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The antimicrobial effects of subgingival chlorhexidine (CH) irrigations on the pathogenic flora in advanced periodontal lesions were assessed. Changes in the patterns of colonization within the subgingival sites were monitored by differential dark-field microscopy, in 16 patients, over a period of 10 weeks. In addition, changes in the clinical parameters of the diseased sites were also monitored. Initial base-line evaluations were made for both the clinical and microbiological parameters. 4 sites of moderate to advanced periodontal disease were selected in each patient. These were randomly irrigated with a single dose of either 0.2% CH gel, 0.2% CH solution, or physiological saline, while 1 site was left as a control. The patients were seen weekly, until the 5th week, then at the 7th and 10th weeks. At each appointment, a microbiological sample was taken from the subgingival region of each site, together with an assessment of the clinical indices. Results indicated that a single irrigation of an 0.2% solution of CH or 0.2% CH gel had a marked effect in decreasing the % of spirochaetes and, to some extent, motile bacteria. There was a concomitant shift in colonization to cocci, fusiform and filamentous organisms in pockets that were irrigated; this coincided with a reduction in the % of bleeding sites. Various patterns of colonization were observed which have been described and may assist in differential dark field (DDF) monitoring of lesions. Bleeding on blunt probing was found to be correlated with a flora dominated by spirochaetes. No other correlations were found over the 10-week period between the other parameters. The therapeutic effect of a single application of CH gel and solution did not exceed 10 weeks and a peak response was recognised at 2 to 4 weeks. It was concluded that treatment regimes involving CH irrigation could be undertaken on a monthly basis. No differences in efficacy could be found between the use of CH gel and solution. [ABSTRACT FROM AUTHOR]

After gingival health had been achieved in four subjects they were instructed to cease all oral hygiene measures. At 0, 8 and 21 days Plaque and Gingival Indices were recorded and gingival biopsies were removed from the buccal aspect of a first molar. Frozen sections of the gingival oral epithelium were stained for ATPase and 5'-nucleotidase to determine the number of Langerhans cells in a defined cross-sectional area. It was found that, as plaque accumulated, there was a statistically significant increase in the number of Langerhans cells in oral epithelium, particularly in the stratum spinosum. These results indicate that dental plaque can elicit a response in Langerhans cells located in the oral epithelium of the gingiva. [ABSTRACT FROM AUTHOR]

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Epithelial Langerhans cells in samples of healthy and diseased gingival tissue were studied using ATPase histochemistry and the monoclonal antibodies OKT6 and anti HLA-DR. In healthy gingiva Langerhans cells were seen in both oral and sulcular epithelium; they were generally positioned in the basal layers. No Langerhans cells were seen in junctional epithelium. In diseased tissue there was a large increase in the number of Langerhans cells in both oral and sulcular epithelium with many more being situated in the stratum spinosum. There was an increase in the expression of the Class 2 antigen, HLA-DR, and morphological polarization occurred with dendrites preferentially orientated towards the surface. No Langerhans cells were seen in the pocket lining epithelium of periodontally diseased gingiva. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by vasoconstriction and remodeling of small pulmonary arteries (PAs). Central to the remodeling process is a switch of pulmonary vascular cells to a proliferative, apoptosis-resistant phenotype. Plasminogen activator inhibitors-1 and -2 (PAI-1 and PAI-2) are the primary physiological inhibitors of urokinase-type and tissue-type plasminogen activators (uPA and tPA), but their roles in PAH are unsettled. Here, we report that: 1 ) PAI-1, but not PAI-2, is deficient in remodeled small PAs and in early-passage PA smooth muscle and endothelial cells (PASMCs and PAECs) from subjects with PAH compared with controls; 2 ) PAI-1 -/- mice spontaneously develop pulmonary vascular remodeling associated with upregulation of mTORC1 signaling, pulmonary hypertension (PH), and right ventricle (RV) hypertrophy; and 3 ) pharmacological inhibition of uPA in human PAH PASMCs suppresses proproliferative mTORC1 and SMAD3 signaling, restores PAI-1 levels, reduces proliferation, and induces apoptosis in vitro, and prevents the development of SU5416/hypoxia-induced PH and RV hypertrophy in vivo in mice. These data strongly suggest that downregulation of PAI-1 in small PAs promotes vascular remodeling and PH due to unopposed activation of uPA and consequent upregulation of mTOR and transforming growth factor-β (TGF-β) signaling in PASMCs, and call for further studies to determine the potential benefits of targeting the PAI-1/uPA imbalance to attenuate and/or reverse pulmonary vascular remodeling and PH. NEW & NOTEWORTHY This study identifies a novel role for the deficiency of plasminogen activator inhibitor (PAI)-1 and resultant unrestricted uPA activity in PASMC remodeling and PH in vitro and in vivo, provides novel mechanistic link from PAI-1 loss through uPA-induced Akt/mTOR and TGFβ-Smad3 upregulation to pulmonary vascular remodeling in PH, and suggests that inhibition of uPA to rebalance the uPA-PAI-1 tandem might provide a novel approach to complement current therapies used to mitigate this pulmonary vascular disease.

