Heterogeneity of Alzheimer's disease identified by neuropsychological test profiling.

Alzheimer's disease (AD) is a highly heterogeneous disorder. Untangling this variability could lead to personalized treatments and improve participant recruitment for clinical trials. We investigated the cognitive subgroups by using a data-driven clustering technique in an AD cohort. People with mild-moderate probable AD from Taiwan was included. Neuropsychological test results from the Cognitive Abilities Screening Instrument were clustered using nonnegative matrix factorization. We identified two clusters in 112 patients with predominant deficits in memory (62.5%) and non-memory (37.5%) cognitive domains, respectively. The memory group performed worse in short-term memory and orientation and better in attention than the non-memory group. At baseline, patients in the memory group had worse global cognitive status and dementia severity. Linear mixed effect model did not reveal difference in disease trajectory within 3 years of follow-up between the two clusters. Our results provide insights into the cognitive heterogeneity in probable AD in an Asian population.

Community and facility-level barriers to achieving UHC in Kono District, Sierra Leone and Maryland County, Liberia.

Universal Health Coverage (UHC) is achieved when individuals and communities receive the health services they need without suffering financial hardship. However, many countries face barriers to building health systems that enable the availability of affordable, accessible care. The goal of this study was to present a model of local monitoring of barriers and to provide a roadmap for designing interventions that improve access to and use of healthcare delivery systems. We conducted household, individual, and health facility surveys in seven catchment areas in Sierra Leone and Liberia between December 2019 and March 2020. A two-stage cluster sampling method was used to sample households and individuals, and all health facilities were included. We divide access barriers into demand (patient-side care seeking behavior), supply (availability of facilities and services), and their intersection (affordability, spending, and use rates). Among the 2,576 respondents within our 1,051 surveyed households, the propensity to seek care when ill was reported at 90% in Sierra Leone (n = 1,283) and 70% in Liberia (n = 806). We estimated that 31% of households spent greater than 10% of their total expenditure on healthcare in a month, and that 14.5% of households spent greater than 25%. Overall, the general service readiness index mean score for all health centers was around 70%. The greatest hindrance to service readiness was the availability of essential medicines, with facilities reporting an average score of 32% in Sierra Leone and 63% in Liberia. Our evidence suggests that the cost of care is both a barrier to care-seeking and a persisting problem among care-seeking patients. Lack of service availability (essential equipment and medicines), poses a risk to high-quality care. The research team recommends deploying interventions (visit cost subsidies, supply chain improvements) targeted at resolving these issues in order to advance the goal of achieving UHC.

Maximize the safety and efficacy of fertility preservation by random start/dual ovarian stimulation for early breast cancer patients.

OBJECTIVE: What is the more efficient and safer protocol during controlled ovarian hyperstimulation (COH) for early-stage breast cancer patients seeking emergency fertility preservation before adjuvant chemo/radiotherapy? MATERIALS AND METHODS: This retrospective, case-series study involved two early-stage (Ia) breast cancer patients that requested for fertility preservation within 3 weeks. Random start/dual stimulation protocols with aromatase inhibitor (AI) were used to maximize oocyte yield and suppress serum estradiol (E2) level. RESULTS: E2 levels on trigger day during dual COH were between 112.0 and 407.0 pg/mL. Duration of COH could be shortened to only 17 days, and up to 41 oocytes were successfully retrieved with two retrievals. CONCLUSION: This remarkable efficient and safe protocol involves the combination of random start/dual stimulation with step-up AI dosage beforehand which not only maximize oocyte yield within the shortest possible timeframe, but also to maintain the low level of E2 to avoid over-stimulating estrogen-sensitive cancer cells and to decrease the risk of developing ovarian hyperstimulation syndrome (OHSS).

Seromucinous Cystadenoma Presenting as Endometriosis Complications in a 57-Year-Old Female: A Case Report.

