Comparison of different dosages of propofol combined with its equivalent alfentanil in outpatient abortion: a prospective, double-blinded, randomized trial.

OBJECTIVE: This study aimed at determining the optimal dose combination of alfentanil and propofol for outpatient abortion anesthesia. PATIENTS AND METHODS: The study was separated into two parts. In the first part, patients were to determine the median effective dose (ED50) and the 95% effective dose (ED95) of alfentanil in combination with 2.5 mg·kg-1 propofol to inhibit body movements during the abortion using the Dixon up-and-down sequential allocation method. In the second part, 170 patients were randomly divided into group C (2.0 mg·kg-1 propofol with alfentanil 12.16 µg·kg-1) and group E (2.5 mg·kg-1 propofol with its ED95) to compare the anesthetic effect. The primary outcome was the sedation level during general anesthesia. The secondary outcomes were circulation, respiratory complications, and postoperative recovery quality. RESULTS: The ED50 and the ED95 values of alfentanil were 3.37 µg·kg-1 (95% CI: 2.58-3.97 µg·kg-1) and 4.68 µg·kg-1 (95% CI: 4.04-9.32 µg·kg-1). The frequency of deep sedation in group E was significantly higher than in group C (76.5% vs. 60%). Patients in group C showed more wakefulness even during the surgery (14.3% vs. 4.4%). The results of our exploratory analyses did not reveal differences in respiratory depression, circulatory depression, postoperative side effects, or recovery outcomes. CONCLUSIONS: The combination of 2.5 mg·kg-1 propofol and 4.68 µg·kg-1 alfentanil produces a better sedative effect than the combination of 2.0 mg·kg-1 propofol and 12.16 µg·kg-1 alfentanil without increasing additional risks associated with anesthesia.

[Analysis of disease composition and primary surgical procedures in pediatric secondary glaucoma inpatients: a single-center study].

Objective: To analyze the disease composition and primary surgical procedures in pediatric inpatients with secondary glaucoma. Methods: A retrospective case series study was conducted. Clinical data of children aged≤16 years with secondary glaucoma who were admitted to the Zhongshan Ophthalmic Center, Sun Yat-sen University, between January 1, 2017, and December 31, 2021, were included. The patients were classified according to the Childhood Glaucoma Research Network (CGRN) classification system, and their diagnoses, underlying factors, gender, age of onset, affected eye(s), age and type of initial surgery, and ophthalmic examination data were analyzed. Statistical analysis was performed using Kruskal-Wallis rank sum test and χ2 test. Results: A total of 540 patients (744 eyes) were included in this study, comprising 319 males (59.1%) and 221 females (40.9%). Unilateral disease was observed in 336 cases (62.2%), while bilateral involvement was present in 204 cases (37.8%). The age of onset was 4.0 (0.0, 9.0) years, and the median age of the first anti-glaucoma surgery was 5.0 (0.7, 10.0) years. Among them, there were 195 cases (36.1%) of secondary glaucoma associated with non-acquired ocular anomalies (SCG-O), with a median age of onset of 0.0 (0.0, 4.0) years, and 97 of these cases (49.7%) were male. secondary glaucoma associated with non-acquired systemic disease or syndrome (SCG-S) were observed in 68 cases (12.6%), with a median age of glaucoma onset of 0.1 (0.0, 4.0) years, and 47 of these cases (69.1%) were male. Secondary glaucoma associated with acquired conditions (SCG-A) accounted for 192 cases (35.6%), with a median age of onset of 9.0 (5.0, 13.0) years, and 125 of these cases (65.1%) were male. There were 85 cases (15.7%) of secondary glaucoma following cataract surgery (SCG-C), with a median age of onset of 3.0 (0.8, 7.0) years, and 50 of these cases (58.8%) were male. Male patients were predominant in SCG-S and SCG-A, with 47 cases (69.1%) and 125 cases (65.1%), respectively (χ2=9.94, 17.52; P=0.002,<0.001). Except for SCG-O, all other types of pediatric secondary glaucoma predominantly affected only one eye: SCG-S in 52 cases (76.5%), SCG-A in 128 cases (66.7%), and SCG-C in 54 cases (63.5%) (χ2=19.06, 21.33, 6.22; all P<0.05). The highest proportion of SCG-O was attributed to congenital ectropion uveae (46 cases, 23.6%). Sturge-Weber syndrome was the most common SCG-S (45 cases, 66.3%), while SCG-A mostly resulted from trauma (59 cases, 30.8%) and corticosteroid use (56 cases, 29.2%). Trabeculectomy (211 eyes, 30.8%) and glaucoma drainage device implantation (197 eyes, 28.7%) were the most frequently performed primary surgical procedures. Conclusions: SCG-O and SCG-A were found to be common types of pediatric secondary glaucoma. The age of onset and the choice of primary anti-glaucoma surgical procedures varied among different types of pediatric secondary glaucoma. However, overall, trabeculectomy and glaucoma drainage device implantation were the primary surgical procedures predominantly employed.

