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Objective We present prenatal diagnosis of mosaic trisomy 16 by amniocentesis in a pregnancy associated with an abnormal first-trimester screening result, intrauterine growth restriction (IUGR) and a favorable outcome. Case report A 27-year-old woman underwent amniocentesis at 18 weeks of gestation because of an abnormal first-trimester screening result with maternal serum free β-hCG of 1.474 multiples of the median (MoM), pregnancy associated plasma protein-A (PAPP-A) of 0.122 MoM and placental growth factor (PlGF) of 0.101 MoM, and a Down syndrome risk of 1/45. Amniocentesis revealed a karyotype of 47,XY,+16 [9]/46,XY [16] and an abnormal array comparative genomic hybridization (aCGH) result of arr (16) × 3 [0.54] compatible with 54% mosaicism for trisomy 16 in uncultured amniocytes. At 24 weeks of gestation, repeat amniocentesis revealed a karyotype of 47,XY,+16 [4]/46,XY [16] and an aCGH result of arr 16p13.3q24.3 (96,766–90,567,357) × 2.25 with a log2 ratio = 0.2 compatible with 20–30% mosaicism for trisomy 16 in uncultured amniocytes. Quantitative fluorescent polymerase chain reaction (QF-PCR) excluded uniparental disomy (UPD) 16. Interphase fluorescence in situ hybridization (FISH) analysis on uncultured amniocytes revealed 19.4% (12/62 cells) mosaic trisomy 16. Prenatal ultrasound revealed IUGR. At 36 weeks of gestation, a phenotypically normal baby was delivered with a body weight of 1900 g. The cord blood had a karyotype of 46,XY. QF-PCR analysis confirmed biparentally inherited disomy 16 in the cord blood and maternal-origin of trisomy 16 in the placenta. When follow-up at age two months, FISH analysis on 101 buccal mucosal cells and 32 urinary cells revealed no signal of trisomy 16. Conclusion Mosaic trisomy 16 at amniocentesis can be associated with IUGR and an abnormal first-trimester screening result with low PAPP-A and low PlGF. Mosaic trisomy 16 without UPD 16 at amniocentesis can have a favorable outcome, and the abnormal triosmy 16 cell line may disappear after birth.

Presbyphagia is age-related changes in swallowing function, which imposes a high risk of aspiration in older adults. Considering olfactory stimulation (OS) can influence behavioral activities by modulating neuronal excitability, the present study aims to determine whether OS could improve the swallowing function of aged rats through activating the central neuronal networks and downstream muscular activities participated in the control of swallowing. Aged male Wistar rats received OS by inhaling a mixture of plant-based volatile molecules twice a day for 12 days were subjected to functional magnetic resonance imaging (fMRI) and c-fos, choline acetyltransferase (ChAT) immunostaining to detect the neuronal activities of the orbitofrontal cortex (OFC) and medullary nuclei engaged in swallowing control, respectively. The functional effects of OS on downstream pharyngeal muscle activity were examined by evaluating the dihydropyridine receptor–ryanodine receptor (DHPR–RyR)-mediated intramuscular Ca2+ expression, and analyzing the amplitude/frequency of muscle contraction, respectively. In untreated rats, only moderate signal of fMRI and mild c-fos/ChAT expression was detected in the OFC and medullary nuclei, respectively. However, following OS, intense signals of fMRI and immunostaining were clearly expressed in the orbitofronto-medullary networks. Functional data corresponded well with above findings in which OS significantly enhanced DHPR–RyR-mediated intramuscular Ca2+ expression, effectively facilitated a larger amplitude of pharyngeal muscle contraction, and exhibited better performance in consuming larger amounts of daily dietary. As OS successfully activates the neuromuscular activities participated in the control of swallowing, applying OS may serve as an effective, easy, and safe strategy to greatly improve the swallow function of aging populations.

Objective We present prenatal diagnosis of mosaicism for double aneuploidy of 47, XXY and trisomy 7 (48,XXY,+7) at amniocentesis in a pregnancy with a favorable outcome. Case report A 33-year-old woman underwent amniocentesis at 17 weeks of gestation because of an increased risk for Down syndrome in maternal serum screening. Amniocentesis revealed a karyotype of 48,XXY,+7[8]/46,XY[16]. Simultaneous array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes revealed the result of arr [GRCh37] (7) × 3 [0.54], (X) × 2 [0.52], (Y) × 1, compatible with trisomy 7 mosaicism and Klinefelter syndrome mosaicism. The parental karyotypes and prenatal ultrasound findings were normal. Repeat amniocentesis performed at 23 weeks of gestation revealed a karyotype of 48,XXY,+7[13]/46,XY[7]. Simultaneous molecular cytogenetic analyses on uncultured amniocytes revealed 30% mosaicism for 48,XXY,+7 by aCGH and 37% (37/100 cells) mosaicism for trisomy 7 and disomy X by interphase fluorescence in situ hybridization (FISH) analysis. Polymorphic DNA marker analysis excluded uniparental disomy (UPD) 7 and indicated a maternal origin of the chromosome aberration. The pregnancy was continued to 39 weeks of gestation, and a 3070-g healthy male baby was delivered. The cord blood had a karyotype of 46,XY, the umbilical cord had a karyotype of 48,XXY,+7[3]/46,XY[37], and the placenta had a karyotype of 48,XXY,+7. At age one month, the neonate was phenotypically normal, and interphase FISH analysis revealed 4.8% (5/105 cells) mosaicism on buccal mucosal cells and 8.9% (8/90 cells) mosaicism on urinary cells for trisomy 7 and disomy X, compared with 2% in normal control. Interphase FISH analysis on buccal mucosal cells at age two months revealed normal findings in 100/100 cells. Conclusion Mosaic 48,XXY,+7 at amniocentesis without UPD 7 can be associated with a favorable fetal outcome. Cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes may occur in mosaic 48,XXY,+7 at amniocentesis.

Objective We present prenatal diagnosis of a 15q11.2-q14 deletion of paternal origin associated with increased nuchal translucency (NT), mosaicism for de novo multiple unbalanced translocations involving 15q11-q14, 5qter, 15qter, 17pter and 3qter, and Prader–Willi syndrome (PWS). Case report A 32-year-old, primigravid woman underwent amniocentesis at 18 weeks of gestation because of an increased NT thickness of 5.6 mm and abnormal maternal serum screening results in the first trimester. The pregnancy was conceived by in vitro fertilization and embryo transfer. Amniocentesis revealed a karyotype of 45,XX,der(5)t(5;15)(q35;q14),-15 [16]/45,XX,-15,der(17)t(15;17)(q14;p13)[3]/45,XX,der(15)t(15;15)(q35;q14),-15[2]. The parental karyotypes were normal. Prenatal ultrasound findings were unremarkable. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from cultured amniocytes revealed the result of arr 15q11.2q14 (22,765,628–38,651,755) × 1.0 [GRCh37 (hg19)] with a 15.886-Mb 15q11.2-q14 deletion encompassing TUBGCP5, CYFIP1, NIPA2, NIPA1, SNRPN, SNURF, SNORD116-1, IPW, UBE3A, ACTC1 and MEIS2. The pregnancy was subsequently terminated, and a malformed fetus with facial dysmorphism was delivered. The cord blood had a karyotype of 45,XX,der(5)t(5;15)(q35;q14),-15[46]/45,XX,der(3)t(3;15) (q29;q14),-15[2]/45,XX,-15,der(17)t(15;17)(q14;p13)[2]. The placenta had a karyotype of 45,XX,der(5) t(5;15)(q35;q14),-15. Polymorphic DNA marker analysis confirmed a paternal origin of the proximal 15q deletion. Conclusion Increased NT and abnormal maternal serum screening results may prenatally be associated with PWS. Chromosome 15 rearrangements in PWS include mosaicism for de novo multiple unbalanced translocations.

