Understanding the long-term impact of incident osteoporotic fractures on healthcare utilization and costs in Korean postmenopausal women.

This study provides long-term evidence that healthcare resource utilization and costs of care in women who experienced incident osteoporotic fractures remained higher than those in women without fractures over a span of 5 years. These findings emphasize the importance of early diagnostics and treatment for osteoporosis. PURPOSE: To evaluate healthcare resource utilization (HCRU) and costs of care over 5 years after the incident osteoporotic fractures (OF) in postmenopausal women. METHODS: We used data from the National Health Insurance Service databases 2011-2018. Women aged ≥ 50 years with incident OF (OF group) were matched to women without OF (non-OF group). HCRU (inpatient, outpatient, and emergency room [ER] visits) and costs of care (inpatient, outpatient, and ER visits) during the 5-year follow-up period were derived after propensity score matching (PSM). Additionally, we identified women with subsequent fractures within the first 2 years after the incident OF. RESULTS: After PSM, 47,238 OF and 134,813 non-OF women were identified. HCRU rates and costs of care were highest in the first year after OF and decreased substantially, but remained higher in the OF group during the entire follow-up period. The increase in cumulative HCRU rates over 5 years was highest in inpatient admissions with ER visits (138% higher in OF vs non-OF). The cumulative total costs over 5 years were 73% higher in the OF group than in the non-OF group, which was mostly driven by inpatient costs. Trends were similar for women with subsequent fractures, but they generally showed higher HCRU and costs than those in the total OF group. CONCLUSION: OF imposes a substantial and sustained economic burden on women, resulting in an approximately twofold increase in the cumulative cost over 5 years compared to women without fracture, which highlights the need for early diagnostics and treatment of osteoporosis.

Estimating the economic burden of osteoporotic fractures in a multinational study: a real-world data perspective.

Fracture-related costs vary by country. A standardized methodology and presentations were proposed to fairly assess the economic burden of osteoporotic fracture. Results indicated substantial costs of osteoporotic fractures for pharmacy, hospitalization, emergency care, and outpatient visits in women aged ≥ 50 years in Australia, Germany, South Korea, Spain, and the USA. PURPOSE: The objective of this multinational, retrospective matched cohort study was to use a standardized methodology across different healthcare systems to estimate the burden of osteoporotic fracture (OF) in women aged ≥ 50 years in Australia, Germany, South Korea, Spain, and the USA. METHODS: Within each country, healthcare resource utilization and direct costs of care were compared between patients with newly identified OF and a propensity score-matched cohort without OF during follow-up periods of up to 5 years. RESULTS: Across all five countries, the OF cohort had significantly higher rates and length of inpatient admissions compared with the non-OF cohort. In each country, the adjusted total costs of care ratio between OF and non-OF cohorts were significant. The adjusted cost ratios for pharmacy, inpatient care, emergency care, and outpatient visits were similarly higher in the OF cohort across countries. CONCLUSION: The current study demonstrates the substantial economic burden of OF across different countries when compared with matched non-OF patients. The findings would assist stakeholders and policymakers in developing appropriate health policies.

Sphingolipid identification and skin barrier recovery capacity of a milk sphingolipid-enriched fraction (MSEF) from buttermilk powder.

OBJECTIVE: In this study, we isolated the milk sphingolipid-enriched fraction (MSEF) of sweet buttermilk powder and conducted a clinical trial for evaluating its efficacy in skin barrier recovery. METHODS: Milk sphingolipid-enriched fraction was isolated via solvent extraction of buttermilk powder, and further concentrated by removing the phospholipids and neutral lipids. A cream containing 1% MSEF was used during clinical trials to assess for water holding and skin barrier recovery capacities. RESULTS: The main components of the MSEF were sphingomyelin, glucosylceramide and lactosylceramide, confirmed by TLC, HPLC, MS and NMR. The MSEF cream-treated group had a significantly higher (P < 0.05) water holding capacity, compared with the base cream (vehicle) group. Compared with that in the base cream group, transepidermal water loss (TEWL) recovery increased in the presence of the sphingolipid-containing MSEF cream (MSEF group), with a significant difference (P < 0.05) recorded on day 14. CONCLUSION: The MSEF cream contributed to improving the water holding capacity and skin barrier recovery of damaged skin. Therefore, sphingolipid-containing MSEF can be useful for strengthening or repairing skin barrier function.