[Clinical features of young inpatients with angle-closure glaucoma].

Objective: To analyze the composition of diagnosis in young inpatients with angle-closure glaucoma and to compare the clinical characteristics between primary angle-closure glaucoma (PACG) and secondary angle-closure glaucoma (SACG). Methods: This was a retrospective case series study. Angle-closure glaucoma patients aged 40 years or younger and hospitalized in Zhongshan Ophthalmic Center from January 2012 to December 2019 were included. The clinical diagnosis, gender, onset age, and results of general ophthalmic examination, A-scan ultrasonography measurements, ultrasound biomicroscopy, optical coherence tomography and visual field were recorded. The proportions and composition of PACG and SACG, as well as the misdiagnosis ratio, were analyzed. The onset age, visual acuity, visual field, and ocular parameters were compared between patients with PACG and SACG. Non-normally distributed data were represented by M (Q1, Q3). The difference between groups were compared by Mann-Whitney U test, Chi square test, and independent sample t test. Results: A total of 243 patients (243 eyes) were included in this study. The mean onset age was (28±9) years, and the male-to-female ratio was 1∶1.79. There were 93 patients (38.3%) in PACG group and 150 (61.7%) in SACG group. The age of PACG [34(28, 38)] was older than that of SACG [28(19, 34)], and the proportion of males in the SACG group (44.0%, 66/150) was significantly higher than that in the PACG group (22.6%, 21/93) (Z=-5.34, χ2=11.46; both P<0.01). Nanophthalmos (22.7%, 34 cases), autosomal recessive bestrophinopathy (ARB) (19.3%, 29 cases), uveitis (18.7%, 28 cases) and retinitis pigmentosa (14.0%, 21 cases) were the most common causes of SACG. The best corrected visual acuity (logarithm of the minimum angle of resolution) was 0.10 (0.00, 0.48) and 0.40 (0.06, 1.00), mean deviation of visual field was -8.07 (-27.49, -2.09) and -15.04 (-28.75, -5.97) dB, and subfoveal choroidal thickness was (452.3±130.7) and (396.3±120.9) µm in the PACG and SACG groups, respectively. The differences were statistically significant (Z=-4.86, -2.14; t=2.37; all P<0.05). There was no statistical difference in intraocular pressure, cup-to-disc ratio, extent of peripheral anterior synechia, central anterior chamber depth, lens thickness, mean retinal nerve fiber layer thickness between these two groups (all P>0.05). The misdiagnosis ratio was 10.7% (26/243) in all patients, while the misdiagnosis ratio of the SACG group (16.7%, 25/150) was higher than that of the PACG group (1.1%, 1/93) (χ²=14.61, P<0.001). Conclusions: PACG, nanophthalmos and ARB are the most common etiologies in young inpatients with angle-closure glaucoma. Compared to PACG, patients with SACG are younger, with worse visual acuity and more severe visual field defects, and easier to be misdiagnosed.

[Survey on the stunting of children under seven years of age in nine cities of China].