Objective We present prenatal diagnosis and molecular cytogenetic characterization of a small supernumerary marker chromosome (sSMC) derived from chromosome 15 in a pregnancy associated with recurrent Down syndrome. Case report A 33-year-old, gravida 4, para 2, woman underwent amniocentesis at 16 weeks of gestation because of a previous child with Down syndrome and a karyotype of 46,XY,der(14;21)(q10; q10),+21. In this pregnancy, amniocentesis revealed a karyotype of 47,XX,+21[12]/48,XX,+21,+mar[3]. The parental karyotypes were normal. The pregnancy was terminated, and a malformed fetus was delivered with characteristic craniofacial appearance of Down syndrome and hypoplastic middle phalanx of the fifth fingers. The placenta had a karyotype of 47,XX,+21[37]/48,XX,+21,+mar[3]. The umbilical cord had a karyotype of 47,XX,+21[38]/48,XX,+21,+mar[2]. In addition to trisomy 21, array comparative genomic hybridization (aCGH) on the DNA extracted from umbilical cord revealed 40∼50% mosaicism for a 2.604-Mb duplication of 15q25.2–q25.3, or arr 15q25.2q25.3 (83,229,665–85,834,131) × 2.4 [GRCh37 (hg19)] encompassing 19 Online Mendelian Inheritance in Man (OMIM) genes. Quantitative fluorescent polymerase chain reaction (QF-PCR) using the DNAs extracted from cultured amniocytes and parental bloods revealed maternal origin of the sSMC(15) and the extra chromosome 21. Conclusion: aCGH is useful for identification of the nature of sSMC, and QF-PCR is useful for determination of the parental origin of the aberrant chromosomes.

Objective We present mosaic Xq duplication, or 46,X,der(X)dup(X)(q22.1q22.2)dup(X)(q25q22.3)/46,XX at amniocentesis in a pregnancy with a favorable outcome. Case Report A 40-year-old woman underwent amniocentesis at 16 weeks of gestation because of advanced maternal age. Amniocentesis revealed a result of 46,X,der(X)dup(X)(q22.1q22.2)dup(X)(q25q22.3)[7]/46,XX[20]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (1–22, X) × 2. Cytogenetic analysis on maternal blood revealed a karyotype of 46,XX. At 22 weeks of gestation, she underwent repeat amniocentesis which revealed a karyotype of 46,XX in 22/22 colonies of cultured amniocytes and an aCGH result of (1–22, X) × 2 in the uncultured amniocytes. Prenatal ultrasound findings were unremarkable. The parents decided to continue the pregnancy, and a healthy female baby was delivered at 39 weeks of gestation with a body weight of 3510 g and a body length of 49 cm. The cord blood had a karyotype of 46,X,der(X)dup(X)(q22.1q22.2)dup(X)(q25q22.3)[3]/46,XX[37]. At age two months, interphase fluorescence in situ hybridization (FISH) analysis on buccal mucosal cells showed Xq duplication signals in 1.25% (1/80 cells), compared with 0% (0/90 cells) in the normal control. At age nine months, the neonate had normal physical and psychomotor development. Her body weight was 9.6 Kg (85th - 97th centile), and body length was 72 cm (50th - 85th centile). Cytogenetic analysis of peripheral blood revealed a karyotype of 46,X,der(X)dup(X) (q22.1q22.2)dup(X)(q25q22.3)[1]/46,XX[39]. Interphase FISH analysis on 100 buccal mucosal cells revealed no abnormal signal. Conclusion In case of mosaicism for an Xq duplication with a normal euploid cell line at amniocentesis, the in-vitro culture process of amniocytes may cause over-estimation of the mosaic level for the aberrant chromosome because of culture artifacts, and the abnormal cell line can decline after birth.

Background Household incense burning is a common ritual behaviour in the Asia-Pacific region but has been associated with inferior developmental outcomes in term infants. We aimed to examine these associations among preterm infants. Methods Information from 1190 mother-infant pairs during six- and eighteen-months follow-up to the Taiwan Birth Cohort Study was examined for associations between household incense burning exposure and infant neurodevelopmental milestone achievement using multivariable Cox proportional hazard model with propensity score weighting, along with stratified, sensitivity and decomposition analysis. Results Household incense burning exposure was associated with delayed gross motor milestone achievement among all preterm infants according to the Cox model and after propensity score weighting. Meanwhile, associations for delayed development were found in gross motor domain milestones among late preterm infants, while fine motor domain delay were found among other preterm infants. Furthermore, the associations between household incense burning status and gross motor milestone delays were attenuated by the interaction between higher education level and household incense burning exposure status. Conclusions Household incense burning exposure was associated with delays, and the motor domains affected differed according to degree of prematurity. These associations were modified by the attenuation upon higher maternal educational status and exposure status interaction.

Objective: We present mosaic double trisomy involving trisomy 7 and trisomy 20 at amniocentesis in a pregnancy with a favorable outcome. Case report: A 41-year-old woman underwent amniocentesis at 16 weeks of gestation because of advanced maternal age. Amniocentesis revealed a result of 48,XY,+7,+20[6]/46,XY[26] in cultured amniocytes. At 19 weeks of gestation, repeat amniocentesis was performed, which revealed a result of 48,XY,+7,+20[4]/46,XY[21] in cultured amniocytes. Simultaneous molecular cytogenetic analyses on uncultured amniocytes at repeat amniocentesis revealed no genomic imbalance in array comparative genomic hybridization (aCGH) analysis, no trisomy 7 and no trisomy 20 signals in 114/114 cells in interphase fluorescence in situ hybridization (FISH) analysis, and no uniparental disomy (UPD) 7 and no UPD 20 in quantitative fluorescent polymerase chain reaction (QF-PCR) analysis. Interphase FISH analysis on cultured amniocytes revealed double trisomy of trisomy 7 and trisomy 20 in 5/105 cells (4.7%) compared with 0/100 cells (0%) in the normal control. Prenatal ultrasound findings were unremarkable. The parental karyotypes were normal. The woman decided to continue the pregnancy, and a healthy 2880-g phenotypically normal male baby was delivered at 34 weeks of gestation without any structural abnormality. The cord blood had a normal karyotype. Interphase FISH analysis of the urinary cells revealed no trisomy 7 and no trisomy 20 signals in 51/51 urinary cells. Conclusion: Cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes can occur in mosaicism for double trisomy involving trisomy 7 and trisomy 20 at amniocentesis. Molecular cytogenetic analyses such as aCGH, FISH and QF-PCR on uncultured amniocytes are useful for rapid distinguishing true mosaicism from pseudomosaicism under such a circumstance. Keywords: Mosaicism, Trisomy 7, Trisomy 20, UPD 7, UPD 20

