Intracellular infection of Cutibacterium acnes in macrophages of extensive peri-implantitis lesions: A clinical case series.

Cutibacterium acnes is a facultative anaerobic, gram-positive rod, and a commensal bacterium of the body surface including oral cavity. A causal relationship between C. acnes and chronic granulomatous diseases, such as sarcoidosis and orthopedic implant-associated infections, has been previously reported. Typically, C. acnes has been observed inside macrophages, allowing evasion of host immunity, and triggering a persistent inflammatory response. However, such findings have not been reported in peri-implantitis lesions. In this case series, we collected inflamed tissues from extensive peri-implantitis lesions of eight patients. Out of the eight samples, seven tested positive for the 16 s rRNA gene of C. acnes by polymerase chain reaction, and six were positive by immunohistochemistry. Immunohistochemical staining revealed the presence of C. acnes in the cytoplasm of macrophages, suggesting a role in lesion formation. This finding may enhance our understanding of the pathophysiology of persistent peri-implantitis lesions and provide implications for future therapy.

The Economic Burden of Non-Typhoidal Salmonella and Invasive Non-Typhoidal Salmonella Infection: A Systematic Literature Review.

Non-typhoidal Salmonella (NTS) infection and invasive non-typhoidal Salmonella (iNTS) infection cause a significant global health and economic burden. This systematic review aims to investigate the reported economic burden of NTS and iNTS infection, identify research gaps, and suggest future research directions. Data from PubMed and Embase databases up to April 2022 were reviewed, and articles were screened based on predefined criteria. Cost data were extracted, categorized into direct medical costs (DMCs), direct non-medical costs (DNMCs), and indirect costs (ICs), and converted into US dollars (year 2022). Data primarily originated from high-income countries (37 out of 38), with limited representation from Africa and resource-limited settings. For inpatients, DMCs were the primary cost driver for both NTS and iNTS illnesses, with estimates ranging from USD 545.9 (Taiwan, a region of China) to USD 21,179.8 (Türkiye) for NTS and from USD 1973.1 (Taiwan, a region of China) to USD 32,507.5 (United States of America) for iNTS per case. DNMCs and ICs varied widely across studies. Although study quality improved over time, methodological differences persisted. This review underscores the lack of economic data on NTS and iNTS in resource-limited settings. It also highlights the need for economic burden data in resource-limited settings and a standardized approach to generate global datasets, which is critical for informing policy decisions, especially regarding future vaccines.

Red Fluorescence from Organic Microdots: Leveraging Foldamer-Linked Azobenzene for Enhanced Stability and Intensity in Bioimaging Applications.

Azobenzene, while relevant, has faced constraints in biological system applications due to its suboptimal quantum yield and short-wavelength emission. This study presents a pioneering strategy for fabricating organic microdots by coupling foldamer-linked azobenzene, resulting in robust fluorescence intensity and stability, especially in aggregated states, thereby showing promise for bioimaging applications. Comprehensive experimental and computational examinations elucidate the mechanisms underpinning enhanced photostability and fluorescence efficacy. In vitro and in vivo evaluations disclose that the external layer of cis-azo-foldamer microdots performs a self-sacrificial function during photo-bleaching. Consequently, these red-fluorescent microdots demonstrate extraordinary structural and photochemical stabilities over extended periods. The conjugation of a ß-peptide foldamer to the azobenzene chromophore through a glycine linker instigates a blue-shifted and amplified π*-n transition. Molecular dynamics simulations reveal that the aggregated state of cis-azo-foldamers fortifies the stability of cis isomers, thereby augmenting fluorescence efficiency. This investigation furnishes crucial insights into conceptualizing novel, biologically inspired materials, promising stable and enduring imaging applications, and carries implications for diverse arenas such as medical diagnostics, drug delivery, and sensing technologies.

In vivo experimental study comparing alveolar ridge preservation versus guided bone regeneration after unassisted socket healing at intact and damaged sites in narrow alveolar ridges.

