Standardization and quantification of backscattered electron imaging in scanning electron microscopy.

Backscattered electron (BSE) imaging based on scanning electron microscopy (SEM) has been widely used in scientific and industrial disciplines. However, achieving consistent standards and precise quantification in BSE images has proven to be a long-standing challenge. Previous methods incorporating dedicated calibration processes and Monte Carlo simulations have still posed practical limitations for widespread adoption. Here we introduce a bolometer platform that directly measures the absorbed thermal energy of the sample and demonstrates that it can help to analyze the atomic number (Z) of the investigated samples. The technique, named Atomic Number Electron Microscopy (ZEM), employs the conservation of energy as the foundation of standardization and can serve as a nearly ideal BSE detector. Our approach combines the strengths of both BSE and ZEM detectors, simplifying quantitative analysis for samples of various shapes and sizes. The complementary relation between the ZEM and BSE signals also makes the detection of light elements or compounds more accessible than existing microanalysis techniques.

First Report of Tomato Leaf Curl Cebu Virus Associated with Stachytarpheta jamaicensis Golden Yellow Mosaic Disease in Taiwan.

Stachytarpheta jamaicensis (L.) Vahl, also known as snack weed, is an exotic plant in Taiwan. In April 2021, severe golden yellow mosaic leaves (Fig. S1) were observed on S. jamaicensis plants in Taichung City, Taiwan. Samples from eight symptomatic and two asymptomatic plants were collected from the public flowerbed. Total DNA was extracted from each of the collected samples by using a modified CTAB method (Echevarría-Machado et al. 2005). PCR with Begomovirus degenerate primers (PAL1v1978/PAR1c715; Rojas et al. 1993) was conducted. The expected 1.5-kb fragment was amplified only from the 8 symptomatic samples. Two randomly selected amplicons were cloned on pCRII-TOPO TA vector (Invitrogen Co., San Diego, CA, USA) and sequenced with the ABI3730 automatic sequencer (Applied Biosystems, Hammonton, NJ, USA) at National Chung Hsing University (NCHU). After NCBI BLASTn analysis, the sequences were shown to be most closely related to tomato leaf curl Cebu virus (ToLCCeV) isolates (EU487042, EU487025, KU946997), with 92.4-92.5% nucleotide sequence identity by using the CLUSTAL W method of MegAlign program (DNASTAR, Inc., Madison, WI, USA). A ToLCCeV specific primer pair (FJJ2021-165 /166 5'-ACTTACAGGCCCATGTATCG-3' / 5'-GAATGGGTATCCGAGCACG-3') was designed to amplify and sequence the remaining half of viral DNA. The expected 1.6-kb amplicon was amplified only from the symptomatic samples. The full-length of DNA-A consisted of 2.7-kb nucleotides (ToLCCeV isolate stachy, ON525110 and ON525111) and contained six open reading frames (two in viral sense, V1 to V2 and four in the viral complementary sense, C1 to C4) and the conserved nonanucleotide motif (TAATATTAC). The full-length DNA-A of ToLCCeV stachy isolates shared 99.9% nucleotide identity to each other and 91.2-92.4% and 91.3-92.5% nucleotide identities to other ToLCCeV isolates (EU487042, EU487025, KU946997) available in NCBI GenBank. Besides, ToLCCeV is a monopartite begomovirus that harbors no DNA-B. Thus, there were no bands amplified from the degenerate primer pair for DNA-B (DNABLC2 / DNABLV2; Green et al. 2001). Furthermore, the infectious clone was constructed by using phi29 DNA polymerase (New England Biolabs, Ipswich, MA, USA) for rolling circle amplification (RCA). The RCA product was partially digested with ApaI (NEB) and ligated into the binary vector pCambia0380 (AF234290). The resulting recombinant vector was transformed into Agrobacterium tumefaciens C58. A. tumefaciens C58, containing the infectious ToLCCeV-Stachy DNA-A vector, was grown overnight in LB broth containing kanamycine (50 µg/ml) at 28°C. S. jamaicensis and Nicotiana benthamiana (Nb, four to six leaf stage) plants were agroinoculated to confirm the infectivity of the ToLCCeV clone. The leaf curling and blister symptoms were observed on the Nb systemic leaves 17-day post inoculation (dpi) and the golden yellow mosaic symptom noticed on S. jamaicensis systemic leaves 30-dpi. The presence of the viral DNA in the inoculated plants was confirmed by PCR using the specific primer pair of ToLCCeV. To the best of our knowledge, this is the first report of the monopartite begomovirus, ToLCCeV, associated with golden yellow mosaic disease in S. jamaicensis in Taiwan. The existence of ToLCCeV might severely impact the tomato and pepper industry because they are the natural hosts of ToLCCeV (Tsai et al. 2011) and ToLCCeV may be transmitted by the whitefly, Bemisia tabaci, in Taiwan (Ko et al. 2005).