Objective: We present prenatal diagnosis and molecular cytogenetic characterization of de novo distal 5p deletion and distal 22q duplication. Case report: A 34-year-old woman was underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a derivative chromosome 5 [der(5)] with an abnormal distal 5p segment of unknown origin. The parental karyotypes were normal. Array comparative genomic hybridization (aCGH) analysis was performed on the cultured amniocytes, and the result was arr 5p15.33p13.3 (22,149–29,760,922) × 1.0, arr 22q13.2q13.33 (42, 192, 065–51,178,264) × 3.0 [GRCh37 (hg19)] with a 29.739-Mb deletion of 5p15.33-p13.3 encompassing 55 [Online Mendelian Inheritance in Man (OMIM)] genes including TPPP, TERT, SRD5A1, SEMA5A and CTNND2, and an 8.986-Mb duplication of 22q13.2-q13.33 encompassing 82 OMIM genes including TRMU, SCO2, TYMP, CPT1B and SHANK3. The fetal karyotype was 46,XY,der(5)t(5; 22)(p13.3; q13.2)dn. The pregnancy was subsequently terminated, and a malformed fetus was delivered with facial dysmorphism. Postnatal polymorphic DNA marker analysis confirmed a maternal origin of the aberrant chromosome 5. Conclusion: aCGH and polymorphic DNA marker analyses can determine the nature and parental origin of the de novo chromosome aberration, and the information acquired is useful for genetic counseling. Keywords: 5p deletion, 22q duplication, Prenatal diagnosis

Herpes simplex virus 1 (HSV-1) infects the majority of the human population and can induce encephalitis, which is the most common cause of sporadic, fatal encephalitis. An increase of microglia is detected in the brains of encephalitis patients. The issues regarding whether and how microglia protect the host and neurons from HSV-1 infection remain elusive. Using a murine infection model, we showed that HSV-1 infection on corneas increased the number of microglia to outnumber those of infiltrating leukocytes (macrophages, neutrophils, and T cells) and enhanced microglia activation in brains. HSV-1 antigens were detected in brain neurons, which were surrounded by microglia. Microglia depletion increased HSV-1 lethality of mice with elevated brain levels of viral loads, infected neurons, neuron loss, CD4 T cells, CD8 T cells, neutrophils, interferon (IFN)-β, and IFN-γ. In vitro studies demonstrated that microglia from infected mice reduced virus infectivity. Moreover, microglia induced IFN-β and the signaling pathway of signal transducer and activator of transcription (STAT) 1 to inhibit viral replication and damage of neurons. Our study reveals how microglia protect the host and neurons from HSV-1 infection.

Objectives RAB14 is a member of small GTPase RAB family which localizes at the endoplasmic reticulum (ER), Golgi apparatus and endosomal compartments. RAB14 acts as molecular switches that shift between a GDP‐bound inactive state and a GTP‐bound active state and regulates circulation of vesicles between the Golgi and endosomal compartments. In present study, we investigated the roles of RAB14 during oocyte meiotic maturation. Materials and methods Microinjection with siRNA and exogenous mRNA for knock down and rescue, and immunofluorescence staining, Western blot and real‐time RT‐PCR were utilized for the study. Results Our results showed that RAB14 localized in the cytoplasm and accumulated at the cortex during mouse oocyte maturation, and it was also enriched at the spindle periphery. Depletion of RAB14 did not affect polar body extrusion but caused large polar bodies, indicating the failure of asymmetric division. We found that absence of RAB14 did not affect spindle organization but caused the spindle migration defects, and this might be due to the regulation on cytoplasmic actin assembly via the ROCK‐cofilin signalling pathway. We also found that RAB14 depletion led to aberrant Golgi apparatus distribution. Exogenous Myc‐Rab14 mRNA supplement could significantly rescue these defects caused by Rab14 siRNA injection. Conclusions Taken together, our results suggest that RAB14 affects ROCK‐cofilin pathway for actin‐based spindle migration and Golgi apparatus distribution during mouse oocyte meiotic maturation., RAB14 localized in the cytoplasm and accumulated at the cortex during mouse oocyte maturation, and it was also enriched at the spindle periphery. Depletion of RAB14 caused large polar bodies, indicating the failure of asymmetric division. Absence of RAB14 did not affect spindle organization but caused the spindle migration defects, and this might be due to the regulation on cytoplasmic actin assembly via the ROCK‐cofilin signalling pathway. We also found that RAB14 depletion led to aberrant Golgi apparatus distribution. Exogenous Myc‐Rab14 mRNA supplement could significantly rescue these defects caused by Rab14 siRNA injection. Our results suggest that RAB14 affects ROCK‐cofilin pathway for actin‐based spindle migration and Golgi apparatus distribution during mouse oocyte meiotic maturation.

Objective We present low-level mosaic trisomy 13 at amniocentesis associated with a favorable outcome in a pregnancy. Case report A 39-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XY,+13[8]/46,XY[20]. The woman underwent cord blood sampling at 22 weeks of gestation. Cytogenetic analysis of cord blood revealed a karyotype of 47,XY,+13[2]/46,XY[98]. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from cord blood revealed 10% gene dosage increase in chromosome 13. Prenatal ultrasound findings were unremarkable. After genetic counseling, the parents decided to continue the pregnancy, and a 2,280-g healthy male baby was delivered at 38 weeks of gestation. The parental karyotypes were normal. The cord blood at birth had a karyotype of 47,XY,+13[1]/46,XY[49]. At age one month, interphase fluorescence in situ hybridization (FISH) analysis revealed no trisomy 13 signals in 100/100 buccal mucosal cells, and trisomy 13 signals in 2/54 (3.7%) urinary cells compared with 0/60 cells in the normal control. The neonate was doing well and presented neither phenotypic abnormalities nor psychomotor disorders at age two months. Conclusion Low-level true mosaic trisomy 13 at amniocentesis without ultrasound abnormalities can be associated with a favorable outcome.

Objective We present prenatal diagnosis of a familial normal euchromatic variant of dup(15)(q11.2q11.2) in a pregnancy with a favorable outcome. Case report A 32-year-old woman underwent elective amniocentesis at 17 weeks of gestation because of anxiety. Amniocentesis revealed a karyotype of 46,XX,dup(15)(q11.2q11.2). Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (1–22, X) × 2 with no genomic imbalance. Cytogenetic analysis of the parental bloods showed that the mother had a karyotype of 46,XX,dup(15)(q11.2q11.2), and the father had a karyotype of 46,XY. Prenatal ultrasound findings were unremarkable. A healthy 2948 g female baby was delivered at 39 weeks of gestation without any phenotypic abnormality. Cytogenetic analysis of the cord blood revealed a karyotype of 46,XX,dup(15)(q11.2q11.2). Conclusion Prenatal diagnosis of dup(15)(q11.2q11.2) should include a differential diagnosis of a 15q11.2 (BP1-BP2) microduplication encompassing TUBGCP5, CYFIP1, NIPA2 and NIPA1, and aCGH analysis is useful for the differential diagnosis under such a circumstance.

Objective We present detection of paternal origin of fetal trisomy 21 in a pregnancy with isolated ventriculomegaly but without advanced parental age. Case report A 29-year-old pregnant woman was admitted to the hospital at 18 weeks of gestation for tocolytic treatment because of irregular uterine contractions. Her husband was 30 years old. The couple had a healthy daughter. Prenatal ultrasound incidentally found isolated ventriculomegaly, and subsequent amniocentesis revealed a karyotype of 47,XX,+21 in 20/20 colonies of cultured amniocytes. The pregnancy was terminated, and the fetus manifested characteristic craniofacial appearance of Down syndrome and hyposplastic middle phalanx of the fifth finger. Postnatal polymorphic DNA marker analysis on the DNAs extracted from the cord blood and parental bloods using quantitative fluorescent polymerase chain reaction (QF-PCR) showed a paternal origin of fetal trisomy 21. The father had a karyotype of 46, XY in 40/40 blood lymphocytes. Conclusion QF-PCR is useful for rapid confirmation of prenatally detected fetal trisomy 21 and determination of paternal origin of fetal trisomy 21 especially in pregnancies with fetal structural abnormalities but without advanced parental age.

