The brain‐derived neutrophic factor val66met polymorphism and sudden unexpected infant death

Aim: Findings of hypoxia prior to death and involvement of a dysregulation of the serotonergic network in sudden infant death syndrome (SIDS) may indicate that brain‐derived neutrophic factor (BDNF) also is of importance with regard to sudden unexpected infant death. Based on this, the purpose of this study was to investigate the BDNF val66met polymorphism in SIDS cases, cases of infectious death and controls. Methods: The polymorphism was investigated in 163 SIDS cases, 34 cases of infectious death and 121 controls, using real‐time PCR and fluorescence melting curve analysis. Results: There were no differences in val66met genotype distribution between neither the SIDS cases nor the cases of infectious death and controls (p = 0.95 and p = 0.52, respectively). Conclusion: The study indicates that the val66met polymorphism is not important for sudden unexpected infant death. However, several other SNPs in the BDNF gene, as well as in other genes involved in this pathway, including G‐protein, have to be investigated to fully exclude any involvement of BDNF in SIDS.     

ImmPort: disseminating data to the public for the future of immunology

The immunology database and analysis portal (ImmPort) system is the archival repository and dissemination vehicle for clinical and molecular datasets created by research consortia funded by the National Institute of Allergy and Infectious Diseases Division of Allergy, Immunology, and Transplantation. With nearly 100 datasets now publicly available and hundreds of downloads per month, ImmPort is an important source for raw data and protocols from clinical trials, mechanistic studies, and novel methods for cellular and molecular measurements. To facilitate data transfer, templates for data representation and standard operating procedures have also been created and are also publicly available. ImmPort facilitates transparency and reproducibility in immunology research, serves as an important resource for education, and enables newly generated hypotheses and data-driven science.     

Contact angle, protein adsorption and osteoblast precursor cell attachment to chitosan coatings bonded to titanium

Chitosan, a derivative of the bio-polysaccharide chitin, has shown promise as a bioactive material for implant, tissue engineering and drug-delivery applications. The aim of this study was to evaluate the contact angle, protein adsorption and osteoblast precursor cell attachment to chitosan coatings bonded to titanium. Rough ground titanium (Ti) coupons were solution cast and bonded to 91.2% de-acetylated chitosan (1 wt% chitosan in 0.2% acetic acid) coatings via silane reactions. Non-coated Ti was used as controls. Samples were sterilized by ethylene oxide gas prior to experiments. Contact angles on all surfaces were measured using water. 5 x 10(4) cells/ml of ATCC CRL 1486 human embryonic palatal mesenchyme (HEPM) cells, an osteoblast precursor cell line, were used for the cell attachment study. SEM evaluations were performed on cells attached to all surfaces. Contact angles and cell attachment on all surfaces were statistically analyzed using ANOVA. The chitosan-coated surfaces (76.4 +/- 5.1 degrees) exhibited a significantly greater contact angle compared to control Ti surfaces (32.2 +/- 6.1 degrees). Similarly, chitosan-coated surfaces exhibited significantly greater (P < 0.001) albumin adsorption, fibronectin adsorption and cell attachment, as compared to the control Ti surfaces. Coating chitosan on Ti surfaces decreased the wettability of the Ti, but increased protein adsorption and cell attachment. Increased protein absorption and cell attachment on the chitosan-coated Ti may be of benefit in enhancing osseointegration of implant devices.     

阿克拉霉素A聚氰基丙烯酸异丁酯毫微粒冻干针剂体内外抗肝癌活性

阿克拉霉素A聚氰基丙烯酸异丁酯毫微粒的冻干针剂,能明显抑制体外培养人肝癌细胞株7703的生长,IC50为0.28μg·ml^-1。在0.8μg·ml^-1浓度时,克隆形成抑制率为90%,抑制作用有明显剂量依赖关系而未见明显时间依赖关系。静脉给药后,对常位移植人肝癌模型裸小鼠的抑瘤率为86.84%,肿瘤细胞增殖活性阳性率为20.83%。体内外均显示明显的抗肝癌活性,且体内抗肝癌活性比阿克拉霉素A冻干针剂强。     

Conception after early IVF pregnancy loss: should we wait?

