Pharmacogenomic study-A pilot study of the effect of pharmacogenomic phenotypes on the adequate dosing of verapamil for migraine prevention.

OBJECTIVE: To investigate factors affecting the efficacy and tolerability of verapamil for migraine prevention using individual pharmacogenomic phenotypes. BACKGROUND: Verapamil has a wide range of dosing in headache disorders without reliable tools to predict the optimal doses for an individual. METHODS: This is a retrospective chart review examining adults with existing pharmacogenomic reports at Mayo Clinic who had used verapamil for migraine. Effects of six cytochrome P450 phenotypes on the doses of verapamil for migraine prevention were assessed. RESULTS: Our final analysis included 33 migraine patients (82% with aura). The mean minimum effective and maximum tolerable doses of verapamil were 178.2(20-320) mg and 227.9(20-480) mg. A variety of CYP2C9, CYP2D6, and CYP3A5 phenotypes were found, without significant association with the verapamil doses after adjusting for age, sex, body mass index, and smoking status. CONCLUSIONS: We demonstrated a wide range of effective and tolerable verapamil doses used for migraine in a cohort with various pharmacogenomic phenotypes.

A large language model-based generative natural language processing framework fine-tuned on clinical notes accurately extracts headache frequency from electronic health records.

OBJECTIVE: To develop a natural language processing (NLP) algorithm that can accurately extract headache frequency from free-text clinical notes. BACKGROUND: Headache frequency, defined as the number of days with any headache in a month (or 4 weeks), remains a key parameter in the evaluation of treatment response to migraine preventive medications. However, due to the variations and inconsistencies in documentation by clinicians, significant challenges exist to accurately extract headache frequency from the electronic health record (EHR) by traditional NLP algorithms. METHODS: This was a retrospective cross-sectional study with patients identified from two tertiary headache referral centers, Mayo Clinic Arizona and Mayo Clinic Rochester. All neurology consultation notes written by 15 specialized clinicians (11 headache specialists and 4 nurse practitioners) between 2012 and 2022 were extracted and 1915 notes were used for model fine-tuning (90%) and testing (10%). We employed four different NLP frameworks: (1) ClinicalBERT (Bidirectional Encoder Representations from Transformers) regression model, (2) Generative Pre-Trained Transformer-2 (GPT-2) Question Answering (QA) model zero-shot, (3) GPT-2 QA model few-shot training fine-tuned on clinical notes, and (4) GPT-2 generative model few-shot training fine-tuned on clinical notes to generate the answer by considering the context of included text. RESULTS: The mean (standard deviation) headache frequency of our training and testing datasets were 13.4 (10.9) and 14.4 (11.2), respectively. The GPT-2 generative model was the best-performing model with an accuracy of 0.92 (0.91, 0.93, 95% confidence interval [CI]) and R2 score of 0.89 (0.87, 0.90, 95% CI), and all GPT-2-based models outperformed the ClinicalBERT model in terms of exact matching accuracy. Although the ClinicalBERT regression model had the lowest accuracy of 0.27 (0.26, 0.28), it demonstrated a high R2 score of 0.88 (0.85, 0.89), suggesting the ClinicalBERT model can reasonably predict the headache frequency within a range of ≤ ± 3 days, and the R2 score was higher than the GPT-2 QA zero-shot model or GPT-2 QA model few-shot training fine-tuned model. CONCLUSION: We developed a robust information extraction model based on a state-of-the-art large language model, a GPT-2 generative model that can extract headache frequency from EHR free-text clinical notes with high accuracy and R2 score. It overcame several challenges related to different ways clinicians document headache frequency that were not easily achieved by traditional NLP models. We also showed that GPT-2-based frameworks outperformed ClinicalBERT in terms of accuracy in extracting headache frequency from clinical notes. To facilitate research in the field, we released the GPT-2 generative model and inference code with open-source license of community use in GitHub. Additional fine-tuning of the algorithm might be required when applied to different health-care systems for various clinical use cases.

