A case of breast milk-acquired cytomegalovirus infection in an extremely low birth weight infant.

INTRODUCTION: Although breast milk is considered the optimal nutrition for infants, it is also the primary cause of postnatal cytomegalovirus (CMV) infection. Preterm infants with postnatal CMV infections are susceptible to a variety of life-threatening conditions. CASE SUMMARY: Twin male infants were delivered via emergency caesarian section at 27 weeks' gestation secondary to maternal complete uterine rupture. The Apgar scores at 1 and 5 min were 1 and 1 for the older twin (Twin A) and 0 and 3 for the younger twin (Twin B). Their birth weights were 1203 g (+ 0.65SD) and 495 g (- 3.79SD) respectively. On day 41, laboratory blood test results for Twin B showed a moderate elevation in C-reactive protein (CRP), thrombocytopenia. CMV quantitative polymerase chain reaction (qPCR) tests in Twin B's urine and blood as well as in the mother's breast milk were positive, but stored, dried umbilical cord CMV qPCR tests were negative. Twin B was diagnosed with a postnatal CMV infection secondary to infected breast milk and ganciclovir was commenced on day 52. Treatment was switched to valganciclovir at 74 days of age, but a negative CMV-DNA level in the blood was not achieved. Postnatal CMV infection in this infant led to an exacerbation of pre-existing bronchopulmonary dysplasia (BPD) and he demised at 182 days of age. CONCLUSION: Postnatal cytomegalovirus infections may lead to exacerbations of BPD. Early use of raw breast milk in preterm infants should be done with careful consideration of this potential complication.

Synaptic pruning of murine adult-born neurons by microglia depends on phosphatidylserine.

New neurons, continuously added in the adult olfactory bulb (OB) and hippocampus, are involved in information processing in neural circuits. Here, we show that synaptic pruning of adult-born neurons by microglia depends on phosphatidylserine (PS), whose exposure on dendritic spines is inversely correlated with their input activity. To study the role of PS in spine pruning by microglia in vivo, we developed an inducible transgenic mouse line, in which the exposed PS is masked by a dominant-negative form of milk fat globule-EGF-factor 8 (MFG-E8), MFG-E8D89E. In this transgenic mouse, the spine pruning of adult-born neurons by microglia is impaired in the OB and hippocampus. Furthermore, the electrophysiological properties of these adult-born neurons are altered in MFG-E8D89E mice. These data suggest that PS is involved in the microglial spine pruning and the functional maturation of adult-born neurons. The MFG-E8D89E-based genetic approach shown in this study has broad applications for understanding the biology of PS-mediated phagocytosis in vivo.

Verification of the Usefulness of an Assessment and Risk Control Sheet that Promotes Management of Cancer Drug Therapy.

Background: Proper management of adverse events is crucial for the safe and effective implementation of anticancer drug treatment. Showa University Hospital uses our interview sheet (assessment and risk control [ARC] sheet) for the accurate evaluation of adverse events. On the day of anticancer drug treatment, a nurse conducts a face-to-face interview. As a feature of the ARC sheet, by separately describing the symptoms the day before treatment and the day of treatment and sharing the information on the medical record, it is possible to clearly determine the status of adverse events. In this study, we hypothesized that the usefulness and points for improvement of the ARC sheet would be clarified by using and evaluating a patient questionnaire. Methods: This study included 174 patients (144 at Showa University Hospital (Hatanodai Hospital) and 30 at Showa University Koto Toyosu Hospital (Toyosu Hospital) who underwent pre-examination interviews by nurses and received cancer chemotherapy at the outpatient center of Hatanodai and Toyosu Hospital. In the questionnaire survey, the ARC sheet's content and quality, respondents' satisfaction, structural strengths, and points for improvement were evaluated on a five-point scale. Results: The patient questionnaire received responses from 160 participants, including the ARC sheet use group (132 people) and the non-use group (28 people). Unlike the ARC sheet non-use group, the ARC sheet use group recognized that the sheet was useful to understand the adverse events of aphthous ulcers (p = 0.017) and dysgeusia (p = 0.006). In the satisfaction survey questionnaire, there was a high sense of security in the pre-examination interviews by nurses using the ARC sheet. Conclusions: The ARC sheet is considered an effective tool for comprehensively evaluating adverse events. Pre-examination interviews by nurses using ARC sheets accurately determined the adverse events experienced by patients with anxiety and tension due to confrontation with physicians.