BACKGROUND: To compare bone regeneration and dimensional alteration of alveolar ridge at intact and damaged extraction sockets after alveolar ridge preservation (ARP) and implant placement versus unassisted socket healing followed by guided bone regeneration (GBR) with simultaneous implant placement. METHODS: In 6 beagle dogs, 3 types of extraction sockets in the mandible were created: (1) intact sockets, (2) 1-wall defect sockets and (3) 2-wall defect sockets. The sockets were allocated to undergo either (1) ARP and implant placement 8 weeks later (ARP group) or (2) GBR with simultaneous implant placement after 8 weeks of unassisted socket healing (GBR group). After an additional healing period of 8 weeks, bone regeneration and dimensional changes were evaluated radiographically and histologically. RESULTS: GBR showed superior bone formation and greater bone gains compared to ARP, regardless of the initial extraction-socket configuration. Although ARP maintained the preexisting alveolar ridge dimensions, peri-implant bone defects were still detected at 8 weeks of follow-up. Histomorphometric analyses confirmed that GBR increased dimensions of the alveolar ridge compared to baseline, and the augmentation and bone regeneration were greater with GBR than with ARP. CONCLUSION: Early implant placement with ARP can mitigate alveolar ridge changes in the narrow alveolar ridge. However, early implant placement with simultaneous GBR creates the conditions for enhanced bone regeneration around the implant and greater ridge augmentation compared to ARP, irrespective of the extraction-socket configuration.

Professional dental care and survival rates in long-term care recipients: A cohort study of 1 459 163 individuals in South Korea.

OBJECTIVES: To determine the dental care pattern and survival rates of participants who received long-term care (LTC) and a matched control cohort in South Korea. BACKGROUND: Global ageing trends and the development of superaged societies pose healthcare challenges. South Korea's LTC system aids those with chronic illnesses and disabilities. Despite the link between oral health and systemic diseases, providing dental care in LTC facilities often reflects social neglect. METHODS: We identified 1 459 163 individuals eligible for LTC insurance in the Korean National Health Insurance Service database from July 2008 to 2015 (LTC cohort) and 1 459 544 individuals matched through propensity-score matching (matched cohort). The LTC recipients were further categorised into subgroups based on their care type (institutional, home or mixed care). Population of utilising dental services and the average number of dental visits were counted in each cohort, and the survival rate of the LTC cohort was determined according to dental utilisation. RESULTS: Population of utilising dental services increased steadily in all cohorts except for institutional care, with the highest utilisation (around 30%) observed in the matched cohort. Lower independence in LTC cohorts was associated with lower dental utilisation: 18-27% for home care, 12-18% for mixed care, and 10% for institutional care. The survival rates in the LTC cohort were significantly lower than in the matched cohort (P < .0001), with 28.1% survival in LTC vs 59.3% in the matched cohort. CONCLUSION: Long-term care recipients experience social neglect for oral care, while higher survival rates were observed in those utilised dental services.

A Two-Year Observational Study to Evaluate Conversion Rates from High- and Low-Risk Patients with Amnestic Mild Cognitive Impairment to Probable Alzheimer's Disease in a Real-World Setting.

Background: Predicting conversion to probable Alzheimer&s disease (AD) from amnestic mild cognitive impairment (aMCI) is difficult but important. A nomogram was developed previously for determining the risk of 3-year probable AD conversion in aMCI. Objective: To compare the probable AD conversion rates with cognitive and neurodegenerative changes for 2 years from high- and low risk aMCI groups classified using the nomogram. Methods: This prospective, multicenter, observational study was conducted in Korea. A total of patients were classified as high- or low-risk aMCI according to the nomogram and followed-up for 2 years to compare the annual conversion rate to probable AD and brain structure changes between the two groups. Results: In total, 176 (high-risk, 85; low-risk, 91) and 160 (high-risk, 77; low-risk, 83) patients completed the 1-year and 2-year follow-up, respectively. The probable AD conversion rate was significantly higher in the high-risk (Year 1, 28.9%; Year 2, 46.1%) versus low-risk group (Year 1, 0.0%; Year 2, 4.9%, both p < 0.0001). Mean changes from baseline in Seoul Neuropsychological Screening Battery-Dementia Version, Clinical Dementia Rating-Sum of Box, and Korean version of the Instrumental Activities of Daily Living scores and cortical atrophy index at Years 1 and 2 were significantly greater in the high-risk group (p < 0.0001). Conclusions: The high-risk aMCI group, as determined by the nomogram, had a higher conversion rate to probable AD and faster cognitive decline and neurodegeneration change than the low-risk group. These real-world results have clinical implications that help clinicians in accurately predicting patient outcomes and facilitating early decision-making.Trial Registration: ClinicalTrials.gov (NCT03448445).