Objective: To survey the children under 7 years of age in nine cities of China for a better understanding of the current situation of childhood stunting. Methods: According to a stratified cluster sampling design, a cross-sectional survey on children under 7 years of age was carried out in 9 cities (Beijing, Harbin and Xi'an in northern China; Shanghai, Nanjing and Wuhan in central China; and Guangzhou, Fuzhou and Kunming in southern China) from June to November in 2016. A total of 110 499 children were recruited. Height of children was evaluated using the growth standards for Chinese children (2009 edition) .Children with height less than the 3rd percentile of the growth standards were considered as stunting, and children with height between the 3rd and 10th percentiles of the growth standards were considered as relatively short stature. Chi-square test was used for comparison between data of boys and girls, urban and suburban, as well as among different ages and regions. Results: Totally 113 084 children under 7 years of age should be investigated and actually 110 499 children were investigated, with a rate of 97.7%. The prevalence of stunting was 1.9% (2 141/110 499) among all the children. The prevalence of stunting in urban children (1.6%, 904/55 524) was lower than that in suburban children (2.3%, 1 237/54 975, χ(2)=56.246, P<0.01). The gender difference in stunting prevalence was not statistically significant (1.9% (1 121/57 921) in boys and 1.9% (1 020/52 578) in girls, χ(2)=0.003, P=0.965). The prevalence of stunting decreased with age for children younger than 3 years, from 1.8% (312/17 080) in 0-<1 year of age group to 1.2% (168/13 740) in 2-<3 years of age group, but increased to 2.2% (240/11 073) at 6-<7 years group. Comparison among different regions showed that the stunting prevalence in southern region was higher than those in the central and northern regions (0.9% (193/20 374) in northern urban, 0.8% (154/18 486) in central urban, and 3.3% (557/16 664) in southern urban children), showing a statistical significance (χ(2)=437.736, P<0.01); 1.1% (241/21 924) in northern suburban, 1.4% (227/16 775) in central suburban and 4.7% (769/16 276) in southern suburban children, showing a statistical significance (χ(2)=646.533, P<0.01). In urban areas, the difference between the central and northern regions showed no statistical significance (χ(2)=1.429, P=0.232) and the stunting prevalence of central Chinese children was slightly higher than that of northern Chinese children in suburban areas (χ(2)=5.130, P=0.024). Among the nine cities, the stunting prevalence of Guangzhou (6.1%, 613/10 019) was higher than those of other cities (χ(2)=1 559.64, P<0.01). Among the stunting children, 78.4% (1 679/2 141) were classified as borderline or mild and only 7.2% (154/2 141) were classified as severe. The prevalence of relatively short stature was 5.2% (5 721/110 499). Conclusions: The prevalence of stunting among children under 7 years of age in nine cities of China is low and most of the stunting children were classified as mild; the prevalence of stunting in suburban children is higher than that in urban children; the gender difference show no statistical significance; and the prevalence of stunting in southern Chinese children is higher than those in central and northern Chinese children.

[Association between both maternal pre-pregnancy body mass index/gestational weight gain and overweight/obesity children at preschool stage].

Objective: To investigate the association of both maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) with childhood overweight and adiposity in preschool children. Methods: A total of 4 303 preschool children aged 3-5 years were enrolled in our study during June and November 2016 in Guangzhou. Children defined as overweight and obesity were according to the criteria of WHO while weight status during maternal pre-pregnancy was using the China Adult Reference. Gestational weight gain was defined according to the Institute of Medicine guidelines. Results: After adjusting the possible confounding factors, results from the logistic regression analysis showed that both maternal pre-pregnancy overweight and obesity would increase the risk for both childhood overweight and obesity (OR=1.820, 95%CI: 1.368-2.422). The analysis of covariance results also showed that both maternal overweight and obesity before pregnancy and excessive maternal weight gain during pregnancy increased the BMI Z-score in children. Maternal GWG over the recommended level were associated with both the childhood overweight and obesity (OR=1.296, 95%CI: 1.007-1.667). Joint associations of pre-pregnancy BMI and inappropriate GWG were also noticed in the study. Stratified analysis was conducted in three groups according to the pre-pregnancy BMI of the mothers. Result showed that there was no statistical difference in the risks of either overweight or obesity in children (P>0.05). However, when compared to mothers with adequate pre-pregnancy higher BMI and adequate GWG, under the combination of high pre-pregnancy BMI and excessive GWG, their adverse effects on childhood overweight and obesity were much higher (OR=1.574, 95%CI: 1.029-2.409). Conclusions: Both high pre-pregnancy BMI and inappropriate GWG were associated with greater BMI of their offspring. Pregnant women should follow the appropriate weight gain program and help their children to prevent from becoming obese.