Change in 1-year hospitalization of overall and older patients with major depressive disorder after second-generation antipsychotics augmentation treatment.

BACKGROUND: Studies on second-generation antipsychotics (SGA) augmentation treatment for older adults with major depressive disorder (MDD) remain limited. We aimed to investigate the effectiveness of SGA augmentation for overall and older patients with MDD inpatient history by assessing the change in 1-year hospitalization before and after SGA augmentation using the latest National Health Insurance Research Database (NHIRD) in Taiwan. METHODS: The samples were MDD patients (ICD-9 CM code: 296.2 and 296.3) who had psychiatric inpatient history. A total of 2602 MDD patients including 430 elderly subjects (age ≥ 60 years) who received SGA augmentation for 8 weeks between January 1998 and December 2012 were included in this 1-year mirror-image study. Outcome measures included number and length of psychiatric and all-cause hospitalizations. RESULTS: After 8-week continuous SGA augmentation in the study subjects, the total number and days of psychiatric hospitalizations among overall patients reduced by 33.57% (p < .0001) and 18.24% (p < .0001), respectively; the total number and days of psychiatric hospitalizations among older patients (age ≥ 60) reduced by 44.52% (p < .0001) and 27.95% (p < .0001), respectively. Similarly, the total number and days of all-cause hospitalizations were significantly reduced. LIMITATIONS: MDD patients without inpatient history were not included due to data limitation; hence, the results may not be generalized to all patients. CONCLUSIONS: The results support that SGA may be effective in reducing psychiatric and all-cause hospitalization among overall and elderly MDD patients. More studies focusing on the safety of SGA among older MDD patients is warranted.

High-resolution monochromator using a high-efficiency single-mode x-ray resonator at Laue incidence.

We report a high-resolution and high-efficiency monochromator with energy resolution, ΔE/E∼2.08*10-7, utilizing a hard x-ray single-mode Fabry-Perot (FP) resonator at Laue incidence at 14.4388 keV. Instead of using multiple-crystal diffraction via several asymmetric-cut crystals, a 3 meV single-peak is generated from the interference of a Si-made two-plate cavity with a thickness of 70 µm and a gap of 45 µm, where a (0-40) Laue reflection is used to excite the backreflection (12 4 0) for the enhancement of the FP efficiency. Due to the large angular acceptance of (12 4 0) and (0-40), the energy tunability can be achieved by changing the incident angle into the resonator. The application of x-ray resonators at Laue incidence as a monochromator can be further implemented to x-ray optics.

Sentinel Artery in Double Eyelid Blepharoplasty: Identification, Prevention, Management.

In double eyelid blepharoplasty, unexpected bleeding may cause intraoperative hematoma, swelling, and temporary ptosis, which could cause asymmetry and prolong recovery time. In 1725 patients (3450 eyes), double eyelid blepharoplasties were performed on Chinese patients from January 2014 to July 2016 by our senior author. In 36 eyes, the authors identified a variant artery, which the authors named the "sentinel artery," located in the inferolateral superficial orbital septum. The sentinel artery courses between the orbital septum and the levator palpebrae finally drain into the peripheral arcade. This artery is uncommon since only 1.04% of eyes have it. If the artery is severed accidentally, the cleaved arterial end will retract into the levator palpebrae and bleed causing a large hematoma to rapidly form posterior to the levator palpebrae. The authors actively avoided unexpected bleeding caused by tearing up this artery while opening the orbital septum during double eyelid blepharoplasty procedure.