OBJECTIF: Dans la présente étude, nous avons isolé la fraction enrichie en sphingolipides du lait (milk sphingolipid-enriched fraction, MSEF) du lait de baratte doux en poudre et mené un essai clinique pour évaluer l'efficacité de la récupération de la barrière cutanée. MÉTHODES: La fraction enrichie en sphingolipides du lait est isolée par l'extraction de solvant du lait de baratte en poudre, et ensuite concentrée en enlevant les phospholipides et les lipides neutres. Une crème contenant un pourcent (1%) de la fraction enrichie en sphingolipides du lait (MSEF) est utilisée pendant des essais cliniques visant à évaluer les capacités de la rétention d'eau et de la récupération de la barrière cutanée. RÉSULTATS: Les principales composantes de la fraction enrichie en sphingolipides du lait (MSEF) étaient la sphingomyéline, la glucosylcéramide, et le lactosylcéramide, confirmées par la chromatographie sur couche mince (TLC), la chromatographie liquide à haute performance (CLHP), la spectrométrie de masse (MS) et la RMN(NMR). La groupe traitée par la crème enrichie en sphingolipides du lait (MSEF) avait une capacité de la rétention d'eau beaucoup plus élevée (P < 0.05), par rapport au groupe utilisant la crème de base (véhicule). Comparé au groupe utilisant la crème de base, la récupération de la perte d'eau transépidermique (TEWL) a augmenté en présence de la fraction enrichie en sphingolipides du lait (MSEF), avec une différence significative (P < 0.05) enregistrée au 14ème jour. CONCLUSION: La crème enrichie en sphingolipides du lait (MSEF) a contribué à améliorer les capacités de la rétention d'eau et de la récupération de la barrière cutanée de la peau endommagée. Par conséquent, la fraction enrichie en sphingolipides du lait (MSEF) peut être utile pour renforcer ou réparer la fonction de barrière cutanée.

Disc degeneration induces a mechano-sensitization of disc afferent nerve fibers that associates with low back pain.

OBJECTIVE: We aimed to investigate mechano-sensitivity at the afferent nerve fibers projecting to degenerated intervertebral disc (IVD) and nociceptive behaviour in a rat model of low back pain (LBP). DESIGN: Animal model with LBP was established by lumbar 4/5 IVD puncture and nucleus pulposus aspiration. In vivo single nerve recordings (n = 121) were introduced to measure discharge frequency at the afferent nerve fiber innervating the IVD during mechanical stimulations (von Frey filament or intradiscal pressure). Nerve growth factor (NGF) expression levels in the IVD (n = 20) were assessed by Western blot. LBP-related behaviour (n = 22) was assessed by measuring changes in rearing, mechanical paw-withdrawal threshold, and dynamic weight bearing in a freely walking rat. Inhibitory effect of morphine on the neuronal excitability (n = 19) and painful behaviour (n = 28) was also assessed. RESULTS: Compared to those with sham or naïve IVD, animal group with degenerated IVD displayed the sensitized neuronal responses and painful behaviour, with hyperexcitability of the afferent nerve fibers in any range of mechanical stimulations (von Frey filament stimulation; 1, 2, and 26 g; intradiscal pressure, 1,500-3,000 mm Hg), strong upregulation of NGF (200-250 % increase), and LBP-like behaviour such as failure of rearing, front limbs-dependent walking pattern, and hypersensitivity in hind-paws. However, the neuronal hyperexcitability and pain behaviour were attenuated after local (30 µM) or systemic (3 mg kg-1) morphine administration. CONCLUSIONS: Our study suggests that enhanced mechano-sensitivity at the afferent nerve fiber innervating degenerated IVD is deeply correlated with LBP development, which supports the hypothesis that hyperexcited responses at the nerve fibers represent a decisive source of LBP.

Antihistamine use and the risk of injurious falls or fracture in elderly patients: a systematic review and meta-analysis.

