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With the Appalachian Trail (AT) as our research setting, grounded theory as our methodological approach, and qualitative interviews and archival analysis as our methods, we investigate the role crowdsourced data, social media, and smartphone apps could play in sustainable resource management (SRM). Centering the perspectives of AT resource managers, our analysis reveals that digital technologies can create new challenges and exacerbate existing ones. Place-centered challenges intensified by digital technologies are overcrowding and trail infrastructure degradation. Experience-centered challenges posed by digital technologies include information overload, limited operational capacity, and tensions between the traditional "AT experience" and digital life. Further, our analysis illuminates the technological, organizational, ethical, and experiential challenges and barriers to the systemic adoption of digital technologies for SRM. These empirical insights result in a management framework that focuses attention on the humanistic and organizational needs of resource managers that could be used for designing and implementing socio-technical systems that better align with social and cultural values of resource management contexts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Early mortality among hospitalized HIV-associated tuberculosis (TB/HIV) patients is high despite treatment. The pharmacokinetics of rifampicin, isoniazid, and pyrazinamide were investigated in hospitalized TB/HIV patients and a cohort of outpatients with TB (with or without HIV) to determine whether drug exposures differed between groups., Methods: Standard first-line TB treatment was given daily as per national guidelines, which consisted of oral 4-drug fixed-dose combination tablets containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol. Plasma samples were drawn on the 3rd day of treatment over eight hours post-dose. Rifampicin, isoniazid, and pyrazinamide in plasma were quantified and NONMEM ® was used to analyze the data., Results: Data from 60 hospitalized patients (11 of whom died within 12 weeks of starting treatment) and 48 outpatients were available. Median (range) weight and age were 56 (35 - 88) kg, and 37 (19 - 77) years, respectively. Bioavailability and clearance of the three drugs were similar between TB/HIV hospitalized and TB outpatients. However, rifampicin's absorption was slower in hospitalized patients than in outpatients; mean absorption time was 49.9% and 154% more in hospitalized survivors and hospitalized deaths, respectively, than in outpatients. Higher levels of conjugated bilirubin correlated with lower rifampicin clearance. Isoniazid's clearance estimates were 25.5 L/h for fast metabolizers and 9.76 L/h for slow metabolizers. Pyrazinamide's clearance was more variable among hospitalized patients. The variability in clearance among patients was 1.70 and 3.56 times more for hospitalized survivors and hospitalized deaths, respectively, than outpatients., Conclusions: We showed that the pharmacokinetics of first-line TB drugs are not substantially different between hospitalized TB/HIV patients and TB (with or without HIV) outpatients. Hospitalized patients do not seem to be underexposed compared to their outpatient counterparts, as well as hospitalized patients who survived vs who died within 12 weeks of hospitalization., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Abdelgawad N et al.)

Background Low-level laser treatment (LLLT) was thought to increase bone quality during osseointegration when combined with dental implants. However, there is no sufficient information on its impact on dental implants in diabetics. Osteoprotegerin (OPG) has been described as a marker for bone turnover to determine implant prognosis. The current research aims to evaluate the effect of low-level laser therapy (LLLT) on bone density (BD) and osteoprotegerin levels in peri-implant crevicular fluid (PICF) in type II diabetic patients. Methods This study comprised 40 individuals with type II diabetes mellitus (T2DM). Implants were randomly placed in 20 non-lasered T2DM patients (control) and 20 lasered T2DM patients (LLLT group). At the follow-up stages, BD and OPG levels in the PICF were evaluated in both groups. Results Significant variations were shown among control and LLLT groups concerning OPG level and BD (p≤0.001). OPG was significantly decreasing with follow-up points (p≤0.001). There was a significant decrease in OPG with time in both groups with a higher decrease in the control group. Conclusion LLLT is promising in controlled T2DM patients due to its outstanding influence on BD and estimated crevicular levels of OPG. Regarding its clinical significance, LLLT significantly improved bone quality during osseointegration on dental implants in T2DM. LLLT is considered potentially important for T2DM patients during implant placement. Trial registration The study was registered on ClinicalTrial.gov under registration number NCT05279911 (registration date: March 15, 2022) (https://clinicaltrials.gov/ct2/show/NCT05279911)., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Attia et al.)