Genetics in neovascular age-related macular degeneration susceptibility and treatment response to anti-VEGF intravitreal injection: A case series study.

BACKGROUND: To identify genotypes associated with neovascular age-related macular degeneration (nAMD) and investigate the associations between genotype variations and anti-vascular endothelial growth factor (VEGF) treatment response. METHODS: This observational, retrospective, case series study enrolled patients diagnosed with nAMD who received anti-VEGF treatment in National Taiwan University Hospital with at least one-year follow-up between 2012 and 2020. A genome-wide association study (GWAS) was conducted on enrolled patients and controls. Correlations between the genotypes identified from GWAS and the treatment response of functional/anatomical biomarkers, including visual acuity (VA), presence of intraretinal or subretinal fluid (SRF), serous or fibrovascular pigmented epithelium detachment (PED), and disruption of the ellipsoid zone (EZ), were analysed. RESULTS: In total, 182 patients with nAMD and 1748 controls were enrolled. GWAS revealed 16 single nucleotide polymorphisms (SNPs) as risk loci for nAMD, including seven loci in CFH and ARMS2/HTRA1 and nine novel loci, including rs117517872 and rs79835234(COPB2-DT), rs7525578(RAP1A), rs2123738(LOC105376755), rs1374879(CNTN3), rs3812692(SAR1A), rs117501587(PRKCA), rs9965945(CNDP1), and rs189769231(MATK). Our study revealed rs800292(CFH), rs11200638(HTRA1), and rs2123738(LOC105376755) correlated with poor treatment response in VA (P = 0.005), SRF (P = 0.044), and fibrovascular PED (P = 0.007), respectively. Rs9965945(CNDP1) was correlated with poor response in disruption of EZ (P = 0.046) and serous PED (P = 0.049). CONCLUSIONS: Among the 16 SNPs found in the GWAS, four loci-CFH, ARMS2/HTRA1, and two novel loci-were correlated with the susceptibility of nAMD and anatomical/functional responses after anti-VEGF treatment.

Laparoscopic training workshop to assess medical students' skill acquisition and interest in surgical careers.

BACKGROUND: With its minimally invasive approach, laparoscopic surgery has transformed the medical landscape. As the demand for these procedures escalates, there is a pressing need for adept surgeons trained in laparoscopic techniques. However, current training often falls short of catering to medical school education. This study evaluates the impact of a custom-designed laparoscopic training workshop on medical students' surgical skills and career aspirations. METHODS: This prospective experimental study was conducted at the E-Da hospital in Kaohsiung City, Taiwan. Medical students from Taiwanese medical schools undergoing Clerk 5, Clerk 6, and Postgraduate Year 1 and 2 were invited to participate. Medical students (n = 44) underwent an endoscopic skill training workshop consisting of lectures, box training, and live tissue training. The trainees performed multiple tasks before and after training using our objective evaluation system. The primary outcome was assessed before and after training through a questionnaire assessing the influence of training on students' interest in surgery as a career. The secondary outcome measured improvement in skill acquisition, comparing the task completion time pre- and post-workshop. For the primary outcome, descriptive statistics were used to summarize the questionnaire responses, and paired t-tests were performed to determine significant changes in interest levels post-workshop. For the secondary outcome, paired t-tests were used to compare the time recorded pre- and post-training. RESULTS: Post-training, participants exhibited significant proficiency gains, with task completion times reducing notably: 97 s (p = 0.0015) for Precision Beads Placement, 88.5 s (p < 0.0001) for Beads Transfer Exercise, 95 s (p < 0.0001) for Precision Balloon Cutting, and 137.8 s (p < 0.0001) for Intracorporeal Suture. The primary outcome showcased an increased mean score from 8.15 pre-workshop to 9.3 post-workshop, indicating a bolstered interest in surgery as a career. Additionally, post-training sentiment analysis underscored a predominant inclination toward surgery among 88% of participants. CONCLUSION: The custom-designed laparoscopic workshop significantly improved technical skills and positively influenced students' career aspirations toward surgery. Such hands-on training workshops can play a crucial role in medical education, bridging the gap between theoretical knowledge and practical skills and potentially shaping the future of budding medical professionals.