Enhancing guided bone regeneration with cross-linked collagen-conjugated xenogeneic bone blocks and membrane fixation: A preclinical in vivo study.

OBJECTIVE: To determine whether combining cross-linked (CL) collagen-integrated xenogeneic bone blocks stabilized with the fixation of resorbable collagen membranes (CM) can enhance guided bone regeneration (GBR) in the overaugmented calvarial defect model. MATERIALS AND METHODS: Four circular defects with a diameter of 8 mm were prepared in the calvarium of 13 rabbits. Defects were randomly assigned to receive one of the following treatments: (i) non-cross-linked (NCL) porcine-derived collagen-embedded bone block covered by a CM without fixation (NCL + unfix group); (ii) NCL bone block covered by CM with fixation using bone-tack (NCL + fix group); (iii) cross-linked (CL) porcine-derived collagen-embedded bone block covered by CM without fixation (CL + unfix group); and (iv) CL bone block covered by CM with fixation using bone-tack fixation (CL + fix group). The efficacy of GBR was assessed through histological and molecular analyses after 2 and 8 weeks. RESULTS: At 2 weeks, there were no significant differences in histologically measured areas of newly formed bone among the groups. At 8 weeks, however, the CL + fix group exhibited a larger area of new bone (5.08 ± 1.09 mm2, mean ± standard deviation) compared to the NCL + unfix (1.62 ± 0.42 mm2; p < .0083), NCL + fix (3.97 ± 1.39 mm2) and CL + unfix (2.55 ± 1.04 mm2) groups. Additionally, the expression levels of tumour necrosis factor-alpha, fibroblast growth factor-2, vascular endothelial growth factor, osteocalcin and calcitonin receptor were significantly higher in the CL + fix group compared to the other three groups (p < .0083). CONCLUSION: Cross-linked bone blocks stabilized with collagen membrane fixation can significantly enhance GBR.

Ultra-Wideband Vertical Transition in Coplanar Stripline for Ultra-High-Speed Digital Interfaces.

A design method for an ultra-wideband coplanar-stripline-based vertical transition that can be used for ultra-high-speed digital interfaces is proposed. A conventional via structure, based on a differential line (DL), inherently possesses performance limitations (<10 GHz) due to difficulties in maintaining constant line impedance and smooth electric field transformation, in addition to the effects of signal skews, FR4 fiber weave, and unbalanced EM interferences. DL-based digital interfaces may not meet the demands of ultra-high-speed digital data transmission required for the upcoming 6G communications. The use of a coplanar stripline (CPS), a type of planar balanced line (BL), for the vertical transition, along with the ultra-wideband DL-to-CPS transition, mostly removes the inherent and unfavorable issues of the DL and enables ultra-high-speed digital data transmission. The design process of the transition is simplified using the analytical design formulas, derived using the conformal mapping method, of the transition. The characteristic line impedances of the transition are calculated and found to be in close agreement with the results obtained from EM simulations. Utilizing these results, the CPS-based vertical transition, maintaining the characteristic line impedance of 100 Ω, is designed and fabricated. The measured results confirm its ultra-wideband characteristics, with a maximum of 1.6 dB insertion loss and more than 10 dB return loss in the frequency range of DC to 30 GHz. Therefore, the proposed CPS-based vertical transition offers a significantly wider frequency bandwidth, i.e., more than three times that of conventional DL-based via structures.

