Female reproductive factors and risk of joint replacement arthroplasty of the knee and hip due to osteoarthritis in postmenopausal women: a nationwide cohort study of 1.13 million women.

OBJECTIVES: Previous studies of the relationships between female reproductive factors and osteoarthritis (OA) have shown conflicting results. In this study, we aimed to explore the relationships between reproductive factors and joint replacement arthroplasty of the knee (TKRA) and hip (THRA) in a large nationwide population-based cohort of postmenopausal Korean women. METHODS: We included 1,134,680 subjects who participated in national health examinations in 2009 in the study. The study outcomes were incident THRA or TKRA due to severe hip or knee OA. The relationships between reproductive factors and THRA or TKRA were evaluated using a multivariable-adjusted proportional hazards model. RESULTS: During a mean follow-up duration of 8.2 years, 1,610 incident THRA cases and 60,670 incident TKRA cases were observed. Later age at menarche, longer breastfeeding, HRT and OC use were associated with increased risk of TKRA for severe knee OA, while later age at menopause and longer reproductive span were associated with decreased risk. With regard to THRA for severe hip OA, later menarche, longer breastfeeding, HRT more than 5 years, and OC use more than 1 year were associated with higher risk. The associations between reproductive factors and severe OA were more pronounced in underweight and younger subjects. CONCLUSION: We found that shorter estrogen exposure was associated with higher risk of TKRA due to severe knee OA, and such associations were more pronounced in underweight and younger subjects. The association between shorter estrogen exposure and THRA was not robust.

Three-percent sucrose acts as a thermostabilizer for cell-adapted foot-and-mouth disease virus without any negative effect on viral growth.

AIMS: As cell-adapted foot-and-mouth disease virus (FMDV) with H56R mutation in VP3 has reduced thermostability, this study aimed to investigate the effect of thermostabilizers on cell-adapted FMDV for vaccine production. METHODS AND RESULTS: We examined the effect of 3% sucrose, 10% (or 25%) glycerol or 10% FBS on cell-adapted FMDV O/SKR/JC/2014, containing H56R mutation in VP3, as vaccine seed virus at -80, 4, 25 or 37°C for 2, 4 or 7 days. The stabilizing effect of 3% sucrose on O/SKR/JC/2014 was observed at 25, 37°C, and after repeated freeze-thaw cycles. Additionally, we tested the effect of 3% sucrose on the growth of FMDV or cells and did not observe any decrease in either viral growth or cell viability. CONCLUSIONS: Our study showed the protective effect of 3% sucrose on FMDV infectivity at various temperatures; this virus stock in 3% sucrose could be used for infecting cells without the removal of sucrose. SIGNIFICANCE AND IMPACT OF THE STUDY: We suggest that 3% sucrose-containing medium could be beneficial for the stable storage and transport of cell-adapted FMDV.

Environmental lung diseases: clinical and imaging findings.

Environmental lung diseases are caused by exposure to adverse environmental conditions, such as atmospheric pressure changes or the ingestion or inhalation of toxic agents. The development of environmental lung diseases depends on the intensity and duration of exposure, the physiological and biological susceptibility of the host, and the toxic effects of the adverse environmental conditions encountered. A combination of clinical features, related exposure history, imaging findings, and a review of previous reports that support an association between exposure and the disease process is required for diagnosis.

Ethnic and sex differences in the distributions of body mass index and waist circumference among adults: a binationally representative study in South Korea and the United States.

OBJECTIVE: The ethnic and sex differences in the distributions of body mass index (BMI) and waist circumference (WC) among adults are largely unknown. Therefore, we aimed to investigate the percentiles of BMI and WC in groups divided according to age, sex, and ethnicity. PATIENTS AND METHODS: We conducted a population-based binational study of adults aged ≥20 years based on data from two sources: US National Health and Nutrition Examination Survey (2015 to 2020) and Korea National Health and Nutrition Examination Survey (2016 to 2019). RESULTS: Weight, height, and WC were measured in 13,144 American adults and 30,191 Korean adults. Overall, BMI increased at younger ages and decreased at older ages, which indicates a reversed U-shaped relationship, and differed in terms of age, sex, and ethnicity. Women in the other Hispanic, non-Hispanic white, non-Hispanic black, and "other ethnic groups" showed a common BMI peak at ages 50-54 years. The patterns of WC distribution were similar to those of BMI distribution. CONCLUSIONS: In this binational representative study, we found varied distributions of ethnic and sex differences in BMI and WC. Considering the differences in these distributions may help improve individual and personalized treatment strategies.