Pulmonary arterial hypertension (PAH) is a devastating and progressive disease with limited treatment options. Endothelial dysfunction plays a central role in the development and progression of PAH, yet the underlying mechanisms are incompletely understood. The endosome-lysosome system is important to maintain cellular health, and the small GTPase RAB7 regulates many functions of this system. Here, we explored the role of RAB7 in endothelial cell (EC) function and lung vascular homeostasis. We found reduced expression of RAB7 in ECs from patients with PAH. Endothelial haploinsufficiency of RAB7 caused spontaneous pulmonary hypertension (PH) in mice. Silencing of RAB7 in ECs induced broad changes in gene expression revealed via RNA-Seq, and RAB7-silenced ECs showed impaired angiogenesis and expansion of a senescent cell fraction, combined with impaired endolysosomal trafficking and degradation, suggesting inhibition of autophagy at the predegradation level. Furthermore, mitochondrial membrane potential and oxidative phosphorylation were decreased, and glycolysis was enhanced. Treatment with the RAB7 activator ML-098 reduced established PH in rats with chronic hypoxia/SU5416. In conclusion, we demonstrate for the first time to our knowledge the fundamental impairment of EC function by loss of RAB7, causing PH, and show RAB7 activation to be a potential therapeutic strategy in a preclinical model of PH.

Our understanding of the pathophysiology of pulmonary arterial hypertension (PAH) has evolved over recent years, with the recognition that endothelial cell (EC) dysfunction and inflammation play an integral role in the development of this disease. ECs within the pulmonary vasculature play a unique role in maintaining vascular integrity and barrier function, regulating gas exchange, and contributing to vascular tone. Using single-cell transcriptomics, research has shown that there are multiple, unique EC subpopulations with different phenotypes. In response to injury or certain stressors such as hypoxia, there can be a dysregulated response with aberrant endothelial injury repair involving other pulmonary vascular cells and even immune cells. This aberrant signaling cascade is potentially a primary driver of pulmonary arterial remodeling in PAH. Recent studies have examined the role of EC clonal expansion, immune dysregulation, and genetic mutations in the pathogenesis of PAH. This review summarizes the existing literature on EC subpopulations and the intricate mechanisms through which ECs develop aberrant physiologic phenotypes and contribute to PAH. Our goal is to provide a framework for understanding the unique pulmonary EC biology and pathophysiology that is involved in the development of PAH., Competing Interests: The authors declare that this review article was written in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Newcomb and Farkas.)

Introduction: Response to anticoagulation varies during management of acute hospitalized pulmonary embolism. We aimed to study thrombus histology in pulmonary embolism samples removed during acute surgical embolectomy to evaluate whether thrombus morphology was similar between patients and whether there was an association with duration of symptoms and/or resolution on follow up imaging., Methods: This was a retrospective observational single center study at the University of Rochester Medical Center. We evaluated patients that underwent acute surgical embolectomy and followed up in our clinic 2 - 4 months after the event with Ventilation/Perfusion (V/Q) scan obtained for all regardless of symptoms. Thromboemboli were formalin fixed and processed for light microscopy in the hospital histopathology laboratory. Four-micron thick sections were stained with hematoxylin and eosin, Masson trichrome, and Verhoeff elastic tissue stains. Immunohistochemistry was performed using anti-CD31 and anti-CD68. Slides were independently evaluated for time-dependent microscopic changes using Irniger's classification by two blinded pathologists., Results: Sixteen patients underwent embolectomy with fifteen having V/Q imaging at follow up. The majority of patients were female. Samples showed a generally similar overall architecture that included a central core composed primarily of red blood cells and fibrin and an outer layer of platelets and monocytes. Two samples had evidence of fibrosis and recanalization., Conclusions: We found heterogeneous histopathology in samples obtained during acute embolectomy. Further prospective studies should systematically characterize clot morphology and evaluate treatment response and outcomes. Careful thrombus specimen measurement and consistent sampling for sections will be required to draw firm conclusions., (Copyright © 2021 Elsevier Inc. All rights reserved.)

One of the important steps in the annotation of genomes is the identification of regions in the genome which code for proteins. One of the tools used by most annotation approaches is the use of signals extracted from genomic regions that can be used to identify whether the region is a protein coding region. Motivated by the fact that these regions are information bearing structures we propose signals based on measures motivated by the average mutual information for use in this task. We show that these signals can be used to identify coding and noncoding sequences with high accuracy. We also show that these signals are robust across species, phyla, and kingdom and can, therefore, be used in species agnostic genome annotation algorithms for identifying protein coding regions. These in turn could be used for gene identification.

Melioidosis is caused by the gram-negative bacillus Burkholderia pseudomallei , endemic to northern Australia and Southeast Asia. We present a patient who traveled to Mexico, returned to the United States, and developed progressive manifestations of melioidosis, culminating as central nervous system disease. Standard therapy was contraindicated, and a prolonged intensive phase was employed.

