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Journal of Dairy Science May 2024Podermatitis aseptica hemorrhagica circumscripta is associated with metalloproteinase 2 weakening of distal phalangeal suspensory structures and sinkage of the distal...
Molecular evidence sterile tissue damage during pathogenesis of pododermatitis aseptica hemorrhagica circumscripta is associated with disturbed epidermal-dermal homeostasis.
Podermatitis aseptica hemorrhagica circumscripta is associated with metalloproteinase 2 weakening of distal phalangeal suspensory structures and sinkage of the distal phalanx in the claw capsule. Pressure from the tuberculum flexorium on the sole epidermis and dermis produces hemorrhagic tissue injury and defective horn production appearing as yellow-red, softened claw horn in region 4 of the sole. A model of the MAPK/ERK signal cascade orchestrating epidermal-dermal homeostasis was employed to determine if sterile inflammatory responses are linked to disturbed signal transduction for epidermal homeostasis in sole epidermis and dermis. The objective was to assess shifts in target genes of inflammation, up- and downstream MAPK/ERK signal elements, and targeted genes supporting epidermal proliferation and differentiation. Sole epidermis and dermis was removed from lateral claws bearing lesions of podermatitis aseptica hemorrhagica circumscripta, medial claws from the same limb and lateral claws from completely normal limbs of multiparous, lactating Holstein cows. The abundance levels of targeted transcripts were evaluated by real-time QPCR. Lesion effects were assessed by ANOVA, and mean comparisons were performed with t-tests to assess variations between mean expression in ulcer-bearing or medial claw dermis and epidermis and completely normal lateral claw dermis and epidermis or between ulcer-bearing dermis and epidermis and medial claw dermis and epidermis. The lesions were sterile and showed losses across multiple growth factors, their receptors, several downstream AP1 transcription components, CMYC, multiple cell cycle and terminal differentiation elements conducted by MAPK/ERK signals and β 4, α 6 and collagen 17A hemidesmosome components. These losses coincided with increased cytokeratin 6, β 1 integrin, proinflammatory metalloproteinases 2 and 9, IL1B and physiologic inhibitors of IL1B, the decoy receptor and receptor antagonist. Medial claw epidermis and dermis from limbs with lateral claws bearing podermatitis aseptica hemorrhagica circumscripta showed reductions in upstream MAPK/ERK signal elements and downstream targets that paralleled those in hemorrhagic lesions. Inhibitors of IL1B increased in the absence of real increases in inflammatory targets in the medial claw dermis and epidermis. Losses across multiple signal path elements and downstream targets were associated with negative effects on targeted transcripts supporting claw horn production and wound repair across lesion-bearing lateral claws and lesion-free medial claw dermis and epidermis. It was unclear if the sterile inflammation was causative or a consequence of these perturbations.
PubMed: 38825113
DOI: 10.3168/jds.2023-24577 -
Journal of Dairy Science May 2024The aim of this study was to evaluate transcriptional changes in sole epidermis and dermis of bovine claws with septic sole ulceration of the lateral claw. Assessment...
