Spontaneous Septostomy in a Twin Pregnancy Causing Fatal Amniotic Band Syndrome

Complications due to spontaneous septostomy of the dividing membrane in monochorionic diamniotic pregnancies are rarely described. Herein, we report the case of a preterm female neonate from a monochorionic diamniotic twin pregnancy delivered by caesarean section at 32 weeks of gestation. She was born with a broad band of a transparent membrane-like material firmly attached to her lower abdomen. Postnatally, she developed respiratory distress syndrome and persistent pulmonary hypertension, complicated by bilateral pneumothorax. She died due to respiratory failure when she was 1 day old. Her twin sister survived with no malformations. At postmortem examination, the neonate had severe lung hypoplasia, and the attached material was diagnosed as the dividing septum. We hypothesize that the lung hypoplasia was secondary to local oligohydramnios, which developed as a consequence of the twin being firmly stuck in the defect of the dividing membrane. To our best knowledge, spontaneous septostomy causing an ultimately fatal amniotic band syndrome has not previously been described.

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Dyspnea in Pregnancy: A Case Report of a Third Trimester Mediastinal Mass in Pregnancy.

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Dyspnea in Pregnancy: A Case Report of a Third Trimester Mediastinal Mass in Pregnancy.

Am J Case Rep. 2018 Dec 28;19:1536-1540

Authors: Reeder CF, Hambright AA, Fortner KB

Abstract
BACKGROUND Dyspnea in pregnancy is common and attributable to a variety of etiologies including normal physiology. The obstetric provider is challenged with distinguishing between physiologic versus pathologic dyspnea. CASE REPORT A 31-year-old G2 P1001 female at 34 weeks gestation presented with dyspnea, tachycardia, and inability to lie supine. Imaging revealed a large heterogeneous anterior mediastinal mass (14.8×11.5 cm). Multidisciplinary coordinated care led to diagnosis of B cell lymphoma, delivery via cesarean section under regional anesthesia in steep Trendelenberg position, followed by chemotherapy postpartum. CONCLUSIONS Dyspnea in pregnancy is common but might represent underlying pathology. While an obstetrician is knowledgeable of physiologic pregnancy changes, he or she should remain vigilant for underlying pathologic causes of dyspnea, including malignancy. Anterior mediastinal masses propose unique anesthetic challenges including respiratory impairment and cardiopulmonary collapse requiring collaborative care and planning.

PMID: 30591704 [PubMed - in process]

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L-Carnosine protects against Oxaliplatin-induced peripheral neuropathy in colorectal cancer patients: A perspective on targeting Nrf-2 and NF-κB pathways.

L-Carnosine protects against Oxaliplatin-induced peripheral neuropathy in colorectal cancer patients: A perspective on targeting Nrf-2 and NF-κB pathways.

Toxicol Appl Pharmacol. 2018 Dec 25;:

Authors: Magdy R, Saleh S, El Abhar H, Shafik A, Schaalan M

Abstract
BACKGROUND: Chemotherapy-induced peripheral neuropathy is a common side effect afflicting cancer patients treated with oxalipatin based chemotherapy.
AIM: The study investigated the potential prophylactic effect of L-carnosine against acute oxaliplatin neurotoxicity in colorectal cancer patients with emphasis on the redox (Nrf-2, MDA), inflammatory (NF-κB, TNF-α), and apoptotic (caspase-3) parameters.
METHODS: In this pilot study, 65 patients were recruited using a prospective randomized controlled study design and enrolled randomly into two arms; Arm A, 31 patients received FOLFOX-6 regimen (oxaliplatin, 5FU & leucovorin) and Arm B, 34 patients received FOLFOX-6 regimen and daily oral L-carnosine (500 mg) along the treatment period. Patients were followed up for three months, then both arms were analyzed for neuropathy incidence/grade and any additional toxicities according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTC version 4).
RESULTS: The neuropathy grading evaluation of Arm B vs Arm A revealed that 17 patients (56.7%) vs 11 patients (35.5%) suffered grade 1, one patient (3.3%) vs 19 patients (61.3%) suffered grade 2, while 12 patients (40%) vs one patient (3.2%) were normal. In arm B, the addition of L-carnosine decreased significantly the levels/activity of NF-κB (27%) and TNF-α (36.6%); this anti-inflammatory effect entailed also its anti-oxidative and anti-apoptotic effects, thus MDA level (51.8%) and caspase-3 activity (49%) were also reduced, whereas Nrf-2 was increased (38.7%) as compared to Arm A. In both arms a significant correlation was only evident between TNF-α and the neuropathy grading score (P < .03); the correlation analysis was significantly positive between NF-κB and both Nrf-2 and caspase 3.
CONCLUSION: L-Carnosine exerted a neuroprotective effect against oxaliplatin-induced peripheral neuropathy in colorectal cancer patients by targeting Nrf-2 and NF-κB pathways.

PMID: 30592963 [PubMed - as supplied by publisher]

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Relationship between cyclosporine area-under-the curve and acute graft versus host disease in pediatric patients undergoing hematopoietic stem cell transplant: A prospective, multicenter study.

Relationship between cyclosporine area-under-the curve and acute graft versus host disease in pediatric patients undergoing hematopoietic stem cell transplant: A prospective, multicenter study.

Pediatr Hematol Oncol. 2018 Dec 28;:1-9

Authors: Schechter T, Lewis VA, Schultz KR, Mitchell D, Chen S, Seto W, Teuffel O, Gibson P, Doyle JJ, Gassas A, Sung L, Lee Dupuis L

Abstract
Traditionally in hematopoietic stem cell transplant (HSCT), cyclosporine doses are individualized using cyclosporine trough concentrations (C0) while area under the concentration vs time curve (AUC) is used in solid organ transplant. AUC potentially has an important relationship with the development of acute graft-versus-host-disease (aGVHD). We conducted a prospective study to describe the relationship between severe (grade III-IV) aGVHD and cyclosporine AUC in pediatric HSCT recipients. Pediatric patients who underwent allogeneic myeloablative HSCT and scheduled to receive cyclosporine for aGVHD prophylaxis participated in this multicenter study. Cyclosporine doses were adjusted based on C0 according to each center's standard of care. Cyclosporine AUC was determined weekly until neutrophil engraftment or Day +42, whichever was later. Associations between severe aGVHD and cyclosporine AUC and other patient and treatment-related factors were evaluated. Of the 110 children enrolled, 97 were evaluable. Thirty-seven (38%) children developed aGVHD; 13 (13.4%) had severe aGVHD. On univariate analysis, there was no association between severe aGVHD and cyclosporine AUC at any time point before engraftment. Future research should focus on refinement of C0 targets for cyclosporine therapeutic drug monitoring in HSCT.

PMID: 30592246 [PubMed - as supplied by publisher]

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Promoting shared decision making in advanced cancer: Development and piloting of a patient communication aid.

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Promoting shared decision making in advanced cancer: Development and piloting of a patient communication aid.

Patient Educ Couns. 2018 Dec 14;:

Authors: Henselmans I, Brugel SD, de Haes HCJM, Wolvetang KJA, de Vries LM, Pieterse AH, Baas-Thijssen MCM, de Vos FYF, van Laarhoven HWM, Smets EMA

Abstract
OBJECTIVE: To learn how to configure a patient communication aid (PCA) to facilitate shared decision-making (SDM) about treatment for advanced cancer.
METHODS: The PCA consists of education about SDM, a question prompt list, and values clarification methods. Study 1. A first version was presented to 13 patients, 8 relatives and 14 bereaved relatives in interviews. Study 2. A second version was used by 18 patients in a pilot study. Patients and oncologists were interviewed, patients were surveyed, and consultations were audio-recorded.
RESULTS: Respondents reported that the aid facilitated patient control over information, raised choice awareness and promoted elaboration. Risks were identified, most importantly that the aid might upset patients. Also, some respondents reported that the PCA did not, or would not support decision making because they felt sufficiently competent, did not perceive a role for themselves, or did not perceive that the decision required elaboration.
CONCLUSIONS: Opinions on the usefulness of the PCA varied. It was challenging to raise awareness about the presence of a choice, and to find a balance between comprehensive information and sensitivity.
PRACTICE IMPLICATIONS: A future study should demonstrate whether the PCA can improve SDM, and whether this effect is stronger when oncologists receive training.

PMID: 30591283 [PubMed - as supplied by publisher]

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CD38 targeted treatment for multiple myeloma.

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CD38 targeted treatment for multiple myeloma.

Vnitr Lek. 2018;64(10):939-948

Authors: Jelínek T, Mihályová J, Hájek R

Abstract
CD38 antigen is highly and uniformly expressed on plasma cells and thus represents an ideal target for the treatment of multiple myeloma (MM) with anti-CD38 monoclonal antibodies (mAbs). Daratumumab is the most advanced anti-CD38 mAb in the clinical development with approval in several indications, nevertheless isatuximab that targets completely different epitope of CD38 molecule is also very promising drug. Anti-CD38 possess pleiotropic mechanism of action that have been described also in other mAbs, but quite specific, novel and very important seems to be the immunomodulatory effect provided by depletion of several CD38+ immunosuppressive immune cell populations. CD38-targeted mAbs induce partial response or better in approximately 30 % of heavily pre-treated myeloma patients as monotherapy. Based on their favourable toxicity profile and distinct mechanism of action, anti-CD38 mAbs represents very attractive partner to back-bone anti-myeloma drugs. Indeed, daratumumab is already approved as a part of three distinct combination regimens in relapsed setting. The combination of daratumumab with lenalidomide and dexamethasone is considered to be the best treatment option in relapsed myeloma with unprecedented prolongation of median PFS, including high rate of good quality responses. CD38 targeted therapy is rapidly moving toward the first line treatment. Anti-CD38 mAbs have been also successfully tested in other plasma cell dyscrasias (such as AL amyloidosis), and they are examined in other hematological malignancies (such as CLL, ALL, AML, etc.) and even in solid oncology as well as in autoimmune disorders. Implementation of CD38 targeted mAbs have been significant milestone in the treatment of MM, similar to that of CD20 targeted mAbs in CLL or non-Hodgkin lymphomas. We believe that this drug may eventually help to reach the cure at least in a subset of MM patients in the near future. Key words: acute myeloid leukemia - CD38 - daratumumab - isatuximab - multiple myeloma.

PMID: 30590941 [PubMed - in process]

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The Asymmetric Aza-silyl-Prins Reaction: Synthesis of Enantiopure Piperidines.