Recently, we showed that triggering receptor expressed on myeloid cells 1 (TREM1) was involved in the pathogenesis of Alzheimer’s disease (AD) since it modulated microglial phagocytic functions and thus affected amyloid-β clearance in the brain. Interestingly, a soluble form of TREM1 (sTREM1) can be detected in the plasma of human. To date, whether sTREM1 concentrations were altered in the plasma under AD context remained unclear. In this study, we compared the plasma concentrations of sTREM1 between 110 AD patients and 128 age- and gender-matched controls. Meanwhile, the relationship of sTREM1 concentrations with total tau levels in the plasma of AD patients was also assessed. We revealed that the concentrations of sTREM1 were significantly increased in AD patients. Meanwhile, the sTREM1 concentrations were gradually increased during disease progression. More importantly, we showed that the sTREM1 concentrations were positively correlated with the levels of total tau in the plasma of AD patients (r = 0.61, P

Background Cholinesterase inhibitors and memantine have been approved for management of Alzheimer’s disease (AD), but there has been no consensus about the choice of various types and doses of drugs at different stages. Hence, we compared and ranked the efficacy and tolerability of these available drugs. Methods We searched PubMed, the Cochrane Central Register of Controlled Trials, and Embase for randomized controlled trials (RCTs) published from database inception to July 21, 2017. The primary outcomes were the mean overall changes in cognitive function and responders who had any adverse events. We conducted a random-effects network meta-analysis. Results Forty-one RCTs were included in this study. Compared with placebo, galantamine 32 mg daily (standardized mean difference – 0.51, 95% credible interval – 0.67 to − 0.35), galantamine 24 mg daily (− 0.50, − 0.61 to − 0.40), and donepezil 10 mg daily (− 0.40, − 0.51 to − 0.29) were probably the most effective agents on cognition for mild to moderate AD, and memantine 20 mg combined with donepezil 10 mg (0.76, 0.39 to 1.11) was recommended for moderate to severe patients. Memantine showed the best profile of acceptability. Rivastigmine transdermal 15-cm2 patch was the best optional treatment both in function and global changes. None of the medicines was likely to improve neuropsychiatric symptoms through this analysis. Conclusions Pharmacological interventions have beneficial effects on cognition, function, and global changes, but not on neuropsychiatric symptoms, through current network meta-analysis. The choice of drugs may mainly depend on the disease severity and clinical symptoms. Electronic supplementary material The online version of this article (10.1186/s13195-018-0457-9) contains supplementary material, which is available to authorized users.

Background: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections have been increasingly reported worldwide and are associated with nasal colonization. In Taiwan, available data disclosed a similar trend. We conducted a study for the updated childhood nasal MRSA carriage. Methods: From July 2005 to December 2010, children aged between 2 months and 5 years who presented for a well-child health care visit to a medical center or from kindergarten/daycare center were invited and a nasal swab specimen was obtained for the detection of MRSA. All MRSA isolates were characterized. Results: A total of 3226 children were included and the rate of nasal MRSA carriage was 10.2%. Children aged 2–6 months and >3 years were significantly associated with MRSA carriage, while pneumococcus colonization (p = 0.033) and breastfeeding (p = 0.025) were negatively associated with MRSA carriage. Of the 330 MRSA isolates, a total of 13 pulsotypes with two major patterns (type C, 47.0% and D, 29%) were identified. Most MRSA isolates belonged to two major clones, characterized as sequence type 59 (ST59)/pulsotype C/staphylococcal cassette chromosome (SCCmec) IV/Panton-Valentine leukocidin (PVL)-negative (45.8%) and ST59/pulsotype D/SCCmec VT/PVL-positive (22.7%). Two new clones as ST 508/SCCmec IV (9.7%) and ST573/SCCmec IV (7.3%) emerged and increased markedly since 2007. Conclusion: Between 2005 and 2010, 10.2% of healthy children in northern Taiwan carried MRSA in anterior nares, with the highest carriage rate for infants aged 2–6 months. Two emerging clones, ST 508 and ST 573, were identified and the clinical significance needs further surveillance. Keywords: Methicillin-resistant Staphylococcus aureus, Community-associated, Sequence type 59, Taiwan, Children, Colonization

GBF1 [Golgi brefeldin A (BFA) resistance factor 1] is a member of the guanine nucleotide exchange factors Arf family. GBF1 localizes at the cis-Golgi and endoplasmic reticulum (ER)-Golgi intermediate compartment where it participates in ER-Golgi traffic by assisting in the recruitment of the coat protein COPI. However, the roles of GBF1 in oocyte meiotic maturation are still unknown. In the present study, we investigated the regulatory functions of GBF1 in mouse oocyte organelle dynamics. In our results, GBF1 was stably expressed during oocyte maturation, and GBF1 localized at the spindle periphery during metaphase I. Inhibiting GBF1 activity led to aberrant accumulation of the Golgi apparatus around the spindle. This may be due to the effects of GBF1 on the localization of GM130, as GBF1 co-localized with GM130 and inhibiting GBF1 induced condensation of GM130. Moreover, the loss of GBF1 activity affected the ER distribution and induced ER stress, as shown by increased GRP78 expression. Mitochondrial localization and functions were affected, as the mitochondrial membrane potential was altered. Taken together, these results suggest that GBF1 has wide-ranging effects on the distribution and functions of Golgi apparatus, ER, and mitochondria as well as normal polar body formation in mouse oocytes.

Funder: ZHANGJIANG LAB, Tianqiao and Chrissy Chen Institute, and the State Key Laboratory of Neurobiology and Frontiers Center for Brain Science of Ministry of Education, Fudan University, Background: Genome-wide association studies have identified more than 30 Alzheimer’s disease (AD) risk genes, although the detailed mechanism through which all these genes are associated with AD pathogenesis remains unknown. We comprehensively evaluate the roles of the variants in top 30 non-APOE AD risk genes, based on whether these variants were associated with altered mRNA transcript levels, as well as brain amyloidosis, tauopathy, and neurodegeneration. Methods: Human brain gene expression data were obtained from the UK Brain Expression Consortium (UKBEC), while other data used in our study were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. We examined the association of AD risk allele carrier status with the levels of gene expression in blood and brain regions and tested the association with brain amyloidosis, tauopathy, and neurodegeneration at baseline, using a multivariable linear regression model. Next, we analyzed the longitudinal effects of these variants on the change rates of pathology using a mixed effect model. Results: Altogether, 27 variants were detected to be associated with the altered expression of 21 nearby genes in blood and brain regions. Eleven variants (especially novel variants in ADAM10, IGHV1-68, and SLC24A4/RIN3) were associated with brain amyloidosis, 7 variants (especially in INPP5D, PTK2B) with brain tauopathy, and 8 variants (especially in ECHDC3, HS3ST1) with brain neurodegeneration. Variants in ADAMTS1, BZRAP1-AS1, CELF1, CD2AP, and SLC24A4/RIN3 participated in more than one cerebral pathological process. Conclusions: Genetic variants might play functional roles and suggest potential mechanisms in AD pathogenesis, which opens doors to uncover novel targets for AD treatment.

