Timp1 Deletion Induces Anxiety-like Behavior in Mice.

The hippocampus is essential for learning and memory, but it also plays an important role in regulating emotional behavior, as hippocampal excitability and plasticity affect anxiety and fear. Brain synaptic plasticity may be regulated by tissue inhibitor of matrix metalloproteinase 1 (TIMP1), a known protein inhibitor of extracellular matrix (ECM), and the expression of TIMP1 in the hippocampus can be induced by neuronal excitation and various stimuli. However, the involvement of Timp1 in fear learning, anxiety, and hippocampal synaptic function remains to be established. Our study of Timp1 function in vivo revealed that Timp1 knockout mice exhibit anxiety-like behavior but normal fear learning. Electrophysiological results suggested that Timp1 knockout mice showed hyperactivity in the ventral CA1 region, but the basic synaptic transmission and plasticity were normal in the Schaffer collateral pathway. Taken together, our results suggest that deletion of Timp1 in vivo leads to the occurrence of anxiety behaviors, but that Timp1 is not crucial for fear learning.

Knowledge Tensor-Aided Breast Ultrasound Image Assistant Inference Framework.

Breast cancer is one of the most prevalent cancers in women nowadays, and medical intervention at an early stage of cancer can significantly improve the prognosis of patients. Breast ultrasound (BUS) is a widely used tool for the early screening of breast cancer in primary care hospitals but it relies heavily on the ability and experience of physicians. Accordingly, we propose a knowledge tensor-based Breast Imaging Reporting and Data System (BI-RADS)-score-assisted generalized inference model, which uses the BI-RADS score of senior physicians as the gold standard to construct a knowledge tensor model to infer the benignity and malignancy of breast tumors and axes the diagnostic results against those of junior physicians to provide an aid for breast ultrasound diagnosis. The experimental results showed that the diagnostic AUC of the knowledge tensor constructed using the BI-RADS characteristics labeled by senior radiologists achieved 0.983 (95% confidential interval (CI) = 0.975-0.992) for benign and malignant breast cancer, while the diagnostic performance of the knowledge tensor constructed using the BI-RADS characteristics labeled by junior radiologists was only 0.849 (95% CI = 0.823-0.876). With the knowledge tensor fusion, the AUC is improved to 0.887 (95% CI = 0.864-0.909). Therefore, our proposed knowledge tensor can effectively help reduce the misclassification of BI-RADS characteristics by senior radiologists and, thus, improve the diagnostic performance of breast-ultrasound-assisted diagnosis.

Contrast-enhanced US with Perfluorobutane to Diagnose Small Lateral Cervical Lymph Node Metastases of Papillary Thyroid Carcinoma.

Background Although metastasis of lateral cervical lymph nodes (LNs) is common in papillary thyroid carcinoma (PTC), correctly diagnosing small metastatic LNs with US remains challenging. The use of contrast-enhanced US (CEUS), especially the postvascular phase of CEUS with perfluorobutane contrast material, might contribute to improved diagnosis of metastatic LNs in PTC. Purpose To assess the diagnostic value of the postvascular phase of CEUS with perfluorobutane in suspicious small lateral cervical LNs (short-axis diameter ≤8 mm) in patients with PTC. Materials and Methods This single-center study prospectively enrolled consecutive participants with confirmed PTC and suspicious LNs at US from October 2020 to October 2021. All participants underwent CEUS, 1 week before biopsy or surgery, with intravenous perfluorobutane contrast material to visualize the LNs in the vascular phase (5-60 seconds after injection) and postvascular phase (10-30 minutes after injection). The reference standard was cytologic and surgical histologic assessment of the LNs. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of sonographic features were calculated, and the diagnostic performance of US, CEUS, and the combination of postvascular phase and US features was assessed using multivariable logistic regression models. Results A total of 135 participants (median age, 36 years [IQR, 30-46 years]; 100 women) with 161 suspicious LNs at US were evaluated, including 67 metastatic and 94 benign LNs. The specificity of perfusion defect as a sonographic feature in the vascular phase reached 96% (90 of 94 LNs), and the negative predictive value of non-isoenhancement (ie, hypoenhancement, partial enhancement, and no enhancement) in the postvascular phase reached 100% (83 of 83 LNs). The area under the receiver operating characteristic curve (AUC) of the combination of postvascular phase and US features was 0.94 (95% CI: 0.89, 0.97), significantly higher than that of US features alone (AUC, 0.73; 95% CI: 0.65, 0.79; P < .001). Conclusion The postvascular phase of CEUS with perfluorobutane demonstrated excellent performance for diagnosing suspicious small lateral cervical LNs in participants with PTC. Published under a CC BY 4.0 license Supplemental material is available for this article. See also the editorial by Gunabushanam in this issue.

Prepregnancy body mass index and gestational weight gain affect the offspring neurobehavioral development at one year of age.

OBJECTIVE: Recent data show that maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) are associated with offspring neurobehavior in childhood. However, little is known about the effect on infants that less than 20 months of age, and whether this association has sex differences. METHODS: In this birth cohort study, a total of 661 mother-infant pairs were enrolled in Shanghai, China, between February 2017 and April 2019. Maternal prepregnancy BMI was categorized according to the Chinese classification and GWG according to the 2009 Institute of Medicine (IOM). Neurobehavioral development for infants of 12 months of age was assessed by Gesell Developmental Scale (GDS), which contained five subscales of gross motor, fine motor, adaptive behavior, language, and social behavior. RESULTS: Abnormal maternal prepregnancy BMI and excessive GWG were associated with infant birth weight and/or birth length (p < .05), while no influence was found on yearling weight or length. Women who were overweight/obese prior to pregnancy or excessive GWG during pregnancy had infants who were more deficient in neurobehavioral developmental including language (p < .01) and/or social behavior (p < .05). Specifically, excessive GWG was associated with lower language ability in girls but not boys (p < .05). CONCLUSIONS: Aberrant prepregnancy BMI and excessive GWG not only affect the body size of newborn infants, but also impair their neurobehavioral development, suggesting that general guidance to the women should be advised to attain optimal prepregnancy BMI and GWG.