Synchrotron Analysis of Damaged Extraction Sockets Augmented Using a Synthetic Bone Block: A Pilot Study.

This study aimed to investigate the dimensional stability and quality of the alveolar ridge augmented using a synthetic bone block (SBB) at damaged extraction sockets. Four participants were included, and socket augmentation was performed using SBB and a collagen membrane. Intraoral and CBCT scans were performed before extraction (baseline), immediately postoperative (IP), and at 6 months postoperative (6M). At 6M, a trephine biopsy sample was obtained during implant placement, and the sample was observed using synchrotron. Soft tissue profile changes were assessed using profilometric analysis of the intraoral scan data, while dimensional changes in hard tissue were evaluated based on CBCT measurements. Bone quality was analyzed using synchrotron imaging. There were minimal changes in the soft tissue profile between baseline and IP, baseline and 6M, and IP and 6M (0.11 ± 1.08 mm3, 0.02 ± 0.8 mm3, and -0.65 ± 0.82 mm3, respectively). Horizontal bone width was measured at 1-mm increments from the augmented bone crest to 5 mm apically and revealed only a slight reduction (< 1 mm) at all levels between IP and 6M. The augmented bone height was well maintained from IP until 6M (-0.21 ± 0.53 mm). Synchrotron analysis revealed low to moderate bone quality after 6M (percentage of new bone: 16.49% ± 4.91%). Socket augmentation using SBB appears to be a viable technique for regenerating damaged extraction sockets, with the augmented ridge dimensions maintained up to 6M. Further long-term randomized clinical trials are needed.

Immediate loading on two adjacent single dental implants with definitive nonsplinted restorations: A proof of concept in the posterior zone.

OBJECTIVES: To evaluate clinical, clinician- and patient-reported outcomes (PROs) of two adjacent single posterior implants immediately loaded with definitive single crowns up to 1 year. Ten patients in need of two adjacent posterior single implants were included. All implants were placed applying a fully digital workflow. Definitive screw-retained single zirconia crowns were delivered within 72 h after implant placement. Clinical parameters, patient- and clinician-reported outcomes were assessed up to 1 year of follow-up. CLINICAL CONSIDERATIONS: Clinical outcomes remained stable, with no implant failures or technical and biological complications throughout the observation period. Patient satisfaction was very high at baseline (crown delivery) and remained consistently high at 6 and 12 months of follow-up. Crown insertion 3 days after implant placement was rated as an easy procedure by clinicians. CONCLUSIONS: Two adjacent single implants with immediate definitive restorations (<72 h) in the posterior region appear to be a viable and easy treatment option to shorten the overall treatment time and potentially enhancing patient satisfaction. However, randomized controlled trials are needed to confirm the advantages of this treatment protocol over a delayed loading approach. CLINICAL SIGNIFICANCE: In selected cases, immediate implant loading with definitive restorations in the posterior region appears a valuable and straightforward option to shorten the overall treatment time.

The Full Value of Vaccine Assessments Concept-Current Opportunities and Recommendations.

For vaccine development and adoption decisions, the 'Full Value of Vaccine Assessment' (FVVA) framework has been proposed by the WHO to expand the range of evidence available to support the prioritization of candidate vaccines for investment and eventual uptake by low- and middle-income countries. Recent applications of the FVVA framework have already shown benefits. Building on the success of these applications, we see important new opportunities to maximize the future utility of FVVAs to country and global stakeholders and provide a proof-of-concept for analyses in other areas of disease control and prevention. These opportunities include the following: (1) FVVA producers should aim to create evidence that explicitly meets the needs of multiple key FVVA consumers, (2) the WHO and other key stakeholders should develop standardized methodologies for FVVAs, as well as guidance for how different stakeholders can explicitly reflect their values within the FVVA framework, and (3) the WHO should convene experts to further develop and prioritize the research agenda for outcomes and benefits relevant to the FVVA and elucidate methodological approaches and opportunities for standardization not only for less well-established benefits, but also for any relevant research gaps. We encourage FVVA stakeholders to engage with these opportunities.