Identification of the Time Period during Which BMP Signaling Regulates Proliferation of Neural Progenitor Cells in Zebrafish.

Bone morphogenetic protein (BMP) signaling regulates neural induction, neuronal specification, and neuronal differentiation. However, the role of BMP signaling in neural progenitors remains unclear. This is because interruption of BMP signaling before or during neural induction causes severe effects on subsequent neural developmental processes. To examine the role of BMP signaling in the development of neural progenitors in zebrafish, we bypassed the effect of BMP signaling on neural induction and suppressed BMP signaling at different time points during gastrulation using a temporally controlled transgenic line carrying a dominant-negative form of Bmp receptor type 1aa and a chemical inhibitor of BMP signaling, DMH1. Inhibiting BMP signaling from 8 hpf could bypass BMP regulation on neural induction, induce the number of proliferating neural progenitors, and reduce the number of neuronal precursors. Inhibiting BMP signaling upregulates the expression of the Notch downstream gene hairy/E(spl)-related 2 (her2). Inhibiting Notch signaling or knocking down the Her2 function reduced neural progenitor proliferation, whereas inactivating BMP signaling in Notch-Her2 deficient background restored the number of proliferating neural progenitors. These results reveal the time window for the proliferation of neural progenitors during zebrafish development and a fine balance between BMP and Notch signaling in regulating the proliferation of neural progenitor cells.

Heterotopic Digital Replantation in Mutilating Hand Injuries: An Algorithmic Approach Based on 53 Cases and Literature Review.

BACKGROUND: Reconstruction of the mutilated hand is one of the most difficult challenges for hand microsurgeons. When multiple digits are amputated, orthotopic digital replantation of the available remnants may not adequately restore the hand function. In such cases, heterotopic digital replantation may provide a more functional reconstruction. METHODS: Between 1997 and 2018, 53 patients with mutilating hand injuries were treated with heterotopic digital replantation at our institution. A retrospective chart review was conducted to determine the details of the injury, indications for heterotopic digital replantation, and functional outcomes. RESULTS: In total, 173 digits were amputated from 53 patients (one patient suffered from bilateral hand injuries, so totally 54 hands). Sixty-eight digits underwent heterotopic digital replantation, 30 digits had orthotopic digital replantation, and 75 stumps were terminalized. The survival rate of digits treated by heterotopic digital replantation and orthotopic digital replantation was 83.8% (57/68) and 86.7% (26/30), respectively (p = 1). Tripod grip was achieved in 83.3% (45/54) of patients following replantation and optional secondary reconstructive surgeries. CONCLUSION: Heterotopic digital replantation is a practical and reliable method for achieving optimal hand function following mutilating hand injuries. The basic principles are to restore a functional thumb in the first instance, followed by at least two adjacent fingers against which the thumb can oppose. This method is particularly indicated when orthotopic digital replantation of the available amputated parts would yield a suboptimal result.

Clinical characteristics and long-term outcome of cerebral cavernous malformations-related epilepsy.