The aim of this study was to evaluate transcriptional changes in sole epidermis and dermis of bovine claws with septic sole ulceration of the lateral claw. Assessment included changes in transcripts orchestrating epidermal homeostatic processes including epidermal proliferation, differentiation, inflammation, and cell signaling. Sole epidermis and dermis was removed from region 4 of lesion-bearing lateral and lesion-free medial claws of pelvic limbs in multiparous, lactating Holstein cows. Control sole epidermis and dermis was obtained from region 4 of lateral claws of normal pelvic limbs. Transcript abundances were evaluated by real-time QPCR and relative expression analyzed by ANOVA. Relative to normal lateral claws, sole epidermis and dermis in ulcer-bearing claws exhibited downregulation of genes associated with growth factors, growth factor receptors, activator protein 1 (AP-1) and proto-oncogene (CMYC) transcription components, cell cycle elements, lateral cell-to-cell signaling elements and structures of early and late keratinocyte differentiation. These changes were accompanied by upregulation of pro-inflammatory transcripts interleukin 1 α (IL1A), interleukin1 β (IL1B), interleukin 1 receptor 1 (IL1R1), inducible nitric oxide synthase (NOS2), the inflammasome components NOD like receptor protein 3 (NLRP3), pyrin and caspase recruitment domain (PYCARD), and caspase-1 interleukin converting enzyme (CASPASE), the matrix metalloproteinases (MMP2 and MMP9), and anti-inflammatory genes interleukin 1 receptor antagonist (IL1RN) and interleukin1 receptor 2 (IL1R2). Transcript abundance varied across epidermis and dermis from the ulcer center, margin and epidermis and dermis adjacent to the lesion. Sole epidermis and dermis of lesion-free medial claws exhibited changes paralleling those in the adjacent lateral claws in an environment lacking inflammatory transcripts and downregulated IL1A, interleukin 18 (IL18), tumor necrosis factor α (TNFA) and NOS2. These data imply perturbations in signal pathways driving epidermal proliferation and differentiation are associated with, but not inevitably linked to epidermis and dermis inflammation. Further work is warranted to better define the role of crushing tissue injury, sepsis, metalloproteinase activity, and inflammation in sole ulceration.
PubMed: 38825108
DOI: 10.3168/jds.2023-24578 -
Turkish Journal of Medical Sciences 2023To evaluate and compare magnetic resonance imaging (MRI) sequences that could potentially be used in the diagnosis of coronavirus disease 2019 (COVID-19). (Comparative Study)
Comparative Study
BACKGROUND AND AIM
To evaluate and compare magnetic resonance imaging (MRI) sequences that could potentially be used in the diagnosis of coronavirus disease 2019 (COVID-19).
MATERIALS AND METHODS
Included in the study were 42 patient who underwent thorax computed tomography (CT) for COVID-19 pneumonia and thorax MRI for any reason within 24 h after CT. The T2-weighted fast spin echo periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) (T2W-FSE-P), fast imaging employing steady-state acquisition, T2 fat-saturated FSE, axial T1 liver acquisition with volume acceleration (LAVA) and single-shot FSE images were compared in terms of their ability to show COVID-19 findings.
RESULTS
The mean age of the patients was 47.2 ± 24 years. Of the patients, 22 were male (52.4%) and 20 (47.6%) were female. The interobserver intraclass coefficient (ICC) for the image quality score was the highest in the T2W-FSE-P sequence and lowest in the T1 LAVA sequence. All of the lesion-based evaluations of the interobserver agreement were statistically significant, with the kappa value varying between 0.798 and 0.998.
CONCLUSION
All 5 sequences evaluated in the study were successful in showing the parenchymal findings of COVID-19. Since the T2W-FSE-P sequence had the best scores in both interobserver agreement and ICC for the image quality score, it was considered that it can be included in thorax MRI examinations to assist the diagnosis of COVID-19.
Topics: Humans; COVID-19; Male; Female; Middle Aged; Magnetic Resonance Imaging; Adult; SARS-CoV-2; Thorax; Tomography, X-Ray Computed; Aged; Lung
PubMed: 38813029
DOI: 10.55730/1300-0144.5687 -
European Respiratory Review : An... Apr 2024With the emergence of lung cancer screening programmes and newly detected localised and multifocal disease, novel treatment compounds and multimodal treatment... (Review)
Review
With the emergence of lung cancer screening programmes and newly detected localised and multifocal disease, novel treatment compounds and multimodal treatment approaches, the treatment landscape of non-small cell lung cancer is becoming increasingly complex. In parallel, in-depth molecular analyses and clonality studies are revealing more information about tumorigenesis, potential therapeutical targets and the origin of lesions. All can play an important role in cases with multifocal disease, oligoprogression and oligorecurrence. In multifocal disease, it is essential to understand the relatedness of separate lesions for treatment decisions, because this information distinguishes separate early-stage tumours from locally advanced or metastatic cancer. Clonality studies suggest that a majority of same-histology lesions represent multiple primary tumours. With the current standard of systemic treatment, oligoprogression after an initial treatment response is a common scenario. In this state of induced oligoprogressive disease, local ablative therapy by either surgery or radiotherapy is becoming increasingly important. Another scenario involves the emergence of a limited number of metastases after radical treatment of the primary tumour, referred to as oligorecurrence, for which the use of local ablative therapy holds promise in improving survival. Our review addresses these complex situations in lung cancer by discussing current evidence, knowledge gaps and treatment recommendations.