Endometriosis should be considered when a female patient reports symptoms of severe pain/tenderness in the pelvic area associated with a frequent need for urination, bloating, vomiting, or nausea. Clinical suspicion is increased if the patient has a history of endometriosis. However, many patients with endometriosis can be asymptomatic, which is why physicians and providers must keep an open mind and have a broad differential. Examinations that aid in the diagnosis of endometriosis include but are not limited to a pelvic examination, an ultrasound, magnetic resonance imaging (MRI), and an exploratory laparoscopy. In this case study, we present a 57-year-old postmenopausal female patient who presented to her obstetrics and gynecology (OBGYN) physician with hot flashes and an abnormal ultrasound revealing an ovarian cyst. Seventeen years prior, at the age of 40, the patient was found to have endometriosis and endometrial polyps and underwent a left oophorectomy. Due to the patient's history, symptoms, and current scans, it was assumed that the present cyst was a complication of endometriosis. Ultimately, the cyst, right ovarian cyst wall, right fallopian tube, and uterine fibroids were surgically removed and sent to pathology. Upon further review of the patient's pathology reports, it was found that the cyst removed was a seromucinous cyst with focal borderline features.

Verifying a C-arm-based roentgen stereophotogrammetric analysis protocol for assessing tibial implant movement in total knee arthroplasty.

Roentgen stereophotogrammetric analysis (RSA) is the "gold standard" technique for measuring sub-millimetric relative motion between implant and bone to quantify post-operative implant migration over time. The vast majority of RSA studies addressing implant motion in knee replacements, however, have been conducted using expensive biplanar radiography systems and commercial software that are not readily available at many institutions. In this study, we evaluated the feasibility of performing RSA using ordinary, readily available C-arm fluoroscopes and open-source software to assess tibial component migration.We developed an assessment protocol using a Siemens Arcadis Orbic C-arm and the open-source XROMM software and evaluated its accuracy and precision through a series of phantom-based verification tests. The results were highly promising: accuracies were in the range of - 39 to 11 µm for translations and - 0.025 to 0.029° for rotations, while system precisions ranged between 16 to 27 µm for translations and 0.041 to 0.059° for rotations. This performance is comparable to specialized RSA systems reported in the literature. The proposed RSA protocol is therefore capable of accurately measuring the relative motion of knee replacement implants in phantom scenarios, which justifies further the development of the protocol towards use in prospective clinical assessments of new implant designs and surgical techniques.

Incorporating neck biomechanics in helmet testing: Evaluation of commercially available WaveCel helmets.

BACKGROUND: Cycling helmets often incorporate elements aimed to dissipate rotational energies, which is widely acknowledged to play a key role in concussion mechanics. In this study, we investigated the mechanics of an oblique helmet test protocol that induced helmet rotation while using it to evaluate the effectiveness of three helmet models: two standard expanded polystyrene helmets and a commercially-available helmet equipped with a liner designed to mitigate linear and rotational energies. METHODS: Helmets equipped with WaveCel were tested against two expanded polystyrene helmet models through guided drops using a Hybrid III (HIII) head-and-neck surrogate. The three helmet models were tested across four impact conditions (n = 5) of different speeds and impact surface angles. FINDINGS: Across all tests, a similar sequence of head motion was observed - first a flexion phase followed by an extension phase. The extension phase lacked evidence of biofidelity and was likely attributable to the energy stored in the neckform during the flexion phase; it was therefore neglected from analysis. Results showed WaveCel reduced the probability of AIS2 head injury across all tests (3 to 27% reductions in 4.8 m/s impacts; 36 to 37% reductions in 6.2 m/s impacts). INTERPRETATION: The two-phased response of the HIII suggests that boundary condition selection can influence results and should thus be reported in studies using similar methods. While this protocol involved both axial and tangential impact components and were thus representative of real-world collisions, the efficacy of WaveCel should be further investigated through additional laboratory studies and tracking real-world cycling injury statistics.