Lactone form 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) stimulate the osteoblastic differentiation of mouse periodontal ligament cells via the ERK pathway.

BACKGROUND AND OBJECTIVE: Recent studies reported that the lactone forms of 3-hydroxy- 3-methylglutaryl-coenzyme A reductase inhibitors, which are also known as statins, have a bone stimulatory effect. However, there are few reports on the effect of statins on periodontal ligament cells. This study examined the statin-induced osteoblastic differentiation of mouse periodontal ligament cells as well as its mechanism. MATERIAL AND METHODS: Mouse periodontal ligament cells were cultured with lovastatin or simvastatin, and their viability was measured. The levels of alkaline phosphatase (ALP), osteocalcin, bone sialoprotein and bone morphogenetic protein-2 mRNA expression were evaluated by RT-PCR. The osteoblastic differentiation was characterized by the ALP activity and Alizarin Red-S staining for calcium deposition. The activity of the osteocalcin gene (OG2) and synthetic osteoblast-specific elements (6× OSE) promoter with statins was also measured using a luciferase assay. For the signal mechanism of statins, the ERK1/2 MAPK activity was determined by western blot analysis. RESULTS: A statin treatment at concentrations < 1 µM did not affect the cell viability. Lovastatin or simvastatin at 0.1 µM increased the levels of ALP, osteocalcin, bone sialoprotein and bone morphogenetic protein-2 mRNA in mouse periodontal ligament cells. In addition, the ALP activity, mineralized nodule formation and OG2 and OSE promoter activity were higher in the lovastatin- or simvastatin-treated cells than the control cells. Western blot analysis confirmed that the statins stimulated the phosphorylation of ERK1/2. CONCLUSION: Lovastatin and simvastatin may stimulate the osteoblastic differentiation of periodontal ligament cells via the ERK1/2 pathway. This suggests that the statins may be useful for regenerating periodontal hard tissue.

Formulation, pharmacokinetics and biodistribution of Ofloxacin-loaded albumin microparticles and nanoparticles.

Albumin microparticles containing Ofloxacin (Fluoroquinolone derivative commonly used in hospitals) were formulated by the spray dry method. By decreasing the pump feed rate or the total polymer concentration, a mixture of albumin/hypromellose acetate succinate (HPMCAS) microparticles and nanoparticles (MP/NP), containing Ofloxacin, were formulated. MP/NP were characterized, in vitro (particle size, zeta potential, and encapsulation efficiency). A comparison of the pharmacokinetics and biodistribution of aqueous Ofloxacin and Ofloxacin-loaded MP/NP, in Balb/c mice, revealed that peak concentrations were reduced in the serum, liver, spleen and brain, and a more sustained release was observed in serum and all of the organs tested for Ofloxacin MP/NP, compared to aqueous Ofloxacin. The MP/NP formulation allowed extended release by 24 h in the liver and more than 48 h in the brain. In serum, the elimination rate of Ofloxacin MP/NP is slower, the half life is longer, area under the plasma concentration time curve is decreased and volume of distribution is increased.

A federalist strategy for nuclear waste management.

The federal government plans to rely on a policy of "consultation and concurrence" with state governments in developing nuclear waste repositories. The weaknesses of the concurrence approach are analyzed, and an alternative institutional framework for locating a waste repository is proposed: a siting jury that provides representation for state and local interests, while maintaining a high level of technical review. The proposal could be tested in the siting of away-from-reactor storage facilities for spent nuclear fuel.

Pathogenic characteristics of the Korean 2002 isolate of foot-and-mouth disease virus serotype O in pigs and cattle.

Experimental infection of susceptible cattle and pigs showed that the O/SKR/AS/2002 pig strain of foot-and-mouth disease virus (FMDV) causes an infection that is highly virulent and contagious in pigs but very limited in cattle. Pigs directly inoculated with, or exposed to swine infected with, strain O/SKR/AS/2002 showed typical clinical signs, including gross vesicular lesions in mouth and pedal sites. In addition, FMDV was isolated from, and FMDV genomic RNA was detected in, blood, serum, nasal swabs and oesophageal-pharyngeal (OP) fluid early in the course of infection. Antibodies against the non-structural protein (NSP) 3ABC were detected in both directly inoculated and contact pigs, indicating active virus replication. In contrast, the disease in cattle was atypical. After inoculation, lesions were confined to the infection site. A transient viraemia occurred 1 and 2 days after inoculation, and this was followed by the production of antibodies to NSP 3ABC, indicating subclinical infection. No clinical disease was seen, and no antibodies to NSP 3ABC were present in contact cattle. Additionally, no virus or viral nucleic acid was detected in blood, nasal swab and OP fluid samples from contact cattle. Thus, the virus appeared not to be transmitted from infected cattle to contact cattle. In its behaviour in pigs and cattle, strain O/SKR/AS/2002 resembled the porcinophilic FMDV strain of Cathay origin, O/TAW/97. However, the latter, unlike O/SKR/AS/2002, has reduced ability to grow in bovine-derived cells. The porcinophilic character of O/TAW/97 has been attributed to a deletion in the 3A coding region of the viral genome. However, O/SKR/AS/2002 has an intact 3A coding region.