Topics: Humans; Lung Neoplasms; Disease Progression; Neoplasm Recurrence, Local; Treatment Outcome; Risk Factors; Carcinoma, Non-Small-Cell Lung; Neoplasms, Multiple Primary; Clinical Decision-Making; Genetic Predisposition to Disease; Biomarkers, Tumor; Neoplasm Staging
PubMed: 38811031
DOI: 10.1183/16000617.0200-2023 -
Frontiers in Immunology 2024Chronic Pelvic Pain Syndrome or Chronic Prostatitis (CPPS/CP) is the most prevalent urologic affliction among young adult men. It is a challenging condition to treat,...
INTRODUCTION
Chronic Pelvic Pain Syndrome or Chronic Prostatitis (CPPS/CP) is the most prevalent urologic affliction among young adult men. It is a challenging condition to treat, which significantly decreases patient quality of life, mostly because of its still uncertain aetiology. In that regard, an autoimmune origin is a prominent supported theory. Indeed, studies in patients and in rodent models of Experimental Autoimmune Prostatitis (EAP) have provided compelling evidence suggesting a key role of CD4 Th1 cells in disease pathogenesis. However, the implication of other prominent effectors of the immune system, such as CD8 T cells, has yet to be studied.
METHODS
We herein analyzed the induction of prostatitis and the development of chronic pelvic pain in EAP using CD8 T cell-deficient animals.
RESULTS
We found similarly elevated PA-specific immune responses, with high frequencies of specific IFNg+CD4+ and IL17+CD4+ T cells in prostate draining lymph nodes from PA-immunized either CD8 KO or wild type animals with respect to controls. Moreover, these peripheral immune responses were paralleled by the development of significant chronic pelvic pain, and accompanied by prostate histological lesions, characterized by hemorrhage, epithelial cell desquamation, marked periglandular leukocyte infiltration, and increased collagen deposition in both, PA-immunized CD8 KO and wild type animals. As expected, control animals did not develop prostate histological lesions.
DISCUSSION
Our results indicate that CD8 T cells do not play a major role in EAP pathogenesis and chronic pelvic pain development. Moreover, our results corroborate the previous notion that a CD4 Th1 associated immune response drives the induction of prostate tissue inflammation and the development of chronic pelvic pain.
Topics: Prostatitis; Male; Animals; CD8-Positive T-Lymphocytes; Pelvic Pain; Autoimmune Diseases; Mice; Mice, Knockout; Disease Models, Animal; Chronic Pain; CD4-Positive T-Lymphocytes; Mice, Inbred C57BL; Prostate
PubMed: 38807587
DOI: 10.3389/fimmu.2024.1387142 -
Journal of Neuroinflammation May 2024The lectin pathway (LP) of complement mediates inflammatory processes linked to tissue damage and loss of function following traumatic brain injury (TBI). LP activation...