The Validity and Reliability of Two Commercially Available Load Sensors for Clinical Strength Assessment.

OBJECTIVE: Handheld dynamometers are common tools for assessing/monitoring muscular strength and endurance. Health/fitness Bluetooth load sensors may provide a cost-effective alternative; however, research is needed to evaluate the validity and reliability of such devices. This study assessed the validity and reliability of two commercially available Bluetooth load sensors (Activ5 by Activbody and Progressor by Tindeq). METHODS: Four tests were conducted on each device: stepped loading, stress relaxation, simulated exercise, and hysteresis. Each test type was repeated three times using the Instron ElectroPuls mechanical testing device (a gold-standard system). Test-retest reliability was assessed through intraclass correlations. Agreement with the gold standard was assessed with Pearson's correlation, interclass correlation, and Lin's concordance correlation. RESULTS: The Activ5 and Progressor had excellent test-retest reliability across all four tests (ICC(3,1) ≥ 0.999, all p ≤ 0.001). Agreement with the gold standard was excellent for both the Activ5 (ρ ≥ 0.998, ICC(3,1) ≥ 0.971, ρc ≥ 0.971, all p's ≤ 0.001) and Progressor (ρ ≥ 0.999, ICC(3,1) ≥ 0.999, ρc ≥ 0.999, all p's ≤ 0.001). Measurement error increased for both devices as applied load increased. CONCLUSION: Excellent test-retest reliability was found, suggesting that both devices can be used in a clinical setting to measure patient progress over time; however, the Activ5 consistently had poorer agreement with the gold standard (particularly at higher loads).

Serum levels of alpha1-antitrypsin isoforms in patients with ovarian clear cell carcinoma: An exploratory study.

BACKGROUND: Ovarian clear cell carcinoma (OCCC) is frequently associated with endometriosis. Since serum levels of cancer antigen 125 (CA125) have limited diagnostic and prognostic value in this malignancy, there is an unmet need for reliable and specific biomarkers. Previous findings indicated that alpha 1-antitrypsin isoforms (isoAAT) are significantly increased in the peritoneal fluid of patients with endometriosis. This study was undertaken to examine whether serum isoAAT levels in patients with OCCC differ from those measured in women with endometriosis or benign ovarian tumors. We also investigated whether this biomarker may be useful for predicting survival in OCCC. METHODS: Paired serum samples before and after debulking surgery were collected from 27 patients with OCCC. All sera from patients with endometriosis (n = 44) and benign ovarian tumors (n = 32) were obtained in the pretreatment phase. Serum isoAAT levels were assayed using a proprietary ELISA kit. RESULTS: The highest levels of serum isoAAT (median, range) were identified in patients with OCCC (preoperative values: 160.9 ng/mL, range, 101.4-1098.8 ng/mL), followed by patients with endometriosis (125.0 and 83.4-473.2 ng/mL), and those with benign tumors (125.2 and 60.5-191.3 ng/mL). The differences in serum isoAAT levels between patients with OCCC and benign tumors were significant (p = 0.041). Debulking surgery of OCCC resulted in a significant decrease in serum isoAAT levels compared with the preoperative period (median, 160.9 versus 113.0 ng/mL, respectively, p = 0.012). As for prognostic prediction, we found that none of the nine patients with OCCC and serum isoAAT levels ≤130 ng/mL died of disease. CONCLUSION: Serum isoAAT levels may be diagnostically useful to distinguish OCCC from benign ovarian tumors and could also serve as a potential prognostic marker.

Orthopaedic Surgeon Brain Radiation During Fluoroscopy: A Cadaver Model.

