gene and protein expression levels for the proinflammatory cytokines TNF-α and IL-1β, were higher in both T1D and T2D animals. Additionally, the frequencies of myeloid cells/mm in the sub-basal neural plexus (SBNP) were significantly higher in T1D and T2D compared to non-diabetic mice. DK clinical manifestations were observed four weeks post-induction, including significantly lower tear production, corneal sensitivity, and epitheliopathy. Nerve density in the SBNP and intraepithelial terminal endings per 40x field were lower in both models compared to the normal controls. The findings of this study indicate that DM alters the immune quiescent state of the cornea during disease onset, which may be associated with the progressive development of the clinical manifestations of DK.
Topics: Humans; Mice; Animals; Diabetes Mellitus, Type 1; Cornea; Corneal Diseases; Diabetes Mellitus, Type 2; Streptozocin
PubMed: 38534376
DOI: 10.3390/cells13060532 -
The British Journal of Ophthalmology Apr 2024To evaluate the bilateral changes in the sub-basal nerve plexus of the cornea and ocular surface function after unilateral small incision lenticule extraction (SMILE)...
AIMS
To evaluate the bilateral changes in the sub-basal nerve plexus of the cornea and ocular surface function after unilateral small incision lenticule extraction (SMILE) and transepithelial photorefractive keratectomy (tPRK) procedures.
METHODS
34 patients were enrolled in the study and underwent unilateral SMILE (21 of 34 patients) or unilateral tPRK (13 of 34 patients). Complete ophthalmic examinations, tear film function tests and Cochet-Bonnet esthesiometry were conducted to assess the effects of the surgeries on the corneal nerves and tear function. Morphological changes were assessed using in vivo confocal microscopy to evaluate the corneal sub-basal nerve plexus and dendritic cells. ELISA was used to measure the tear neuromediators. Clinical and morphological data at each follow-up point were compared with preoperative baseline values.
RESULTS
All patients who underwent unilateral SMILE or tPRK procedures exhibited bilateral corneal nerve degenerative changes, decreased corneal sensitivity, worsening of dry eye symptoms and changes in bilateral tear neuromediators. In the SMILE group, bilateral corneal sensitivity was positively correlated with corneal nerve fibre length and negatively correlated with dendritic cell area. The dry eye severity was negatively correlated with corneal sensitivity. Tear levels of substance P and nerve growth factor were positively correlated with mean dendritic cell area and dry eye severity, but negatively correlated with corneal sensitivity. In the tPRK group, bilateral corneal sensitivity was positively correlated with corneal nerve fibre density.
CONCLUSIONS
Unilateral refractive surgery may bilaterally affect the morphology and function of corneal nerves and ocular surface status postoperatively.
PubMed: 38527771
DOI: 10.1136/bjo-2023-324358 -
Clinical Proteomics Mar 2024Human tear protein biomarkers are useful for detecting ocular and systemic diseases. Unfortunately, existing tear film sampling methods (Schirmer strip; SS and...
BACKGROUND
Human tear protein biomarkers are useful for detecting ocular and systemic diseases. Unfortunately, existing tear film sampling methods (Schirmer strip; SS and microcapillary tube; MCT) have significant drawbacks, such as pain, risk of injury, sampling difficulty, and proteomic disparities between methods. Here, we present an alternative tear protein sampling method using soft contact lenses (SCLs).
RESULTS
We optimized the SCL protein sampling in vitro and performed in vivo studies in 6 subjects. Using Etafilcon A SCLs and 4M guanidine-HCl for protein removal, we sampled an average of 60 ± 31 µg of protein per eye. We also performed objective and subjective assessments of all sampling methods. Signs of irritation post-sampling were observed with SS but not with MCT and SCLs. Proteomic analysis by mass spectrometry (MS) revealed that all sampling methods resulted in the detection of abundant tear proteins. However, smaller subsets of unique and shared proteins were identified, particularly for SS and MCT. Additionally, there was no significant intrasubject variation between MCT and SCL sampling.
CONCLUSIONS
These experiments demonstrate that SCLs are an accessible tear-sampling method with the potential to surpass current methods in sampling basal tears.
PubMed: 38481131
DOI: 10.1186/s12014-024-09475-8