Despite their anticholinergic side effects, first-generation antihistamines are widely prescribed to elderly patients. A systematic review was conducted to synthesize real-world evidence. First-generation antihistamine use is considerably associated with an increased risk of injurious falls or fracture among the elderly. INTRODUCTION: First-generation antihistamines are considered potentially inappropriate for elderly patients owing to anticholinergic side effects. We aimed to determine whether elderly patients taking antihistamines are at increased risk of injurious falls or fracture. METHODS: We identified studies in MEDLINE, EMBASE, and several local databases through November 2016. Observational studies on the association between antihistamine use and the risk of injurious falls or fracture were selected. Quality of the studies and the level of evidence were assessed. The random-effects model was employed for meta-analysis, and heterogeneity was examined based on I-square and Cochrane's Q test. Subgroup analyses were performed when the heterogeneity among studies could not be explained. RESULTS: From 473 identified studies, five (three case-control studies, one cohort study, and one case-crossover study) were included in our analysis based on eligibility criteria. First-generation antihistamine use showed significantly increased risk of injurious falls or fracture (odds ratio [OR] 2.03, 95% confidence interval [CI] 1.49-2.76, heterogeneity: p = 0.41, I2 = 0%). Studies including antihistamines of all generations or containing no generation information were dealing with falls during hospitalization. Among these studies, the association was statistically significant without heterogeneity (OR 2.89, 95% CI 1.71-4.89, heterogeneity: p = 0.42, I2 = 0%). Due to the small number of studies included and unadjusted results, meaningful interpretation based on subgroup analysis was limited. CONCLUSIONS: First-generation antihistamine use is considerably associated with increased risk of injurious falls or fracture among the elderly. Clinicians need to exercise caution when prescribing first-generation antihistamines to elderly patients.

Analysis of the number of enlarged pores according to site, age, and sex.

BACKGROUND: Increasing the number of enlarged pores causes cosmetic problems. The difference in the number of enlarged pores according to facial site, age, and sex is unclear. OBJECTIVE: To analyze the distribution of the number of enlarged pores according to facial site, age, and sex. METHODS AND MATERIALS: We analyzed the number of the enlarged pores and the percentage of wrinkles in the nose, forehead, and cheek from 434 polarized images. The measurement results were analyzed according to site, age, and sex. Relationship between enlarged pore counts and wrinkle severity was also analyzed. The study was conducted by using DermaVision,™ which can take cross-polarization, parallel polarization, and ultraviolet light images. RESULTS: The enlarged pores of the nose and forehead were more prominent than in the cheeks. Pore counts were increased with age, and the increment was significant between the 30's and 40's. There was no significant difference by gender. Enlarged pore counts were related to wrinkle severity. CONCLUSIONS: The number of enlarged pores differs depending on body site and increased with age. The enlarged pore counts correlate with wrinkle severity and the correlation varies depending on the body site.

The Processing Time for Recanalization and Size of Ischemic Lesions on DWI is Related With Complete Reperfusion After Mechanical Thrombectomy.

Recent studies demonstrated that modified thrombolysis in cerebral infarction (TICI) 3 reperfusion have better functional outcomes than modified TICI 2b after mechanical thrombectomy in acute ischemic stroke with large vessel occlusion. The purpose of this study was to determine significant factors to forecast the presence of complete reperfusion after mechanical thrombectomy based on multimodal magnetic resonance imaging (MRI). We investigated 96 consecutive patients with acute large intracranial artery occlusion of anterior circulation who based on multimodal MRI. Also, we compared clinical and radiologic parameters between patients with modified TICI 3 and those with modified TICI 0-2b. Among 96 eligible subjects received mechanical thrombectomy, 39 patients (40.6%) showed complete reperfusion and 57 partial or nonreperfusion (mTICI 2b-26, mTICI 2a-9, mTICI 1-8, and mTICI 0-14) after mechanical thrombectomy. Patients with mTICI 3 had significantly smaller initial Diffusion weighted images (DWI) lesion volume (P < .01) and much shorter time interval from onset to reperfusion (P < .01) than those patients with mTICI (0-2b). In multivariate analysis, smaller initial DWI volume (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.23-2.57; P < .01) and faster reperfusion time (OR, 1.07; 95% CI 1.01-1.14; P = .015) had an independence significance for complete reperfusion after mechanical thrombectomy. In this study, the ischemic lesion volume on DWI and faster processing time are critical factor to predict the state of complete reperfusion after mechanical thrombectomy.