Efficacy of a high quality O1/Campos foot-and-mouth disease vaccine upon challenge with a heterologous Korean O Mya98 lineage virus in pigs.

In 2010 serotype O foot-and-mouth disease virus of the Mya98 lineage/SEA topotype spread into most East Asian countries. During 2010-2011 it was responsible for major outbreaks in the Republic of Korea where a monovalent O/Manisa vaccine (belonging to the ME-SA topotype) was applied to help control the outbreaks. Subsequently, all susceptible animals were vaccinated every 6 months with a vaccine containing the O/Manisa antigen. Despite vaccination, the disease re-occurred in 2014 and afterwards almost annually. This study focuses on the in vivo efficacy in pigs of a high quality monovalent commercial O1/Campos vaccine against heterologous challenge with a representative 2015 isolate from the Jincheon Province of the Republic of Korea. Initially, viral characterizations and r1 determinations were performed on six viruses recovered in that region during 2014-2015, centering on their relationship with the well characterized and widely available O1/Campos vaccine strain. Genetic and antigenic analysis indicated a close similarity among 2014-2015 Korean isolates and with the previous 2010 virus, with distinct differences with the O1/Campos strain. Virus neutralisation tests using O1/Campos cattle and pig post vaccination sera and recent Korean outbreak viruses predicted acceptable cross-protection after a single vaccination, as indicated by r1 values, and in pigs, by expectancy of protection. In agreement with the in vitro estimates, in vivo challenge with a selected field isolate indicated that O1/Campos primo vaccinated pigs were protected, resulting in a PD50 value of nearly 10. The results indicated that good quality oil vaccines containing the O1/Campos strain can successfully be used against isolates belonging to the O Mya98/SEA topotype.

Why alpha-antiplasmin must be converted to a derivative form for optimal function.

BACKGROUND: Human alpha(2)-antiplasmin (alpha(2)AP), the primary inhibitor of fibrinolysis, is secreted from the liver into plasma as a 464-residue protein with Met as the N-terminus. An R6W polymorphism has been suggested to affect fibrinolytic rate. Within circulating blood, antiplasmin-cleaving enzyme (APCE) cleaves Met-alpha(2)AP(R6) faster than Met-alpha(2)AP(W6) at the Pro12-Asn13 bond to yield Asn-alpha(2)AP. OBJECTIVES: To compare Met-alpha(2)AP(R6), Met-alpha(2)AP(W6) and Asn-alpha(2)AP for crosslinking with fibrin and the ability to protect fibrin from digestion by plasmin. METHODS AND RESULTS: Asn-alpha(2)AP utilizes Gln2 (Gln14 in Met-alpha(2)AP) to become crosslinked to fibrin approximately twelvefold faster than Met-alpha(2)AP(R6) or Met-alpha(2)AP(W6), and this enhances the resistance of fibrin to plasmin. All three forms of alpha(2)AP inhibit plasmin at identical rates. The N-terminal 12-residue peptide of Met-alpha(2)AP slows crosslinking of Met-alpha(2)AP(R6) or Met-alpha(2)AP(W6) by limiting access of factor XIIIa to Gln14 rather than shifting crosslinking to other Gln residues. Edman sequencing and mass analyses of tryptic peptides from each alpha(2)AP crosslinked with 5-(biotinamido)pentylamine showed Gln14 as the only major crosslinking site. Residues 5-8, GRQL in Met-alpha(2)AP(R6), and residues 1-8, MEPLGWQL in Met-alpha(2)AP(W6), slow fibrin crosslinking. CONCLUSION: Gln14 in both Met-alpha(2)AP(R6) and Met-alpha(2)AP(W6) is sheltered by the N-terminal 12-residue peptide, which, when cleaved, yields Asn-alpha(2)AP, which is rapidly crosslinked to fibrin and maximally protects it from plasmin. The R6 W polymorphism in Met-alpha(2)AP does not affect its crosslinking to fibrin, but it does slow cleavage by APCE and reduces the amount of Asn-alpha(2)AP available for rapid crosslinking to fibrin.