[Influence of antiretroviral prophylaxis on growth of HIV-exposed uninfected infants].

Objective: To evaluate the influence of antiretroviral prophylaxis on the growth and development of HIV-exposed uninfected infants in Guangzhou. Methods: Data were from the national information system for prevention of mother-to-child transmission of HIV infection, syphilis and hepatitis B. After excluding death and perinatal HIV infection cases, 564 HIV-exposed uninfected infants were included. The infants were divided into three groups, nevirapine (NVP) group, zidovudine (AZT) group and untreated group. The influences of antiretroviral prophylaxis on the body weight and height of the HIV-exposed uninfected infants were analyzed by using generalized estimating equations. Results: The HIV-exposed uninfected infants at 1-month old had lower Z scores of body weight-for-age and body height-for-age than the World Health Organization's reference standard. The prevalence of wasting in AZT group (17.5%) was higher than that in NVP group (6.2%) for 1-month old infants. Taking NVP or AZT was a protective factor for Z score of body length-for-age (P<0.05). Intrauterine exposure to triple antiviral drugs was a risk factor for the Z scores of body weight-for-age and body length-for-age (P<0.05). Conclusion: The physical growth and development of HIV-exposed uninfected infants at 1-month old was not well, and HIV-exposed uninfected infants who taking AZT had a higher incidence of wasting. Attention should be paid to these infants.

Imaging of cerebral α4ß2* nicotinic acetylcholine receptors with (-)-[(18)F]Flubatine PET: Implementation of bolus plus constant infusion and sensitivity to acetylcholine in human brain.

The positron emission tomography (PET) radioligand (-)-[(18)F]flubatine is specific to α4ß2(⁎) nicotinic acetylcholine receptors (nAChRs) and has promise for future investigation of the acetylcholine system in neuropathologies such as Alzheimer's disease, schizophrenia, and substance use disorders. The two goals of this work were to develop a simplified method for α4ß2(⁎) nAChR quantification with bolus plus constant infusion (B/I) (-)-[(18)F]flubatine administration, and to assess the radioligand's sensitivity to acetylcholine fluctuations in humans. Healthy human subjects were imaged following either bolus injection (n=8) or B/I (n=4) administration of (-)-[(18)F]flubatine. The metabolite-corrected input function in arterial blood was measured. Free-fraction corrected distribution volumes (VT/fP) were estimated with modeling and graphical analysis techniques. Next, sensitivity to acetylcholine was assessed in two ways: 1. A bolus injection paradigm with two scans (n=6), baseline (scan 1) and physostigmine challenge (scan 2; 1.5mg over 60min beginning 5min prior to radiotracer injection); 2. A single scan B/I paradigm (n=7) lasting up to 240min with 1.5mg physostigmine administered over 60min beginning at 125min of radiotracer infusion. Changes in VT/fP were measured. Baseline VT/fP values were 33.8±3.3mL/cm(3) in thalamus, 12.9±1.6mL/cm(3) in cerebellum, and ranged from 9.8 to 12.5mL/cm(3) in other gray matter regions. The B/I paradigm with equilibrium analysis at 120min yielded comparable VT/fP values with compartment modeling analysis of bolus data in extrathalamic gray matter regions (regional means <4% different). Changes in VT/fP following physostigmine administration were small and most pronounced in cortical regions, ranging from 0.8 to 4.6% in the two-scan paradigm and 2.8 to 6.5% with the B/I paradigm. These results demonstrate the use of B/I administration for accurate quantification of (-)-[(18)F]flubatine VT/fP in 120min, and suggest possible sensitivity of (-)-[(18)F]flubatine binding to physostigmine-induced changes in acetylcholine levels.

Additional chromosomal abnormalities in core-binding factor acute myeloid leukemia.