The oral microbiome in alcohol use disorder: a longitudinal analysis during inpatient treatment.

BACKGROUND: Alcohol use disorder (AUD)-induced disruption of oral microbiota can lead to poor oral health; there have been no studies published examining the longitudinal effects of alcohol use cessation on the oral microbiome. AIM: To investigate the oral microbiome during alcohol cessation during inpatient treatment for AUD. METHODS: Up to 10 oral tongue brushings were collected from 22 AUD patients during inpatient treatment at the National Institutes of Health. Alcohol use history, smoking, and periodontal disease status were measured. Oral microbiome samples were sequenced using 16S rRNA gene sequencing. RESULTS: Alpha diversity decreased linearly during treatment across the entire cohort (P = 0.002). Alcohol preference was associated with changes in both alpha and beta diversity measures. Characteristic tongue dorsum genera from the Human Microbiome Project such as Streptococcus, Prevotella, Veillonella and Haemophilus were highly correlated in AUD. Oral health-associated genera that changed longitudinally during abstinence included Actinomyces, Capnocytophaga, Fusobacterium, Neisseria and Prevotella. CONCLUSION: The oral microbiome in AUD is affected by alcohol preference. Patients with AUD often have poor oral health but abstinence and attention to oral care improve dysbiosis, decreasing microbiome diversity and periodontal disease-associated genera while improving acute oral health.

Impact of the Coronavirus Disease 2019 Outbreak on Activity and Exercise Levels among Older Patients.

OBJECTIVES: This study aimed to clarify the impact of the coronavirus disease 2019 outbreak on the levels of activity among older patients with frailty or underlying diseases. A total of 175 patients (79.0±7.0 years) undergoing outpatient or home-based rehabilitation, stratified into groups, based on frailty status. The percentage of patients who went out at least once a week decreased after the outbreak from 91% to 87%, from 65% to 46%, and from 47% to 36% in the non-frail, frail, and nursing care requirement groups, respectively. The proportion of older patients participating in exercise during the outbreak was 75%, 51%, and 41% in the non-frail, frail, and nursing care requirement groups, respectively. The proportion of older patients participating in voluntary exercise after instruction was lowest in the frail group (35%). Older patients with frailty are susceptible to the negative effects of refraining from physical activity and require careful management.

Influence of rotational speed on torque/force generation and shaping ability during root canal instrumentation of extracted teeth with continuous rotation and optimum torque reverse motion.

AIM: To evaluate how different rotational speeds affect the torque/force generation and shaping ability of rotary root canal instrumentation using JIZAI (MANI, Utsunomiya, Japan) nickel-titanium instruments in continuous rotation and optimum torque reverse (OTR) motion. METHODOLOGY: Mesial root canals of extracted mandibular molars were instrumented up to size 25, 0.04 taper using JIZAI instruments, and anatomically matched canals were selected based on geometric features of the canal [canal volume (mm3 ), surface area (mm2 ), length, 15°-20° curvature and radius of curvature (4-8 mm)] after micro-computed tomographic scanning. An automated root canal instrumentation and torque/force analysing device was programmed to permit a simulated pecking motion (2 s downward and 1 s upward at 50 mm min-1 ). The selected canals were prepared with size 25, 0.06 taper JIZAI instruments using continuous rotation or OTR motion and further subdivided according to the rotational speed (300 or 500 rpm, n = 10 each). Real-time clockwise/counterclockwise torque and downward/upward force were recorded using a custom-made torque/force analysing device. Then, the registered pre- and post-operative micro-computed tomographic datasets were examined to evaluate the canal volume changes and centring ratios at 1, 3, 5 and 7 mm from the apical foramen. Data were analysed using two-way analysis of variance or the Kruskal-Wallis test and Mann-Whitney U test with Bonferroni correction (α = 5%). RESULTS: Maximum upward force and clockwise torque were significantly smaller in 500 rpm groups than in 300 rpm groups (P < .05); however, no significant difference was found between continuous rotation and OTR motion (P > .05). OTR motion developed higher maximum counterclockwise torque than continuous rotation (P < .05). Maximum downward force, canal volume changes and centring ratios were not significantly different among all groups (P > .05). There was no file fracture in any of the groups. CONCLUSIONS: Under laboratory conditions using JIZAI instruments, a rotational speed of 500 rpm generated significantly lower maximum screw-in forces and torque values than rotational speed of 300 rpm. Continuous rotation and OTR motion performed similarly in shaping the canals.