Background: Acute leukemia during pregnancy (P-AL) is a rare disease with limited data regarding the management and outcomes of mothers and fetuses. Methods: We retrospectively analyzed the characteristics, pregnancy outcomes and maternal and neonatal prognoses of 52 patients with P-AL admitted to the First Affiliated Hospital of Soochow University from January 2013 to December 2020. Findings: Twelve, 21, and 19 patients were diagnosed during the first, second, and third trimesters, respectively. Seventeen (32·7%) patients received chemotherapy during pregnancy (exposed cohort), while 35 (67·3%) received chemotherapy after abortion/delivery (nonexposed cohort). Twenty-six (50·0%) pregnancies ended with abortion, and 26 (50·0%) babies were born through spontaneous delivery or cesarean section. Seven (26·9%) of the 26 babies had been exposed to chemotherapeutic agents in utero. Fetuses in the exposed cohort had lower gestational ages (P=0·030) and birth weights (P=0·049). Considering the safety of the fetus, eight patients in the exposed cohort received low-dose chemotherapy. The low-dose cohort had a lower complete remission (CR) rate (P=0·015), and more patients in this group received HSCT (P=0·015) than patients in the standard cohort. Patients who delayed chemotherapy in the nonexposed cohort experienced a trend toward a higher mortality rate than patients who received timely chemotherapy (P=0·191). The CR, OS, and DFS were similar between the exposed and nonexposed cohorts. Overall, the 4-year overall survival (OS) and disease-free survival (DFS) rates were estimated at 49·1% and 57·8%, respectively. All newborns were living, without deformities, or developmental and intellectual disabilities. Interpretation: Our study indicated that fetuses exposed to chemotherapy in the uterus grown and developed healthily with full protection. Low-dose or delayed chemotherapy might decrease the efficacy and survival of patients, and individualized treatment was needed for patients with P-AL. Funding: This work was supported in part by grants from the National Natural Science Foundation of China (81730003, 81870120, 81900151, 82070187), the Natural Science Foundation of Jiangsu Province (BK20171205, BK20190176), the Social Development Project of Jiangsu Province (BE2019655), the Jiangsu Province Key R&D Program (BE2019798), the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), and the National Key Research and Development Program (2017ZX09304021, 2017YFA0104500, 2019YFC0840604). Declaration of Interest: We declare no competing interests. Ethical Approval: The Ethics Committee of the First Affiliated Hospital of Soochow University approved our study.

Background A high dose of folic acid during pregnancy may increase the risk of asthma, wheezing, and respiratory disease in childhood. Folate acid can modify inflammation and immune susceptibility of offspring with some epigenetic differentiation, including DNA methylation. This study evaluated associations between maternal folate levels during pregnancy and childhood wheezing; furthermore, the study assessed whether maternal folate-modified DNA methylation is related to asthma. Methods Participants in the current study were 6651 mother-child pairs who had complete data on characteristics and who had completed at least one of the International Study of Asthma and Allergies in Childhood questionnaires when the child was 1, 2, 4, and 7 years of age. Moreover, a case-control study to assess DNA methylation at 7 years of age was conducted among 136 children who experienced wheezing and a control group of 139 children with no history of allergies. Results The median of maternal serum was 16.76 nmol/L, assayed by chemiluminescent immunoassay. We found significantly increased adjusted odds ratios of childhood wheezing at 2 years age according to maternal folate levels, compared with the lowest folate quartile (odds ratio [95% confidence interval] = highest; 1.27 [1.03, 1.56], and second, 1.27 [1.05, 1.55]), however, no changes were observed at 1, 4, and 7 years of age. In a case-control study, no association of maternal folate levels with DNA methylation was observed. Conclusion Our results suggest that maternal folate did not affect persistent wheezing in school-aged children, or DNA methylation of gasdermin B, orosomucoid-like 3, and Ikaros family zinc finger 3 at 7 years of age.

Background: Evidence on preventing Alzheimer's disease (AD) is challenging to interpret due to varying study designs with heterogeneous endpoints and credibility. We completed a systematic review and meta-analysis of current evidence with prospective designs to propose clinical recommendations on AD prevention. Methods: Electronic databases and relevant websites were searched from inception to March 1, 2019. Both observational prospective studies (OPSs) and randomized controlled trials (RCTs) were included. The multivariable-adjusted effect estimates were pooled by random-effects models, with credibility assessment according to its risk of bias, inconsistency, and imprecision. Levels of evidence and classes of recommendations were summarized. Findings: A total of 44,676 reports were identified, and 243 OPSs and 153 RCTs were eligible for analysis after exclusion based on pre-decided criteria, among which 104 modifiable factors and 11 interventions were included for the meta-analyses. In the OPSs, 26 risk factors and 8 protective factors were found to significantly modify AD risk by an effect size of over 25%, amongst which eight factors were rated at a moderate-to-high level of evidence. Among the interventions tested in RCTs, physical exercise and the homocysteine lowering treatment were the most promising interventions to reduce AD risk. Finally, 21 recommendations are proposed based on the consolidated evidence, with 'Class I' recommendations targeting 19 factors: ten are with 'Level A' strong evidence (cognitive activity, hyperhomocysteinemia, high BMI in late-life, depression, stress, diabetes, head trauma, hypertension in midlife, orthostatic hypotension, and education) and nine with 'Level B' weaker evidence (obesity in midlife, weight loss in late-life, physical exercise, smoking, sleep, CVD, frailty, atrial fibrillation, and Vitamin C). In contrast, two interventions are not recommended: estrogen replacement therapy (Level A2) and acetylcholinesterase inhibitors (Level B). Interpretation: Our study mapped the current evidence profile and assessed the findings in order to guide future research directions for AD prevention. Evidence-based recommendations are proposed, offering clinicians and stakeholders current guidance for the prevention of AD. Funding Statement: The authors stated: "There was no direct funding source for this study." Declaration of Interest: JTY serves as an associate editor-in-chief for Annals of Translational Medicine, is senior editor for Journal of Alzheimer's Disease. SA has received grants from Europe, Ipsen, and France Alzheimer, served as a consultant for Ipsen, Pierre Fabre, Lilly, Nestle, Sanof, and Servier, and received non-financial support from Biogen, Nutrition Sante, Pfzer, and Icon, and other support from the AMPA Association. SG has received clinical trial support from Lilly and Roche in DIAN-TU, TauRx Therapeutics (TauRx), and Lundbeck; has been a data safety monitoring board (DSMB) member of ADCS, ATRI, API, and Eisai; and has been a scientific adviser to Affiris, BoehringerIngelheim, Lilly, Roche, Servier, Sanofi, Schwabe, Takeda, and TauRx. PSA has received grants from the US Alzheimer’s Association, Janssen, Lilly, the US National Institute on Aging, and Toyama; and consulting fees from Abbott, Abbvie, Amgen, Anavex, AstraZeneca, Biogen Idec, Biotie, Bristol-Myers Squibb, Cardeus, Cohbar, Eisai, Elan, Eli Lilly, Genentech, Ichor, iPerian, Janssen, Lundbeck, Medivation, Merck, NeuroPhage, Novartis, Pfizer, Probiodrug, Roche, Somaxon, and Toyama, outside the submitted work. BV reports grants from Pierre Fabre, Avid, Exonhit, AbbVie, Lilly, Lundbeck, MSD, Otsuka, Regenron, Sanof, Roche, AstraZeneca, LPG Systems, Nestle, and Alzheon, and personal fees from Lilly, Lundbeck, MSD, Otsuka, Roche, Sanof, Biogen, Nestle, Transition Therapeutics, and Takeda. All other authors declare no competing interests. Ethics Approval Statement: The authors followed the recommendations by the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2009 guidelines.