The effect of cranioplasty in cognitive and functional improvement: Experience of post traumatic brain injury inpatient rehabilitation.

To investigate the effect of cranioplasty on rehabilitation of post-traumatic brain injury (TBI) patients, 37 patients with TBI were arranged by retrospectively assessment study. Those TBI patients receiving in-hospital rehabilitation in the Department of Rehabilitation in a medical center of South Taiwan from 2010 to 2015 were assigned into two groups: A and B. All patients entered the multidisciplinary holistic in-patient rehabilitation training for about 1 month. Patients in Group A received decompressive craniectomy (DC), patients in Group B received DC and cranioplasty. All assessments were arranged right on admission and before discharge. The functional activity evaluation included muscle power and Barthel index (BI), and cognitive function evaluation, including the Rancho Los Amigo Scale, Mini Mental State Examination (MMSE), Community Mental State Examination (CMSE), and the Luria-Nebraska Neuropsychological Battery-Screening Test Short Form (LNNBS). The results showed that there were synergetic effects of cranioplasty on post-TBI patients with rehabilitation training, especially in the BI score, and cognitive improvement in CMSE and LNNBS.

Regulation of miR-21 expression in human melanoma via UV-ray-induced melanin pigmentation.

Excessive environmental ultraviolet (UV) radiation produces genetic mutations that can lead to skin cancer. This study was designed to assess the potential inhibitory activity of microRNA-21 (miR-21) on the UV irradiation-stimulated melanogenesis signal pathway in melanoma cells. The molecular mechanism of miR-21-induced inhibitory activity on UV-ray-stimulated melanogenesis-regulating proteins was examined in A375.S2 human melanoma and B16F10 mouse melanoma cells. UV irradiation for 30 min induced melanogenesis signal pathway by increasing melanin production and the number of A375.S2 cells. Similarly, UV radiation increased the expression of α-melanocyte-stimulating hormone (α-MSH) protein and decreased the melanogenesis-regulating signal, such as EGFR and Akt phosphorylation. Notably, miR-21 overexpression in UV-ray-stimulated A375.S2 cells decreased α-MSH expression and increased EGFR and Akt phosphorylation levels. Furthermore, miR-21 on UV-ray- induced melanogenesis was down-regulated by the Akt inhibitor and the EGFR inhibitor (Gefitinib). Results suggest that the suppressive activity of miR-21 on UV-ray-stimulated melanogenesis may involve the down-regulation of α-MSH and the activation in both of EGFR and Akt.

Evaluation of antibiotic pressurized pulse lavage for contaminated retromuscular abdominal wall reconstruction.

BACKGROUND: Despite patient risk factors such as diabetes and obesity, contamination during surgery remains a significant cause of infections and subsequent wound morbidity. Pressurized pulse lavage (PPL) has been utilized as a method to reduce bacterial bioburden with promising results in many fields. Although existing methods of lavage have been utilized during abdominal operations, no studies have examined the use of PPL during complex hernia repair. METHODS: Patients undergoing abdominal wall reconstruction (AWR) in clean-contaminated or contaminated fields with antibiotic PPL, from January 2012 to May 2013, were prospectively evaluated. Primary outcome measures studied were conversion of retrorectus space culture from positive to negative after PPL and 30-day surgical site infection (SSI) rate. RESULTS: A total of 56 patients underwent AWR, with 44 patients (78.6 %) having clean-contaminated fields and 12 patients (21.4 %) having contaminated ones. Twenty-two patients (39.3 %) had positive pre-PPL cultures, 18 of which (81.8 %) converted to negative cultures after PPL. Eleven patients (19.6 %) developed SSIs. Those with persistently positive cultures after PPL had the highest rate of SSI, where two out of four patients (50.0 %) developed an SSI. Contrastingly, only 5 of 18 patients (27.8 %) who converted from a positive to negative culture after PPL developed an SSI. CONCLUSION: Our findings demonstrate that antibiotic PPL is an effective method to reduce bacterial bioburden during AWR in clean-contaminated and contaminated fields. While complete conversion and eradication of SSI were not achieved, we believe that PPL may be a useful adjunct to standard operative asepsis in preventing prosthetic contamination during contaminated AWR.