Effect of probiotics on digestibility and immunity in infants: A study protocol for a randomized controlled trial.

The gastrointestinal (GI) tract of a fetus in utero is sterile but it becomes colonized with environmental microorganisms shortly after birth. Since the gut microbiota undergoes substantial changes in early life, healthy gut microflora is essential to an infant's gut health and immune system and probably also has an effect on overall health status in later life. Probiotics, defined as viable microbial preparations that have a beneficial effect on the health of the host, represent a rapidly expanding field. Although randomized controlled trials using probiotics in infants have shown promising results in the prevention and treatment of common diseases such as diarrhea and allergy, little is known about whether probiotics could offer benefits to healthy infants. We have designed a randomized controlled trial to test the hypothesis that an oral preparation of probiotics is superior to placebo in improving digestive and immune function in healthy infants.The trial will be a randomized, double-blind, placebo-controlled, 2-parallel-group study in Shanghai, China. After a 2-week run-in period, 200 exclusively formula-fed healthy infants aged 4 to 6 months will be randomly allocated to receive either a probiotic product containing Bifidobacterium infantis R0033, Bifidobacterium bifidum R0071, and Lactobacillus helveticus R0052 or an identical placebo once daily for 4 weeks and will be followed up for 8 weeks. The duration of the subject's participation will be 14 weeks, with a total of 5 visits: inclusion (Visit 1, Day 1), start of intervention (V2, D15), end of intervention (V3, D44), and follow-up (V4 and V5, D72 and D100). Stool and saliva samples will be collected at the first 3 visits to measure microbial populations and secretory immunoglobulin A (SIgA), respectively. Physical examination will be performed at each visit, and tolerance records will be completed 1 day prior to each visit. The primary endpoints will be the changes in the composition of fecal microbiota, particularly the Bifidobacterium bifidum population. The secondary endpoints will include the change in salivary SIgA level, growth parameters, digestive tolerance, and adverse events.An effective, practical, and acceptable probiotic intervention in manipulating the gut microbiota and boosting the immune system in formula-fed infants would represent a major clinical advance. The administration of probiotic supplementation or follow-on formula to infant may be associated with some clinic benefits.

Associations of maternal pre-pregnancy body mass index and gestational weight gain with birth outcomes in Shanghai, China.

Recent data suggests that abnormal maternal pre-pregnancy body mass index (BMI) or gestational weight gain (GWG) is associated with unfavorable delivery outcomes. However, limited clinical evidence is available to support this correlation in China. Participating 510 mother-infant pairs were recruited from the Shanghai First Maternity and Infant Hospital, China, between January 1st and 30th 2016. Maternal pre-pregnancy BMI was categorized according to the China's classification and GWG according to the 2009 Institute of Medicine recommendations (IOM). Linear regression tested the associations between pre-pregnancy BMI or GWG and length of gestation, birthweight, length, and head circumference. Logistic regression assessed the associations between pre-pregnancy BMI or GWG and macrosomic, small- (SGA) and large- (LGA) for-gestational-age infants. Overweight/obese women showed increased length of gestation and birthweight, but did not have a higher risk of macrosomic and LGA infants compared with normal weight women. Women with excessive GWG showed increased length of gestation, birthweight, length, and head circumference, and were more likely to deliver macrosomic and LGA infants compared with women with adequate GWG. Although a relatively low proportion of women from Shanghai area are overweight/obese or exhibit excessive GWG, both high pre-pregnancy BMI and excessive GWG influence perinatal outcomes.

Dual-doping to suppress cracking in spinel LiMn2O4: a joint theoretical and experimental study.

Electrochemical cycling stabilities were compared for undoped and Al/Co dual-doped spinel LiMn2O4 synthesized by solid state reactions. We observed the suppression of particle fracture in Al/Co dual-doped LiMn2O4 during charge/discharge cycling and its distinguishable particle morphology with respect to the undoped material. Systematic first-principles calculations were performed on undoped, Al or Co single-doped, and Al/Co dual-doped LiMn2O4 to investigate their structural differences at the atomistic level. We reveal that while Jahn-Teller distortion associated with the Mn(3+)O6 octahedron is the origin of the lattice strain, the networking -i.e. the distribution of mixed valence Mn ions - is much more important to release the lattice strain, and thus to alleviating particle cracking. The calculations showed that the lattice mismatching between Li(+) intercalation and deintercalation of LiMn2O4 can be significantly reduced by dual-doping, and therefore also the volumetric shrinkage during delithiation. This may account for the near disappearance of cracks on the surface of Al/Co-LiMn2O4 after 350 cycles, while some obvious cracks have developed in undoped LiMn2O4 at similar particle size even after 50 cycles. Correspondingly, Al/Co dual-doped LiMn2O4 showed a good cycling stability with a capacity retention of 84.1% after 350 cycles at a rate of 1C, 8% higher than the undoped phase.