BACKGROUND: The aims of this study were to quantify exposure of the surgeon's brain to radiation during short cephalomedullary (SC) nailing, to extrapolate lifetime dose, and to determine the effects of personal protective equipment (PPE) on brain dose. METHODS: Two cadaveric specimens were used: (1) a whole cadaveric body representing the patient, with a left nail inserted to act as the scatter medium, and (2) an isolated head-and-neck cadaveric specimen representing a surgeon, with radiation dosimeters placed in specific locations in the brain. The "patient" cadaver's left hip was exposed in posteroanterior and lateral radiographic planes. Measurements were performed without shielding of the head-and-neck specimen and then repeated sequentially with different PPE configurations. An average surgeon career was estimated to be 40 years (ages 25 to 65 years) with the caseload obtained from the department's billing data. RESULTS: The mean radiation dose to the surgeon brain without PPE was 3.35 µGy (95% confidence interval [CI]: 2.4 to 4.3) per nail procedure. This was significantly reduced with use of a thyroid collar (2.94 µGy [95% CI: 1.91 to 3.91], p = 0.04). Compared with use of the thyroid collar in isolation, there was no significant additional reduction in radiation when the collar was used with leaded glasses (2.96 µGy [95% CI: 2.15 to 3.76], p = 0.97), with a lead cap (3.22 µGy [95% CI: 2.31 to 4.13], p = 0.55), or with both (2.31 µGy [95% CI: 1.61 to 3.01], p = 0.15). The extrapolated lifetime dose over 40 working years for SC nailing without PPE was 2,146 µGy (95% CI: 1,539 to 2,753), with an effective dose of 21.5 µSv. CONCLUSIONS: The extrapolated cumulative lifetime radiation to a surgeon's brain from SC nailing based on our institution's workload and technology is low and comparable with radiation during a one-way flight from London to New York. Of note, we studied only one of many fluoroscopy-aided procedures and likely underestimated total lifetime exposure if exposures from other procedures are included. This study also demonstrates that thyroid collars significantly reduce brain dose for this procedure whereas other head/neck PPE such as lead caps appear to have minimal additional effect. This study provides a methodology for future studies to quantify brain dose for other common orthopaedic procedures. CLINICAL RELEVANCE: This study, based on our institutional data, demonstrates that although the lifetime brain dose from SC nailing is low, thyroid collars significantly reduce this dose further. As such, in accordance with the "as low as reasonably achievable" radiation exposure principle, radiation safety programs and individual surgeons should consider use of thyroid collars in this setting.

Computational analysis for identification of the extracellular matrix molecules involved in endometrial cancer progression.

Recurrence and poorly differentiated (grade 3 and above) and atypical cell type endometrial cancer (EC) have poor prognosis outcome. The mechanisms and characteristics of recurrence and distal metastasis of EC remain unclear. The extracellular matrix (ECM) of the reproductive tract in women undergoes extensive structural remodelling changes every month. Altered ECMs surrounding cells were believed to play crucial roles in a cancer progression. To decipher the associations between ECM and EC development, we generated a PAN-ECM Data list of 1516 genes including ECM molecules (ECMs), synthetic and degradation enzymes for ECMs, ECM receptors, and soluble molecules that regulate ECM and used RNA-Seq data from The Cancer Genome Atlas (TCGA) for the studies. The alterations of PAN-ECM genes by comparing the RNA-Seq expressions profiles of EC samples which have been grouped as tumorigenesis and metastasis group based on their pathological grading were identified. Differential analyses including functional enrichment, co-expression network, and molecular network analysis were carried out to identify the specific PAN-ECM genes that may involve in the progression of EC. Eight hundred and thirty-one and 241 PAN-ECM genes were significantly involved in tumorigenesis (p-value <1.571e-15) and metastasis (p-value <2.2e-16), respectively, whereas 140 genes were in the intersection of tumorigenesis and metastasis. Interestingly, 92 of the 140 intersecting PAN-ECM genes showed contrasting fold changes between the tumorigenesis and metastasis datasets. Enrichment analysis for the contrast PAN-ECM genes indicated pathways such as GP6 signaling, ILK signaling, and interleukin (IL)-8 signaling pathways were activated in metastasis but inhibited in tumorigenesis. The significantly activated ECM and ECM associated genes in GP6 signaling, ILK signaling, and interleukin (IL)-8 signaling pathways may play crucial roles in metastasis of EC. Our study provides a better understanding of the etiology and the progression of EC.