The Asymmetric Aza-silyl-Prins Reaction: Synthesis of Enantiopure Piperidines.

Org Lett. 2018 Dec 28;:

Authors: Mittapalli RR, Guesné SJJ, Parker RJ, Klooster WT, Coles SJ, Skidmore J, Dobbs AP

Abstract
The design and development of the first asymmetric aza-silyl-Prins reaction is reported, giving rise to valuable and diverse piperidines and pipecolic acid derivatives in both high yields and as single enantiomers. The creation of a novel chiral auxiliary-homoallylic amine for the aza-silyl-Prins reaction is essential to its success.

PMID: 30592613 [PubMed - as supplied by publisher]

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CXCL8 derived from mesenchymal stromal cells supports survival and proliferation of acute myeloid leukemia cells through the PI3K/AKT pathway.

CXCL8 derived from mesenchymal stromal cells supports survival and proliferation of acute myeloid leukemia cells through the PI3K/AKT pathway.

FASEB J. 2018 Dec 28;:fj201801931R

Authors: Cheng J, Li Y, Liu S, Jiang Y, Ma J, Wan L, Li Q, Pang T

Abstract
The role of proinflammatory cytokines secreted by the bone marrow mesenchymal stromal cells (BM-MSCs) in the progression of acute myeloid leukemia (AML) is poorly understood. We compared C-X-C motif chemokine ligand (CXCL)8 expression levels in the BM-MSCs of patients with AML and normal control subjects and detected significantly higher levels in the former. Furthermore, CXCL8 was up-regulated in cocultures of BM-MSCs and leukemic cell lines compared with either monoculture. CXCL8 expression was significantly higher in MSCs compared with mononuclear cells in patients with de novo AML. To elucidate the function of paracrine CXCL8 in AML, we blocked CXCL8 binding to the C-X-C motif chemokine receptor (CXCR)2 in the AML cells using SB225002. Inhibition of CXCL8/CXCR2 binding decreased proliferation in the AML cells by inducing cell cycle arrest at the G0/G1 phase and apoptosis via decreased AKT phosphorylation. Blocking the PI3K/AKT signaling pathway by a specific inhibitor induced similar apoptosis induction and lower proliferation, suggesting that the PI3K/AKT signaling pathway was also involved in CXCL8 action. Taken together, our findings demonstrate that BM-MSCs are the main source of CXCL8 in the AML bone marrow microenvironment and promote leukemogenesis via the PI3K/AKT signaling pathway, indicating a novel therapeutic target.-Cheng, J., Li, Y., Liu, S., Jiang, Y., Ma, J., Wan, L., Li, Q., Pang, T. CXCL8 derived from mesenchymal stromal cells supports survival and proliferation of acute myeloid leukemia cells through the PI3K/AKT pathway.

PMID: 30592634 [PubMed - as supplied by publisher]

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Crosstalk between Phosphoinositide 3-kinase/Akt signaling pathway with DNA damage response and oxidative stress in cancer.

Crosstalk between Phosphoinositide 3-kinase/Akt signaling pathway with DNA damage response and oxidative stress in cancer.

J Cell Biochem. 2018 Dec 28;:

Authors: Karimian A, Mir SM, Parsian H, Refieyan S, Mirza-Aghazadeh-Attari M, Yousefi B, Majidinia M

Abstract
The phosphatidylinositol 3-kinases (PI3K)/Akt signaling pathway is one of the well-characterized and most important signaling pathways activated in response to DNA damage. This review discusses the most recent discoveries on the involvement of PI3K/Akt signaling pathway in cancer development, as well as stimulation of some important signaling networks involved in the maintenance of cellular homeostasis upon DNA damage, with an exploration of how PI3K/Akt signaling pathway contributes to the regulation of modulators and effectors underlying DNA damage response, the intricate, protein-based signal transduction network, which decides between cell cycle arrest, DNA repair, and apoptosis, the elimination of irreparably damaged cells to maintain homeostasis. The review continues by looking at the interplay between cell cycle checkpoints, checking the repair of damage inflicted to the DNA before entering DNA replication to facilitate DNA synthesis, and PI3K/Akt signaling pathway. We then investigate the challenges the cells overcome to ameliorate damages induced by oxidative activities, for example, the recruitment of many pathways and factors to maintain integrity and hemostasis. Finally, the review provides a discussion of how cells use the PI3K/Akt signaling pathway to regulate the balance between these networks.

PMID: 30592328 [PubMed - as supplied by publisher]

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Integrating modern approaches to pathogenetic concepts of malignant transformation of endometriosis.

Integrating modern approaches to pathogenetic concepts of malignant transformation of endometriosis.

Oncol Rep. 2018 Dec 21;:

Authors: Kobayashi H, Yamada Y, Kawahara N, Ogawa K, Yoshimoto C

Abstract
In the present study, we summarize the role of the shared and independent (epi)genetic background between endometrioid carcinoma (EC) and clear cell carcinoma (CCC), two histological subtypes of endometriosis-associated ovarian cancer (EAOC). Using the PubMed database, we conducted a literature review of various studies related to the malignant transformation of endometriosis. Both endometriosis and EAOC face potential environmental hazards, including hemoglobin (Hb), heme and free iron, which induces DNA damage and mutations. Although EC is distinguished from CCC due to different morphologies, both represent common environmental profiles and maintain the similar (epi)genomic abnormalities with multiple overlaps and share similar molecular signatures. By contrast, EAOC also has disease-specific gene signatures corresponding with each histological subtype: Estrogen receptor promotes EC cell proliferation ('go') and hepatocyte nuclear factor-1β (HNF-1β) induces CCC cell cycle arrest ('stop') under oxidative stress conditions. This model underscores a subtype-dependent 'go or stop' dichotomy, possibly through better ability to adapt in a changing environment. It was found that cyst fluid Hb and iron concentrations were significantly lower in EAOC when compared to benign ovarian endometrioma (OE), supporting the hypothesis that the redox imbalance plays a key role in the pathogenesis of EAOC. There are at least two phases of iron carcinogenesis and tumor progression: The initial wave of iron-induced oxidative stress and DNA mutations would be followed by the second big wave of subsequent synthesis of the antioxidants, which diminishes cellular oxidative stress capacity, increases apoptosis resistance and promotes tumor initiation and progression. Special emphasis is given to novel pathophysiological concepts of malignant transformation of endometriosis.

PMID: 30592289 [PubMed - as supplied by publisher]

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miR‑498 inhibits the growth and metastasis of liver cancer by targeting ZEB2.

miR‑498 inhibits the growth and metastasis of liver cancer by targeting ZEB2.

Oncol Rep. 2018 Dec 21;:

Authors: Zhang X, Xu X, Ge G, Zang X, Shao M, Zou S, Zhang Y, Mao Z, Zhang J, Mao F, Qian H, Xu W

Abstract
MicroRNAs (miRNAs) play critical roles in the growth, metastasis and therapeutic resistance of liver cancer. Accumulating evidence suggests that miR‑498 is aberrantly expressed in several human malignancies. However, the role and underlying mechanism of miR‑498 in liver cancer remain unclear. In the present study, we investigated the potential roles and clinical value of miR‑498 in liver cancer. We found that the miR‑498 expression level was significantly lower in liver cancer patient tissues than that in healthy control tissues. The expression of miR‑498 was also decreased in liver cancer cell lines compared to that noted in a normal human normal liver cell line. miR‑498 overexpression markedly inhibited liver cancer cell proliferation, migration and invasion. miR‑498 overexpression induced cell cycle arrest and apoptosis while it suppressed epithelial‑mesenchymal transition (EMT) in liver cancer cells. Bioinformatic analysis and luciferase reporter assay further identified zinc finger E‑box binding homeobox 2 (ZEB2) as a novel target of miR‑498. Furthermore, ZEB2 knockdown recapitulated the inhibitory effects of miR‑498 overexpression in liver cancer cells. ZEB2 overexpression rescued the inhibition of liver cancer cell proliferation, migration, and invasion by miR‑498, indicating that ZEB2 acts as a downstream effector of miR‑498 in liver cancer cells. Thus, we demonstrated that miR‑498 suppresses the growth and metastasis of liver cancer cells, partly at least, by directly targeting ZEB2, suggesting that miR‑498 may serve as a potential biomarker for the diagnosis and therapy of liver cancer.

PMID: 30592286 [PubMed - as supplied by publisher]

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Gambogenic acid inhibits the proliferation of small‑cell lung cancer cells by arresting the cell cycle and inducing apoptosis.

Gambogenic acid inhibits the proliferation of small‑cell lung cancer cells by arresting the cell cycle and inducing apoptosis.

Oncol Rep. 2018 Dec 21;:

Authors: Huang T, Zhang H, Wang X, Xu L, Jia J, Zhu X

Abstract
Gambogenic acid (GNA), which is an important active compound present in gamboge, exerts anticancer activity in various types of tumor cells. However, the effect of GNA on small‑cell lung cancer (SCLC) cell lines and the underlying mechanism involved still remain unclear. In the present study, GNA inhibited the proliferation and cell cycle progression of SCLC cells. GNA also promoted the apoptosis of SCLC cells in a dose‑dependent manner, which is associated with modulating the levels of proteins involved in apoptosis pathways in NCI‑H446 and NCI‑H1688 cells. The results demonstrated that GNA increased the level of cleaved caspase‑3, ‑8 and ‑9, and Bax but decreased the expression of anti‑apoptotic protein, Bcl‑2. Furthermore, similar results were obtained in a mouse tumor xenograft model. Additionally, GNA exhibit low toxicity in tissues when administered to mice in the SCLC xenograft models. Collectively, our findings demonstrated that GNA significantly inhibited the proliferation of SCLC cells and promoted cell apoptosis via cell cycle arrest and induction of apoptosis.

PMID: 30592285 [PubMed - as supplied by publisher]

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Etomidate Suppresses Invasion and Migration of Human A549 Lung Adenocarcinoma Cells.

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Etomidate Suppresses Invasion and Migration of Human A549 Lung Adenocarcinoma Cells.