The lectin pathway (LP) of complement mediates inflammatory processes linked to tissue damage and loss of function following traumatic brain injury (TBI). LP activation triggers a cascade of proteolytic events initiated by LP specific enzymes called MASPs (for Mannan-binding lectin Associated Serine Proteases). Elevated serum and brain levels of MASP-2, the effector enzyme of the LP, were previously reported to be associated with the severity of tissue injury and poor outcomes in patients with TBI. To evaluate the therapeutic potential of LP inhibition in TBI, we first conducted a pilot study testing the effect of an inhibitory MASP-2 antibody (α-MASP-2), administered systemically at 4 and 24 h post-TBI in a mouse model of controlled cortical impact (CCI). Treatment with α-MASP-2 reduced sensorimotor and cognitive deficits for up to 5 weeks post-TBI. As previous studies by others postulated a critical role of MASP-1 in LP activation, we conducted an additional study that also assessed treatment with an inhibitory MASP-1 antibody (α-MASP-1). A total of 78 mice were treated intraperitoneally with either α-MASP-2, or α-MASP-1, or an isotype control antibody 4 h and 24 h after TBI or sham injury. An amelioration of the cognitive deficits assessed by Barnes Maze, prespecified as the primary study endpoint, was exclusively observed in the α-MASP-2-treated group. The behavioral data were paralleled by a reduction of the lesion size when evaluated histologically and by reduced systemic LP activity. Our data suggest that inhibition of the LP effector enzyme MASP-2 is a promising treatment strategy to limit neurological deficits and tissue loss following TBI. Our work has translational value because a MASP-2 antibody has already completed multiple late-stage clinical trials in other indications and we used a clinically relevant treatment protocol testing the therapeutic mechanism of MASP-2 inhibition in TBI.
Topics: Animals; Mannose-Binding Protein-Associated Serine Proteases; Brain Injuries, Traumatic; Mice; Disease Models, Animal; Male; Mice, Inbred C57BL; Cognition Disorders; Maze Learning
PubMed: 38807149
DOI: 10.1186/s12974-024-03133-4 -
Bioactive Materials Sep 2024Spheroids and organoids have attracted significant attention as innovative models for disease modeling and drug screening. By employing diverse types of spheroids or...
Spheroids and organoids have attracted significant attention as innovative models for disease modeling and drug screening. By employing diverse types of spheroids or organoids, it is feasible to establish microphysiological systems that enhance the precision of disease modeling and offer more dependable and comprehensive drug screening. High-throughput microphysiological systems that support optional, parallel testing of multiple drugs have promising applications in personalized medical treatment and drug research. However, establishing such a system is highly challenging and requires a multidisciplinary approach. This study introduces a dynamic Microphysiological System Chip Platform (MSCP) with multiple functional microstructures that encompass the mentioned advantages. We developed a high-throughput lung cancer spheroids model and an intestine-liver-heart-lung cancer microphysiological system for conducting parallel testing on four anti-lung cancer drugs, demonstrating the feasibility of the MSCP. This microphysiological system combines microscale and macroscale biomimetics to enable a comprehensive assessment of drug efficacy and side effects. Moreover, the microphysiological system enables evaluation of the real pharmacological effect of drug molecules reaching the target lesion after absorption by normal organs through fluid-based physiological communication. The MSCP could serves as a valuable platform for microphysiological system research, making significant contributions to disease modeling, drug development, and personalized medical treatment.
PubMed: 38800720
DOI: 10.1016/j.bioactmat.2024.05.019 -
MedRxiv : the Preprint Server For... May 2024Cerebrovascular damage from small vessel disease (SVD) occurs in healthy and pathological aging. SVD markers, such as white matter hyperintensities (WMH), are commonly...
Cerebrovascular damage from small vessel disease (SVD) occurs in healthy and pathological aging. SVD markers, such as white matter hyperintensities (WMH), are commonly found in individuals over 60 and increase in prevalence with age. WMHs are detectable on standard MRI by adhering to the STRIVE criteria. Currently, visual assessment scales are used in clinical and research scenarios but is time-consuming and has rater variability, limiting its practicality. Addressing this issue, our study aimed to determine the most precise WMH segmentation software, offering insights into methodology and usability to balance clinical precision with practical application. This study employed a dataset comprising T1, FLAIR, and DWI images from 300 cognitively healthy older adults. WMHs in this cohort were evaluated using four automated neuroimaging tools: Lesion Prediction Algorithm (LPA) and Lesion Growth Algorithm (LGA) from Lesion Segmentation Tool (LST), Sequence Adaptive Multimodal Segmentation (SAMSEG), and Brain Intensity Abnormalities Classification Algorithm (BIANCA). Additionally, clinicians manually segmented WMHs in a subsample of 45 participants to establish a gold standard. The study assessed correlations with the Fazekas scale, algorithm performance, and the influence of WMH volume on reliability. Results indicated that supervised algorithms were superior, particularly in detecting small WMHs, and can improve their consistency when used in parallel with unsupervised tools. The research also proposed a biomarker for moderate vascular damage, derived from the top 95th percentile of WMH volume in healthy individuals aged 50 to 60. This biomarker effectively differentiated subgroups within the cohort, correlating with variations in brain structure and behavior.