OBJECTIVE: Cerebral cavernous malformations (CCMs) present variably, and epileptic seizures are the most common symptom. The factors contributing to cavernoma-related epilepsy (CRE) and drug resistance remain inconclusive. The outcomes of CRE after different treatment modalities have not yet been fully addressed. This study aimed to characterize the clinical features of patients with CRE and the long-term seizure outcomes of medical and surgical treatment strategies. METHODS: This was a retrospective cohort of 135 patients with CCM who were diagnosed in 2007-2011 and followed up for 93.6 months on average. The patients were divided into drug-resistant epilepsy (DRE; n = 29), non-DRE (n = 45), and no epilepsy (NE; n = 61). RESULTS: Temporal CCM was the factor most strongly associated with the development of both CRE and DRE. The majority of patients with single temporal CCMs had CRE (86.8%, n = 33), and 50% had DRE, whereas only 14.7% (n = 5) with a nontemporal supratentorial CCM had DRE (p < .05). The most common lesion site in the DRE group was the mesiotemporal lobe (50%). Multiple CCMs were more frequently observed in the CRE (29.2%) than the NE (11.5%) group (p < .05). In patients with CRE, multiple lesions were associated with a higher rebleeding rate (odds ratio = 11.1), particularly in those with DRE (odds ratio = 15.4). The majority of patients who underwent resective surgery for DRE (76.5%, n = 13) achieved International League Against Epilepsy Class I and II seizure outcomes even after a long disease course. SIGNIFICANCE: Temporal CCM not only predisposes to CRE but also is a major risk factor for drug resistance. The mesiotemporal lobe is the most epileptogenic zone. Multiple CCMs are another risk factor for CRE and increase the rebleeding risk in these patients. Surgical resection could provide beneficial long-term seizure outcomes in patients with DRE.

Lower starting dose of afatinib for the treatment of metastatic lung adenocarcinoma harboring exon 21 and exon 19 mutations.

BACKGROUND: Afatinib has shown favorable response rates (RRs) and longer progression free survival (PFS) in lung cancer patients harboring EGFR mutations compared with standard platinum-based chemotherapy. However, serious adverse drug reactions (ADRs) limit the clinical application of afatinib. METHODS: We designed a retrospective study, enrolling all patients with metastatic lung adenocarcinoma who were diagnosed and treated with 30 or 40 mg daily afatinib as their initial treatment in three Kaohsiung Medical University-affiliated hospitals in Taiwan. RESULTS: A total of 179 patients were enrolled in the study, of which 102 (57%) and 77 (43%) received 30 mg and 40 mg afatinib daily as their initial treatment, respectively. The patients initially using 30 mg afatinib daily had a similar RR (75% vs. 83%, p = 0.1672), median PFS (14.5 vs. 14.8 months, log-rank p = 0.4649), and median OS (34.0 vs. 25.2 months, log-rank p = 0.5982) compared with those initially using 40 mg afatinib daily. Patients initially receiving 30 mg afatinib daily had fewer ADRs compared with those using 40 mg daily. The overall incidence of moderate and severe ADRs was significantly lower in patients receiving 30 mg afatinib daily compared with those using 40 mg daily (49% vs. 77%, p = 0.002); similar findings was observed in terms of severe ADRs (7% vs. 24%, p < 0.0001). CONCLUSION: Patients receiving 30 mg afatinib daily as their initial treatment had similar RR, PFS, OS, but significantly fewer serious ADRs, as compared with those using 40 mg as their starting dose.

A Double-Blind, Randomized, Controlled Trial of Lovastatin in Early-Stage Parkinson's Disease.