Adjunctive sarcosine plus benzoate improved cognitive function in chronic schizophrenia patients with constant clinical symptoms: A randomised, double-blind, placebo-controlled trial.

Objectives Hypofunction of NMDA receptor is implicated in the pathophysiology, particularly cognitive impairment, of schizophrenia. Sarcosine, a glycine transporter I (GlyT-1) inhibitor, and sodium benzoate, a d-amino acid oxidase (DAAO) inhibitor, can both enhance NMDA receptor-mediated neurotransmission. We proposed simultaneously inhibiting DAAO and GlyT-1 may be more effective than inhibition of either in improving the cognitive and global functioning of schizophrenia patients. Methods This study compared add-on sarcosine (2 g/day) plus benzoate (1 g/day) vs. sarcosine (2 g/day) for the clinical symptoms, as well as the cognitive and global functioning, of chronic schizophrenia patients in a 12-week, double-blind, randomised, placebo-controlled trial. Participants were measured with the Positive and Negative Syndrome Scale and the Global Assessment of Functioning Scale every 3 weeks. Seven cognitive domains, recommended by the Measurement and Treatment Research to Improve Cognition in Schizophrenia Committee, were measured at weeks 0 and 12. Results Adjunctive sarcosine plus benzoate, but not sarcosine alone, improved the cognitive and global functioning of patients with schizophrenia, even when their clinical symptoms had not improved. Conclusions This finding suggests N-methyl-d-aspartate receptor-enhancement therapy can improve the cognitive function of patients with schizophrenia, further indicating this pro-cognitive effect can be primary without improvement in clinical symptoms.

RISK OF NEW ONSET TYPE II DM IN MDD PATIENTS RECEIVING SECOND-GENERATION ANTIPSYCHOTICS TREATMENT: A NATIONWIDE COHORT STUDY.

BACKGROUND: Second-generation antipsychotics (SGA) augmentation treatment has showed better efficacy in patients with major depressive disorder (MDD). However, the association between SGA and diabetes mellitus (DM) in MDD patients deserves further investigation. The study aimed to examine the risk of new onset type II DM in MDD patients receiving SGA treatment. METHODS: From the Psychiatric Inpatient Medical Claim Dataset, MDD patients treated with SGA continuously for more than 8 weeks were analyzed in a 1:1 propensity score matched pair sample to 1,049 patients that had never been treated with SGA. Patients were followed up to 5 years based on ICD-9 CM codes indicating incident type II DM. Cumulative incidences of type II DM were calculated and the Cox proportional hazards model with competing risk was applied to determine the risk factors for type II DM onset. RESULTS: Cumulative incidences of new-onset type II DM between the two groups were similar. Use of SGA showed no significant increase in risk for new-onset type II DM (hazard ratio [HR] = 0.898; 95% confidence interval [CI], 0.605-1.334; P-value = 0.596). Increased risk for type II DM was shown to be associated with aging (per year) (HR = 1.039; 95% CI, 1.026-1.053; P-value < 0.001) and history of hyperlipidemia (HR = 2.323; 95% CI, 1.469-3.675; P-value < 0.001). CONCLUSIONS: This study indicated that there is no significant difference in the risk of developing type II DM between MDD patients with and without SGA exposure. More studies focused on the benefit-risk assessment of SGA treatment in patients with MDD are warranted.

High-resolution interference-monochromator for hard X-rays.

An X-ray interference-monochromator combining a Fabry-Perot resonator (FPR) and a double-crystal monochromator (DCM) is proposed and realized for obtaining single-mode X-rays with 3.45 meV energy resolution. The monochromator is based on the generation of cavity interference fringes from a FPR and single-mode selection of the transmission spectrum by a DCM of a nearly backward symmetric reflection geometry. The energy of the monochromator can be tuned within 2500 meV(= ΔE) by temperature control of the FPR and the DCM crystals in the range of ΔT = 70 K at room temperature. The diffraction geometry and small size of the optical components used make the interference-monochromator very easy to be adapted in modern synchrotron beamlines and X-ray optics applications.