Effects of potato resistant starch intake on insulin sensitivity, related metabolic markers and appetite ratings in men and women at risk for type 2 diabetes: a pilot cross-over randomised controlled trial.

BACKGROUND: The intake of certain types of resistant starch (RS) has been associated in some studies with increased whole-body insulin sensitivity. This randomised, cross-over pilot trial evaluated the effect of consuming cooked, then chilled potatoes, a source of RS, compared to isoenergetic, carbohydrate (CHO)-containing control foods, on insulin sensitivity and related markers. METHODS: Nineteen adults with body mass index 27.0-39.9 kg m-2 consumed 300 g day-1 RS-enriched potatoes (approximately two potatoes; ~18 g RS) or CHO-based control foods, as part of lunch, evening and snack meals, over a 24-h period. After an overnight fast, insulin sensitivity, CHO metabolism markers, free fatty acids, breath hydrogen levels and appetite were assessed for up to 5 h after the intake of a standard breakfast. The primary endpoint was insulin sensitivity, assessed with the Matsuda index. P < 0.05 (one-sided) was considered statistically significant. RESULTS: Insulin sensitivity was not significantly different between the potato and control conditions. The potato intervention resulted in higher postprandial breath hydrogen (P = 0.037), lower postprandial free fatty acid concentrations (P = 0.039) and lower fasting plasma glucose (P = 0.043) compared to the control condition. Fullness ratings were significantly lower after potato versus control (P = 0.002). No other significant effects were observed; however, there was a trend toward lower fasting insulin (P = 0.077) in the potato versus the control condition. CONCLUSIONS: The results of this pilot study suggest RS-enriched potatoes may have a favourable impact on carbohydrate metabolism and support the view that additional research in a larger study sample is warranted.

Addition of L-cysteine to the N- or C-terminus of the all-D-enantiomer [D(KLAKLAK)2] increases antimicrobial activities against multidrug-resistant Pseudomonas aeruginosa, Acinetobacter baumannii and Escherichia coli.

BACKGROUND: Antimicrobial peptides have a broad spectrum of antimicrobial activities and are attracting attention as promising next-generation antibiotics against multidrug-resistant (MDR) bacteria. The all-d-enantiomer [D(KLAKLAK)2] has been reported to have antimicrobial activity against Escherichia coli and Pseudomonas aeruginosa, and to be resistant to protein degradation in bacteria because it is composed of D-enantiomer compounds. In this study, we demonstrated that modification of [D(KLAKLAK)2] by the addition of an L-cysteine residue to its N- or C- terminus markedly enhanced its antimicrobial activities against Gram-negative bacteria such as MDR Acinetobacter baumannii, E. coli, and P. aeruginosa. METHODS: The peptides [D(KLAKLAK)2] (DP), DP to which L-cysteine was added at the N-terminus C-DP, and DP to which L-cysteine was added at the C-terminus DP-C, were synthesized at >95% purity. The minimum inhibitory concentrations of peptides and antibiotics were determined by the broth microdilution method. The synergistic effects of the peptides and the antibiotics against MDR P. aeruginosa were evaluated using the checkerboard dilution method. In order to assess how these peptides affect the survival of human cells, cell viability was determined using a Cell Counting Kit-8. RESULTS: C-DP and DP-C enhanced the antimicrobial activities of the peptide against MDR Gram-negative bacteria, including A. baumannii, E. coli, and P. aeruginosa. The antimicrobial activity of DP-C was greater than that of C-DP, with these peptides also having antimicrobial activity against drug-susceptible P. aeruginosa and drug-resistant P. aeruginosa overexpressing the efflux pump components. C-DP and DP-C also showed antimicrobial activity against colistin-resistant E. coli harboring mcr-1, which encodes a lipid A modifying enzyme. DP-C showed synergistic antimicrobial activity against MDR P. aeruginosa when combined with colistin. The LD50 of DP-C against a human cell line HepG2 was six times higher than the MIC of DP-C against MDR P. aeruginosa. The LD50 of DP-C was not altered by incubation with low-dose colistin. CONCLUSION: Attachment of an L-cysteine residue to the N- or C-terminus of [D(KLAKLAK)2] enhanced its antimicrobial activity against A. baumannii, E. coli, and P. aeruginosa. The combination of C-DP or DP-C and colistin had synergistic effects against MDR P. aeruginosa. In addition, DP-C and C-DP showed much stronger antimicrobial activity against MDR A. baumannii and E. coli than against P. aeruginosa.