Despite sharing a similar genetic abnormality, patients with core binding factor acute myeloid leukemia (CBF-AML), which is characterized by the presence of t(8;21) or inv(16)/t(16;16), show heterogeneous survival. Other molecular or cytogenetic factors are supposed to have an impact on the prognosis. We enrolled 24 CBF-AML patients to determine the impact of cytogenetic abnormality, and c-KIT, FLT3, NPM1, and CEBPA mutations on the prognosis. Only three patients had the c-KIT mutation (3/24, 12.5%) and one had the FLT3 mutation. However, over half of the patients (14/24) harbored additional cytogenetic changes, including ten with loss of sexual chromosomes (LOS) [all in the t(8;21) group], and six had additional abnormalities (two cases had both LOS and additional abnormalities). From this small-number study, no association was found between c-KIT mutation and survival and relapse rate. However, additional chromosome abnormalities had a significant association with relapse of the disease (P = 0.027). Stem cell transplant had a trend of benefitting patients after relapse (P = 0.065). This implies that chromosome abnormalities occur in CBF-AML and might take part in the heterogeneous nature of CBF-AML.

Development of primer pairs from diverse chloroplast genomes for use in plant phylogenetic research.

Variation in the chloroplast DNA sequence is useful for plant phylogenetic studies. However, the number of variable sequences provided by chloroplast DNA for suggested genes or genomic regions in plant phylogenetic analyses is often inadequate. To identify conserved regions that can be used to design primers and amplify variable sequences for use in plant phylogenetic studies, the complete chloroplast genomic sequences of six plant species (including Oryza sativa, Arabidopsis thaliana, Glycine max, Lotus japonicus, Medicago truncatula, and Phaseolus vulgaris), searched from the taxonomy database of NCBI were investigated. A total of 93 conserved regions, 32 in large single copy and 61 in inverted repeat regions, were identified. A set of five primer pairs were designed according to the conserved sequences located in the psbA~trnK, psbB~psbH, rpl23~trnI, trnR~trnN, and trnY~trnD regions to amplify variable DNA fragments. An additional 18 plant accessions from 14 species were used to validate their utility. Each of the tested species could be distinguished by length polymorphisms of fragments amplified with the five primer pairs. trnR~trnN and rpl23~trnI amplified fragments specific to monocot and legume species, respectively. Three primer pairs located in the psbA~trnK, psbB~psbH, and trnR~trnN regions were applied to amplify variable DNA sequences for phylogenetic analysis using the maximum parsimony method. The consistent result between taxonomy and phylogenetic analysis on the variable sequences amplified with these three primer pairs was revealed. The five newly developed primer pairs are recommended as tools for use in the identification of plant species and in phylogenetic studies.

Value of human brain natriuretic peptide in treatment of acute anterior myocardial infarction evaluated via three-dimensional speckle tracking imaging.

Three-dimensional ultrasound speckle tracking imaging was used to evaluate the effects of recombinant human brain natriuretic peptide (rhBNP) in acute anterior and extensive anterior myocardial infarction. Ninety patients with acute anterior or extensive myocardial infarction were randomly divided into 3 groups: Group A [emergency percutaneous coronary intervention (PCI)], Group B (emergency PCI + rhBNP early treatment), and Group C (emergency PCI + late rhBNP treatment). Within 6 h of admission and at 1 week and 3 and 6 months after PCI, patients underwent routine transthoracic echocardiography and real-time three-dimensional echocardiography. At 1 week, 1 month, 3 months, 6 months, and 12 months, ejection fraction values in groups B and C were significantly greater than those in group A (P < 0.05), and left ventricular end-diastolic volume and left ventricular end-systolic volume values in groups B and C were less than those in group A (P < 0.05). Within 6 h of admission in each group, long-axis, radial, circumferential, and area variables corresponding to anterior descending artery segments showed no significant difference (all P > 0.05). However, at 1 week, 1 month, 3 months, 6 months, and 12 months, long-axis, radial, circumferential and area variables in groups B and C were significantly less than those in group A (P < 0.05). Intervention with rhBNP can im-prove resilience of the local myocardium, left ventricular mechanical function, and cardiac remodeling. Within 6 h of admission or after PCI, rhBNP application showed no significant difference in heart function improvement or myocardial remodeling inhibition.