BACKGROUND: Recent evidence indicates that lipophilic statins have a neuroprotective benefit in animal models of Parkinson's disease (PD). The objective of this study was to evaluate whether lovastatin has the potential to slow motor symptom progression in patients with early-stage PD. METHODS: This double-blind, randomized, placebo-controlled trial enrolled 77 patients with early-stage PD between May 23, 2017, and July 12, 2018, with follow-up ending September 1, 2019. Lovastatin 80 mg/day or placebo with 1:1 randomization was administered for 48 weeks. Mean change in the parts I-III scores of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), changes in the striatal dopamine uptake ratio measured by 18 F-dopa PET scan, and changes in PD medications between baseline and the week 48 visit were measured. RESULTS: Of the 77 randomized patients, 70 (90.9%) completed the study. There was a slightly beneficial trend of the MDS-UPDRS motor score in the lovastatin group (-3.18 ± 5.50) compared with the placebo group (-0.50 ± 6.11); P = 0.14 adjusted for age, sex, disease duration, and baseline LEDD. Mean percentage change in the striatal 18 F-dopa uptake ratio deteriorated less in the lovastatin group than in the placebo group on the dominant side of caudate (1.2% ± 7.3% vs -7.1% ± 8.2%, P < 0.01) and putamen (2.3% ± 7.1% vs -6.4% ± 8.1%, P < 0.01). We found no between-group differences in the change in part I or part II MDS-UPDRS scores. Lovastatin was generally well tolerated. CONCLUSIONS: Lovastatin treatment in patients with early-stage PD was associated with a trend of less motor symptom worsening and was well tolerated. A future larger long-term follow-up study is needed to confirm our findings. © 2021 International Parkinson and Movement Disorder Society.

Effects of Focal Radiation on [18 F]-Fluoro-D-Glucose Positron Emission Tomography in the Brains of Miniature Pigs: Preliminary Findings on Local Metabolism.

OBJECTIVES: It would be a medically important advance if durable and focal neuromodulation of the brain could be delivered noninvasively and without ablation. This ongoing study seeks to elucidate the effects of precisely delivered ionizing radiation upon focal brain metabolism and the corresponding cellular integrity at that target. We hypothesize that focally delivered ionizing radiation to the brain can yield focal metabolic changes without lesioning the brain in the process. MATERIALS AND METHODS: We used stereotactic radiosurgery to deliver doses from 10 Gy to 120 Gy to the left primary motor cortex (M1) of Lee Sung miniature pigs (n = 8). One additional animal served as a nonirradiated control. We used positron emission tomography-computed tomography (PET-CT) to quantify radiation dose-dependent effects by calculating the ratio of standard uptake values (SUV) of 2-deoxy-2-[18 F]-fluoro-D-glucose (18 F-FDG) between the radiated (left) and irradiated (right) hemispheres across nine months. RESULTS: We found that the FDG-PET SUV ratio at the targeted M1 was significantly lowered from the pre-radiation baseline measurements for animals receiving 60 Gy or higher, with the effect persisting at nine months after radiosurgery. Only at 120 Gy was a lesion suggesting ablation visible at the M1 target. Animals treated at 60-100 Gy showed a reduced signal in the absence of an identifiable lesion, a result consistent with the occurrence of neuromodulation. CONCLUSION: Focal, noninvasive, and durable changes in brain activity can be induced without a magnetic resonance imaging (MRI)-visible lesion, a result that may be consistent with the occurrence of neuromodulation. This approach may provide new venues for the investigation of neuromodulatory treatments for disorders involving dysfunctional brain circuits. Postmortem pathological analysis is needed to elucidate whether there have been morphological changes not detected by MRI.

Outcomes of conventional versus virtual surgical planning of orthognathic surgery using surgery-first approach for class III asymmetry.

OBJECTIVES: To determine if patient outcome variables differ between conventional and virtual surgical planning of orthognathic surgery for class III asymmetry. MATERIAL AND METHODS: This retrospective case-control study examined 95 patients with class III asymmetry who had been consecutively treated with at least a Le Fort I osteotomy and a bilateral sagittal split osteotomy with a surgery-first approach. Two groups were examined: 51 patients treated with conventional surgical planning and 44 with virtual surgical planning. After treatment, quantitative assessment was determined with measurements of midline symmetry, contour symmetry, and overall facial symmetry using standardized frontal photographs. Subject assessments were analyzed with questionnaires regarding self-perception of overall appearance, satisfaction with appearance, and quality of life. RESULTS: Conventional and virtual surgical planning resulted in significant improvements in outcomes for all patients. However, facial midline and overall facial symmetry were significantly greater for the virtual compared with the conventional group. There were no significant differences in subjective measures of appearance, satisfaction with appearance, and quality of life for patients treated with conventional or virtual surgical planning; measures were high for both groups. CONCLUSIONS: Conventional and virtual surgical planning of surgery-first bimaxillary orthognathic surgery resulted in quantitative and qualitative improvements in facial symmetry. Although patient satisfaction was similar for both approaches, virtual surgical planning was superior to conventional surgical planning for the improvement of midline and overall asymmetry. CLINICAL RELEVANCE: Improvements with virtual surgical planning in facial midline, facial contour, and overall facial symmetry are as good as or better than conventional surgical planning.