Single-mode selection for hard x-ray cavity resonance.

Single-mode selection is realized for hard x-ray cavity resonance using a three-mirror crystal device. The developed device consists of two coupled Si Fabry-Perot resonators (FPRs) and uses (12 4 0) backward diffraction to reflect back and forth the incident 14.4388 keV x-ray beam. The coupling between the two cavities gives an effective single-mode spectrum with a bandwidth of 0.81 meV. This method can be used to enhance the longitudinal coherent length without affecting transverse coherence, and is potentially useful in generating nearly total coherent beams in synchrotron or free-electron laser facilities.

Peroral endoscopic myotomy (POEM) leads to similar results in patients with and without prior endoscopic or surgical therapy.

INTRODUCTION: Traditional treatment for the esophageal motility disorder, achalasia, ranges from endoscopic botulinum toxin (Botox) injections or balloon dilatation, to laparoscopic or open surgical myotomy. Recent advances in endoscopic therapy have led to peroral endoscopic myotomy (POEM) as a viable alternative to traditional techniques for myotomy. Uncertainty exists as to whether the procedure is feasible for patients who have already received prior endoscopic or surgical procedures for therapy, as these groups experience higher failure rates as well as intraoperative mucosal perforations and technical difficulty during Heller myotomy. We describe our first 40 patients who have undergone POEM and compare outcomes between patients who have or have not received previous treatment for achalasia. METHODS AND PROCEDURES: We evaluated our prospectively collected database of POEM procedures performed by two surgeons (JLP and JMM) at a single institution. Perioperative data was collected for operative and hospital outcomes. Patients completed pre- and postoperative GERD-Health-Related Quality of Life Questionnaires (GERD-HRQL) and SF-12 surveys for symptom scoring. RESULTS: Forty patients received a POEM procedure between 2011 and 2013. Of these, 40% (n = 16) had had at least one prior endoscopic or surgical procedure. Nine had prior Botox injections, 7 had balloon dilations, 3 had both Botox and dilations, and 3 received prior laparoscopic Heller myotomy (two with Dor fundoplication). Mean operative time was 102 min for patients with prior procedures (Prior Tx) and 118 min for patients without any prior procedure (No Tx) (p = 0.07). Intraoperative complication rates for the Prior Tx group were 12.5 versus 16.7% for the No Tx group. Mean follow-up was 10 months. Both groups independently demonstrated clinical improvement in both the GERD-HRQL and SF-12 scores following POEM. There were no statistical differences between the two groups for GERD-HRQL reflux and dysphagia subset scores, or SF-12 mental component summary. CONCLUSION: We found favorable outcomes following POEM in patients who have had prior endoscopic or surgical treatments for achalasia, as well as for patients without prior intervention. There were no significant differences between these two groups with regards to operative times, GERD-HRQL scores, and mental component SF-12 scores. One complication requiring intervention occurred in a patient that had received multiple prior Botox injections and balloon dilatations. POEM appears to be a viable alternative for treatment of achalasia compared to traditional techniques, however, long-term data are needed to establish the durability of this technique and to determine whether symptoms will recur necessitating re-intervention.

Effectiveness of aripiprazole, olanzapine, quetiapine, and risperidone augmentation treatment for major depressive disorder: a nationwide population-based study.