Antimelanogenic effects of luteolin 7-sulfate isolated from Phyllospadix iwatensis Makino.

BACKGROUND: Abnormal deposition of melanin may cause an aesthetic skin problem; therefore, the control of unwanted excessive melanin synthesis is the major goal of cosmetic research. OBJECTIVES: To identify novel tyrosinase (TYR) inhibitors from marine plants and examine their cellular antimelanogenic effects. METHODS: The extracts of 50 marine plants endemic to Korea were screened against human TYR. Active constituents were then isolated from the selected plant extracts that showed potential and their chemical structures elucidated. Furthermore, their antimelanogenic effects were examined using murine melanoma B16/F10 cells and human epidermal melanocytes (HEM). RESULTS: Among the tested extracts, that of Phyllospadix iwatensis Makino exhibited the strongest human TYR inhibitory activity. The active constituents were purified from the butanol fraction of the P. iwatensis extract and identified as hispidulin 7-sulfate and luteolin 7-sulfate. Luteolin 7-sulfate inhibited human TYR more strongly than hispidulin 7-sulfate, luteolin, hispidulin and arbutin. Furthermore, luteolin 7-sulfate showed lower cytotoxicity than luteolin in both B16/F10 cells and HEM. Luteolin 7-sulfate attenuated cellular melanin synthesis more effectively in B16/F10 cells and HEM stimulated by α-melanocyte-stimulating hormone and l-tyrosine than arbutin. CONCLUSIONS: This study demonstrates that luteolin 7-sulfate isolated from P. iwatensis is a human TYR inhibitor with advantageous antimelanogenic properties, and would be useful for development as a therapeutic agent for the control of unwanted skin pigmentation.

Investigation of Werner protein as an early DNA damage response in actinic keratosis, Bowen disease and squamous cell carcinoma.

BACKGROUND: Werner protein (WRN) has DNA helicase activity and participates in recombination, replication and repair of DNA. Loss-of-function mutations in WRN gives rise to genetic instability and diseases such as premature ageing and cancer. Upregulation of WRN promotes proliferation and survival of cancer cells. AIM: To evaluate the expression pattern of WRN in closely related skin cancers and their correlation with age, sex and UV exposure. METHODS: Immunohistochemistry was used to investigate expression of WRN in formalin-fixed, paraffin wax-embedded tissue specimens of 9 squamous cell carcinoma (SCC), 15 actinic keratosis (AK), 11 Bowen disease (BD) and 11 normal-appearing peripheral tissue samples, obtained from patients during surgical resections. RESULTS: WRN expression was significantly increased in BD, AK and SCC compared with normal controls, with the mean WRN staining score being highest in BD, followed by AK and SCC. However, age, sex and sun exposure were not associated with WRN expression. CONCLUSIONS: To our knowledge, this is the first report to date investigating the expression of WRN in skin cancers. The overtly high expression of WRN in premalignant lesions and in in situ cancer, with relatively low WRN expression in SCC, may indicate that WRN contributes as a checkpoint for early DNA damage response in skin tumorigenesis.

Improving acne keloidalis nuchae with targeted ultraviolet B treatment: a prospective, randomized, split-scalp comparison study.

BACKGROUND: Acne keloidalis nuchae (AKN) is a chronic scarring folliculitis with fibrotic papules on the occipital scalp. Its treatment is limited and unsatisfactory. OBJECTIVES: To determine whether targeted ultraviolet B (tUVB) phototherapy will (i) improve the clinical appearance of AKN and (ii) induce extracellular matrix remodelling in affected lesions. METHODS: Eleven patients with AKN were enrolled in a prospective, randomized, split-scalp comparison study. One randomly selected side of the scalp was treated with tUVB up to three times weekly for 8 weeks. After week 8, both sides were treated for eight additional weeks. Assessment included lesion counts in two 3 × 3-cm regions of interest (ROIs), one on each side of the scalp (ROI-1: tUVB weeks 0-16, ROI-2: tUVB weeks 9-16), patient self-assessment and analysis of MMP1, MMP9, TGFB1 and COL1A1 mRNA expression by quantitative reverse-transcription polymerase chain reaction. RESULTS: Before treatment, the mean lesion count was similar between tUVB-treated and untreated sides (14·8 vs. 15·0). After 8 weeks of tUVB, the mean lesion count decreased significantly to 9·4 ± 1·2 (P =  0·03), with no change on the untreated side. With continued treatment, the mean lesion count in ROI-1 decreased further to 7 ± 1·5 (P = 0·04) after 16 weeks of tUVB. CONCLUSIONS: tUVB significantly improved the clinical appearance of AKN, led to patient satisfaction and was well tolerated.