Research questionIs the interval length between an early pregnancy loss and the following treatment cycle a predictor for achieving clinical pregnancy among IVF patients?DesignThis retrospective cohort study of 257 women who reinitiated treatment after first-trimester IVF pregnancy loss was conducted at a tertiary, university-affiliated medical centre between 1 January 2014 to 1 January 2018. Women aged 18–40 years, with normal uterine cavity, who experienced first-trimester pregnancy loss at less than 14 weeks after IVF, were included. Miscarriages were classified as spontaneous, biochemical, medical or surgical.ResultsAmong 257 women, interval to subsequent IVF treatment was not associated with achieving pregnancy. Patients after biochemical pregnancy (72.7 ± 56.4, median 60 days) or spontaneous miscarriage (97.7 ± 93.1, median 66 days) had shorter intervals to next cycle, compared with medical (111.9 ± 103.2, median 65 days) or surgical (123.4 ± 111.1, median 84 days) (Kaplan–Meier, P = 0.03) miscarriages.Logistic regression analysis showed that the chance of subsequent pregnancy was affected by the number of embryos transferred (P = 0.009) and the type of miscarriage. Medical (P = 0.005) and surgical (P = 0.017) miscarriages were related to lower likelihood of pregnancy compared with biochemical pregnancy (reference group).When pregnancy was achieved in the first post-miscarriage cycle, the chance of live birth increased with shorter intervals (median 57.5 days), whereas second miscarriage was related to longer intervals (median 82.5 days) between miscarriage and subsequent IVF cycle (P = 0.03).ConclusionOn the basis of this cohort, IVF should not be postponed after pregnancy loss, as shorter intervals were associated with greater likelihood of live birth.     

Thawing day 3 embryos and culturing to day 5 may be a better method for frozen embryo transfer

Purpose

Does thawing cleavage embryos and culturing them for transfer as blastocysts improve pregnancy and perinatal outcomes compared to transferring thawed blastocysts?

Methods

Retrospective, observational cohort study performed at two assisted reproductive technology centers, 2014 to 2020. A total of 450 patients with 463 thawed embryo transfer cycles were divided into 2 groups according to the embryonic developmental stage at cryopreservation and transfer: 231 thawed blastocysts (day 5 group) and 232 thawed cleavage embryos that were cultured for 2 days and transferred as blastocysts (day 3–5 group). The two groups were compared for demographics, routine parameters of IVF treatment, pregnancy rates, and perinatal outcomes.

Results

Multivariable logistic regression analysis for ongoing pregnancy and delivery demonstrated that the day 3–5 group had a greater likelihood of achieving ongoing pregnancy and delivery compared to the day 5 group (OR 1.58, 95%CI 1.062–2.361, p?=?0.024). Perinatal outcomes were comparable between the three groups.

Conclusion

Our results support culturing post-thaw cleavage embryos for 2 days and transferring them as blastocysts to increase chances of ongoing pregnancy and delivery.

     

Detection of the hemoglobin E mutation using the color complementation assay: application to complex genotyping

The color complementation assay (CCA) is a method of allele-specific DNA amplification by which competitive priming and extension of fluorescently labeled oligonucleotide primers determine the color of DNA amplification product. This diagnostic method precludes the need for radioisotopes, electrophoresis, and multiple high-stringency reaction conditions. The multiplicity of mutant globin genes present in Southeast Asians complicates clinical diagnosis and underscores the importance of DNA-based diagnostic methods. We have applied CCA to distinguish beta A and beta E alleles. Competing 15mer primers were a fluorescein-labeled complement to beta A and a rhodamine-labeled complement to beta E, identical except for their central nucleotides. A common unlabeled primer was used to amplify DNA product, the color of which was determined by the perfectly complementary primer. Color photography and spectrofluorometry, as well as a method of black-white photography that we developed to distinguish fluorescein- and rhodamine- labeled DNA, were used to record results. We applied CCA to define the complex genotype of a Thai woman with thalassemia intermedia, 96% HbE, and 4% HbF whose possible genotypes included several permutations of alpha-thalassemia, beta-thalassemia, and beta E genes. zeta-Globin gene mapping of DNA doubly digested with Bg/II and Asp 718 showed the -alpha 3.7/--SEA genotype, and CCA confirmed homozygous beta E/beta E. The CCA is useful for diagnosing the compound hemoglobin genotypes of Southeast Asians and could be applied also to prenatal diagnosis in this population.     