Decreased Level of Neurotrophic Factor Neuritin 1 in Women with Ovarian Endometriosis after Receiving Gonadotropin-Releasing Hormone Agonist Treatment.

This study aimed to investigate the effect of gonadotropin-releasing hormone agonist (GnRHa) treatment on the expression of neuritin 1 (NRN1) in women with ovarian endometriosis. We collected tissues and serum from women with endometriosis treated with (n = 45) or without (n = 37) GnRHa. NRN1 mRNA and protein levels were measured using qPCR and Western blot. Immunolocalization of NRN1 in endometriotic tissues was examined using immunohistochemistry. In addition, a follow-up study was carried out to monitor the serum level of NRN1 in patients before and after GnRHa treatment. Both mRNA (p = 0.046) and protein (p = 0.0155) levels of NRN1 were significantly lower in endometriotic tissues from patients receiving GnRHa treatment compared to the untreated group. Both epithelial and stromal cells of endometriotic tissues from untreated women with endometriosis exhibited stronger staining of NRN1 but not in those who were treated with GnRHa. The follow-up study showed that the serum level of the NRN1 concentration decreased significantly from 1149 ± 192.3 to 379.2 ± 80.16 pg/mL after GnRHa treatment (p = 0.0098). The expression of NRN1 was significantly lower in women with ovarian endometriosis treated with GnRHa. These results suggest that NRN1 may be a biomarker response to the effect of GnRHa treatment for patients with ovarian endometriosis.

Gelatin-epigallocatechin gallate nanoparticles with hyaluronic acid decoration as eye drops can treat rabbit dry-eye syndrome effectively via inflammatory relief.

INTRODUCTION: Dry-eye syndrome (DES) is a general eye disease. Eye drops are the common ophthalmological medication. However, the ocular barrier makes it difficult to attain high drug bioavailability. Nanomedicine is a promising alternative treatment for ocular diseases and may increase drug content in the affected eye. METHODS: To explore this potential, we constructed nanoparticles (NPs) containing an anti-inflammatory agent for DES treatment. The NPs were made of gelatin-epigallocatechin gallate (EGCG) with surface decoration by hyaluronic acid (HA) and designated "GEH". The particle size, surface charge, and morphology were evaluated. The in vitro biocompatibility and anti-inflammation effect of nanoparticles were assayed via culturing with human corneal epithelium cells (HCECs) and in vivo therapeutic effect was examined in a DES rabbit's model. RESULTS: The synthesized GEH NPs had a diameter of approximately 250 nm and were positively charged. A coculture experiment revealed that 20 µg/mL GEH was not cytotoxic to HCECs and that an EGCG concentration of 0.2 µg/mL downregulated the gene expression of IL1B and IL6 in inflamed HCECs. Large amounts of GEH NPs accumulated in the cytoplasm of HCECs and the ocular surfaces of rats and rabbits, indicating the advantage of GEH NPs for ocular delivery of medication. Twice-daily topical treatment with GEH NPs was performed in a rabbit model of DES. The ocular surface of GEH-treated rabbits displayed normal corneal architecture with no notable changes in inflammatory cytokine levels in the cornea lysate. The treatment improved associated clinical signs, such as tear secretion, and fluorescein staining recovered. CONCLUSION: We successfully produced GEH NPs with high affinity for HCECs and animal eyes. The treatment can be delivered as eye drops, which retain the drug on the ocular surface for a longer time. Ocular inflammation was effectively inhibited in DES rabbits. Therefore, GEH NPs are potentially valuable as a new therapeutic agent delivered in eye drops for treating DES.