Associations between the GNB3 C825T polymorphism and obesity-related metabolic risk factors in Korean obese women.

PURPOSE: It is important to identify a 'metabolically unhealthy obese' subset with higher cardiovascular risk among obese individuals. We investigated the associations between the GNB3 C825T polymorphism and obesity-related metabolic risk factors among Korean obese women. METHODS: This study was a sub-investigation of a double-blind randomized controlled trial that examined the additive effect of or list at on weight loss with sibutramine. A sample of 111 obese women were divided into T-carriers (CT/TT) or a homozygous CC group, according to the presence of the 825T allele at GNB3. These groups were compared to determine their associations with obesity-related metabolic risk factors, i.e., fasting plasma glucose, serum lipids, serum insulin/insulin resistance, and abdominal fat amounts. RESULTS: The allele frequencies of the GNB3 polymorphism were C allele = 59.5% and T allele = 40.5%. The T allele was found to be significantly associated with greater visceral fat and higher serum lipids, and these significances remained robust after adjusting for potential covariates. CONCLUSIONS: The GNB3 825T polymorphism is significantly associated with greater visceral fat and higher serum lipids in Korean obese women and it suggests that the GNB3 C825T is a determinant of obesity-related metabolic traits in this population.

Effect of the G-protein ß3 subunit 825T allele on the change of body adiposity in obese female.

No clinical studies on the lipolytic effect of guanine nucleotide-binding protein ß3 subunit gene (GNB3) 825T polymorphism have been performed. This study was a subinvestigation of a 12-week randomized controlled trial (NCT01184560) for the additive effect of orlistat on sibutramine treatment. The analysis involved 101 obese females aged 18-49 years, genotyped at the GNB3 825 locus. To exclude any influence from potential confounders, we used an analysis of covariance model. After the intervention, fat mass proportion in total weight loss was significantly lower in subjects with a T allele than in those without a T allele (p = 0.034). GNB3 825T allele was associated with blunted fat mass reduction in obese females.

To restrict or not to restrict? Practical considerations for optimizing dietary protein interactions on levodopa absorption in Parkinson's disease.

Administration of levodopa for Parkinson's disease (PD) has remained the most effective therapy for symptom management despite being in use for over 50 years. Advancing disease and age, changing tolerability and gastrointestinal (GI) dysfunction may result in change in dietary habits and body weight, as well as unpredictable motor fluctuations and dyskinesias. Dietary proteins which convert into amino acids after digestion are implicated as major factors that inhibit levodopa absorption. For people living with PD (PwP) who experience motor fluctuations, low protein diets (LPD) and protein redistribution diets (PRD) may be effective and are often recommended as a non-pharmacologic approach for improving levodopa bioavailability. However, there is a lack of consensus on a standard definition of these diets and appropriate treatment algorithms for usage. This may be due to the paucity of high-level evidence of LPD and PRD in PwP and whether all or specific subgroups of patients would benefit from these strategies. Managing diet and protein intake with proper education and monitoring may reduce complications associated with these diets such as dyskinesias and unintentional weight loss. Additionally, alterations to medications and GI function may alter levodopa pharmacokinetics. In this narrative review we focus on 1) mechanisms of dietary protein and levodopa absorption in the intestine and blood brain barrier, 2) dietetic approaches to manage protein and levodopa interactions and 3) practical issues for treating PwP as well as future directions to be considered.

The use of drug-eluting stents in the management of transplant renal artery stenosis.