Anticancer Res. 2019 Jan;39(1):215-223

Authors: Chu CN, Wu KC, Chung WS, Zheng LC, Juan TK, Hsiao YT, Peng SF, Yang JL, Ma YS, Wu RS, Chung JG

Abstract
BACKGROUND/AIM: Etomidate, an intravenous anesthetic, has been shown to have anticancer effects, including induction of cell-cycle arrest and apoptosis. However, to our knowledge, there are no reports about the anti-metastasis effects of etomidate on A549 human lung adenocarcinoma cells.
MATERIALS AND METHODS: The cell viability, cell adhesion, gelatin zymography assay, transwell migration and invasion assay, and western blotting analysis were used to investigate the effects of etomidate on A549 cells.
RESULTS: In our study, etomidate showed low cytotoxicity, inhibited cell adhesion, and suppressed the migration and invasion in A549 cells. The activity of matrix metallopeptidase 2 (MMP2) was reduced by 48 h treatment of etomidate. Results of western blotting analysis indicated that etomidate down-regulated the expression of protein kinase C, MMP7, MMP1, MMP9, and p-p-38, but up-regulated that of RAS, phosphoinositide 3-kinase, and phosphor-extracellular-signal related kinase after 24 and 48 h treatment, in A549 cells.
CONCLUSION: Etomidate suppressed the migration and invasion of lung adenocarcinoma A549 cells via inhibiting the expression of MMP1, MMP2, MMP7 and MMP9, and provides potential therapeutic targets for lung cancer treatment.

PMID: 30591461 [PubMed - in process]

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Combination of Biochanin A and Temozolomide Impairs Tumor Growth by Modulating Cell Metabolism in Glioblastoma Multiforme.

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Combination of Biochanin A and Temozolomide Impairs Tumor Growth by Modulating Cell Metabolism in Glioblastoma Multiforme.

Anticancer Res. 2019 Jan;39(1):57-66

Authors: Desai V, Jain A, Shaghaghi H, Summer R, Lai JCK, Bhushan A

Abstract
BACKGROUND/AIM: Several epidemiological studies have reported the chemopreventive potential of biochanin A, in cancer development and progression. We investigated the anticancer potential of combination of biochanin A and temozolomide against U-87 MG and T98 G [glioblastoma multiforme (GBM)] cells.
MATERIALS AND METHODS: We evaluated the effect of biochanin A and temozolomide treatment on cell viability, expression of survival proteins, cell cycle, cell metabolism and mitochondrial function.
RESULTS: Enhanced inhibitory effects of the combination treatment were observed on cell viability, expression of cell survival proteins EGFR, p-ERK, p-AKT, c-myc and MT-MMP1, and increased expression of the tumor suppressor, p-p53. Combination treatment also induced arrest in the G1 phase of the cell cycle. A shift in the metabolic phenotype of cells from glycolytic to oxidative phosphorylation was observed on combination treatment and the permeabilized cells showed a significant impairment in complex IV activity.
CONCLUSION: Biochanin A significantly enhanced the anticancer efficacy of temozolomide in GBM cells.

PMID: 30591440 [PubMed - in process]

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Inhibitory effects of Schisandrin B on human prostate cancer cells.

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Inhibitory effects of Schisandrin B on human prostate cancer cells.

Oncol Rep. 2019 Jan;41(1):677-685

Authors: Nasser MI, Han T, Adlat S, Tian Y, Jiang N

Abstract
Prostate cancer is a serious affliction worldwide. Although much progress has been made in the study of prostate cancer prevention and treatment, less attention has been paid to the molecular mechanism of the disease. The molecular arrangement by which Schisandrin B (Sch B) induces human prostate cancer cytotoxicity was comprehensively examined in the present study. As indicated by the results of flow cytometric and western blot analysis, Sch B could inhibit prostate cancer cell proliferation and promote DU145 and LNCaP cell apoptosis and S‑phase cell arrest. Moreover, real‑time PCR, flow cytometry and western blot result revealed that the cell apoptosis process induced by Sch B in LNCaP cells was associated with its capacity to generate oxidative stress, its inhibition of androgen receptor and the phosphorylation of PI3K/AKT and STA3/JAK2. The data from the present study demonstrated the antitumor effects and the potential pharmacological application of Sch B as an efficient drug for prostate cancer.

PMID: 30320364 [PubMed - indexed for MEDLINE]

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Hepatocellular carcinoma-related cyclin D1 is selectively regulated by autophagy degradation system.

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Hepatocellular carcinoma-related cyclin D1 is selectively regulated by autophagy degradation system.

Hepatology. 2018 07;68(1):141-154

Authors: Wu SY, Lan SH, Wu SR, Chiu YC, Lin XZ, Su IJ, Tsai TF, Yen CJ, Lu TH, Liang FW, Li CY, Su HJ, Su CL, Liu HS

Abstract
Dysfunction of degradation machineries causes cancers, including hepatocellular carcinoma (HCC). Overexpression of cyclin D1 in HCC has been reported. We previously reported that autophagy preferentially recruits and degrades the oncogenic microRNA (miR)-224 to prevent HCC. Therefore, in the present study, we attempted to clarify whether cyclin D1 is another oncogenic factor selectively regulated by autophagy in HCC tumorigenesis. Initially, we found an inverse correlation between low autophagic activity and high cyclin D1 expression in tumors of 147 HCC patients and three murine models, and these results taken together revealed a correlation with poor overall survival of HCC patients, indicating the importance of these two events in HCC development. We found that increased autophagic activity leads to cyclin D1 ubiquitination and selective recruitment to the autophagosome (AP) mediated by a specific receptor, sequestosome 1 (SQSTM1), followed by fusion with lysosome and degradation. Autophagy-selective degradation of ubiquitinated cyclin D1 through SQSTM1 was confirmed using cyclin D1/ubiquitin binding site (K33-238 R) and phosphorylation site (T286A) mutants, lentivirus-mediated silencing autophagy-related 5 (ATG5), autophagy-related 7 (ATG7), and Sqstm1 knockout cells. Functional studies revealed that autophagy-selective degradation of cyclin D1 plays suppressive roles in cell proliferation, colony, and liver tumor formation. Notably, an increase of autophagic activity by pharmacological inducers (amiodarone and rapamycin) significantly suppressed tumor growth in both the orthotopic liver tumor and subcutaneous tumor xenograft models. Our findings provide evidence of the underlying mechanism involved in the regulation of cyclin D1 by selective autophagy to prevent tumor formation.
CONCLUSION: Taken together, our data demonstrate that autophagic degradation machinery and the cell-cycle regulator, cyclin D1, are linked to HCC tumorigenesis. We believe these findings may be of value in the development of alternative therapeutics for HCC patients. (Hepatology 2018;68:141-154).

PMID: 29328502 [PubMed - indexed for MEDLINE]

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Transcriptome sequencing identifies ANLN as a promising prognostic biomarker in bladder urothelial carcinoma.

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Transcriptome sequencing identifies ANLN as a promising prognostic biomarker in bladder urothelial carcinoma.

Sci Rep. 2017 06 09;7(1):3151

Authors: Zeng S, Yu X, Ma C, Song R, Zhang Z, Zi X, Chen X, Wang Y, Yu Y, Zhao J, Wei R, Sun Y, Xu C

Abstract
The prognosis of bladder urothelial carcinoma (BLCA) varies greatly even for patients with similar pathological characteristics. We conducted transcriptome sequencing on ten pairs of BLCA samples and adjacent normal tissues to identify differentially expressed genes. Anillin (ANLN) was identified as a transcript that was significantly up-regulated in BLCA samples compared with normal tissues. Prognostic power of candidate gene was studied using qRT-PCR and immunohistochemistry on 40 and 209 patients, respectively. Patients with elevated ANLN expression level was correlated with poorer cancer-specific (median, 22.4 vs. 37.3 months, p = 0.001), progression-free (median, 19.7 vs. 27.9 months, p = 0.001) and recurrence-free survival (median, 17.1 vs. 25.2 months, p = 0.011) compared with low ANLN expression. Public datasets TCGA and NCBI-GEO were analyzed for external validation. Knockdown of ANLN in J82 and 5637 cells using small interfering RNA significantly inhibited cell proliferation, migration, and invasion ability. Moreover, knockdown of ANLN resulted in G2/M phase arrest and decreased expression of cyclin B1 and D1. Microarray analysis suggested that ANLN played a major role in cell migration and was closely associated with several cancer-related signaling pathways. In conclusion, ANLN was identified as a promising prognostic biomarker which could be used to stratify different risks of BLCA.

PMID: 28600503 [PubMed - indexed for MEDLINE]

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Diagnosis of Systemic Lupus Erythematosus in a Polynesian Male with a History of Rheumatic Fever: A Case Report and Literature Review

The presence of rheumatic heart disease (RHD) and systemic lupus erythematosus (SLE) has rarely been described in one patient. This report describes an adolescent Polynesian male with RHD who developed SLE years later. Initially, he fulfilled modified Jones criteria for rheumatic fever with aortic insufficiency, transient arthritis, elevated streptococcal titers, and a high erythrocyte sedimentation rate with a negative antinuclear antibody (ANA). He responded well to nonsteroidal anti-inflammatory and penicillin prophylaxis, which supported the diagnosis of rheumatic fever. Five years after his RHD diagnosis, he developed pancreatitis with glomerulonephritis, nephrosis, and pancytopenia. In addition, laboratory results revealed that he had multiple autoantibodies: anti-Sm and extremely elevated anti-dsDNA and ANA, fulfilling diagnostic criteria for SLE. The patient was treated, and he responded to pulse steroids followed by oral steroid therapy. To our knowledge, there are no known reported cases of a patient who was diagnosed with both RHD and SLE and met the clinical criteria for both diseases. The rarity of this concurrent disease process in one patient suggests a possible overlap in humoral immunity toward self-antigens as well as ethnic variability that increases predisposition to rheumatologic diseases.

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Rubber oxygenases

Abstract

Natural rubber (NR), poly(cis-1,4-isoprene), is used in an industrial scale for more than 100 years. Most of the NR-derived materials are released to the environment as waste or by abrasion of small particles from our tires. Furthermore, compounds with isoprene units in their molecular structures are part of many biomolecules such as terpenoids and carotenoids. Therefore, it is not surprising that NR-degrading bacteria are widespread in nature. NR has one carbon-carbon double bond per isoprene unit and this functional group is the primary target of NR-cleaving enzymes, so-called rubber oxygenases. Rubber oxygenases are secreted by rubber-degrading bacteria to initiate the break-down of the polymer and to use the generated cleavage products as a carbon source. Three main types of rubber oxygenases have been described so far. One is rubber oxygenase RoxA that was first isolated from Xanthomonas sp. 35Y but was later also identified in other Gram-negative rubber-degrading species. The second type of rubber oxygenase is the latex clearing protein (Lcp) that has been regularly found in Gram-positive rubber degraders. Recently, a third type of rubber oxygenase (RoxB) with distant relationship to RoxAs was identified in Gram-negative bacteria. All rubber oxygenases described so far are haem-containing enzymes and oxidatively cleave polyisoprene to low molecular weight oligoisoprenoids with terminal CHO and CO–CH₃ functions between a variable number of intact isoprene units, depending on the type of rubber oxygenase. This contribution summarises the properties of RoxAs, RoxBs and Lcps.