The distance of insertion points from wound margins in interrupted and vertical mattress sutures influences the tensile load capacity: An in vitro experimental study.

AIM: To determine the tensile load capacity (TLC) and the tearing characteristics for interrupted and vertical mattress sutures with different insertion points from the wound margin, and the effect of the bite size when using vertical mattress sutures. MATERIALS AND METHODS: A total of 120 gingiva and lining mucosa samples obtained from pig jaws were divided into groups according to the suturing technique (interrupted and vertical mattress sutures), distance of the insertion points from the wound margin (margin, 1, 3, and 5 mm) and bite size (1, 3, and 5 mm). The TLC of the suture and the tearing characteristics were evaluated using a tensile tester device. RESULTS: The TLC was significantly higher for vertical mattress sutures than for interrupted sutures regardless of the distance of the insertion points from the wound margin (intergroup p < .001). This distance significantly influenced the TLC for vertical mattress sutures (p < .05) but not for interrupted sutures (p > .05). Testing the tearing characteristics revealed that no tissue tearing occurred in groups when the insertion points were more than 3 mm from the wound margin. CONCLUSION: The TLC is higher for vertical mattress sutures than for interrupted sutures, and it increases when the insertion points are farther from the wound margin.

Risk of post-operative bleeding after dentoalveolar surgery in patients taking anticoagulants: a cohort study using the common data model.

This retrospective study aimed to determine risk factors associated with post-operative bleeding after dentoalveolar surgery in patients taking anticoagulants. Patients taking anticoagulants who were planned to undergo periodontal flap operation, tooth extraction or implant surgery were included. Patients were divided into two subgroups according to the maintenance of anticoagulants following medical consultation: (1) maintenance group and (2) discontinuation group. The analysed patient-related factors included systemic diseases, maintenance of anticoagulants and types of anticoagulant. Intra- and post-operative treatment-related factors, haemostatic methods and post-operative bleeding were collected for statistical analyses. There were 35 post-operative bleeding complications (6.5%) in the 537 included patients: 21 (8.6%) in maintenance group and 14 (4.8%) in discontinuation group. The type of anticoagulant (p = 0.037), tooth extraction combined with bone grafting (p = 0.016) and type of implant surgery (p = 0.032) were significantly related to the post-operative bleeding rate. In the maintenance group, atrial fibrillation [odds ratio (OR) = 6.051] and vitamin K inhibitors (OR = 3.679) were associated with a significantly higher bleeding risk. From this result, it can be inferred that the decision to continue anticoagulants should be made carefully based on the types of anticoagulant and the characteristics of dentoalveolar surgeries performed: extraction with bone grafting, multiple implantations and involvement of maxillary arch.

Correction: Nguyen et al. Green Silver Nanoparticles Formed by Phyllanthus urinaria, Pouzolzia zeylanica, and Scoparia dulcis Leaf Extracts and the Antifungal Activity. Nanomaterials 2020, 10, 542.

In the original publication [...].

Changes in dementia treatment patterns associated with changes in the National Policy in South Korea among patients with newly diagnosed Alzheimer's disease between 2011 and 2017: results from the multicenter, retrospective CAPTAIN study.