OBJECTIVE: Previous studies suggested that antidepressants augmented with second-generation antipsychotics (SGAs), including aripiprazole, olanzapine, quetiapine, and risperidone, resulted in better treatment response or higher rates of remission in patients with major depressive disorder (MDD). However, population-based study on SGA augmentation for patients with MDD remains limited. The purpose of this study was to investigate the effectiveness of SGA augmentation for treatment of MDD using the National Health Insurance Research Database in Taiwan. METHOD: The subjects were patients with MDD (ICD-9-CM code: 296.2 and 296.3) who were initially admitted to psychiatric inpatient settings for the first time between January 1, 1996, and December 31, 2007, and could be tracked until December 31, 2011. To assess the treatment effect of SGA augmentation, 993 MDD patients who received aripiprazole, olanzapine, quetiapine, or risperidone augmentation treatment for 8 weeks or more were included in this 1-year mirror-image study. Outcome measures included length of psychiatric hospitalization and number of psychiatric admissions and emergency room (ER) visits. RESULTS: After patients received SGA augmentation treatment, key psychiatric service use (including length of psychiatric hospitalization [P < .0001], number of psychiatric admissions [P < .0001], and ER visits [P = .0006]) due to MDD diagnosis was significantly reduced. Subgrouping analysis for each SGA drug also showed significant reduction in number of psychiatric admissions for MDD patients who received aripiprazole (P < .0001), olanzapine (P = .003), quetiapine (P < .0001), and risperidone (P < .0001). CONCLUSIONS: The study provides support that aripiprazole, olanzapine, quetiapine, and risperidone augmentation therapy could be effective in reducing psychiatric service utilization among MDD patients.

Preliminary results of antiscarring therapy in the prevention of postendoscopic esophageal mucosectomy strictures.

BACKGROUND: Esophageal endoscopic submucosal dissection (ESD) is an effective minimally invasive therapy for early esophageal cancer and high-grade Barrett dysplasia. However, esophageal stricture formation after circumferential or large ESD has limited its wide adoption. Mitomycin C (MMC), halofuginone (Hal), and transforming growth factor ß3 (TGF-ß3) exhibits antiscarring effects that may prevent post-ESD stricture formation. METHODS: Using endoscopic mucosectomy (EEM) technique, an 8- to 10-cm-long circumferential esophageal mucosal segment was excised in a porcine model. The site was either untreated (control, n = 6) or received 40 evenly distributed injections of antiscarring agent immediately and at weeks 1 and 2. High and low doses were used: MMC 5 mg (n = 2), 0.5 mg (n = 2); Hal 5 mg (n = 2), 1.5 mg (n = 2), 0.5 mg (n = 2); TGF-ß3 2 µg (n = 2), 0.5 µg (n = 2). The degree of stricture formation was determined by the percentage reduction of the esophageal lumen on weekly fluoroscopic examination. Animals were euthanized when strictures exceeded 80 % or the animals were unable to maintain weight. RESULTS: The control group had a luminal diameter reduction of 78.2 ± 10.9 % by 2 weeks and were euthanized by week 3. Compared at 2 weeks, the Hal group showed a decrease in mean stricture formation (68.4 % low dose, 57.7 % high dose), while both TGF-ß3 dosage groups showed no significant change (65.3 % low dose, 76.2 % high dose). MMC was most effective in stricture prevention (53.6 % low dose, 35 % high dose). Of concern, the esophageal wall treated with high-dose MMC appeared to be necrotic and eventually led to perforation. In contrast, low dose MMC, TGF-ß3 and Hal treated areas appeared re-epithelialized and healthy. CONCLUSIONS: Preliminary data on MMC and Hal demonstrated promise in reducing esophageal stricture formation after EEM. More animal data are needed to perform adequate statistical analysis in order to determine overall efficacy of antiscarring therapy.

Commercially available biological mesh does not prevent stricture after esophageal mucosectomy.

BACKGROUND AND STUDY AIMS: Endoscopic mucosal resection (EMR) offers a minimally invasive therapy for advanced esophageal dysplasia and early cancers but stricture formation limits its applicability. We aimed at assessing the efficacy of placement of a commercially available biological mesh for preventing stricture formation following esophageal EMR. METHODS: 25 swine were submitted to circumferential esophageal EMR with 10-cm extent and divided in five groups: one group with EMR only (control); one receiving an uncovered stent (stent-only group); and three groups receiving a stent covered with one of three extracellular matrices, namely small intestine submucosa (SIS group), acellular dermal matrix (ADM group), or urinary bladder matrix (UBM group). Stricture formation was evaluated with weekly esophagograms. RESULTS: The stent-only group had significantly less stricture formation and survival was extended compared with controls (4.8 vs. 2.4 weeks). Compared with stenting only, the addition of a biological mesh did not reduce stricture formation: percent reductions in esophageal diameter for the groups were SIS 86 %, ADM 94 %, and UBM 94 %, compared with 82 % in the stent-only group. CONCLUSIONS: Placement of commercially available biological meshes did not alter remodeling sufficiently to prevent stricture formation after esophageal EMR.