Visually cued fear conditioning test for memory impairment related to cortical function.

AIM: Fear conditioning tests are intended to elucidate a subject's ability to associate a conditioned stimulus with an aversive, unconditioned stimulus, such as footshock. Among these tests, a paradigm related to precise cortical functions would be increasingly important in drug screening for disorders such as schizophrenia and dementia. Therefore, we established a new fear conditioning paradigm using a visual cue in mice. In addition, the validity of the test was evaluated using a genetically engineered mouse, heterozygous deficient in Mdga1 (Mdga1+/-), which is related to schizophrenia. RESULTS: Mice were given footshocks associated with a visual cue of moving gratings at training in 25-minute sessions. The mice showed the conditioned response of freezing behavior to the visual stimulus at testing 24 hours after the footshocks. In the test for validation, the Mdga1+/- deficient mice showed significantly less freezing than wild-type mice. CONCLUSION: The visually cued fear conditioning paradigm with moving gratings has been established, which is experimentally useful to evaluate animal cortical functions. The validity of the test was confirmed for Mdga1-deficient mice with possible deficiency in cortical functions.

Traceable stimulus-dependent rapid molecular changes in dendritic spines in the brain.

Dendritic spines function as microcompartments that can modify the efficiency of their associated synapses. Here, we analyzed stimulus-dependent molecular changes in spines. The F-actin capping protein CapZ accumulates in parts of dendritic spines within regions where long-term potentiation has been induced. We produced a transgenic mouse line, AiCE-Tg, in which CapZ tagged with enhanced green fluorescence protein (EGFP-CapZ) is expressed. Twenty minutes after unilateral visual or somatosensory stimulation in AiCE-Tg mice, relative EGFP-CapZ signal intensification was seen in a subset of dendritic spines selectively in stimulated-side cortices; this right-left difference was abolished by NMDA receptor blockade. Immunolabeling of α-actinin, a PSD-95 binding protein that can recruit AMPA receptors, showed that the α-actinin signals colocalized more frequently in spines with the brightest EGFP-CapZ signals (top 100) than in spines with more typical EGFP-CapZ signal strength (top 1,000). This stimulus-dependent in vivo redistribution of EGFP-CapZ represents a novel molecular event with plasticity-like characteristics, and bright EGFP-CapZ in AiCE-Tg mice make high-CapZ spines traceable in vivo and ex vivo. This mouse line has the potential to be used to reveal sequential molecular events, including synaptic tagging, and to relate multiple types of plasticity in these spines, extending knowledge related to memory mechanisms.

Functional Analysis of PTH1R Variants Found in Primary Failure of Eruption.

Although many variants of the parathyroid hormone 1 receptor (PTH1R) gene are known to be associated with primary failure of eruption (PFE), the mechanisms underlying the link remains poorly understood. We here performed functional analyses of PTH1R variants reported in PFE patients-namely, 356C>T (P119L), 395C>T (P132L), 439C>T (R147C), and 1148G>A (R383Q)-using HeLa cells with a lentiviral vector-mediated genetic modification. Two particular variants, P119L and P132L, had severe reduction in a level of N-linked glycosylation when compared with wild-type PTH1R, whereas the other 2 showed modest alteration. PTH1R having P119L or P132L showed marked decrease in the affinity to PTH1-34, which likely led to severely impaired cAMP accumulation upon stimulation in cells expressing these mutants, highlighting the importance of these 2 amino acid residues for ligand-mediated proper functioning of PTH1R. To further gain insights into PTH1R functions, we established the induced pluripotent stem cell (iPSC) lines from a patient with PFE and the heterozygous P132L mutation. When differentiated into osteoblastic-lineage cells, PFE-iPSCs showed no abnormality in mineralization. The mRNA expression of RUNX2, SP7, and BGLAP, the osteoblastic differentiation-related genes, and that of PTH1R were augmented in both PFE-iPSC-derived cells and control iPSC-derived cells in the presence of bone morphogenetic protein 2. Also, active vitamin D3 induced the expression of RANKL, a major key factor for osteoclastogenesis, equally in osteoblastic cells derived from control and PFE-iPSCs. In sharp contrast, exposure to PTH1-34 resulted in no induction of RANKL mRNA expression in the cells expressing P132L variant PTH1R, consistent with the idea that a type of heterozygous PTH1R gene mutation would spoil PTH-dependent response in osteoblasts. Collectively, this study demonstrates a link between PFE-associated genetic alteration and causative functional impairment of PTH1R, as well as a utility of iPSC-based disease modeling for future elucidation of pathogenesis in genetic disorders, including PFE.