The Medial Subcoronoid Process Region as a Novel Source of Bone Grafts in Orthognathic Surgery and Genioplasty.

BACKGROUND: Since 2012, the authors have adopted the medial subcoronoid process bone interpositional grafting in OGS and genioplasty procedures. The purpose of this study was to present the technical details and clinical outcomes of this alternative bone interpositional grafting for LeFort I and chin osteotomies. METHODS: Consecutive patients (n = 50) who underwent single-splint bimaxillary OGS with or without genioplasty and received medial subcoronoid bone interpositional grafting were included. Standardized facial and intraoral photographs at early and late postoperative periods (12.2 ±â€Š3.3 and 44.8 ±â€Š8.4 months postsurgery, respectively) were blindly rated to assess facial symmetry, chin, and occlusion status based on qualitative rating scales. Complication and reoperation rates were also reviewed. RESULTS: The medial subcoronoid bone interpositional grafts were adopted to stabilize different LeFort I maxillary movement types or lengthening/advancing genioplasty (36 and 14 patients, respectively). Overall, the early facial symmetry, chin, and occlusion status were maintained at late evolutions. None of the patients had donor-site or bone graft-related complications (i.e., bad split, undesired mandible fracture, infection, fibrous union, nonunion, and/or permanent neurosensory deficit) or revisionary surgery during follow-up. CONCLUSION: The medial subcoronoid process bone grafting was a feasible alternative for bone interpositional defects of LeFort I and chin osteotomies with no significant morbidity and avoiding secondary donor sites.

Spatially and angularly resolved spectroscopy for in-situ estimation of concentration and particle size in colloidal suspensions.

Successful implementation of process analytical technology (PAT) hinges on the ability to make continuous or frequent measurements in-line or at-line of critical product attributes such as composition and particle size, the latter being an important parameter for particulate processes such as suspensions and emulsions. A novel probe-based spatially and angularly-resolved diffuse reflectance measurement (SAR-DRM) system is proposed. This instrument, along with appropriate calibration models, is designed for online monitoring of concentration of chemical species and particle size of the particulate species in process systems involving colloidal suspensions. This measurement system was investigated using polystyrene suspensions of various particle radius and concentration to evaluate its performance in terms of the information obtained from the novel configuration which allows the measurement of a combination of incident light at different angles and collection fibres at different distances from the source fibres. Different strategies of processing and combining the SAR-DRM measurements were considered in terms of the impact on partial least squares (PLS) model performance. The results were compared with those obtained using a bench-top instrument which was used as the reference (off-line) instrument for comparison purposes. The SAR-DRM system showed similar performance to the bench top reference instrument for estimation of particle radius, and outperforms the reference instrument in estimating particle concentration. The investigation shows that the improvement in PLS regression model performance using the SAR-DRM system is related to the extra information captured by the SAR-DRM configuration. The differences in SAR-DRM spectra collected by the different collection fibres from different angular source fibres are the dominant reason for the significant improvement in the model performance. The promising results from this study suggest the potential of the SAR-DRM system as an online monitoring tool for processes involving suspensions. Graphical abstract A probe designed to acquire diffuse reflectance measurements at different source-detector distances for three incidence angles 0°, 30° and 45° was used to estimate particle size and concentration of polystyrene beads in aqueous suspension using partial least squares calibration models.