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Development and application of a colloidal gold test strip for detection of avian leukosis virus

Abstract

Avian leukosis virus (ALV) is an avian oncogenic retrovirus that induces leukemia-like proliferative diseases in chickens. ALV infection can result in the development of immunological tolerance and persistent viremia. Since effective vaccines against ALV are not yet available, its current prevention primarily depends on detection and eradication to establish exogenous ALV-free poultry flocks. In this study, a rapid and simple colloidal gold test strip method, specific for the group-specific antigen, p27 protein, was developed and systematically evaluated for the detection of ALV from different samples. The detection limit of this assay was as low as 6.25 ng/ml for p27 protein and 80 TCID₅₀/ml for different subgroups of ALV. Besides, the test strip showed high specificity in the detection of different subgroups of ALV, including ALV-A, ALV-B, ALV-J, and ALV-K, with no cross-reaction with other avian pathogens. Furthermore, we artificially infected specific pathogen-free (SPF) chickens with ALV-J, collected cloacal swabs, and examined viral shedding using both test strips and ELISA. Results from the test strip were highly consistent with that from ELISA. In addition, 1104 virus isolates from anti-coagulant blood samples, 645 albumen samples, and 4312 meconium samples were tested, and the test strip results agreed with those of ELISA kit up to 97.1%. All the results indicated that the colloidal gold test strip could serve as a simple, rapid, sensitive, and specific diagnostic method for eradication of ALV in poultry farms.

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Isopropylmalate isomerase MoLeu1 orchestrates leucine biosynthesis, fungal development, and pathogenicity in Magnaporthe oryzae

Abstracts

The biosynthesis of branched-chain amino acids (BCAAs) is conserved in fungi and plants, but not in animals. The Leu1 gene encodes isopropylmalate isomerase that catalyzes the conversion of α-isopropylmalate into β-isopropylmalate in the second step of leucine biosynthesis in yeast. Here, we identified and characterized the functions of MoLeu1, an ortholog of yeast Leu1 in the rice blast fungus Magnaporthe oryzae. The transcriptional level of MoLEU1 was increased during conidiation and in infectious stages. Cellular localization analysis indicated that MoLeu1 localizes to the cytoplasm at all stages of fungal development. Targeted gene deletion of MoLEU1 led to leucine auxotrophy, and phenotypic analysis of the generated ∆Moleu1 strain revealed that MoLeu1-mediated leucine biosynthesis was required for vegetative growth, asexual development, and pathogenesis of M. oryzae. We further observed that invasive hyphae produced by the ∆Moleu1 strain were mainly limited to the primary infected host cells. The application of exogenous leucine fully restored vegetative growth and partially restored conidiation as well as pathogenicity defects in the ∆Moleu1 strain. In summary, our results suggested that MoLeu1-mediated leucine biosynthesis crucially promotes vegetative growth, conidiogenesis, and pathogenicity of M. oryzae. This study helps unveil the regulatory mechanisms that are essential for infection-related morphogenesis and pathogenicity of the rice blast fungus.

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Is marine sediment the source of microbes associated with accelerated low water corrosion?

Abstract

Accelerated low water corrosion (ALWC) is a form of microbiologically influenced corrosion (MIC) associated with the degradation of marine structures around the low tide water level. A better understanding of the role of microbes in this degradation and the source of these microbes is required to improve the prediction and mitigation of the costly failures occurring due to ALWC. The microbial communities present in a sediment sample and on an ALWC tubercle on adjacent steel sheet piling from a tidal estuary were studied using culture-based isolation and metabarcoding. A total of 43 pure cultures were isolated from the sediment using a variety of culture conditions. Phylogenetic analysis of their 16S rRNA genes placed them in the Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria (Alphaproteobacteria and Gammaproteobacteria). 16S rRNA gene metabarcoding of the sediment and tubercle revealed similar microbial groups at varying relative abundances. No Deltaproteobacteria were isolated from the sediment but they were present in both samples according to metabarcoding and their high abundance (49.3%) in the tubercle could indicate an important functional role. Although some sediment isolates and operational taxonomic units from the metabarcoding have previously been associated with surface colonisation or biofilm formation in MIC, there was no strong evidence for the notion that the sediment adjacent to ALWC was the source of tubercle microbes. Further isolation strategies and functional investigations of representative bacteria at different stages of corrosion are being carried out for additional laboratory-based corrosion studies.

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Bioinformatics tools to assess metagenomic data for applied microbiology

Abstract

The reduction of the price of DNA sequencing has resulted in the emergence of large data sets to handle and analyze, especially in microbial ecosystems, which are characterized by high taxonomic and functional diversities. To assess the properties of these complex ecosystems, a conceptual background of the application of NGS technology and bioinformatics analysis to metagenomics is required. Accordingly, this article presents an overview of the evolution of knowledge of microbial ecology from traditional culture-dependent methods to culture-independent methods and the last frontier in knowledge, metagenomics. Topics that will be covered include sample preparation for NGS, starting with total DNA extraction and library preparation, followed by a brief discussion of the chemistry of NGS to help provide an understanding of which bioinformatics pipeline approach may be helpful for achieving a researcher's goals. The importance of selecting appropriate sequencing coverage and depth parameters to obtain a suitable measure of microbial diversity is discussed. As all DNA sequencing processes produce base-calling errors that compromise data analysis, including genome assembly and microbial functional analysis, dedicated software is presented and conceptually discussed with regard to potential applications in the general microbial ecology field.

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Microbial biosurfactants for oil spill remediation: pitfalls and potentials

Abstract

Spillage of fossil-based oils during their conveyance through water conduits are sporadic, but significant environmental disasters. As the viscous hydrocarbons of the crude oils spread on water surface and choke aquatic life to death, their effective degradation is crucial for ecological balance. Though chemical and mechanical means are conventional ways to tackle the issues, they are riddled with limitations. In this scenario, coercing the biosurfactant-producing bacteria and fungi are promising avenues. Biosurfactants, the amphiphilic compounds, are capable of reducing interfacial tension, dispersing the oil particles, and degrading them into non-toxic debris. Among the vast array of biosurfactants, the trio of rhamnolipid, sophorolipid, and surfactin have been characterized well. Among the microbes, only Pseudomonas, Bacillus, and Candida have been evaluated, while there can be other exploitable candidates. In this regard, this review discusses the scopes and hurdles in utilization of the microbial surface-active compounds for oil spill management.

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Microbial community shifts in biogas reactors upon complete or partial ammonia inhibition

Abstract

Anaerobic digestion of nitrogen-rich substrate often causes process inhibition due to the susceptibility of the microbial community facing ammonia accumulation. However, the precise response of the microbial community has remained largely unknown. To explore the reasons, bacterial communities in ammonia-stressed reactors and control reactors were studied by amplicon pyrosequencing of 16S rRNA genes and the active methanogens were followed by terminal restriction fragment length polymorphism (T-RFLP) analyses of mcrA/mrtA gene transcripts. The results showed that the diversity of bacterial communities decreased in two parallel ammonia-inhibited reactors compared with two control reactors, but different levels of inhibitions coinciding with different community shifts were observed. In one reactor, the process was completely inhibited, which was preceded by a decreasing relative abundance of the phylum Firmicutes. Despite the same operating conditions, the process was stabilized in the parallel, partially inhibited reactor, in which the relative abundance of Firmicutes greatly increased. In particular, both ammonia-inhibited reactors lacked taxa assumed to be syntrophic bacteria (Thermoanaerobacteraceae, Syntrophomonadaceae, and Synergistaceae). Besides the predominance of the hydrogenotrophic methanogens Methanoculleus and Methanobacterium, activity of Methanosarcina and even of the strictly aceticlastic genus Methanosaeta were found to contribute at very high ammonia levels (> 9 g NH₄-N L⁻¹) in the stabilized reactor (partial inhibition). In contrast, the lack of aceticlastic activity in the parallel reactor might have led to acetate accumulation and thus process failure (complete inhibition). Collectively, ammonia was found to be a general inhibitor while accumulating acetate and thus acidification might be the key factor of complete process failure.

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Roles of saprotrophic fungi in biodegradation or transformation of organic and inorganic pollutants in co-contaminated sites

Abstract

For decades, human activities, industrialization, and agriculture have contaminated soils and water with several compounds, including potentially toxic metals and organic persistent xenobiotics. The co-occurrence of those toxicants poses challenging environmental problems, as complicated chemical interactions and synergies can arise and lead to severe and toxic effects on organisms. The use of fungi, alone or with bacteria, for bioremediation purposes is a growing biotechnology with high potential in terms of cost-effectiveness, an environmental-friendly perspective and feasibility, and often representing a sustainable nature-based solution. This paper reviews different ecological, metabolic, and physiological aspects involved in fungal bioremediation of co-contaminated soils and water systems, not only addressing best methods and approaches to assess the simultaneous presence of metals and organic toxic compounds and their consequences on provided ecosystem services but also the interactions between fungi and bacteria, in order to suggest further study directions in this field.

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Polyhydroxyalkanoate synthesis based on glycerol and implementation of the process under conditions of pilot production

Abstract

The present study addresses the synthesis and properties of polyhydroxyalkanoates (PHA) of different composition synthesized by Cupriavidus eutrophus B-10646 using glycerol as a carbon substrate. Poly(3-hydroxybutyrate) [P(3HB)] was effectively synthesized in fed-batch culture in a 30-L fermenter on glycerol of various purification degrees, with 99.5, 99.7, and 82.1% content of the main component. Purified glycerol (99.7%) was used for 150-L pilot scale fermentation. The total biomass and P(3HB) concentration reached 110 and 85.8 g/L, respectively, after 45 h of fed-batch fermentation. An average volumetric productivity of P(3HB) was 1.83 g/(L h). The degree of crystallinity and molecular weight of P(3HB) synthesized on glycerol were lower than and temperature characteristics were the same as those of P(3HB) synthesized on sugars.