All new patients commencing supportive periodontal therapy (periodontal maintenance) after treatment in a specialist periodontal practice from 1983 to 1986 were identified from practice records. Based on their compliance with the recommended schedule of visits, the patients were classified as either compliant or non-compliant. The results indicated that there were no significant differences between compliant and non-compliant patients with regards to age, sex, number of missing teeth, plaque score, or periodontal disease severity. More non-compliant patients than compliant patients were smokers (P less than 0.05). By contrast, more compliant patients were covered by private dental insurance (P less than 0.01) and more had periodontal surgery during treatment (P less than 0.001). Only 36% of the initial patient sample was found to be compliant at the end of 1989, with the greatest patient loss in the first year of supportive periodontal therapy of about 42%. The annual attrition rate decreased in subsequent years to average about 10% of those remaining in each year, indicating that a patient is more likely to remain compliant if he or she attends for at least 1 year of supportive periodontal treatment. Non-compliant patients were sent a questionnaire seeking reasons for their non-compliance. Forty percent of the questionnaires were returned. The most common reason given for non-compliance was that a general dental practitioner was attending to the patient's periodontal treatment needs. Many considered supportive periodontal therapy to be too expensive, while a significant proportion considered that they no longer required treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

The efficacy of controlling Meloidogyne hapla on potato with water incorporation of ethoprop was compared to physical incorporation before planting. The standard practice of aldicarb application for insect control was also evaluated for M. hapla suppression with and without ethoprop. Physical incorporation before planting by rototilling or discing reduced (P

The adjunctive effects of subgingival chlorhexidine irrigation on gingival response following scaling and root planing were investigated. Changes in clinical parameters, and microbial composition of subgingival plaque as monitored by dark-field microscopy were assessed in 12 patients over a period of 12 weeks. Two test sites and two matched control sites with probing depth ranging from 4 mm to 7 mm were selected in each patient. Oral hygiene instruction and a single episode of scaling and root planing were carried out. In addition test sites were irrigated with one mL of 0.2% chlorhexidine solution by the operator, while control sites were either irrigated with an equal volume of physiological saline or not irrigated. There were significant improvements in the clinical parameters with little difference between test and control sites. Between the beginning and the end of the study there was a marked reduction in the proportion of spirochaetes with a concomitant increase in coccoid organisms with, again, only minor differences between the test and the control sites. It was concluded that subgingival irrigation with a single application of 0.2% chlorhexidine did not enhance gingival healing, or delay recolonization of pockets by certain micro-organisms (as monitored by dark-field microscopy), when scaling and root planing had been thoroughly carried out immediately prior to irrigation.

The relationship between the gingival inflammation and plaque scores of patients who had received kidney transplants and were taking immunosuppressive drugs to combat rejection pheomena was compared with data from a control group. Equivalent plaque scores were associated with less gingival inflammation in the patients taking the immunosuppressive drugs. While there was no signficant difference between the plaque scores of the two groups the control group displayed signficantly more gingival inflammation. The implications of these results with respect to possible etiological mechanisms operating in periodontal disease are discussed.

Gingival tissue from a patient suffering from an unusual form of gingivitis, previously described as plasma cell gingivitis, has been subjected to ultrastructural, histochemical, and immunologic investigation. Macrophages and T-lymphocytes infiltrated the oral epithelium where a dissecting type of injury was produced, predominantly in the lower spinous layer. Interkeratinocyte junctions were disrupted and collections of isolated desmosomes were observed in the intercellular spaces. It is postulated that the primary lesion in this atypical gingivitis lies in the epithelium and that the plasma cell infiltrate in the connective tissue is secondary to this. No allergen could be identified, and over a period of 7 years the condition has shown a tendency to resolve spontaneously.

The morphology and numbers of Langerhans' cells vary in epithelia with different patterns of hyperplasia and keratinization. Langerhans' cells stained for ATPase were compared at five phases of the estrous cycle in murine vaginal epithelium. The cells were more dendritic and sparsely distributed with hyperplasia and were less dendritic and more densely distributed with atrophy. Greater numbers of the cells did not accompany keratinization at estrus. Ultrastructurally, three types of Langerhans' cells were discriminated. The first type, active in protein synthesis and phagocytosis, was commonest in sloughing and atrophic epithelium. The second type, containing accumulated and dispersed, electron-dense bodies presumed to be lysosomes, predominated in hyperplastic epithelium. The third, a mature resting cell, was found only after keratinization was complete. This study shows that Langerhans' cells in murine vaginal epithelium vary in morphology and numbers with the epithelial changes of the estrous cycle which may relate to their immunological role, but does not support the contention that their distribution is important for keratinization.

There was a statistically significant shift towards increased proportions of type I Langerhans cells (containing many Langerhans-cell granules) and reduced proportions of both type II Langerhans cells (containing few granules) and indeterminate cells in diseased oral epithelium when compared to healthy oral epithelium. Langerhans cells and indeterminate cells were also seen in the sulcular epithelium of healthy and diseased specimens but never in junctional or pocket-lining epithelium.