Systemic Inflammatory Response Syndrome is an Independent Predictor of One-Year Mortality in Patients with Acute Myocardial Infarction.

BACKGROUND: Convincing evidence suggests that inflammatory biomarkers are associated with an increased risk among patients with acute myocardial infarction (AMI). However, the impact of systemic inflammatory response (SIRS) on one-year clinical outcomes remains uncertain. Herein we investigated the impact of SIRS on one-year mortality and major adverse cardiovascular events (MACE) in patients with AMI. METHODS: We conducted a retrospective study that enrolled patients admitted due to AMI and who received coronary artery intervention from January 2012 to June 2014. SIRS was defined according to standard criteria as having two or more of the following: (1) body temperature < 36 or > 38 °C, (2) heart rate > 90 beats per minute, (3) respiratory rate > 20, or (4) white blood cell count < 4000/mm3 or > 12,000/mm3. The primary endpoint was one-year mortality. The secondary endpoint was a one-year MACE, including revascularization, AMI, and stroke. RESULTS: A total of 330 AMI patients were enrolled in the study, and 121 study subjects (36.6%) met the SIRS criteria. AMI patients with SIRS on admission had significantly increased one-year all-cause mortality (control vs. SIRS: 21.1% vs. 33.1%, p = 0.026) and one-year MACE (35.9% vs. 53.7%, p = 0.022). Patients with SIRS had a higher incidence of one-year non-fatal myocardial infarction, but not non-fatal stroke. After multivariable adjustment, SIRS [hazard ratio (HR) = 1.773, 95% confidence interval (CI) = 1.097-2.886, p = 0.019] and age (HR = 1.038, 95% CI = 1.018-1.058, p < 0.001) were associated with enhanced risk of one-year mortality. CONCLUSIONS: This study revealed that AMI patients with SIRS on initial admission were associated with increased risk of one-year all-cause mortality.

Comparison of biventricular ejection fractions using cadmium-zinc-telluride SPECT and planar equilibrium radionuclide angiography.

BACKGROUND: We compared biventricular ejection fractions (EFs) from gated blood-pool single-photon emission computed tomography (SPECT) using a cadmium-zinc-telluride camera (CZT-SPECT) with planar equilibrium radionuclide angiography (ERNA) using a NaI gamma camera (NaI-planar). We also evaluated whether imaging time can be reduced without compromising image quality using the CZT camera. METHODS: Forty-eight patients underwent NaI-planar and CZT-SPECT on the same day. CZT-SPECT datasets were re-projected at an LAO orientation similar to ERNA acquisition, forming CZT-repro planar datasets. The resulting biventricular volumetric measurements and EFs were compared. RESULTS: LVEF calculated from CZT-SPECT and CZT-repro correlated better with NaI-planar (r = 0.93 and 0.99, respectively) than RVEF (r = 0.76 and 0.82, respectively). Excellent intra-class correlation and low bias in intra-observer comparisons were observed for the biventricular EFs derived from three datasets. A wider limit of agreement in CZT-SPECT-derived LVEFs, lower correlation and significant bias for NaI-planar, and CZT-repro-derived RVEFs was found in the inter-observer analyses. Nonetheless, the imaging time can be reduced to 4 minutes without increasing variability in EFs using the CZT camera (P = NS). CONCLUSIONS: LVEFs calculated from CZT-SPECT and CZT-repro correlated well with NaI-planar. CZT camera may reduce imaging time while preserving image quality in the assessment of biventricular EFs.

Antimicrobial peptide m2163 or m2386 identified from Lactobacillus casei ATCC 334 can trigger apoptosis in the human colorectal cancer cell line SW480.