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Yeast cultures expressing the Ffase from Schwanniomyces occidentalis , a simple system to produce the potential prebiotic sugar 6-kestose

Abstract

The β-fructofuranosidase Ffase from the yeast Schwanniomyces occidentalis produces potential prebiotic fructooligosaccharides with health-promoting properties, making it of biotechnological interest. Ffase is one of the highest and more selective known producers of 6-kestose by transfructosylation of sucrose. In this work, production of 6-kestose was simplified by directly using cultures of S. occidentalis and Saccharomyces cerevisiae expressing both the wild-type enzyme and a mutated Ffase variant including the Ser196Leu substitution (Ffase-Leu196). Best results were obtained using yeast cultures supplemented with sucrose and expressing the Ffase-Leu196, which after only 4 h produced ~ 116 g/L of 6-kestose, twice the amount obtained with the corresponding purified enzyme. 6-Kestose represented ~ 70% of the products synthesized. In addition, a small amount of 1-kestose and the neofructoligosaccharides neokestose and blastose were also produced. The Ser196Leu substitution skewed production of 6-kestose and neofructooligosaccharides resulting in an increase of ~ 2.2- and 1.5-fold, respectively, without affecting production of 1-kestose. Supplementing yeast cultures with glucose clearly showed that blastose originates from direct fructosylation of glucose, a property that has not been described for other similar proteins from yeasts. Modeling neokestose and blastose into the Ffase-active site revealed the molecular basis explaining the peculiar specificity of this enzyme.

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A stoichio-kinetic model for a DPPH∙ -ferulic acid reaction

Publication date: 1 May 2019

Source: Talanta, Volume 196

Author(s): Daniel Goujot, Marie-Elisabeth Cuvelier, Paola Soto, Francis Courtois

Abstract

Estimates of the activity of antioxidants in the literature often appear inconsistent. In the specific case of the DPPH∙ test, the diversity of measurements may arise from variations in the protocols followed. This paper proposes an unbiased method which models the reduction mechanism. This method is applied to the reduction of DPPH∙ by ferulic acid. A scheme with eight coupled reactions is proposed and has been validated on different solvents and using a wide range of DPPH ̇, ferulic acid, and 5,5′-diferulic acid concentrations, and verified using data from the literature on ferulic acid activity. This modeling approach permits a correction to the bias of the 8th reaction (spontaneous reduction of DPPH ̇), because of its sensitivity to solvent, which in most cases is not taken into account. The best experimental strategy to determine the Efficient Concentration of ferulic acid to reduce 20% (EC20) and 50% (EC50) of DPPH∙ is then detailed in terms of initial DPPH∙ concentrations and the duration of the experiment.

Graphical abstract

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The trouble with surrogates in environmental risk assessment: a daphniid case study

Abstract

The use of indicator species to test for environmental stability and functioning is a widespread practice. In aquatic systems, several daphniids (Cladocera: Daphniidae) are commonly used as indicator species; registration of new pesticides are mandated by the Environmental Protection Agency to be accompanied by daphniid toxicity data. This reliance upon a few species to infer ecosystem health and function assumes similar responses to toxicants across species with potentially very different life histories and susceptibility. Incorporating lab-derived life-history data into a simple mathematical model, we explore the reliability of three different daphniid species as surrogates for each other by comparing their responses to reductions in survivorship and fecundity after simulated exposure to toxicants. Our results demonstrate that daphniid species' responses to toxicant exposure render them poor surrogates for one another, highlighting that caution should be exercised in using a surrogate approach to the use of indicator species in risk assessment.

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Streptomyces : implications and interactions in plant growth promotion

Abstract

With the impending increase of the world population by 2050, more activities have been directed toward the improvement of crop yield and a safe environment. The need for chemical-free agricultural practices is becoming eminent due to the effects of these chemicals on the environment and human health. Actinomycetes constitute a significant percentage of the soil microbial community. The Streptomyces genus, which is the most abundant and arguably the most important actinomycetes, is a good source of bioactive compounds, antibiotics, and extracellular enzymes. These genera have shown over time great potential in improving the future of agriculture. This review highlights and buttresses the agricultural importance of Streptomyces through its biocontrol and plant growth-promoting activities. These activities are highlighted and discussed in this review. Some biocontrol products from this genus are already being marketed while work is still ongoing on this productive genus. Compared to more focus on its biocontrol ability, less work has been done on it as a biofertilizer until recently. This genus is as efficient as a biofertilizer as it is as a biocontrol.

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Safety and efficacy of twice daily administration of KPI-121 1% for ocular inflammation and pain following cataract surgery

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Development of a new algorithm based on FDT Matrix perimetry and SD-OCT to improve early glaucoma detection in primary care

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Incorporating reference guided priors into calibrationless parallel imaging reconstruction

Publication date: Available online 28 December 2018

Source: Magnetic Resonance Imaging

Author(s): Qingyong Zhu, Wei Wang, Jing Cheng, Xi Peng

Abstract

Purpose

To propose and evaluate a new calibrationless parallel imaging method aimed at further improving the reconstruction accuracy of the accelerated multi-channel MR images.

Method

We introduce a new calibrationless parallel imaging method. On top of exploiting joint sparsity cross channels of the target image to be reconstructed, it incorporates similar priors on the grey-level intensity and edge orientation, which both come from a high-spatial resolution reference image that can be easily obtained in many clinical MRI scenarios. The mixed l₂-l₁ norm is used to enforce joint sparsity and a multi-scale gradient orientation operator is applied to extract fine edges from the reference image. Additionally, this optimization problem can be solved via a non-linear conjugate gradient algorithm with line search in this work.

Results

The proposed method is compared with the existing state-of-the-art auto-calibration and calibrationless parallel imaging techniques. The experiments on different in-vivo brain MR datasets show that the proposed method has the superior performance in terms of both artifacts suppression and details preservation.

Conclusion

The reference guided calibrationless parallel imaging method can significantly improve the performance of joint reconstruction of target channel images. Even when the reduction factor is high, it can keep edge structures well.

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Turbulent rectangular compound open channel flow study using multi-zonal approach

Abstract

In this paper, an improved Shiono–Knight model (SKM) has been proposed to calculate the rectangular compound open channel flows by considering a multi-zonal (MZ) approach in modelling turbulence and secondary flows across lateral flow direction. This is an effort to represent natural flows with compound shape more closely. The proposed model improves the estimation of secondary flow by original SKM model to increase the accuracy of depth-averaged velocity profile solution formed within the transitional region between different sections (i.e. between main-channel and floodplain) of compound channel. This proposed MZ model works by sectioning intermediate zones between floodplain and main-channel for running computation in order to improve the modelling accuracy. The modelling results have been validated using the experimental data by national UK Flood Channel Facility. It has been proven to work reasonably well to model secondary flows within the investigated compound channel flow cases and hence produce better representation to their flow lateral velocity profile.

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Adaptive anxious states and down-regulation of dopamine activity under amygdala activation in rats

Publication date: 1 April 2019

Source: Behavioural Brain Research, Volume 361

Author(s): Chien-Wen Lai, Chun-hui Chang

Abstract

All individuals face different challenges every day. Under threats, the basolateral nucleus of the amygdala (BLA) is engaged to initiate proper physiological and behavioral responses. In this study, we pharmacologically activated the BLA in rats with no stress history to examine how animals regulated their anxiety- and despair-like behaviors in face of different task demands, as well as their dopamine (DA) activity in ventral tegmental area (VTA). The number of spontaneously firing VTA DA neurons, defined as "population activity", decides the amplitude of DA response to external stimuli, which can be assessed by the behavioral responses of the animals to amphetamine (AMPH) administration; several studies have shown that the level is positively correlated with the AMPH-induced increase in locomotor activity. Our results showed that for anxiety-like behaviors, rats displayed lower anxiety levels in elevated plus maze (EPM) and marble burying test, but increased anxiety level in social interaction test. For despair-like behaviors, there was no difference in performance in the forced swim test (FST) we conducted. Finally, systemic injection of AMPH increased locomotor activity, which was dampened with BLA activation. The inconsistency in anxiety levels in different tasks demonstrated that rats adapted their behavioral strategies to different experimental settings. Together, our results suggested that BLA activation prepared the animals towards different modality of challenges and down-regulated their DA reward system.

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The effects of oxytocin on primates’ working memory depend on the emotional valence of contextual factors

Publication date: Available online 28 December 2018

Source: Behavioural Brain Research

Author(s): Shahab A. Zarei, Vahid Sheibani, Carlos Tomaz, Farshad A. Mansouri

Abstract

Current models suggest that neuropeptide oxytocin modulates the salience of emotional/social stimuli and consequently influences perceptual, attentional and learning processes that underlie social behaviour. Therefore, oxytocin has been considered as a potential treatment in managing social and communication deficits in neuropsychological disorders. Recent studies indicate that effects of oxytocin on social and cognitive functions greatly vary and even lead to opposite outcomes. The factors leading to such variabilities in behavioural effects of oxytocin and their underlying mechanisms remain unclear.

Here, we examined the effects of exogenously administered (intranasal) oxytocin (48 IU) on cognitive functions of macaque monkeys within a controlled experimental condition in a randomized crossover study.

Monkeys performed a working memory task in which they memorized and subsequently matched stimuli with different emotional/social content (positive, negative, and neutral) at different levels of cognitive difficulties (delay period). Monkeys' accuracy was lower at longer delay intervals indicating that higher cognitive demands adversely affected their performance. There was a significant difference in accuracy and response time between the three emotional conditions. The effects of oxytocin on monkeys' performance were dependent on the emotional content of stimuli so that oxytocin enhanced the adverse effects of negative stimuli, however, moderated the effects of positive stimuli. Our findings in monkeys do not support models suggesting a general effect of oxytocin in enhancing salience or heightening of attention to social stimuli and instead suggest that the cognitive effects of oxytocin depend on the emotional valence of contextual factors.