Hyperglycemia, tumorigenesis, and chronic inflammation.

Hyperglycemia is the most prominent sign that characterizes diabetes. Hyperglycemia favors malignant cell growth by providing energy to cancer cells. Clinical studies also showed an increased risk of diabetes being associated with different types of cancers. In addition, poorly regulated glucose metabolism in diabetic patients is often found with increased levels of chronic inflammatory markers, e.g., interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α, and emerging evidence has highlighted activation of the immune response in the progression and development of cancer cells. Therefore, uncontrolled proinflammatory responses could conceivably create a chronic inflammatory state, promoting a tumor-favorable microenvironment and potentially triggering immune overactivation and cancer growth. To further understand how hyperglycemia contributes to immune overactivation, the tumor microenvironment and the development of chronic inflammation-associated tumors may provide insights into tumor biology and immunology. This paper provides a brief introduction to hyperglycemia-associated diseases, followed by a comprehensive overview of the current findings of regulatory molecular mechanisms of glycosylation on proteoglycans in the extracellular matrix under hyperglycemic conditions. Then, the authors discuss the role of hyperglycemia in tumorigenesis (particularly in prostate, liver, colorectal, and pancreatic cancers), as well as the contribution of hyperglycemia to chronic inflammation. The authors end with a brief discussion on the future perspectives of hyperglycemia/tumorigenesis and potential applications of alternative/effective therapeutic strategies for hyperglycemia-associated cancers.

Noninvasive assessments of liver fibrosis with transient elastography and Hui index predict survival in patients with chronic hepatitis B.

BACKGROUND AND AIMS: The prognostic role of noninvasive assessments of liver fibrosis has been evolving. Our aim was to investigate the prognostic value of liver stiffness measurement (LSM) with transient elastography and serum-based Hui index to predict hepatic events and deaths in chronic hepatitis B (CHB) patients. METHODS: The main prospective cohort included 1555 consecutive CHB patients referred for transient elastography examination; a subgroup of 980 patients underwent follow-up assessments at least 3 years later formed the serial cohort. Cox proportional hazard model was performed to determine the relationship of LSM, Hui index and other clinical variables with hepatic events and deaths. RESULTS: During a mean follow-up of 69 ± 9 months, 119 patients (7.6%) developed hepatic events or deaths. Hepatic event-free survival was significantly decreased with increasing stages of LSM and Hui index. The 5-year cumulative probability of hepatic event-free survival of patients of Stage 1-7 of LSM were 99.3%, 98.8%, 95.7%, 90.9%, 89.6%, 74.6%, and 50.0%, respectively; that of Stage 1 to 3 of Hui index were 98.2%, 93.1%, and 77.5%, respectively. Independent predictors of hepatic event-free survival were age, baseline LSM, and follow-up Hui index. Serum ALT and body mass index affected the accuracy of prediction by LSM. Patients remained early stages of LSM or Hui index at follow-up visit had better survival compared to those remained at late stages. CONCLUSION: Baseline and change in noninvasive parameters of liver fibrosis, LSM and Hui index, are accurate to predict hepatic event-free survival in CHB patients.

Liver stiffness-based optimization of hepatocellular carcinoma risk score in patients with chronic hepatitis B.