Background: Amyloid-β (Aβ) plaques and tau neurofibrillary tangles are two neuropathological hallmarks of Alzheimer’s disease (AD), which both can be visualized in vivo using PET radiotracers, opening new opportunities to study disease mechanisms. Objective: Our study investigated 11 non-PET factors in 5 categories (including demographic, clinical, genetic, MRI, and cerebrospinal fluid (CSF) features) possibly affecting PET amyloid and tau status to explore the relationships between amyloid and tau pathology, and whether these features had a different association with amyloid and tau status. Methods: We included 372 nondemented elderly from the Alzheimer’s Disease Neuroimaging Initiative cohort. All underwent PET amyloid and tau analysis simultaneously, and were grouped into amyloid/tau quadrants based on previously established abnormality cut points. We examined the associations of above selected features with PET amyloid and tau status using a multivariable logistic regression model, then explored whether there was an obvious correlation between the significant features and PET amyloid or tau levels. Results: Our results demonstrated that PET amyloid and tau status were differently affected by patient features, and CSF biomarker features provided most significant values associating PET findings. CSF Aβ42/40 was the most important factor affecting amyloid PET status, and negatively correlated with amyloid PET levels. CSF pTau could significantly influence both amyloid and tau PET status. Besides CSF pTau and Aβ42, APOE ɛ4 allele status and Mini-Mental State Examination scores also could influence tau PET status, and significantly correlated with tau PET levels. Conclusion: Our results support that tau pathology possibly affected by Aβ-independent factors, implicating the importance of tau pathology in AD pathogenesis.

Background Environmental pollution induces oxidative stress and apoptosis in mammalian oocytes, which can cause defects in reproduction; however, the molecular regulation of oxidative stress in oocytes is still largely unknown. In the present study, we identified that dynamin-related protein 1 (DRP1) is an important molecule regulating oocyte mitochondrial function and preventing oxidative stress/apoptosis. DRP1 is a member of the dynamin GTPase superfamily localized at the mitochondrial-endoplasmic reticulum interaction site, where it regulates the fission of mitochondria and other related cellular processes. Results Our results show that DRP1 was stably expressed during different stages of porcine oocyte meiosis, and might have a potential relationship with mitochondria as it exhibited similar localization. Loss of DRP1 activity caused failed porcine oocyte maturation and cumulus cell expansion, as well as defects in polar body extrusion. Further analysis indicated that a DRP1 deficiency caused mitochondrial dysfunction and induced oxidative stress, which was confirmed by increased reactive oxygen species levels. Moreover, the incidence of early apoptosis increased as detected by positive Annexin-V signaling. Conclusions Taken together, our results indicate that DRP1 is essential for porcine oocyte maturation and that a DRP1 deficiency could induce mitochondrial dysfunction, oxidative stress, and apoptosis.

We performed a retrospective study describing the characteristics of myeloid sarcoma (MS) and evaluated the outcome of hematopoietic stem cell transplantation (HSCT) in patients with MS. There were 27 patients with de novo isolated MS, 34 with de novo leukemic MS and 13 with secondary leukemic MS in our study. Sixty-three patients received induction chemotherapy. Following induction therapy, 35 patients underwent HSCT, including 10 autogenous HSCT (auto-HSCT) and 25 allogeneic HSCT (allo-HSCT) cases. Compared with intensive chemotherapy only as consolidation treatment, HSCT (auto-/allo-HSCT) significantly improved the overall survival (OS) of MS patients (p

Funder: ZHANGJIANG LAB, Tianqiao and Chrissy Chen Institute, and the State Key Laboratory of Neurobiology and Frontiers Center for Brain Science of Ministry of Education, Fudan University, Background: Models of Alzheimer’s disease (AD) pathophysiology posit that amyloidosis [A] precedes and accelerates tau pathology [T] that leads to neurodegeneration [N]. Besides this A-T-N sequence, other biomarker sequences are possible. This current work investigates and compares the longitudinal trajectories of Alzheimer’s ATN biomarker profiles in non-demented elderly adults from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Methods: Based on the ATN classification system, 262 individuals were identified before dementia diagnosis and accompanied by baseline and follow-up data of ATN biomarkers (CSF Aβ42, p-tau, and FDG-PET). We recorded the conversion processes in ATN biomarkers during follow-up, then analyzed the possible longitudinal trajectories and estimated the conversion rate and temporal evolution of biomarker changes. To evaluate how biomarkers changed over time, we used linear mixed-effects models. Results: During a 6–120-month follow-up period, there were four patterns of longitudinal changes in Alzheimer’s ATN biomarker profiles, from all negative to positive through the course of the disease. The most common pattern is that A pathology biomarker first emerges. As well as the classical A-T-N sequence, other “A-first,” “T-first,” and “N-first” biomarker pathways were found. The N-A-T sequence had the fastest rate of pathological progression (mean 65.00 months), followed by A-T-N (mean 67.07 months), T-A-N (mean 68.85 months), and A-N-T sequences (mean 98.14 months). Conclusions: Our current work presents a comprehensive analysis of longitudinal trajectories of Alzheimer’s ATN biomarkers in non-demented elderly adults. Stratifying disease into subtypes depending on the temporal evolution of biomarkers will benefit the early recognition and treatment.

Background Per- and polyfluoroalkyl substances (PFAS), such as perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA) and perfluoroundecanoic acid (PFUA), are common persistent environmental organic pollutants. Animal studies have indicated that PFAS influence inflammatory responses and lung development. However, whether prenatal or childhood PFAS exposure affects children's lung function remains unclear. This study aimed to investigate both in utero exposure and childhood exposure to PFAS and the relationships between them and lung function development in childhood. Methods In total, 165 children were recruited from the Taiwan Birth Panel Study (TBPS). Cord blood plasma and children's serum were collected when they were eight years old. PFAS levels were analysed by ultra-high-performance liquid chromatography/tandem mass spectrometry. When these children reached eight years of age, we administered detailed questionnaires and lung function examinations. Results The mean concentrations of PFOA, PFOS, PFNA and PFUA in cord blood among the 165 study children were 2.4, 6.4, 6.0, and 15.4 ng/mL, respectively. The mean concentrations in serum from eight-year-olds were 2.7, 5.9, 0.6, and 0.3 ng/mL, respectively. At eight years of age, the mean FEV1 (forced expiratory volume per sec), FVC (forced vital capacity), PEF (peak expiratory flow) and FEV1/FVC values were 1679 mL, 1835 mL, 3846 mL/s and 92.0%, respectively. PFOA, PFOS, PFNA and PFUA levels in cord blood were inversely associated with FEV1, FVC and PEF values. The PFOS concentration in cord blood was the most consistently correlated with decreasing lung function before and after adjusting for confounding factors. The PFOS concentration was also significantly inversely correlated with lung function in subgroups with lower birth weight and allergic rhinitis. Conclusions Our cohort study revealed that the concentrations of PFOA, PFOS, PFNA and PFUA were higher in cord blood than in serum from eight-year-olds. Some trends were also noted between intrauterine PFOS exposure and children's decreasing FEV1, FVC and PEF, especially in subgroups with lower birth weight and allergic rhinitis. Therefore, intrauterine PFAS exposure, especially PFOS, may play a vital role in lung development.

Under salt stress, the plants need to maintain a low Na+ concentration and Na+/K+ ratio in the cell cytoplasm to keep normal growth and development. High-affinity K+ transporter (HKT) genes are known to play an important role in regulating the transportation of Na+ and K+ in higher plants. However, reports on its potential role in conferring stress tolerance in cotton are rare. In a previous study, we isolated a potassium transporter SbHKT1 from halophyte Salicornia bigelovii. With the intention to assess whether the SbHKT1 gene would improve salt tolerance in cotton, cotton plants overexpressing SbHKT1 were generated by Agrobacterium-mediated transgenic technology. Overexpression of SbHKT1 in cotton increased germination rate and biomass as well as root systems compared with wild-type plants. Transgenic cotton had significantly higher K+ content, lower Na+ content, and lower Na+/K+ ratio than wild-type plants in leaves, stems and roots under salt stress. Moreover, there were significant higher activity of antioxidant enzymes including SOD, POD, and CAT and lower malondialdehyde content which means better cell membrane integrity in transgenic cotton compared to control plants. These results indicated that overexpressing SbHKT1 in cotton improved salt tolerance by increasing the capacity of K+ uptake, K+/Na+ homeostasis, and the scavenging of reactive oxygen species.