BACKGROUND: The South Korean government has been actively involved in plans to combat dementia, implementing a series of national strategies and plans since 2008. In July 2014, eligibility for mandatory long-term care insurance (LTCI) was extended to people with dementia enabling access to appropriate long-term care including the cognitive function training program and home nursing service. This study aimed to investigate changes in treatment patterns for Alzheimer's disease (AD) between July 2011 and June 2017 which spanned the 2014 revision. METHODS: This multicenter, retrospective, observational study of patients with newly diagnosed AD analyzed electronic medical records from 17 general hospitals across South Korea. Based on their time of AD diagnosis, subjects were categorized into Cohort 1 (1 July 2011 to 30 June 2014) and Cohort 2 (1 July 2014 to 30 June 2017). RESULTS: Subjects (N=3,997) divided into Cohorts 1 (n=1,998) and 2 (n=1,999), were mostly female (66.4%) with a mean age of 84.4 years. Cohort 1 subjects were significantly older (P<0.0001) and had a lower number of comorbidities (P=0.002) compared with Cohort 2. Mean Mini-Mental State Examination (MMSE) scores in Cohorts 1 and 2 at the time of AD diagnosis or start of initial treatment were 16.9 and 17.1, respectively (P=0.2790). At 1 year, mean MMSE scores in Cohorts 1 and 2 increased to 17.9 and 17.4, respectively (P=0.1524). Donepezil was the most frequently administered medication overall (75.0%), with comparable rates between cohorts. Rates of medication persistence were ≥98% for acetylcholinesterase inhibitor or memantine therapy. Discontinuation and switch treatment rates were significantly lower (49.7% vs. 58.0%; P<0.0001), and mean duration of initial treatment significantly longer, in Cohort 2 vs. 1 (349.3 vs. 300.2 days; P<0.0001). CONCLUSIONS: Comparison of cohorts before and after revision of the national LTCI system for dementia patients found no significant difference in mean MMSE scores at the time of AD diagnosis or start of initial treatment. The reduction in the proportion of patients who discontinued or changed their initial treatment, and the significant increase in mean duration of treatment, were observed following revision of the LTCI policy which enabled increased patient access to long-term care.

State transitions across the Strep A disease spectrum: scoping review and evidence gaps.

The spectrum of diseases caused by Streptococcus pyogenes (Strep A) ranges from superficial to serious life-threatening invasive infections. We conducted a scoping review of published articles between 1980 and 2021 to synthesize evidence of state transitions across the Strep A disease spectrum. We identified 175 articles reporting 262 distinct observations of Strep A disease state transitions. Among the included articles, the transition from an invasive or toxin-mediated disease state to another disease state (i.e., to recurrent ARF, RHD or death) was described 115 times (43.9% of all included transition pairs) while the transition to and from locally invasive category was the lowest (n = 7; 0.02%). Transitions from well to any other state was most frequently reported (49%) whereas a relatively higher number of studies (n = 71) reported transition from invasive disease to death. Transitions from any disease state to locally invasive, Strep A pharyngitis to invasive disease, and chronic kidney disease to death were lacking. Transitions related to severe invasive diseases were more frequently reported than superficial ones. Most evidence originated from high-income countries and there is a critical need for new studies in low- and middle-income countries to infer the state transitions across the Strep A disease spectrum in these high-burden settings.

Vaccination to Reduce Antimicrobial Resistance Burden-Data Gaps and Future Research.

Antimicrobial resistance (AMR) poses an immediate danger to global health. If unaddressed, the current upsurge in AMR threatens to reverse the achievements in reducing the infectious disease-associated mortality and morbidity associated with antimicrobial treatment. Consequently, there is an urgent need for strategies to prevent or slow the progress of AMR. Vaccines potentially contribute both directly and indirectly to combating AMR. Modeling studies have indicated significant gains from vaccination in reducing AMR burdens for specific pathogens, reducing mortality/morbidity, and economic loss. However, quantifying the real impact of vaccines in these reductions is challenging because many of the study designs used to evaluate the contribution of vaccination programs are affected by significant background confounding, and potential selection and information bias. Here, we discuss challenges in assessing vaccine impact to reduce AMR burdens and suggest potential approaches for vaccine impact evaluation nested in vaccine trials.

The potential global cost-effectiveness of prospective Strep A vaccines and associated implementation efforts.