BACKGROUND & AIMS: CU-HCC score is accurate to predict hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients. However, diagnosis of cirrhosis may be incorrect based on ultrasonography, leading to some errors in HCC prediction. This study aimed to evaluate the accuracy of LSM-HCC score, refined from CU-HCC score with liver stiffness measurement (LSM) using transient elastography to predict HCC. METHODS: A prospective cohort study of 1555 consecutive CHB patients referred for transient elastography examination; 1035 and 520 patients randomly assigned to training and validation cohorts, respectively. Clinical cirrhosis of CU-HCC score was substituted by LSM and analyzed with multivariable Cox regression analysis with other parameters. RESULTS: During a mean follow-up of 69 months, 38 patients (3.7%) in the training cohort and 17 patients (3.4%) in the validation cohort developed HCC. A new LSM-HCC score composed of LSM, age, serum albumin and hepatitis B virus (HBV) DNA levels were derived, which ranges from 0 to 30. Areas under receiver operating characteristic curves of LSM-HCC score were higher than those of CU-HCC score (0.83-0.89 vs. 0.75-0.81). By applying the cutoff value of 11, the score excluded future HCC with high negative predictive value (99.4%-100%) at 5 years. CONCLUSIONS: LSM-HCC score constructed from LSM, age, serum albumin and HBV DNA level is accurate to predict HCC in CHB patients.

Sulforaphane potentiates the efficacy of imatinib against chronic leukemia cancer stem cells through enhanced abrogation of Wnt/ß-catenin function.

Sulforaphane (SFN) has been indicated for the prevention and suppression of tumorigenesis in solid tumors. Herein, we evaluated SFN's effects on imatinib (IM)-resistant leukemia stem cells (LSCs). CD34(+)/CD38(-) and CD34(+)/CD38(+) LSCs were isolated from KU812 cell line flowcytometrically. Isolated LSCs showed high expression of Oct4, CD133, ß-catenin, and Sox2 and IM resistance. Differentially, CD34(+)/CD38(-) LSCs demonstrated higher BCR-ABL and ß-catenin expression and imatinib (IM) resistance than CD34(+)/CD38(+) counterparts. IM and SFN combined treatment sensitized CD34(+)/CD38(-) LSCs and induced apoptosis, shown by increased caspase 3, PARP, and Bax while decreased Bcl-2 expression. Additionally, the combined treatment reduced BCR-ABL and ß-catenin and MDR-1 protein expression. Mechanistically, IM and SFN combined treatment resensitized LSCs by inducing intracellular reactive oxygen species (ROS). Importantly, ß-catenin-silenced LSCs exhibited reduced glutathione S-transferase pi 1 (GSTP1) expression and intracellular GSH level, which led to increased sensitivity toward IM and SFN. We demonstrated that IM and SFN combined treatment effectively eliminated CD34(+)/CD38(-) LSCs. Since SFN has been shown well tolerated in both animals and human, this regimen could be considered for clinical trials.

Magnetic cryopreservation for dental pulp stem cells.

Magnetic cryopreservation has been successfully used for tooth banking with satisfactory implantation outcomes, suggesting that the method preserves human periodontal ligament cells and dental pulp stem cells (DPSCs). Therefore, magnetic cryopreservation may be applied for the preservation of DPSCs; however, this method has not been evaluated yet. A reliable cryopreservation method for live-cell preservation is important for the clinical applications of regenerative medicine. The conventional slow-freezing procedure with 10% dimethylsulfoxide (DMSO) may not be appropriate for stem cell-based therapies because DMSO is cytotoxic. The objective of this study was to investigate whether magnetic cryopreservation can be applied for DPSC cryopreservation. Cells isolated from human dental pulp were subjected to magnetic cryopreservation. Postthawing cell viability, adhesion, proliferation, expression of markers for mesenchymal stem cells (MSCs), differentiation ability of magnetically cryopreserved DPSCs and DNA stability were compared to those of cells subjected to the conventional slow-freezing method. The results indicated that a serum-free cryopreservation medium (SFM) containing 3% DMSO is optimal for magnetic cryopreservation. Post-thaw magnetically cryopreserved DPSCs express MSC markers, and perform osteogenesis and adipogenesis after induction similarly to fresh MSCs. No significant DNA damage was found in magnetically cryopreserved DPSCs. Magnetic cryopreservation is thus a reliable and effective method for storage of DPSCs. The smaller amount of DMSO required in SFM for cryopreservation is beneficial for the clinical applications of post-thaw cells in regenerative medicine.