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Memory generalization after one-trial contextual fear conditioning: effects of sex and neuropeptide S receptor deficiency

Publication date: Available online 28 December 2018

Source: Behavioural Brain Research

Author(s): Josephine Germer, Evelyn Kahl, Markus Fendt

Abstract

One-trial contextual fear conditioning in laboratory mice results in a fear memory which is relatively specific to the original conditioning context shortly after conditioning but becomes more unspecific after an incubation time of one month. This process is called generalization of fear memory and is used to investigate processes which might be involved in the pathogenesis of post-traumatic stress disorder. In the present study, we investigated the effects of sex and neuropeptide S receptor (NPSR) deficiency in one-trial contextual fear conditioning. In addition to contextual fear, we also measured startle reactivity, anxiety and corticosterone plasma levels of the mice. Our data show main effects of sex and NPSR-deficiency on freezing behavior, startle magnitude, and anxiety levels. However, generalization of contextual fear memory after incubation time was not affected by sex. Notably, NPSR-deficient mice had a more specific fear memory shortly after conditioning than their wildtype littermates but after incubation time, all genotypes had a generalized fear memory. The present data further show that plasma corticosterone levels are increased after incubation time. This increase was significantly more pronounced in NPSR-deficient mice. Taken together, our study confirms the suitability of one-trial contextual fear conditioning to study the effects of incubation time on fear memory generalization but also indicates the need for control groups without incubation. We further demonstrate that the increase of plasma corticosterone levels after incubation time is exaggerated in NPSR-deficient mice. The latter finding suggests an important role of the NPS system in the regulation of corticosterone release.

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Endothelin impacts on olfactory processing in rats

Publication date: Available online 28 December 2018

Source: Behavioural Brain Research

Author(s): Bertrand Bryche, Mikaël Le Bourhis, Patrice Congar, Claire Martin, Olivier Rampin, Nicolas Meunier

Abstract

In the olfactory epithelium, olfactory sensitive neurons and their axons are surrounded by glia-like cells called sustentacular cells, which maintain both the structural and ionic integrity of the olfactory mucosa. We have previously found that endothelin-1 (ET-1) can uncouple sustentacular cell gap junctions in vitro similarly as carbenoxolone, a known gap junction uncoupling agent. The role of gap junctions in odorant transduction remains controversial and we explored here if ET-1 naturally produced by the olfactory mucosa could impact odorant detection. Using calcium imaging on olfactory mucosa explant, we first confirmed that ET-1 uncouples gap junctions in an olfactory mucosa preparation preserving the tissue integrity. We next measured the olfactory epithelium responses to odorant stimulation using electro-olfactogram recordings. While the amplitude of the response was not modified by application of ET-1 and carbenoxolone, its repolarizing phase was slower after both treatments. We finally examined the behavioral performances of rat pups in an orientation test based on maternal odor recognition after intranasal instillations of ET-1 or carbenoxolone. While rat pups performances were decreased after ET-1 treatment, it was unchanged after carbenoxolone treatment. Overall, our results indicate that ET-1 modulates olfactory responses at least partly through gap junction uncoupling.

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Inactivated lactobacilli alter both microbiota composition and behaviour

Publication date: Available online 28 December 2018

Source: Behavioural Brain Research

Author(s): Alicja K. Warda, Kieran Rea, Patrick Fitzgerald, Cara Hueston, Enrique Gonzalez-Tortuero, Timothy G. Dinan, Colin Hill

Abstract

Recently it has been proposed to expand the definition of psychobiotics (beneficial bacteria (probiotics) or support for such bacteria (prebiotics) that positively impact mental health) to any exogenous influence whose effect on the brain is bacterially-mediated. This definition would include inactivated microorganisms with anxiolytic and antidepressant effects. The use of inactivated microorganisms has several advantages over living organisms, including no risk of infection in vulnerable individuals and ease of use in terms of storage and delivery options. It has been reported that consumption of inactivated microorganisms can affect behaviour, particularly in chronic or prolonged stress situations, but effects on healthy populations have not been investigated to the same extent. Also, only limited data is available on the effects of inactivated microorganisms on the microbiota of healthy individuals (animal or human). Therefore, we investigated the effect of feeding a standard mouse chow which incorporates ADR-159, a heat-treated fermentate generated by two Lactobacillus strains, on the behaviour and microbiota of healthy mice.

Prolonged consumption of ADR-159 diet had no adverse effect on anthropometrics or general health, but the ADR-159 fed animals demonstrated increased sociability and lower baseline corticosterone levels (stress hormone). The diet also led to subtle but significant changes in the microbiota, with less abundant taxa being most affected. The behavioural, biochemical and microbiological results provide a new light on the impact of inactivated microorganisms and their metabolites on the social behaviour and microbiota of healthy mice.

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Effects of post-learning REM sleep deprivation on hippocampal plasticity-related genes and microRNA in mice

Publication date: Available online 27 December 2018

Source: Behavioural Brain Research

Author(s): Sebahattin Karabulut, Keziban Korkmaz Bayramov, Ruslan Bayramov, Fadime Ozdemir, Tugba Topaloglu, Ergul Ergen, Kamile Yazgan, Ahmet Sevki Taskiran, Asuman Golgeli

Abstract

Sleep is essential for memory consolidation that stabilizes a memory trace. Memory consolidation includes waves of new gene expression and protein synthesis. Recently, microRNAs (miRNAs) have emerged as critical regulators of memory processes. Previous studies demonstrated that rapid eye movement (REM) sleep deprivation (REM SD) during specific time windows after training in the Morris water maze (MWM) task impairs memory consolidation. Here, we showed that the post-learning REM sleep, extending from 3 to 6 h after last training, is critical for spatial learning in the MWM task. Further, we found that the REM SD after training significantly changes the hippocampal expression of brain-derived neurotrophic factor (BDNF) mRNA; however, it causes minimal difference in the hippocampal expressions of calcium-calmodulin-dependent protein kinase II (CAMKII) and cAMP response-element-binding (CREB). In addition, it considerably affected the hippocampal expressions of miR-132, miR-182, and miR-124. In conclusion, after the MWM task, the post-learning REM sleep during specific time windows can modulate spatial memory consolidation, and its deprivation can impact the hippocampal transcriptional processes including memory-related miRNAs and mRNAs.

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The effects of amphetamine on working memory and locomotor activity in adult rats administered risperidone early in life

Publication date: Available online 27 December 2018

Source: Behavioural Brain Research

Author(s): Mark E. Bardgett, Casey Crane, Emily C. Baltes Thompson, Bethanie Cox, Tyler Downnen

Abstract

Antipsychotic drugs are used to manage symptoms of pediatric psychiatric disorders despite the relative absence of research regarding the long-term effects of these drugs on brain development. Using rats as a model, research has demonstrated that administration of the antipsychotic drug, risperidone, during early postnatal development elevates locomotor activity and sensitivity to the locomotor effects of amphetamine during adulthood. Because risperidone targets neurotransmitter receptors and forebrain regions associated with working memory, the present study determined whether early-life risperidone altered working memory during adulthood and its sensitivity to amphetamine-induced impairment. Female and male rats received subcutaneous (sc) injections of risperidone daily on postnatal days 14-42. Early-life risperidone increased spontaneous locomotor activity and amphetamine-induced hyperactivity during adulthood, although the effects were significantly greater in females. Working memory was tested in an operant-based, delayed non-matching-to-sample task. Early-life risperidone did not affect the percentage of correct choices observed during sessions with 0-8 second delays but impaired performance during sessions with 0-24 second delays. In a subsequent set of tests using 0-24 second delays, amphetamine (0.75 and 1.25 mg/kg, sc) significantly reduced the percentage of correct choices at most delays, but risperidone did not exacerbate this effect. These data suggest that early-life risperidone leads to modest deficits in working memory during adulthood, but does not alter the perturbation of working memory by amphetamine.

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Short-term westernized (HFFD) diet fed in adolescent rats: Effect on glucose homeostasis, Hippocampal insulin signaling, apoptosis and related cognitive and recognition memory function

Publication date: Available online 22 December 2018

Source: Behavioural Brain Research

Author(s): Yusuf Hussain, Sunil K. Jain, Puneet K. Samaiya

Abstract

Excessive consumption of high-fat fructose diet (HFFD) is associated with the development of systemic insulin resistance (InsRes) and further progression into type-2 diabetes (T2DM). InsRes induced hippocampal insulin signaling has serious consequence on hampered sensorimotor, cognitive performance and long term potentiation accompined to neuronal cell death in hippocampus. However, short-term HFFD/Streptozotocin (STZ) mediated hippocampal InsRes and related neurobehavioral alterations in adoloscents has not been reported.Therefore, we investigated a one-week HFFD model to augment the state of InsRes along with a single sub-diabetogenic dose of STZ (45 mg/kg i.p) to produced a hampered hippocampal insulin signaling associated with frank hyperglycemia and other biochemical and neurobehavioral alterations in young rats. To achieve this, male wistar rats of age (8-10 weeks) and weight 80–120 g were divided into two main groups: (1) fed with commercial standard normalfat diet (NFD: 6.5 % kcal fat) and (2) fed an in-house prepared high-fat diet [HFFD: 58 % kcal fat] and 20% high-fructose corn syrup in the distilled water. Our results showed that an increase in calorie intake, water intake, body weight and blood glucose levels. Further, an increase in fasting serum insulin and Homeostasis Model Assessment-index (HOMA-I) and oral glucose tolerance test (OGTT) was observed. Whereas, a decrease in hippocampal insulin signaling and translocation of glucose transporter type 4 (GLUT4) to neuronal membrane. Further, HFFD/STZ mediated oxidative stress, lipid peroxidation (LPO) and decreased antioxidant levels, Brain-derived neurotrophic factor (BDNF) levels and further activation of increase caspase-3 was observed indicating biochemical alterations in hippocampus resulting in cognitive dysfunction and hypolocomotion.

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Validation of a multidirectional locomotive dual-task paradigm to evaluate task-related differences in event-related electro-cortical activity

Publication date: Available online 21 December 2018

Source: Behavioural Brain Research

Author(s): Shelley J. Duncan, Angela Gosling, Derek Panchuk, Remco C.J. Polman

Abstract

A fundamental aspect of everyday function is the ability to simultaneously execute both cognitive and motor tasks. The ability to perform such tasks is commonly assessed using a dual-task paradigm that has the capacity to manipulate both cognitive and motor components of an action. Dual-task performance provides an opportunity to obtain an insight into how cognitive and motor function are affected during natural tasks (e.g., locomotion). The following study aimed to determine the effectiveness of using a goal-directed multidirectional locomotor task to measure differences in task-related (tasks of increasing difficulty) electro-cortical activity. In the single-task condition participants walked around a grid-based track, performing directional changes at each intersection in response to a sensory stimulus. In the dual-task condition participants performed the same primary task while performing a simultaneous memory recall task. Behavioural differences in trial completion time and electro-cortical activity were identified in relation to the posterior N2 and P3 component mean amplitudes. The results showed that, while performing a higher-level cognitive task during walking (dual-task), interference arises in a shared system that influences neural mechanisms involved in attention and selection for action, and later cognitive processes recruited in working memory and cognitive control. This study extends previous work and shows that performing a more complex cognitive task while walking, elicits interference effects sensitive to higher-level cognitive processes, and takes the next step towards measurement of electro-cortical activity within naturalistic environments.