Transfemoral percutaneous coronary intervention (PCI) requires strict bed rest, causing pain and discomfort in patients. However, no studies have investigated this issue.To investigate the predictors of discomfort in transfemoral PCI patients.A cross-sectional sample of 110 patients from two coronary care units completed questionnaires on demographic and clinical characteristics, visual analogue pain scale, and discomfort.Eight factors predicted overall discomfort: physiologic pain, physiological discomfort, psychological discomfort, analgesic use after sheath removal, hemostasis method, and bed rest duration. Psychological discomfort was associated with age, chronic obstructive pulmonary disease, analgesic use after sheath removal, successful hemostasis, and hematoma5 cm. A hierarchical regression model explained 70.5% of the variance in overall discomfort.Age and physiologic pain are major predictors of overall discomfort, especially in patients aged60 years having high pain sensitivity. Critical care providers should note patients' physiological and psychological issues throughout the PCI process.

Aim To determine the efficacy of vascular closure devices (VCDs) for hemostasis following transfemoral percutaneous coronary interventions (PCIs). Methods This two-group pre-post-test observational study with purposive sampling enrolled 73 patients between January, 2014 and February, 2015. The patients were allocated to either the intervention (vascular closure devices group, n = 34) or the control group (manual compression [MC] group, n = 39). Questionnaires were used to assess their demographic and clinical characteristics, vascular complications, visual analogue scale score for pain, and discomfort levels. Pain and discomfort were measured before and after the PCI. Results Vascular complications were observed in 15 (44.1%) VCD patients and 13 (33.3%) MC patients, with no significant between-group difference. However, the VCD patients had a higher relative risk of bruising, hematomas, and need for further treatment. After the PCI, the pain scores and discomfort levels increased significantly in both groups, but the VCD patients had more successful hemostasis, less pain, and less physical and psychological discomfort (lower-limb numbness, shoulder pain, restlessness, and worrying about walking ability, being unable to lift heavy objects in the future, and taking time off from work). Conclusion The VCDs seem to be superior to the MCs, providing more successful hemostasis, less pain and discomfort, and earlier ambulation after a transfemoral PCI. These findings aid clinical nurses in understanding the risk of vascular complications, discomfort, and pain that are associated with VCD use for improving the quality of clinical care and help clinicians in determining the appropriate hemostatic method for patients undergoing a transfemoral PCI, particularly in the Chinese population.

Purpose/Aim: Lumbar degenerative diseases (LDDs) cause pain and disability and are treated with lumbar fusion surgery. The aim of this study was to evaluate the efficacy of lumbar fusion surgery with ISOBAR devices versus posterior lumbar interbody fusion (PLIF) surgery for alleviating LDD-associated pain and disability. Materials and Methods: We performed a literature review and meta-analysis conducted in accordance with Cochrane methodology. The analysis included Group Reading Assessment and Diagnostic Evaluation assessments, Jadad Quality Score evaluations, and Risk of Bias in Non-randomized Studies of Interventions assessments. We searched PubMed, MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, the Cochrane Library, ProQuest, the Airiti Library, and the China Academic Journals Full-text Database for relevant randomized controlled trials and cohort studies published in English or Chinese between 1997 and 2017. Outcome measures of interest included general pain, lower back pain, and disability. Results: Of the 18 studies that met the inclusion criteria, 16 examined general pain (802 patients), 5 examined lower back pain (274 patients), and 15 examined disability (734 patients). General pain, lower back pain, and disability scores were significantly lower after lumbar fusion surgery with ISOBAR devices compared to presurgery. Moreover, lumbar fusion surgery with ISOBAR devices was more effective than PLIF for decreasing postoperative disability, although it did not provide any benefit in terms of general pain or lower back pain. Conclusions: Lumbar fusion surgery with ISOBAR devices alleviates general pain, lower back pain, and disability in LDD patients and is superior to PLIF for reducing postoperative disability. Given possible publication bias, we recommend further large-scale studies.

Phthalate exposure is related to the development of allergic diseases; however, studies regarding its effect on lung function are limited. Our study aims to identify an association between phthalate exposure at different ages and lung function in children at age 9 by conducting a cohort study. The Taiwan Birth Panel Study (TBPS) was established from April 2004 to January 2005. Urine samples were collected from children in the TBPS cohort at ages 2, 5, and 9years. Urinary phthalate metabolite concentrations were measured via ultrahigh-performance liquid chromatography coupled with tandem mass spectrometry. Questionnaires, lung function tests and serum IgE levels were obtained from children at the age of 9. Multiple linear regressions adjusted for confounding factors were applied to investigate the associations between phthalate exposure at different ages and lung function at age 9. Our results demonstrate that in children with allergic diseases, a per log unit increase in the urinary phthalate metabolite mono-ethyl phthalate (MEP) concentration at age 9 was associated with a decreasing forced expiratory volume in 1 sec (FEV1) (β=-25.22; 95% CI: -47.53 to -2.91 per log ml/ln-μg/g cr) and forced vital capacity (FVC) (β=-32.3; 95% CI: -63.51 to -1.09 per log ml/ln-μg/g cr). For children with high serum IgE levels (>100kU/L) at age 9, the urinary MEP concentrations at the same age were negatively associated with the FEV1 (β=-30.4; 95% CI: -56.8 to -4.0 per log ml/ln-μg/g cr), FVC (β=-47.6; 95% CI: -84.2 to -11.0 per log ml/ln-μg/g cr) and peak expiratory flow (PEF) (β=-102.4; 95% CI: 180.2 to -24.7 per log ml/ln-μg/g cr). Phthalate exposure at ages 2 and 5 had little effect on lung function at age 9. Our study suggests that concurrent exposure to phthalates, such as MEP, is negatively associated with lung function in children. Further investigation is required to elaborate on this correlation.

Background Phenolic compounds such as bisphenol A (BPA), nonylphenol (NP), and octylphenol (OP) are known as endocrine-disrupting compounds and are commonly used. Their impacts on the neurodevelopment of children are inconclusive. The current study aims to investigate the association between umbilical cord blood levels of BPA, NP, OP and neurodevelopmental outcomes at 2 and 7 years of age. Methods The study was based on the Taiwan Birth Panel Study, a prospective birth cohort. We collected cord blood plasma to measure phenolic compound levels using ultra-performance liquid chromatography-tandem mass spectrometry. In the follow-up, 208 mother-child pairs with 2-year-old children and 148 mother-child pairs with 7-year-old children were recruited in this study. We used the Comprehensive Developmental Inventory for Infants and Toddlers (CDIIT) and the Wechsler Intelligence Scale for Children (WISC-IV) for neurodevelopmental assessments at 2 and 7 years of age, respectively. Multiple linear regressions were used for statistical analysis. Results The detection rates of BPA, NP, and OP were 55.9%, 77.6%, and 68.3%, respectively. In this study, the median BPA, NP, and OP levels in 2-year-olds were 3.3, 72.6, and 3.3 (ng/ml), respectively. However, the median levels of BPA, NP, and OP were 3.2, 49.3, and 6.6 (ng/ml), respectively. The levels of phenolic compounds were log10-transformed for statistical analysis. Gender stratification was performed. In the WISC-IV neurocognitive assessment, we found both a significant negative association and a trend between cord blood plasma BPA levels and full-scale IQ (p for trend Conclusion Prenatal exposure to BPA affects neurocognitive development, and this effect differs between 7-year-old boys and girls. More studies are needed to elucidate the relationship between phenolic compound exposure in utero and children's neurobehavioral development.