Determination of cryoprotectant for magnetic cryopreservation of dental pulp tissue.

Dental pulp, covered with dental hard tissue, is a promising source of mesenchymal stem cells and osteoprogenitor cells for regenerative medicine. Our previous studies showed that 73% of dental pulp cells isolated from magnetically cryopreserved teeth where their viability, morphology, and expression of stem cell surface markers were similar to the cells isolated from fresh teeth, suggesting that magnetic cryopreservation is an applicable method for intact tooth as well as dental pulp tissue banking. However, the cryoprotectant, concentration, contact surface, and equilibration time for magnetic cryopreservation of dental pulp require optimization. In addition, the integrity and viability of post-thawed dental pulp with and without dental hard tissue covering after magnetic cryopreservation were investigated. Lower concentration of the cryoprotectant (5% dimethyl sulfoxide [DMSO]) and shorter preequilibration time are required for magnetic cryopreservation compared with the conventional cryopreservation method. The structure of at least 33% of post-thawed pulp with dental hard tissue from the open end remained intact where >80% of cells were viable. The addition of the cryoprotectant additive trehalose did not replace or improve DMSO's efficacy for magnetic cryopreservation of dental pulp or intact tooth. Tooth banking for transplantation provides an alternative treatment to replace missing teeth. The optimized cryoprotectant conditions for dental pulp tissue during magnetic cryopreservation should lead to more satisfactory outcomes in clinical applications such as autotransplantation and the isolation and expansion of dental pulp stem cells for tissue repair.

Potential biomarkers in saliva for oral squamous cell carcinoma.

Sensitive and reliable early diagnostic markers for oral squamous cell carcinoma (OSCC) remain unavailable. Early identification of recurrence for OSCC is also a challenge. Unlike the other deep cancers, OSCC is located in oral cavity. The DNA, RNA, and protein derived from the living cancer cells and inflammatory cells then can be conveniently obtained from saliva. High-throughput genomic and proteomic approaches have been carried out to identify the potential biomarkers in body fluids such as saliva and blood for diagnosis and prognosis of OSCC. This article reviewed the recently identified biomarkers from saliva for OSCC. In addition, the biomarkers which have been correlated with OSCC tumor malignancy by molecular pathology analysis are also described. Finally, the potential biomarkers that have been demonstrated to associate with the malignant OSCC may be used for salivary screening for high-risk patients are suggested. This article may help to identify the potential biomarkers for screening and the molecular pathology analysis for high-risk patients of OSCC. Effective screening to identify high-risk patients can allow the clinician to provide the appropriate treatment without delay and to reduce the recurrence of OSCC.

Traditional Chinese medicine usage among schizophrenia patients.

OBJECTIVE: This study uses a nationwide population-based dataset to explore factors and patterns associated with traditional Chinese medicine (TCM) usage among schizophrenia patients. DESIGN: A retrospective population-based study. Administrative claims data obtained from the Taiwan National Health Insurance Research Database covering the periods 1996-2004 was used to examine patients hospitalized with schizophrenia between 1996 and 2001 (n=34,100) to determine whether they had visited TCM practitioners in 2004 for treatment of schizophrenia. SETTING: Taiwan. MAIN OUTCOME MEASURES: Independent variables included patient's age, gender, comorbid medical disorders, number of visits to clinics, number of hospitalizations, income and the geographical location and urbanization level of patients' residences. Multivariate logistic regressions were performed to determine the association between these factors and visits to TCM practitioners for the treatment of schizophrenia. RESULTS: 3144 of the patients (9.2%) had visited TCM practitioners during 2004. After adjusting for other factors, the odds of such visits by males were found to be 0.825 times those for females, with the odds decreasing with patient's age and urbanization level. The odds of visits to TCM practitioners for patients hospitalized more than once were 3.557 times as high as those for other patients, while those for patients with >or=50 prior visits to other conventional clinics were 54.9 times those with