Transplant renal artery stenosis (TRAS) is a common occurrence following kidney transplantation with an incidence rate ranging from 6% to 23%. A single-center retrospective study was conducted to examine the use of drug-eluting stents (DES) in eligible patients with hemodynamically significant TRAS. Between March 2008 and January 2011, 12 patients were diagnosed with TRAS with reference vessel diameter measuring <5 mm and underwent endovascular intervention (EVI) with DES placement. TRAS was detected within the first year posttransplantation in a majority of these patients (83%) and manifested as hypertension (100%), allograft dysfunction (100%) and edema (58%). Procedural success rate was 100%. Patients were followed for a mean period of 16 ± 10 months. Blood pressure improved from a mean of 156/82 to 138/73 mmHg at the end of the follow-up period. In 11/12 patients, serum creatinine improved from 3.1 ± 1.3 mg/dL to 2.3 ± 0.5 mg/dL at the end of the follow-up period. TRAS of early onset is readily amenable to EVI with stent placement resulting in improvement in blood pressure control and allograft function.

Cannabinoid receptor expression in HIV encephalitis and HIV-associated neuropathologic comorbidities.

AIMS: Cannabinoids have been proposed for treating various neurodegenerative disorders and as adjunct therapy for HIV+ patients with neurologic sequelae. The expression of cannabinoid receptors (CB1 and CB2) has been reported in neurodegenerative diseases and in simian immunodeficiency virus encephalitis, yet the receptor expression in the central nervous system of HIV+ individuals is not known. METHODS: An anti-CB1 antibody and two anti-CB2 antibodies were employed for immunohistochemistry in the cerebral cortex and white matter of HIV encephalitis (HIVE) and HIV-associated comorbidities, as well as control brains (HIV- and HIV+). RESULTS: By quantitative image analysis, we observed that CB1 was increased in HIVE brains and those with comorbidities, while CB2 was significantly increased in the white matter of HIVE. Morphologically, CB1 was present in neurones, and both CB1 and CB2 were present in meningeal macrophages and subpial glia in all brains. In HIVE, CB1 was found in white matter microglia and perivascular cells, while CB2 was increased in microglia, astrocytes and perivascular macrophages. Double immunofluorescence with cell-specific markers and immunoblots on primary cultured microglia and astrocytes substantiated the glial localization of the cannabinoid receptors and specificity of the antibodies. CONCLUSIONS: Our study indicates that cannabinoid receptor expression occurs in glia in HIVE brains, and this may have ramifications for the potential use of cannabinoid ligands in HIV-infected patients.

The cytoplasmic domains of immunoglobulin (Ig) alpha and Ig beta can independently induce the precursor B cell transition and allelic exclusion.

In mature B cells, signals transduced through membrane immunoglobulin (Ig) produce cellular activation, yet the same receptor can also mediate deletion and silencing of autoreactive B cells. In addition, Ig expression during the antigen-independent phase of B cell development regulates the precursor B (pre-B) cell transition and allelic exclusion. To account for the diverse regulatory functions induced by membrane Ig, it has been proposed that individual receptor components have independent physiologic activities. Here we establish a role for Ig alpha in the pre-B cell transition and allelic exclusion. We find that the cytoplasmic domain of Ig alpha contains sufficient information to trigger both of these antigen-independent events. Direct comparisons of the cytoplasmic domains of Ig alpha and Ig beta show that the two are indistinguishable in the induction of the pre-B cell transition and allelic exclusion. Our experiments suggest that, despite the reported differences in certain biochemical assays, Ig alpha and Ig beta have redundant functions in the developing B cell.

Normal recombination substrate VH to DJH rearrangements in pre-B cell lines from scid mice.

To further analyze the VDJ recombination defect in lymphoid pre-B cells from mice with severe combined immune deficiency (scid mice), we have assayed the ability of Abelson murine leukemia virus (A-MuLV) transformed pre-B cells from scid mice to rearrange a recombination substrate in which inverted VH to DJH joins activate a selectable (gpt) gene. In unselected populations, substrate rearrangements occurred frequently, but were aberrant and probably analogous to the aberrant rearrangements observed at endogenous scid Ig gene loci. In contrast, populations of scid pre-B lines selected for gpt activity within the substrate contained mostly "normal" VH to DJH joins within the introduced substrate. These findings demonstrate that scid pre-B cells can make normal joins at low efficiency and are discussed with respect to the potential mechanism of the scid defect and the occurrence of Igs in leaky scid mice.