Hepatitis C transmission from viremic donors in hematopoietic stem cell transplant.

Transmission of hepatitis C virus (HCV) to recipients of hematopoietic stem cell transplant (HSCT) occurs frequently from HCV viremic donors and causes complications. Here, we report the outcomes of 3 cases from our 265 allogeneic HSCTs, whose donors had HCV infections. Successful prevention of HCV transmission was noted in 1 recipient by pretreatment of the donor with peginterferon/ribavirin to undetectable levels of HCV viremia before stem cell harvest. This case stressed the important role of effective antiviral therapy and HCV RNA seronegativity before cell harvest for prevention of HCV transmission in HSCT.

Clinical doses of atomoxetine significantly occupy both norepinephrine and serotonin transports: Implications on treatment of depression and ADHD.

BACKGROUND: Atomoxetine (ATX), a drug for treatment of depression and ADHD, has a high affinity for the norepinephrine transporter (NET); however, our previous study showed it had a blocking effect similar to fluoxetine on binding of [(11)C]DASB, a selective serotonin transporter (SERT) ligand. Whether the therapeutic effects of ATX are due to inhibition of either or both transporters is not known. Here we report our comparative PET imaging studies with [(11)C]MRB (a NET ligand) and [(11)C]AFM (a SERT ligand) to evaluate in vivo IC50 values of ATX in monkeys. METHODS: Rhesus monkeys were scanned up to four times with each tracer with up to four doses of ATX. ATX or saline (placebo) infusion began 2h before each PET scan, lasting until the end of the 2-h scan. The final infusion rates were 0.01-0.12mg/kg/h and 0.045-1.054mg/kg/h for the NET and SERT studies, respectively. ATX plasma levels and metabolite-corrected arterial input functions were measured. Distribution volumes (VT) and IC50 values were estimated. RESULTS: ATX displayed dose-dependent occupancy on both NET and SERT, with a higher occupancy on NET: IC50 of 31±10 and 99±21ng/mL plasma for NET and SERT, respectively. At a clinically relevant dose (1.0-1.8mg/kg, approx. 300-600ng/mL plasma), ATX would occupy >90% of NET and >85% of SERT. This extrapolation assumes comparable free fraction of ATX in humans and non-human primates. CONCLUSION: Our data suggests that ATX at clinically relevant doses greatly occupies both NET and SERT. Thus, therapeutic modes of ATX action for treatment of depression and ADHD may be more complex than selective blockade of NET.

Tumoral presence of human cytomegalovirus is associated with shorter disease-free survival in elderly patients with colorectal cancer and higher levels of intratumoral interleukin-17.

Infectious diseases are closely related to cancer. Human cytomegalovirus (HCMV) has been implicated in the promotion of tumour growth, and is present in the tumour specimens of colorectal cancer (CRC). This study aimed to investigate whether tumoral presence of HCMV is associated with a different clinical outcome in elderly patients with CRC. We analysed archived tumour specimens from 95 CRC patients aged ≥65 years. HCMV was detected by PCR. Clinical, pathological, disease-free and overall survival data were compared between patients with HCMV-positive and HCMV-negative tumours. A quantitative RT-PCR array was used to evaluate the expression levels of cytokines genes of T-helper subpopulations in tumours. In the Kaplan-Meier analysis of the 81 patients who underwent curative surgery, 39 patients with HCMV-positive tumours had a lower disease-free survival rate (p 0.024). For patients with stage II or stage III tumours, tumoral HCMV status correlated with disease-free survival more closely than the traditional histopathological staging methods. In a multivariate Cox proportional hazard model, tumoral presence of HCMV independently predicted tumour recurrence in 5 years (hazard ratio 4.42; 95% CI 1.54-12.69, p 0.006). The qRT-PCR analysis of ten stage II tumours showed that the gene expression levels of interleukin-17-the signature cytokine of T-helper 17 cells-and its receptor, interleukin-17 receptor C, were higher in the five HCMV-positive tumours. Our results suggest that the presence of HCMV in CRC is associated with poorer outcome in elderly patients. How the virus interacts with the tumour microenvironment should be further investigated.