Inverse association between cancer risks and age in schizophrenic patients: a 12-year nationwide cohort study.

The association between schizophrenia and cancer risk is contentious in the clinical and epidemiological literature. Studies from different populations, tumor sites, or health care systems have provided inconsistent findings. In the present study, we examined a less well-investigated hypothesis that age plays a crucial role in cancer risk in schizophrenia. We conducted a nationwide cohort study using Taiwan's National Health Insurance Research Database (NHIRD) between 1995 and 2007. Overall, gender-, and age-stratified standardized incidence ratios (SIR) were used to investigate the pattern of cancer risk by age. Of the 102 202 schizophrenic patients, 1738 developed cancer after a diagnosis of schizophrenia (SIR = 0.92; 95% confidence interval [CI] 0.90-0.96). However, the age-stratified SIR declined with age (e.g. SIR [95% CI] = 1.97 [1.85-2.33], 0.68 [0.65-0.78], and 0.36 [0.34-0.45] for those aged 20-29, 60-69, and ≥70 years, respectively) in both genders and for major cancers. Cancer risks in schizophrenic patients were lower for cancers that are more likely to develop at an older age in the general population (e.g. stomach cancer [SIR = 0.62; 95% CI 0.57-0.80], pancreatic cancer [SIR = 0.49; 95% CI 0.39-0.84], and prostate cancer [SIR = 0.35; 95% CI 0.29-0.58]). In contrast, cancer risks were higher for cancers that have a younger age of onset, such as cancers of the nasopharynx (SIR = 1.18; 95% CI 1.08-1.49), breast (SIR = 1.50; 95% CI 1.44-1.66) and uterine corpus (SIR = 2.15; 95% CI 1.98-2.74). The unique age structures and early aging potential of schizophrenia populations may contribute to the observed inverse relationship between age and cancer risk. Higher cancer comorbidity in young schizophrenic patients deserves more attention.

Restoration of C/EBPα in dedifferentiated liposarcoma induces G2/M cell cycle arrest and apoptosis.

Well-differentiated liposarcoma (WDLS) and dedifferentiated liposarcoma (DDLS) represent the most common biological group of liposarcoma, and there is a pressing need to develop targeted therapies for patients with advanced disease. To identify potential therapeutic targets, we sought to identify differences in the adipogenic pathways between DDLS, WDLS, and normal adipose tissue. In a microarray analysis of DDLS (n = 84), WDLS (n = 79), and normal fat (n = 23), C/EBPα, a transcription factor involved in cell cycle regulation and differentiation, was underexpressed in DDLS when compared to both WDLS and normal fat (15.2- and 27.8-fold, respectively). In normal adipose-derived stem cells, C/EBPα expression was strongly induced when cells were cultured in differentiation media, but in three DDLS cell lines, this induction was nearly absent. We restored C/EBPα expression in one of the cell lines (DDLS8817) by transfection of an inducible C/EBPα expression vector. Inducing C/EBPα expression reduced proliferation and caused cells to accumulate in G2/M. Under differentiation conditions, the cell proliferation was reduced further, and 66% of the DDLS cells containing the inducible C/EBPα expression vector underwent apoptosis as demonstrated by annexin V staining. These cells in differentiation conditions expressed early adipocyte-specific mRNAs such as LPL and FABP4, but they failed to accumulate intracellular lipid droplets, a characteristic of mature adipocytes. These results demonstrate that loss of C/EBPα is an important factor in suppressing apoptosis and maintaining the dedifferentiated state in DDLS. Restoring C/EBPα may be a useful therapeutic approach for DDLS.