Limited knowledge is available on the pharmacokinetics of rifampicin in children with tuberculous meningitis (TBM) and its penetration into brain tissue, which is the site of infection. In this analysis, we characterize the distribution of rifampicin in cerebrospinal fluid (CSF), lumbar (LCSF) and ventricular (VCSF), and brain extracellular fluid (ECF). Children with TBM were included in this pharmacokinetic analysis. Sparse plasma, LCSF, and VCSF samples were collected opportunistically, as clinically indicated. Brain ECF was sampled using microdialysis (MD). Rifampicin was quantified with liquid chromatography with tandem mass spectrometry in all samples, and 25-desacetyl rifampicin in the plasma samples. The data were interpreted with nonlinear mixed-effects modeling, with the CSF and brain ECF modeled as "effect compartments." Data were available from 61 children, with median (min-max) age of 2 (0.3 to 10) years and weight of 11.0 (4.8 to 49.0) kg. A one-compartment model for parent and metabolite with first-order absorption and elimination via saturable hepatic clearance described the data well. Allometric scaling, maturation, and auto-induction of clearance were included. The pseudopartition coefficient between plasma and LCSF/VCSF was ~5%, while the value for ECF was only ~0.5%, possibly reflecting low recovery of rifampicin using MD. The equilibration half-life between plasma and LCSF/VCSF was ~4 h and between plasma and ECF ~2 h. Our study confirms previous reports showing that rifampicin concentrations in the LCSF are lower than in plasma and provides novel knowledge about rifampicin in the VCSF and the brain tissue. Despite MD being semiquantitative because the relative recovery cannot be quantified, our study presents a proof-of-concept that rifampicin reaches the brain tissue and that MD is an attractive technique to study site-of-disease pharmacokinetics in TBM.

Background: Early mortality among hospitalized HIV-associated tuberculosis (TB/HIV) patients is high despite treatment. The pharmacokinetics of rifampicin, isoniazid, and pyrazinamide were investigated in hospitalized TB/HIV patients and a cohort of outpatients with TB (with or without HIV) to determine whether drug exposures differed between groups., Methods: Standard first-line TB treatment was given daily as per national guidelines, which consisted of oral 4-drug fixed-dose combination tablets containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol. Plasma samples were drawn on the 3rd day of treatment over eight hours post-dose. Rifampicin, isoniazid, and pyrazinamide in plasma were quantified and NONMEM ® was used to analyze the data., Results: Data from 60 hospitalized patients (11 of whom died within 12 weeks of starting treatment) and 48 outpatients were available. Median (range) weight and age were 56 (35 - 88) kg, and 37 (19 - 77) years, respectively. Bioavailability and clearance of the three drugs were similar between TB/HIV hospitalized and TB outpatients. However, rifampicin's absorption was slower in hospitalized patients than in outpatients; mean absorption time was 49.9% and 154% more in hospitalized survivors and hospitalized deaths, respectively, than in outpatients. Higher levels of conjugated bilirubin correlated with lower rifampicin clearance. Isoniazid's clearance estimates were 25.5 L/h for fast metabolizers and 9.76 L/h for slow metabolizers. Pyrazinamide's clearance was more variable among hospitalized patients. The variability in clearance among patients  was 1.70 and 3.56 times more for hospitalized survivors and hospitalized deaths, respectively, than outpatients.   Conclusion. We showed that the pharmacokinetics of first-line TB drugs are not substantially different between hospitalized TB/HIV patients and TB (with or without HIV) outpatients. Hospitalized patients do not seem to be underexposed compared to their outpatient counterparts, as well as hospitalized patients who survived vs who died within 12 weeks of hospitalization., Competing Interests: No competing interests were disclosed., (Copyright: © 2022 Abdelgawad N et al.)

Background: Although the molecular mechanisms that cause the development of hereditary gingival fibromatosis are not fully understood, multiple theories have been suggested to clarify its pathogenesis. However, the overlying keratinocytes' function is poorly comprehended. This work aimed to investigate the expression of TGF-β and MMP-2 in hereditary gingival fibromatosis epithelial cells compared to the normal gingival epithelium to give an insight into the mechanism of the development of this condition., Methods: Biopsies were obtained from 20 hereditary gingival fibromatosis patients and 20 healthy controls. Biopsies were stained immunohistochemically and statistically analyzed for MMP-2 and TGF-β expression., Results: Regarding MMP-2, The hereditary gingival fibromatosis group recorded a higher mean value compared to the normal gingiva, with a mean difference of 3.29 ± 0.34. This difference was statistically significant (p = 0.00). Regarding TGF-β, a higher mean value was recorded in the HGF group compared to the normal gingiva, with a mean difference of 15.88 ± 1.05 The difference was statistically significant (p = 0.00). A strong positive correlation was detected between MMP-2 and TGF-β (R = 0.534, p = 0.015)., Conclusions: In hereditary gingival fibromatosis, the epithelium expresses higher levels of TGF-β and MMP-2 than normal gingival tissue. There was an evident positive correlation between MMP-2 and TGF-β. Our data suggest that the expression of TGF-β and MMP2 by epithelial cells of HGF may play a role in the epithelial-mesenchymal transition pathogenic pathway., Competing Interests: There is no conflict of interest., (© 2022 Craniofacial Research Foundation. Published by Elsevier B.V. All rights reserved.)