Ribosomal synthesized antimicrobial peptides (AMPs) are widely distributed in nature and are toxic to certain microorganisms. Some of these AMPs are found to exhibit cytotoxic activity against the growth of cancer cells and thus have obvious anticancer potential. Here, we have studied the antiproliferation on the human colorectal cancer cell line SW480 of two AMPs, namely m2163 and m2386, identified by us from a lactic acid bacterium Lactobacillus casei ATCC 334 previously. A half maximal inhibitory concentration (IC50) of 40 µg/ml is determined first using the MTT (3-(4, 5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay for either peptide m2163 or m2386. The apoptosis in treated SW480 cells by either peptide m2163 or m2386 is analyzed using flow cytometry with annexin V-fluorescein isothiocyanate (FITC) and propidium iodide double staining. These analyses show that a substantial population of treated SW480 cells can undergo apoptosis by either peptide m2163 or m2386. The real-time quantitative polymerase chain reaction (qPCR) and Western blot analyses are subsequently used to study how the apoptosis is induced in the treated SW480 cells by either peptide m2163 or m2386. While m2163 is found to induce the expression of Fas and TRAILR1, the expression of Fas, TNFR1, and TRAILR1 death receptors on the cell surface of treated SW480 cells is found to be induced by m2386. Further, the expression of some mitochondria-related apoptosis proteins such as Smac is found to be also induced, suggesting that either peptide m2163 or m2386 can trigger both the extrinsic and intrinsic apoptosis pathways. The cell membrane permeability is greatly enhanced upon treatment with either peptide m2163 or m2386 as analyzed by the flow cytometry using both FITC-labeled peptides. The flow cytometry is also used to analyze the fluorescence intensity given by FITC-m2163 in either the mitochondria or cytoplasm fraction of the treated and fractionated SW480 cells. It is found that the detected fluorescence intensity of the mitochondria fraction is much weaker than that of the cytoplasm one, suggesting that most of the FITC-m2163 peptides are located in the cytoplasm rather than the mitochondria. This is further confirmed by a confocal microscopy study that either peptide m2163 or m2386 can localize on the cell membrane for a substantial length of time and then penetrate into the cell cytoplasm to induce the apoptosis.

The radiographic and functional outcome of bilateral mandibular condylar head fractures: a comparison between open and closed treatment.

UNLABELLED: Bilateral mandibular condylar fractures accounts for 24% to 33% of condylar fractures but the indications of open reduction of bilateral condylar fracture are still controversial. It is generally accepted that displaced subcondylar fractures are indicated for open reduction, but the proper treatment of condylar head fractures are still variable. This retrospective study compares the radiographical and functional outcomes of bilateral condylar head fractures between open and closed reduction groups. MATERIALS AND METHODS: From February 1994 to June 2012, a total of 85 patients with bilateral condylar head fractures were retrospectively reviewed. Among this group, 41 cases underwent open reductions while the other 44 cases had closed reductions. Only adult patients with adequate follow-up and complete radiographic study were included in this study: consisting of 20 patients in the open group and 18 patients in the closed group.The subjective symptoms including temporomandibular joints (TMJ) symptoms, complications or adverse sequelae, and functional results, such as maximal mouth opening, were recorded. The outcome of patient's satisfaction was individually assessed by an independent reviewer. The computed tomographic results after treatment were evaluated between both groups. RESULTS: The mean follow-up period was 25.5±13.3 months. The open reduction group had better postoperative chewing functions, less malocclusion rates, less degree of TMJ pain (p=0.046), better radiographic outcome (p=0.036), and an overall satisfaction rate (p=0.039).There were 4 cases of failure in the closed reduction group. Subsequent open reduction (n=2) and redo closed reduction with intermaxillary fixation (n=2) were performed. Eleven patients in the close reduction group presented persistent malocclusion through objective evaluation. The subsequent treatment included further orthognathic surgery (n=1) and orthodontic treatment (n=7). Three of the patients refused further treatment. CONCLUSIONS: Open reduction for bilateral condylar head fractures presented an overall better functional and radiographic outcome, with higher patient satisfaction if condylar fracture segments were still feasible for rigid fixation.