Restorative role of persimmon leaf (Diospyros kaki) to gamma irradiation-induced oxidative stress and tissue injury in rats

Purpose: To evaluate the efficacy of persimmon leaf extract (PL (as a rich plant source) in modulation of radiation-induced liver injury and some metabolic variations in gamma-irradiated rats.

Materials and methods: PL at a dose of 1000?mg/kg body weight (P₁₀₀₀) was administered to male albino rats via gastric intubation for 15 days after whole body γ-irradiation (6?Gy).

Results: Irradiated rats showed significant decreases in hepatic glutathione content (GSH), superoxide dismutase (SOD), catalase (CAT) and xanthine dehydrogenase (XDH) activities with significant increases in malondialdehyde (MDA) level and xanthine oxidase (XO) activity designating oxidative stress. In parallel significant increases in serum aspartate and alanine transaminase (AST, ALT), alkaline phosphatase (ALP), γ-glutamyl-transferase (GGT) activities and bilirubin content were recorded indicating liver injury. In addition, hyperglycemia, hypoinsulinemia and dyslipidemia (elevated total cholesterol, triglycerides, low density lipoprotein-cholesterol and Atherogenic Index and decreased high density lipoprotein-cholesterol) were recorded. PL treatment has significantly attenuated radiation-induced oxidative stress in hepatic tissues concomitant with significant amelioration of liver function and metabolic disturbances.

Conclusion: It is concluded that PL may have therapeutic potential to alleviate the severity of radiation-induced liver injury, hyperglycemia, hypoinsulinemia and dyslipidemia.     

Terminal differentiation surface antigens of myelomonocytic cells are expressed in human promyelocytic leukemia cells (HL60) treated with chemical inducers

The expression of two surface antigens present on the cell membrane of both human granulocytes and monocytes was studied during the process of myelomonocytic differentiation using two monoclonal antibodies (B9.8.1 and B13.4.1). These surface antigens are not present on immature myeloid cells nor on nonmyeloid hematopoietic cells, but can be detected when the cells are terminally differentiated. Among the bone marrow cells, B13.4.1 binds to metamyelocytes and B9.8.1 to metamyelocytes and a fraction (30%) of myelocytes. HL60 human promyelocytic leukemia cells did not react with such monoclonal antibodies. However, when such cells were induced to differentiate in vitro into mature myeloid elements by treatment with retinoic acid or dimethyl sulfoxide, 70%--90% of the differentiated cells expressed both surface antigens. Cell sorting studies on these treated HL60 cells indicated that myelocytes and metamyelocytes were the most immature cells expressing such markers. Expression of the two surface antigens was also observed when HL60 cells were induced to differentiate into monocyte/macrophage cells by treatment with the tumor promoter 12-O- tetradecanoyl-phorbol-13-acetate. Thus, human promyelocytic leukemia cells induced to differentiate in vitro by treatment with specific chemical agents express membrane antigens in the same pattern as normal bone marrow myeloid cells at the corresponding stage of differentiation.     

Effect of menstrual cycle phase on dopamine D2 receptor availability in female cynomolgus monkeys

Sex differences have been reported in a variety of affective and neurodegenerative disorders that involve dysfunctional dopamine (DA) neurotransmission. In addition, there is evidence for differences in sensitivity to the abuse-related effects of psychostimulants across the menstrual cycle which may result from effects of ovarian hormones on DA function. The goal of the present study was to extend previous work examining menstrual cycle-related changes in DA D2 receptor availability in humans to drug-naive female cynomolgus monkeys (n=7) using the selective D2-like receptor ligand [(18)F]fluoroclebopride (FCP) and a high-resolution microPET P4 scanner. Menstrual cycle phase was characterized by daily vaginal swabs and measurements of serum progesterone levels. PET studies were conducted once during the luteal phase and once during the follicular phase. Regions of interest in the caudate nucleus, putamen, and cerebellum were defined on coregistered MRIs. Distribution volumes were calculated for FCP in each structure and the distribution volume ratio (DVR) for both brain regions relative to the cerebellum was used as a measure of D2 receptor availability. FCP DVRs were significantly higher in the luteal phase compared to the follicular phase in both the caudate nucleus (11.7% difference, p=0.02) and putamen (11.6% difference, p=0.03). These findings extend earlier work in humans and suggest that changes in DA receptor availability may be involved in the variation in symptoms of various neuropsychiatric disorders across the menstrual cycle, including differences in sensitivity to the abuse-related effects of stimulants.