Prognostic implication of molecular aberrations in cytogenetically normal acute myeloid leukemia patients receiving allogeneic hematopoietic stem cell transplantation.

Different molecular aberrations can be discriminated into certain prognostic subgroups in cytogenetically normal acute myeloid leukemia (CN-AML) patients but their impact on allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains controversial and studies from Asian populations are lacking. Forty-two adult non-M3 AML patients receiving allo-HSCT from 2002 to 2009 in southern Taiwan were retrospectively reviewed for survey, 23 (54.7%) of whom were CN-AML. NPM1, FLT3-ITD, and CEBPA were analyzed. After a median follow-up of 104 weeks (range, 8 to 384), patients in the good risk group (harboring either NPM1 or CEBPA mutation without concurrent FLT3-ITD) showed a borderline worse overall survival (OS) compared with the intermediate/poor risk group (P = 0.08). Interestingly, a poorer OS was found in patients with the CEBPA mutation (P = 0.003) but not the NPM1 mutation (P = 0.96). No OS difference was found between patients with or without FLT3-ITD (P = 0.15). In patients receiving allo-HSCT at first remission, there was no significant OS benefit in the good risk group (P = 0.33). In patients receiving allo-HSCT beyond first remission, disease status played a major role (P = 0.006), irrespective of molecular aberrations. Allo-HSCT in good risk patients should be carefully evaluated in Taiwanese, especially in patients with the CEBPA mutation. Conversely, allo-HSCT should be considered in first remission in patients with an intermediate/poor risk, where it may overcome the adverse impact of FLT3-ITD. Disease status remained a main issue in patients receiving allo-HSCT beyond first remission.

Decreased expression of PIAS1 and PIAS3 in essential thrombocythemia patients.

Gain of function mutation of Janus kinase 2 (JAK2V617F) has been identified in Philadelphia-negative myeloproliferative diseases; about half of essential thrombocythemia (ET) patients harbor this mutation. The activated JAK-STAT pathway promotes cell proliferation, differentiation and anti-apoptosis. We studied the role of negative regulators of the JAK-STAT pathway, PIAS, and SOCS in ET patients. Twenty ET patients and 20 healthy individuals were enrolled in the study. Thirteen of the ET patients harbored the JAK2V617F mutation based on mutation analysis. Quantitative-PCR was applied to assay the expression of SOCS1, SOCS3, PIAS1, PIAS3. The expression levels of PIAS1 and PIAS3 were significantly lower in ET groups than that in normal individuals. There was no significant difference between JAK2V617F (+) and JAK2V617F (-) patients. SOCS1 and SOCS3 expression did not differ between ET patients and normal individuals, or between JAK2V617F (+) and JAK2V617F (-) patients. We suggest that failed negative regulators of the JAK-STAT pathway take part in the pathomechanism of ET.

Protogenin prevents premature apoptosis of rostral cephalic neural crest cells by activating the α5ß1-integrin.

The bones and connective tissues of the murine jaws and skull are partly derived from cephalic neural crest cells (CNCCs). Here, we report that mice deficient of protogenin (Prtg) protein, an immunoglobulin domain-containing receptor expressed in the developing nervous system, have impairments of the palatine and skull. Data from lineage tracing experiments, expression patterns of neural crest cell (NCC) marker genes and detection of apoptotic cells indicate that the malformation of bones in Prtg-deficient mice is due to increased apoptosis of rostral CNCCs (R-CNCCs). Using a yeast two-hybrid screening, we found that Prtg interacts with Radil, a protein previously shown to affect the migration and survival of NCCs in zebrafish with unknown mechanism. Overexpression of Prtg induces translocation of Radil from cytoplasm to cell membrane in cultured AD293 cells. In addition, overexpression of Prtg and Radil activates α5ß1-integrins to high-affinity conformational forms, which is further enhanced by the addition of Prtg ligand ERdj3 into cultured cells. Blockage of Radil by RNA interference abolishes the effect of ERdj3 and Prtg on the α5ß1-integrin, suggesting that Radil acts downstream of Prtg. Prtg-deficient R-CNCCs display fewer activated α5ß1-integrins in embryos, and these cells show reduced migratory ability in in vitro transwell assay. These results suggest that the inside-out activation of the α5ß1-integrin mediated by ERdj3/Prtg/Radil signaling is crucial for proper functions of R-CNCCs, and the deficiency of this pathway causes premature apoptosis of a subset of R-CNCCs and malformation of craniofacial structures.