Background: Early mortality among hospitalized HIV-associated tuberculosis (TB/HIV) patients is high despite treatment. The pharmacokinetics of rifampicin, isoniazid, and pyrazinamide were investigated in hospitalized TB/HIV patients and a cohort of outpatients with TB (with or without HIV) to determine whether drug exposures differed between groups., Methods: Standard first-line TB treatment was given daily as per national guidelines, which consisted of oral 4-drug fixed-dose combination tablets containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol. Plasma samples were drawn on the 3rd day of treatment over eight hours post-dose. Rifampicin, isoniazid, and pyrazinamide in plasma were quantified and NONMEM ® was used to analyze the data., Results: Data from 60 hospitalized patients (11 of whom died within 12 weeks of starting treatment) and 48 outpatients were available. Median (range) weight and age were 56 (35 - 88) kg, and 37 (19 - 77) years, respectively. Bioavailability and clearance of the three drugs were similar between TB/HIV hospitalized and TB outpatients. However, rifampicin's absorption was slower in hospitalized patients than in outpatients; mean absorption time was 49.9% and 154% more in hospitalized survivors and hospitalized deaths, respectively, than in outpatients. Higher levels of conjugated bilirubin correlated with lower rifampicin clearance. Isoniazid's clearance estimates were 25.5 L/h for fast metabolizers and 9.76 L/h for slow metabolizers. Pyrazinamide's clearance was more variable among hospitalized patients. The variability in clearance among patients  was 1.70 and 3.56 times more for hospitalized survivors and hospitalized deaths, respectively, than outpatients.   Conclusion. We showed that the pharmacokinetics of first-line TB drugs are not substantially different between hospitalized TB/HIV patients and TB (with or without HIV) outpatients. Hospitalized patients do not seem to be underexposed compared to their outpatient counterparts., Competing Interests: No competing interests were disclosed., (Copyright: © 2022 Abdelgawad N et al.)

Background/purpose: Studies have shown that there is a possible correlation between the amount of glycated hemoglobin and the periodontal status. The goal of this study was to investigate the relationship between glycated hemoglobin (HbA1c) and the prevalence of gingival pathogens and circulating interleukin levels in type II diabetic Tunisian subjects., Material and Methods: The research included four groups; 30 healthy subjects (H group), 30 non-diabetic subjects suffering from chronic periodontitis (CP group). Type-II diabetic patients were divided according to HbA1c level into 30 adequately-controlled type-II diabetes subjects (HbA1c ≤ 7 percent (ATIID&CP group)) and 30 inadequately-controlled type-II diabetes subjects and HbA1c > 7 percent (ITIID&CP group). Clinical periodontal condition parameters and assessment of salivary interleukin IL-1beta, IL-6 and IL-10 were assessed. Quantitative Polymerase Chain Reaction used for detection of Subgingival biofilm of periodontal pathogens., Results: Clinical parameters analyzed were positively associated with HbA1c levels (p < 0.05). A. Actinomycetemcomitans were found in 80 percent of ITIID&CP, 65 percent of CP and almost absent in H group. Porphyromonas gingivalis was present in 100 percent of CP, 85 percent of ITIID&CP, 50 percent of ATIID&CP and 3 percent of H group . T. Denticola had an equivalent occurrence. While Tannerella forsythia was scarce in ITIID&CP groups, but abundant in the H group. ITIID&CP had the highest IL-6 and IL-1beta/IL-10 ratios., Conclusion: HBA1c levels affect periodontal status, pathogens and salivary interleukins in Type-II diabetic Tunisians with chronic periodontitis, compared with stable and chronic periodontitis groups and can interact with periodontal infections and increase the inflammatory state., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2020 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Background: This study aimed to investigate the relation between vascular endothelial growth factors (VEGF) and matrix metalloproteinase-2 (MMP-2) in different oral lichen planus (OLP) forms compared to control patients., Methods: Biopsies from 60 patients were selected and equally distributed as follows: reticular/popular OLP (R/PLP), atrophic/erosive OLP (A/ELP) patients, healthy subjects (Control). All biopsies were immune-histochemical stained and statistically analyzed for VEGF and MMP-2 expression., Results: Immune-expression of VEGF was significant between OLP and control ( P -value <0.001). OLP showed a higher epithelial expression of VEGF in A/ELP compared to R/PLP (15.19 ± 2.53). In connective tissue (CT), R/PLP showed a higher VEGF expression (11.57 ± 2.32) compared to A/ELP (9.87 ± 2.48); (p < 0.001), with no significant difference ( P -value ≥ 0.05). A significant epithelial expression of MMP-2 was seen in A/ELP compared to R/PLP (21.32 ± 7.08). R/PLP showed a higher expression of MMP-2 (20.45 ± 6.28) in CT compared to A/ELP group (17.66 ± 6.94), with a non-significant difference ( P -value = 1.000). In A/ELP, a positive correlation between VEGF and MMP-2 was detected in CT, r = 0.761, with a weak correlation was noticed in epithelium r = 0.163. A negative correlation was noted between VEGF and MMP-2 in R/PLP in CT, r = -0.368, with a moderate positive correlation in epithelium, r = 0.655., Conclusion: MMP-2 and VEGF protein profiles support a role in the pathogenesis of OLP. Based the MMP-2 and VEGF findings in the A/ELP group, this pathway may have a role in the malignant transformation of these lesions. Both observations invite further study., Competing Interests: No Conflict of Interest., (© 2020 Craniofacial Research Foundation. Published by Elsevier B.V. All rights reserved.)