Group A Streptococcus causes a wide range of diseases from relatively mild infections including pharyngitis to more severe illnesses such as invasive diseases and rheumatic heart disease (RHD). Our aim is to estimate the cost-effectiveness of a hypothetical Strep A vaccine on multiple disease manifestations at the global-level. Cost-effectiveness analyses were carried out by building on the potential epidemiological impact of vaccines that align with the WHO's Preferred Product Characteristics for Strep A vaccines. Maximum vaccination costs for a cost-effective vaccination strategy were estimated at the thresholds of 1XGDP per capita and health opportunity costs. The maximum cost per fully vaccinated person for Strep A vaccination to be cost-effective was $385-$489 in high-income countries, $213-$312 in upper-income-income countries, $74-$132 in lower-middle-income countries, and $37-$69 in low-income countries for routine vaccination at birth and 5 years of age respectively. While the threshold costs are sensitive to vaccine characteristics such as efficacy, and waning immunity, a cost-effective Strep A vaccine will lower morbidity and mortality burden in all income settings.

Global, regional, and country-level cost of leptospirosis due to loss of productivity in humans.

BACKGROUND: Leptospirosis, a prevalent zoonotic disease with One Health priority and a disease of poverty, lacks global economic burden estimates. This study aims to determine the global, regional, and country-level cost of leptospirosis due to loss of productivity. METHODOLOGY/PRINCIPAL FINDINGS: The cost of leptospirosis due to loss of productivity (referred to as productivity cost hereafter) was estimated by converting the disability-adjusted life years (DALYs) lost due to leptospirosis to a monetary value using the per capita gross domestic product (GDP). The country-specific DALYs lost were obtained from the global burden of leptospirosis study published previously. Non-health GDP per capita (GDP- per capita health expenditure) was used for the cost conversion of DALYs. Country-specific GDP and health expenditure data were obtained from the World Bank data repositories. Estimates were done using both nominal and international dollars. The estimated global productivity cost of leptospirosis in 2019 was Int$ 29.3 billion, with low and high estimates ranging from Int$ 11.6 billion to 52.3 billion. China (Int$ 4.8 billion), India (Int$ 4.6 billion), Indonesia (Int$ 2.8 billion), Sri Lanka (Int$ 2.1 billion), and the United States (Int$ 1.3 billion) had the highest productivity cost due to leptospirosis. Eight out of 10 countries with the highest burden were in the Asia-Pacific region. In addition, lower-middle-income countries had an annual productivity cost of Int$ 13.8 billion, indicating that the disease is poverty-related. CONCLUSION: Although significant, the cost estimate due to loss of productivity is merely a fraction of the overall economic burden of this disease, which also includes other direct, indirect, and intangible costs. The existing partial estimates of the different components of economic cost suggest a profound economic burden that demands the inclusion of leptospirosis in the global health agenda for comprehensive disease control and prevention efforts, including vaccine development.

Medication-related osteonecrosis of the jaw using periodontitis-induced rat before tooth extraction.

OBJECTIVE: This study aimed to investigate the occurrence of medication-related osteonecrosis of the jaw (MRONJ) after tooth extraction due to periodontitis in ovariectomized rats. METHODS: Twenty-four osteoporosis-induced rats were administered with zoledronic acid (ZA; ZA group) or saline (CONT group). In both groups, tooth extraction was performed after inducing periodontitis, and all animals were sacrificed 8-week after tooth extraction. RESULTS: Micro-CT of the tibia showed that the bone volume fraction, bone surface density, trabecular number, and bone mineral density were significantly higher in the ZA group than in the CONT group. Histologically, the proliferative zone on the growth plate was thicker in the ZA group than in the CONT group. Micro-CT of the extraction sites revealed that the bone volume fraction was significantly higher in the ZA group than in the CONT group. Radiologically, the ZA group showed partial healing and delayed healing. Histological analysis revealed normal bone healing status with completely healed epithelium in the extraction sites of the CONT group, whereas abnormal empty osteocytes in the necrotic bone and inflammatory infiltration were observed in the ZA group. CONCLUSION: The incidence of MRONJ increased in the rats administered with ZA.