Elevated brain cannabinoid CB1 receptor availability in post-traumatic stress disorder: a positron emission tomography study.

Endocannabinoids and their attending cannabinoid type 1 (CB1) receptor have been implicated in animal models of post-traumatic stress disorder (PTSD). However, their specific role has not been studied in people with PTSD. Herein, we present an in vivo imaging study using positron emission tomography (PET) and the CB1-selective radioligand [(11)C]OMAR in individuals with PTSD, and healthy controls with lifetime histories of trauma (trauma-exposed controls (TC)) and those without such histories (healthy controls (HC)). Untreated individuals with PTSD (N=25) with non-combat trauma histories, and TC (N=12) and HC (N=23) participated in a magnetic resonance imaging scan and a resting PET scan with the CB1 receptor antagonist radiotracer [(11)C]OMAR, which measures the volume of distribution (VT) linearly related to CB1 receptor availability. Peripheral levels of anandamide, 2-arachidonoylglycerol, oleoylethanolamide, palmitoylethanolamide and cortisol were also assessed. In the PTSD group, relative to the HC and TC groups, we found elevated brain-wide [(11)C]OMAR VT values (F(2,53)=7.96, P=0.001; 19.5% and 14.5% higher, respectively), which were most pronounced in women (F(1,53)=5.52, P=0.023). Anandamide concentrations were reduced in the PTSD relative to the TC (53.1% lower) and HC (58.2% lower) groups. Cortisol levels were lower in the PTSD and TC groups relative to the HC group. Three biomarkers examined collectively--OMAR VT, anandamide and cortisol--correctly classified nearly 85% of PTSD cases. These results suggest that abnormal CB1 receptor-mediated anandamide signaling is implicated in the etiology of PTSD, and provide a promising neurobiological model to develop novel, evidence-based pharmacotherapies for this disorder.

Genetic profile of tuberculosis among the migrant population in Fujian Province, China.

SETTING: The Fujian District in China has a high migrant worker population. Although tuberculosis (TB) among migrants is a serious threat to public health in Fujian, little is known about the molecular characteristics of TB isolates in this population. OBJECTIVE: To investigate the genetic profile of TB among the migrant population in Fujian. RESULTS: Our study enrolled 243 pulmonary TB patients registered in Fujian. Our data demonstrated that the Beijing genotype was the most common genotype in Fujian, and that the proportion of migrants with the Beijing genotype was significantly higher than that of permanent residents. Furthermore, the population structure of Mycobacterium tuberculosis strains in Fujian was diverse, with no difference in the distribution of mycobacterial interspersed repetitive units-variable number of tandem repeat (MIRU-VNTR) subgroups between the migrant and permanent populations. In addition, the discriminatory power of MIRU-VNTR in this study was higher than that found in other regions of China, possibly due to the high percentage of migrants in Fujian. CONCLUSION: The Beijing genotype was the predominant genotype in Fujian. TB strains isolated from this migrant population revealed a genetic profile similar to that of the permanent population. Improvement in public medical and insurance programmes for migrants might be crucial in the effective control of TB in Fujian.

Philadelphia-negative chromosomal evolution during treatment for chronic myeloid leukemia.

Chromosome evolution is one of the major mechanisms of disease progression and resistance in chronic myeloid leukemia (CML) patients. However, the clinical significance of chromosomal evolution in the Philadelphia (Ph)-negative clone during therapy is not fully understood. We evaluated 94 CML patients in the chronic phase of CML during treatment of the disease. Six of them had Ph-negative chromosome abnormalities during treatment. Four patients with a single abnormality and a good molecular response showed no obvious complications from the chromosomal changes, while two other patients who had complex abnormalities and previous treatment had poor outcomes. Our results highlight the need for close monitoring of this kind of patient, not only on a molecular level but also at the cytogenetic level.