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Early Wheel-running Promotes Functional Recovery by Improving Mitochondria Metabolism in Olfactory Ensheathing Cells After Ischemic Stroke in Rats

Publication date: Available online 21 December 2018

Source: Behavioural Brain Research

Author(s): Ce Li, Bei Zhang, Shan Tian, Jian Hu, Beiyao Gao, Peile Liu, Yan Hua, Weiqi Bao, Yihui Guan, Yulong Bai

Abstract

Olfactory ensheathing cells (OECs) has been widely studied in stroke. The present study was aimed at examining the role of wheel-running treatment (WR) on rat olfactory ensheathing cells (rOECs) functions. Thirty adult male Sprague Dawley rats were randomly divided into two groups: the middle cerebral artery occlusion (MCAO) group and WR + MCAO group. Motor behavior was assessed through the footfault test, and the results showed that WR training markedly improved the neurobehavioral outcome. The glucose metabolic status of the brain was assessed with the micro-PET. This training significantly enhanced the glucose uptake of olfactory bulb in the early stage of WR treatment. The function of rOECs mitochondrial was significantly enhanced after 10 days of treatment. Body weight of rats in both of the two groups decreased and then increased slowly following the days. But the growth trend of the WR + MCAO group was no significantly higher than that of the WR group. This training significantly enhanced the glucose uptake, improved the proliferation of rOECs and increased the expression level of cytochrome C (Cyt-c). The mechanism may be associated with the facilitation of mitochondrial function of rOECs cells. Including facilitation of mitochondrial fusion, fission, and accompanying increased quantities of mitochondria. Obtained results indicate that early WR treatment may exert enhanced function on rOECs in vivo and increased mitochondrial amounts, and improved the expression level of Cyt-c after ischemic stroke.

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Sex-based differences in right dorsolateral prefrontal cortex roles in fairness norm compliance

Publication date: Available online 21 December 2018

Source: Behavioural Brain Research

Author(s): Wanting Chen, Shuyue Zhang, Ofir Turel, Youqing Peng, Hong Chen, Qinghua He

Abstract

Social norms are a common motivator or de-motivator of behavior through the need of humans to comply with acceptable behaviors of their social groups. Converging evidence from functional neuroimaging and noninvasive brain stimulation studies suggest that the right dorsolateral prefrontal cortex (rDLPFC) is involved in social norm compliance. Extending this view, we suggest that rDLPFC may not act uniformly when men and women face different types of fairness norm compliance situations, and that there may be a sequential update of norm compliance after experiencing punishment. Using High-Definition Transcranial Direct Current Stimulation (HD-tDCS) on 100 participants playing a sequence of economic game trials, the current study showed that (1) the right dorsolateral prefrontal cortex (rDLPFC) is involved in both voluntary and sanction-induced fairness norm compliance, (2) it has an opposite role in the two types of compliance, (3) there are sex-based differences in rDLPFC roles in fairness norm compliance, and (4) post-punishment fairness compliance is reduced compared to baseline.

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Orexin-A promotes EEG changes but fails to induce anxiety in rats

Publication date: Available online 21 December 2018

Source: Behavioural Brain Research

Author(s): Víctor Manuel Magdaleno-Madrigal, Sandra Morales-Mulia, Humberto Nicolini, Alma Genis-Mendoza, Elizabeth Cázares-Martínez Claudia, Manuel Pérez-Luna José, Marcela Morales-Mulia

Abstract

Orexins (OXs) system has been suggested to play a key role in regulate processes related to arousal, including anxious behaviors. However, until now, the contribution of OXs in anxiogenic-like effects has not been completely clear, particularly in rats, whose results are not yet conclusive in behavioral-tests such as elevated-plus-maze test (EPM-test). The goal of this study was to explore the anxiogenic-like effect induced by orexin-A (OX-A) using two different paradigms; the EPM-test and simultaneously a quantitative index in vivo, the cortical-electroencephalographic-(EEG)-record. This index proposes that a low-frequency domain EEG, particularly 0.5-5-Hz (delta and low portion of theta-waves), is a key indicator to evaluate anxiety levels. We also explored whether the anxious effect of OX-A could be altered by an antagonist of dopamine-D2-receptor (D₂R) sulpiride (SUL). Our results showed that intracerebroventricular (i.c.v.) injection of a low dose of OX-A (140 pmol) did not increase anxiety levels in rats. On the other hand, cortical-EEG-activity showed only a decrease in delta-spectral-power but no changes in theta-potency. These data suggest that the reduction in delta-power induced by OX-A only keeps the animals awake and alert without changes in anxiety levels.

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Prefrontal transcranial alternating current stimulation improves motor sequence reproduction

Publication date: Available online 19 December 2018

Source: Behavioural Brain Research

Author(s): Monica B. Berntsen, Nicholas R. Cooper, Gethin Hughes, Vincenzo Romei

Abstract

Cortical activity in frontal, parietal, and motor regions during sequence observation correlates with performance on sequence reproduction. Increased cortical activity observed during observation has therefore been suggested to represent increased learning. Causal relationships have been demonstrated between M1 and motor sequence reproduction and between parietal cortex and bimanual learning. However, similar effects have not been reported for frontal regions despite a number of reports implicating its involvement in encoding of motor sequences. Investigating causal relations between cortical activity and reproduction of motor sequences in parietal, frontal and primary motor regions can disentangle whether specific regions during simple observation can be selectively ascribed to encoding or reproduction or both. We designed a sensorimotor paradigm that included a strong motor sequence component, and tested the impact of individually adjusted transcranial alternating current stimulation (IAF-tACS) to prefrontal, parietal, and primary motor regions on electroencephalographic motor rhythms (alpha and beta bandwidths) during motor sequence observation and the ability to reproduce the observed sequences. Independently of the stimulated region, IAF-tACS led to a reduction in suppression in the lower beta-range relative to sham. Prefrontal IAF-tACS however, led to significant improvement in motor sequence reproduction, pinpointing the crucial role of prefrontal regions in motor sequence reproduction.

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Beta-carotene as a novel therapy for the treatment of “Autistic like behavior” in animal models of Autism

Publication date: Available online 28 September 2017

Source: Behavioural Brain Research

Author(s): Yosefa Avraham, Elliot M Berry, Marina Donskoy, Wiessam Abu Ahmad, Lia Vorobiev, Amnon Albeck, David Mankuta

Abstract

Autism-affected individuals are characterized by lower plasma oxytocin and its ectoenzyme regulator CD38. Oxytocin, a hypothalamic hormone secreted upon the release of CD38, plays a role in social behavior and bonding. All-trans retinoic acid is a potent inducer of CD38 and can be used as a novel therapeutic strategy in autism. We investigated the role of beta-carotene in rescuing autistic-like behavior in BALB/c and BTBR mice. Beta-carotene derivatives are preferred as they are neither toxic nor teratogenic. Beta-carotene at 0.1–5.0 mg/kg was administered orally to BALB/c and BTBR newborn mice on days 1–7. They were tested at age 2–3 months for five behavioral tests for "autism"; in addition, brain CD38, oxytocin, oxytocin receptor, Brain Derived Neurotrophic Factor (BDNF) and retinoic acid receptor gene expression, serum oxytocin levels, and neurological score were evaluated.

Beta-carotene administered at birth significantly increased T-maze alternations and led to longer time spent with an unfamiliar mouse in the "three-chamber test" and less time spent in the empty chamber. Furthermore, enhanced activity in the open field test; increased time spent in the reciprocal social interaction test; decreased grooming and bedding behaviors; and enhanced brain CD38, oxytocin, oxytocin receptor, BDNF, retinoic acid gene expression, and serum oxytocin levels. No changes in neurological score were observed.

Beta-carotene oral supplementation to BALB/c and BTBR mice at birth significantly reduced restricted and stereotyped behaviors and interests, increased social interactions and communication, CD38, and oxytocin, probably by enhancing brain neuroplasticity without toxicity. Thus, beta-carotene administered after birth to newborns of families predisposed to "autism" has the potential to prevent/ameliorate" autistic like behavior". These results support further clinical studies.

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Spontaneously hypertensive (SHR) rats choose more impulsively than Wistar-Kyoto (WKY) rats on a delay discounting task

Publication date: Available online 27 September 2017

Source: Behavioural Brain Research

Author(s): Carlos F. Aparicio, Paul J. Hennigan, Laurel J. Mulligan, Benigno Alonso-Alvarez

Abstract

Indications of Attention Deficit Hyperactivity Disorder (ADHD) in the spontaneously hypertensive rat (SHR) are not consistent across different tests of impulsivity, questioning the SHR's validity as a rodent model of ADHD. This study used a concurrent-chains procedure to examine possible differences in impulsive choice between SHRs and control-normotensive Wistar Kyoto (WKY) rats. The aim was to extend the generality of findings showing regularities between the hyperbolic-decay model and the generalized matching law fitting delay discounting data from nonhuman animals. The objectives were to: (1) examine differences in impulsive choice between SHRs and WKYs; (2) add evidence suggesting that the SHR is a suitable model of ADHD; (3) demonstrate that concurrent-chains procedures requiring locomotion detect differences in impulsive choice between SHRs and WKYs; (4) support the idea that impulsivity in nonhuman animals increases with training. The initial link used two non-independent random interval schedules arranging entries to the terminal links, where one fixed-time (FT) schedule delayed 1-food pellet and the other FT 4-food pellets. The FT delaying the former was kept constant at 0.1 s and that delaying the latter changed after every 10 food deliveries, defining six delay components (0.1, 5, 10, 20, 40, and 80 s) presented in random order each session. Results showed that the SHRs choose more impulsively than the WKYs, adding to the body of evidence suggesting that the SHR may be a suitable model of ADHD. Both models of choice fitted the impulsive choices of the SHRs and WKYs well; positive correlations between estimates of parameters k and s suggested compatibility between models of choice showing that impulsivity increases with training.