PubMed: 38798616
DOI: 10.1101/2023.03.30.23287946 -
Microorganisms May 2024, or intestinal emphysema, is a condition characterized by the presence of multiple cystic structures within the gut wall and on the serosal surface of the intestine....
, or intestinal emphysema, is a condition characterized by the presence of multiple cystic structures within the gut wall and on the serosal surface of the intestine. Intestinal emphysema represents an accidental finding in swine, although it can be clinically relevant in humans. Its etiology is unknown, and many theories have been proposed. Among them, a bacterial etiology is considered the most likely. Therefore, in this study, the V3-V4 region of the 16S rRNA gene was sequenced from 19 swine ileal tracts, 12 with intestinal emphysema and 7 without lesions, to detect a possible bacterial agent. In parallel, prevalence was estimated. - (13.15%), (7.09%), and (6.60%) were the most abundant species identified. No statistically relevant differences were observed between the pathological and physiological groups. Prevalence ranged from 1.25 to 5.12% depending on the batch. Our results suggest that the gut wall bacterial microbiota greatly match the normal gut microbiota, and that the etiological agent of intestinal emphysema may be (1) undetectable due to the chronicity of the lesions, (2) not considered statistically relevant in comparing the two groups ( < 0.05) and likewise in causing lesions, and (3) undetectable due to contamination. Regarding prevalence, the condition is moderately frequent.
PubMed: 38792810
DOI: 10.3390/microorganisms12050981 -
Postepy Dermatologii I Alergologii Apr 2024Although melasma leads to emotional distress and quality-of-life reduction, indigenous cultures practice female facial tattooing. Facial cues influence personality trait...
INTRODUCTION
Although melasma leads to emotional distress and quality-of-life reduction, indigenous cultures practice female facial tattooing. Facial cues influence personality trait inferences and attractiveness ratings. Skin lesions have been shown to alter gaze patterns, emotion perception, and social evaluations.
AIM
This study aimed to evaluate melasma's impact on visual attention, perceived attractiveness, and social evaluations, considering distinct anatomical areas. Additionally, we sought to compare perceptions of traditional facial tattoos due to their purposeful placement.
MATERIAL AND METHODS
Gaze fixation patterns were examined via eye-tracking, and image-based personality questionnaires were completed for psychological trait assessment. Visual stimuli showcased anatomic melasma variants and tattoo patterns.
RESULTS
Traditional tattoos often follow midline patterns, sparing the upper lip. Both melasma and tattoos significantly affected visual attention ( < 0.001), with chin and upper lip melasma garnering increased attention. Upper lip melasma decreased gaze to the ocular area ( ≤ 0.002). while increasing perioral fixations ( < 0.001) compared to healthy faces. Upper lip tattoos conveyed increased perceived aggressiveness ( = 0.004). Ratings for attractiveness and personality traits were lower for centrofacial melasma than other variants, with no significant difference between centrofacial and isolated upper lip melasma.
CONCLUSIONS
The global avoidance of upper lip pigmentation underscores its perceptual burden. Upper lip pigmentation directs gaze towards anger-signalling regions, increasing perceived aggression and reducing attractiveness. Centrofacial melasma's impact parallels an isolated upper lip pattern, underscoring the disproportionate role of upper lip pigmentation. These findings warrant considering upper lip melasma's significant influence when evaluating quality of life and establishing treatment goals.
PubMed: 38784936
DOI: 10.5114/ada.2024.138678