Numerous studies have explored the associations between environmental pollutants and pediatric health. Recent studies have investigated the issue in Asia, but no systematic review has been published to date. This study aims to elucidate the issue by summarizing relevant epidemiologic evidence for cohorts in Asia, using information from the Birth Cohort Consortium of Asia (BiCCA). Environmental pollutants include mercury, environmental tobacco smoke (ETS), polychlorinated biphenyls (PCB), perfluoroalkyl substances (PFAS) and phthalates. This study sought to classify the effects of such compounds on fetal growth and pregnancy outcomes, neurodevelopment and behavioral problems, allergic disease and immune function and the endocrine system and puberty. These evidences showed ETS has been associated with infant birth weight, children's neurodevelopment and allergy disease; mercury and PCB have been shown to affect children's neurodevelopment; phthalate has effects on endocrine function; PFAS alters children's neurodevelopment, the endocrine system, and the allergic response. However, more consistent and coordinated research is necessary to understand the whole picture of single environmental and/or co-exposure and children's health. Therefore, harmonization and international collaboration are also needed in Asia.

// Rui-Chun Lu 1 , Wu Yang 2 , Lin Tan 1 , Fu-Rong Sun 1 , Meng-Shan Tan 1 , Wei Zhang 1 , Hui-Fu Wang 1 and Lan Tan 1 1 Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China 2 International Department, The Affiliated Hospital of Qingdao University, Qingdao, China Correspondence to: Lan Tan, email: dr.tanlan@163.com Keywords: Alzheimer’s disease, polymorphism, association study, HLA-DRB1, meta-analyses Received: April 19, 2017 Accepted: September 20, 2017 Published: October 04, 2017 ABSTRACT Genome-wide association studies (GWAS) have identified one single-nucleotide polymorphism (SNP) rs9271192 within HLA-DRB1 as a risk factor for Alzheimer's disease (AD) in Caucasians. The effect of rs9271192 on AD needed to be verified in other ethnic cohorts. In order to evaluate the association between HLA-DRB1 rs9271192 polymorphism and late-onset AD (LOAD) in the Northern Han Chinese population, we recruited 982 LOAD patients and 1344 sex- and age-matched healthy controls. The results showed that HLA-DRB1 rs9271192 was associated with LOAD (genotype P = 0.015, allele P = 0.04). The results of logistic regression revealed the C allele homozygosity strongly increased the risk of LOAD under a recessive model in the total sample ( P = 0.004, OR =2.069, 95% CI = 1.262–3.434). When these data were stratified by apolipoprotein E ( APOE ) e4 status, the observed association was confined to APOE e4 non-carriers (additive model: P=0.048, OR =1.191, 95% CI =1.001–1.417; recessive model: P < 0.001, OR = 2.601, 95% CI =1.519–4.566). Furthermore, meta-analysis after sensitive analysis confirmed that rs9271192 within HLA-DRB1 increased the risk of LOAD (OR = 1.12, 95% CI = 1.08–1.15). To summarize, the C allele in HLA-DRB1 rs9271192 may be an independent risk factor for LOAD.

Although studies have evaluated the quality of life (QoL) of patients undergoing permanent pacemaker (PPM) placement, their results are inconsistent. To assess arrhythmia perceptions and QoL in bradyarrhythmia patients following PPM implantation, 137 patients completed demographic, arrhythmia perception, and QoL questionnaires before and six months after implantation. Before implantation, they reported fatigue (74.1%), dizziness (72.9%), dyspnea (64.7%), chest pain (62.4%), and heart fluttering (54.1%). After implantation, arrhythmia perceptions and QoL showed significant improvement ( p < .05), except vitality ( p > .05). However, patients with arrhythmia for more than three years, three or more PPM implants, two or more comorbidities, or were 41-50 years showed no significant QoL improvement. Doctors and hospital educators, rather than nurses, provided the most PPM information to patients. Since nurses provide primary in-hospital care to PPM patients, they should impart more patient education while considering individual characteristics in caring situations to enhance patients’ QoL.

The study evaluates the serum levels of Trimethylamine N-Oxide (TMAO), a gut microbial metabolite, in 286 postmenopausal women with hip fracture. From January 1, 2018 to December 31, 2018, eligible patients were included. Same women without fracture mated age were enrolled. TMAO serum levels were tested by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The serum levels of TMAO were significantly higher in patients with hip fracture than in those controls (P

A coding missense mutation (rs3747742) in triggering receptor expressed on myeloid cell-like 2 (TREML2) has been recently proposed as an important protective factor against Alzheimer’s disease (AD). However, the link between TREML2 and AD pathology remains unclear. Therefore, we explored the association of TREML2 rs3747742 with cognitive function, neuroimaging biomarkers and cerebrospinal fluid (CSF) biomarkers related to AD, including CSF total-tau (T-tau), phosphor-tau (P-tau), and amyloid-β (Aβ1-42). As for cognitive function, related cognitive scores of Clinical Dementia Rating Sum of Boxes (CDRSB), Alzheimer’s Disease Assessment Scale-cognitive section 11 (ADAS-cog 11), Mini-Mental State Examination (MMSE), and Rey Auditory-Verbal Learning Test (RAVLT) were extracted. We used a multiple linear regression model to examine the association of TREML2 rs3747742 with the baseline variables. Furthermore, we also calculated the change rate of above variables influenced by TREML2 rs3747742 via applying a mixed-effects model over a 4-year follow-up. In this analysis, a total of 1,306 individuals from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database were included. Finally, we observed that only in AD patients, but not in normal controls or mild cognitive impairment (MCI) individuals, TREML2 rs3747742 exhibited a strong association with CSF total-tau levels at baseline (β = -22.1210, p = 0.0166) and 4-year follow-up (β = -0.3961, p = 0.0115). Furthermore, no associations were found with CSF Aβ1-42 levels, P-tau levels, neuroimaging biomarkers and cognitive function neither for baseline variables nor for longitudinal data. Thus, this study indicated that TREML2 mediated the risk of AD through influencing AD-related neurodegeneration (abnormal T-tau levels) but not P-tau levels and Aβ pathology.

The life style and child raising environment in Asia are quite different compared with Western countries. Besides, the children's environmental threats and difficulties in conducting studies could be different. To address children's environmental health in Asia area, the Birth Cohort Consortium of Asia (BiCCA) was co-established in 2011. We reviewed the mercury, polychlorinated biphenyls, perfluoroalkyl substances, phthalates, and environmental tobacco smoke in pervious based on birth cohort studies in Asia. The aim of this study was to summarize the traditional environmental pollution and the target subjects were also based on the birth cohort in Asia area. Environmental pollutants included air pollutants, pesticides focusing on organochlorine pesticides, diakylphosphates, and pyrethroid, and heavy metals including lead, arsenic, cadmium, manganese, vanadium, and thallium. Fetal growth and pregnancy outcomes, childhood growth and obesity, neurodevelopment and behavioral problems, and allergic disease and immune function were classified to elucidate the children's health effects. In total, 106 studies were selected in this study. The evidences showed air pollution or pesticides may affect growth during infancy or childhood, and associated with neurodevelopmental or behavioral problems. Prenatal exposure to lead or manganese was associated with neurodevelopmental or behavioral problems, while exposure to arsenic or cadmium may influence fetal growth. In addition to the harmonization and international collaboration of birth cohorts in Asia; however, understand the whole picture of exposure scenario and consider more discipline in the research are necessary.