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Behavioral, inflammatory and neurochemical disturbances in LPS and UCMS-induced mouse models of depression

Publication date: Available online 29 May 2017

Source: Behavioural Brain Research

Author(s): Xinnan Zhao, Fengrui Cao, Qing Liu, Xinsheng Li, Guoyang Xu, Gang Liu, Yanli Zhang, Xiaohan Yang, Shansong Yi, Fenghua Xu, Kai Fan, Jianmei Ma

Abstract

The immuno-inflammatory activation triggered by various stresses play an important role in pathophysiology of depression. The immune responses display differential pathological characters in different stresses. However, comparative data and analysis on behavioural, inflammatory and neurochemical changes in different stress-induced depression is limited. To imitate different stressful situations, in this study, mice were subjected to a single injection of LPS (0.5 mg/kg, i.p.) and UCMS (4 week period), respectively. LPS-stressed mice showed more immobility time in FST and TST, as well as more time in periphery in OFT than UCMS-stressed mice. Further, LPS-stressed mice showed robuster expression and release of TNF-α, IL-1β and IL-6 in serum and depression-related brain areas (prefrontal cortex, hippocampus and striatum) as compared to UCMS-stressed mice. The ELISA results showed that IDO expression was significantly increased following LPS and UCMS stresses, but more increased IDO expression was observed in prefrontal cortex and hippocampus of LPS-stressed mice. The decrease of 5-HT and BDNF was detected only in hippocampus of LPS-stressed mice, but in overall all the brain areas assessed in UCMS-stressed mice as compared to control. The data indicate that LPS induced more severe depressive-like behaviours and robuster immune activation than UCMS. Our study strongly imply that hippocampus is relatively more vulnerable to acute inflammatory challenge in depression, while chronic psychological stress is more likely to cause the multidimensional symptoms of clinical depression. Our findings provide more insight into pathophysiology in various stress-induced depression and also implicate a potential suitability of different stress models.

Graphical abstract

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A paradigm shift in eye banking: how new models are challenging the status quo

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Prospective randomized comparative study between venturi and peristaltic pumps in WhiteStar Signature® phacoemulsification machine

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Effects of Phantom Electrode Stimulation on Vocal Production in Cochlear Implant Users

Objectives: Cochlear implant (CI) users suffer from a range of speech impairments, such as stuttering and vocal control of pitch and intensity. Though little research has focused on the role of auditory feedback in the speech of CI users, these speech impairments could be due in part to limited access to low-frequency cues inherent in CI-mediated listening. Phantom electrode stimulation (PES) represents a novel application of current steering that extends access to low frequencies for CI recipients. It is important to note that PES transmits frequencies below 300 Hz, whereas Baseline does not. The objective of this study was to explore the effects of PES on multiple frequency-related characteristics of voice production. Design: Eight postlingually deafened, adult Advanced Bionics CI users underwent a series of vocal production tests including Tone Repetition, Vowel Sound Production, Passage Reading, and Picture Description. Participants completed all of these tests twice: once with PES and once using their program used for everyday listening (Baseline). An additional test, Automatic Modulation, was included to measure acute effects of PES and was completed only once. This test involved switching between PES and Baseline at specific time intervals in real time as participants read a series of short sentences. Finally, a subjective Vocal Effort measurement was also included. Results: In Tone Repetition, the fundamental frequencies (F0) of tones produced using PES and the size of musical intervals produced using PES were significantly more accurate (closer to the target) compared with Baseline in specific gender, target tone range, and target tone type testing conditions. In the Vowel Sound Production task, vowel formant profiles produced using PES were closer to that of the general population compared with those produced using Baseline. The Passage Reading and Picture Description task results suggest that PES reduces measures of pitch variability (F0 standard deviation and range) in natural speech production. No significant results were found in comparisons of PES and Baseline in the Automatic Modulation task nor in the Vocal Effort task. Conclusions: The findings of this study suggest that usage of PES increases accuracy of pitch matching in repeated sung tones and frequency intervals, possibly due to more accurate F0 representation. The results also suggest that PES partially normalizes the vowel formant profiles of select vowel sounds. PES seems to decrease pitch variability of natural speech and appears to have limited acute effects on natural speech production, though this finding may be due in part to paradigm limitations. On average, subjective ratings of vocal effort were unaffected by the usage of PES versus Baseline. ACKNOWLEDGMENTS: C. J. L. receives grant and research support from Advanced Bionics Corporation and MED-EL Corporation; serves as a consultant for Advanced Bionics, MED-EL, and Oticon Medical; and serves as the Chief Medical Officer of Spiral Therapeutics. The other authors have no other conflicts of interest to disclose. Address for correspondence: Charles J. Limb, 2233 Post Street, 3rd Floor, Rm 325, San Francisco, CA 94115, USA. E-mail: Charles.Limb@ucsf.edu Received June 7, 2017; accepted October 19, 2018. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Masked Sentence Recognition in Children, Young Adults, and Older Adults: Age-Dependent Effects of Semantic Context and Masker Type

Objectives: Masked speech recognition in normal-hearing listeners depends in part on masker type and semantic context of the target. Children and older adults are more susceptible to masking than young adults, particularly when the masker is speech. Semantic context has been shown to facilitate noise-masked sentence recognition in all age groups, but it is not known whether age affects a listener's ability to use context with a speech masker. The purpose of the present study was to evaluate the effect of masker type and semantic context of the target as a function of listener age. Design: Listeners were children (5 to 16 years), young adults (19 to 30 years), and older adults (67 to 81 years), all with normal or near-normal hearing. Maskers were either speech-shaped noise or two-talker speech, and targets were either semantically correct (high context) sentences or semantically anomalous (low context) sentences. Results: As predicted, speech reception thresholds were lower for young adults than either children or older adults. Age effects were larger for the two-talker masker than the speech-shaped noise masker, and the effect of masker type was larger in children than older adults. Performance tended to be better for targets with high than low semantic context, but this benefit depended on age group and masker type. In contrast to adults, children benefitted less from context in the two-talker speech masker than the speech-shaped noise masker. Context effects were small compared with differences across age and masker type. Conclusions: Different effects of masker type and target context are observed at different points across the lifespan. While the two-talker masker is particularly challenging for children and older adults, the speech masker may limit the use of semantic context in children but not adults. ACKNOWLEDGMENTS: This work was funded by The National Institute on Deafness and Other Communication Disorders R01 DC014460 and T32 DC005360. The authors have no conflicts of interest to disclose. Address for correspondence: Emily Buss, Department of Otolaryngology/Head and Neck Surgery, University of North Carolina, 170 Manning Drive, CB 7070, Chapel Hill, NC 27599, USA. E-mail: ebuss@med.unc.edu Received October 19, 2017; accepted November 5, 2018. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Right hemisphere superiority for executive control of attention

Publication date: Available online 29 December 2018

Source: Cortex

Author(s): Alfredo Spagna, Tae Hyeong Kim, Tingting Wu, Jin Fan

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Porous Polyethylene Ear Reconstruction

Publication date: Available online 28 December 2018

Source: Clinics in Plastic Surgery

Author(s): Youssef Tahiri, John Reinisch

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Plaque biofilm microbial diversity in infants aged 12 months and their mothers with or without dental caries: a pilot study

Abstract

Background

A number of studies on oral microbial diversity of early childhood caries (ECC) have tended to focus on mid- or late-stage of ECC, with a lack of research into early stage of tooth eruption and maternal influence. The aims of this study are to compare the supragingival plaque biofilm microbiota diversity between mothers with or without dental caries and their 12-month-old infants, and to explore the relationship of microbial diversity between infants and their mothers, using sequencing analysis.

Methods

Supragingival plaque biofilm samples were collected from 20 pairs of mothers and their infants aged 12 months (10 mothers with dental caries and their 10 infants vs. 10 caries-free mothers and their 10 infants). The basic information of the mothers and infants had been collected through self-completed questionnaire. Pooled plaque biofilm DNA was extracted and DNA amplicons of the V4-V5 hypervariable region of the bacterial 16S rRNA gene were generated. Ilumina Miseq PE300 was used for 16S rRNA sequencing.

Results

The results showed that high bacterial diversity was noted in the plaque biofilm of infants and their mothers with or without dental caries (dental caries mothers vs. caries-free mothers: 774 operational taxonomical units (OTUs) vs. 761 OTUs at a 3% divergence; infants whose mothers have dental caries vs. infants whose mothers are caries-free: 815 OTUs vs. 684 OTUs at 3% divergence). The Shannon microbial diversity index showed no statistically significant differences both on infants and their mothers between two groups (p > 0.05). Mother's microbial diversity was higher than infants' based on Shannon index (p < 0.05). Significant positive correlations were found between mothers' and their infants' Shannon index (r = 0.656, p = 0.002).

Conclusion

Oral microbial diversity is significantly different between mothers and infants regardless of dental caries status, but no significant difference was found between mothers with and without dental caries or between their infants. Mother's oral microbial diversity has an overall impact on the infants aged 12 months.

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Biomimetic and Biocatalytic Synthesis of Bruceol

Bruceol almighty: Fifty‐five years after its isolation, the first total synthesis of bruceol has been achieved using a biomimetic cascade reaction. The original isolated sample of bruceol was used to help correct some historic structural misassignments.

Abstract

The first total synthesis of bruceol has been achieved using a biomimetic cascade cyclization initiated by a stereoselective Jacobsen–Katsuki epoxidation (and kinetic resolution) of racemic protobruceol‐I. A bacterial cytochrome P450 monooxygenase was also found to catalyze the conversion of protobruceol‐I into bruceol. The first full analysis of the NMR data of natural bruceol suggested that "isobruceol" was a previously unrecognized natural product also isolated from Philotheca brucei. This was confirmed by the re‐isolation, synthesis, and X‐ray analysis of isobruceol. In total, eight stereoisomers and structural isomers of bruceol have been synthesized in a highly divergent approach.

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Evidence of Phosphonium‐Carbenium Dication Formation in a Superacid: Precursor to Fluorinated Phosphine Oxides

Superelectrophile: Phosphonium carbenium dications are formed by the protonation of unsaturated phosphine oxides in superacid. The superelectrophilic character of these dications is essential for the syntheses of various novel fluorinated and cyclic phosphine oxides.

Abstract

Unambiguously confirmed by low‐temperature in situ NMR experiments, X‐ray diffraction and vibrational spectroscopy, phosphonium‐carbenium superelectrophiles are shown to be generated in strong acidic conditions. Representing crucial intermediates, their exploitation allows for the synthesis of unprecedented fluorinated (cyclic) phosphine oxides.

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