Noninvasive Neuromonitoring of Hypothermic Circulatory Arrest in Aortic Surgery.

BACKGROUND AND AIMS: Circulatory arrest carries a high risk of neurological damage, but modern monitoring methods lack reliability, and is susceptible to the generalized effects of both anesthesia and hypothermia. The objective of this prospective, explorative study was to research promising, reliable, and noninvasive methods of neuromonitoring, capable of predicting neurological outcome after hypothermic circulatory arrest. MATERIALS AND METHODS: Thirty patients undergoing hypothermic circulatory arrest during surgery of the thoracic aorta were recruited in a single center and over the course of 4 years. Neuromonitoring was performed with a four-channel electroencephalogram montage and a near-infrared spectroscopy monitor. All data were tested off-line against primary neurological outcome, which was poor if the patient suffered a significant neurological complication (stroke, operative death). RESULTS: A poor primary neurological outcome seen in 10 (33%) patients. A majority (63%) of the cases were emergency surgery, and thus, no neurological baseline evaluation was possible. The frontal hemispheric asymmetry of electroencephalogram, as measured by the brain symmetry index, predicted primary neurological outcome with a sensitivity of 79 (interquartile range; 62%-88%) and specificity of 71 (interquartile range; 61%-84%) during the first 6 h after end of circulatory arrest. CONCLUSION: The hemispheric asymmetry of frontal electroencephalogram is inherently resistant to generalized dampening effects and is predictive of primary neurological outcome. The brain symmetry index provides an easy-to-use, noninvasive neuromonitoring method for surgery of the thoracic aorta and postoperative intensive care.

8-Nitro-cGMP is a promoter of osteoclast differentiation induced by RANKL.

Osteoclasts are multinucleated giant cells differentiated from monocyte-macrophage-lineage cells under stimulation of receptor activator of nuclear factor κ-B (RANK) ligand (RANKL) produced by osteoblasts and osteocytes. Although it has been reported that nitric oxide (NO) and reactive oxygen species (ROS) are involved in this process, the mechanism by which these labile molecules promote osteoclast differentiation are not fully understood. In this study, we investigated the formation and function of 8-nitro-cGMP, a downstream molecule of NO and ROS, in the process of osteoclast differentiation in vitro. 8-Nitro-cGMP was detected in mouse bone marrow macrophages and osteoclasts differentiated from macrophages in the presence of RANKL. Inhibition of NO synthase suppressed the formation of 8-nitro-cGMP as well as RANKL-induced osteoclast differentiation from macrophages. On the other hand, RANKL-induced osteoclast differentiation was promoted by addition of 8-nitro-cGMP to the cultures. In addition, 8-nitro-cGMP enhanced the mRNA expression of RANK, the receptor for RANKL. However, 8-bromo-cGMP, a membrane-permeable derivative of cGMP, did not have an effect on either RANKL-induced osteoclast differentiation or expression of the RANK gene. These results suggest that 8-nitro-cGMP is a novel positive regulator of osteoclast differentiation, which might help to explain the roles of NO and ROS in osteoclast differentiation.

Corn oil intake favorably impacts lipoprotein cholesterol, apolipoprotein and lipoprotein particle levels compared with extra-virgin olive oil.

BACKGROUND: Corn oil (CO) and extra-virgin olive oil (EVOO) are rich sources of unsaturated fatty acids (UFA), but UFA profiles differ among oils, which may affect lipoprotein levels. OBJECTIVES: The objective of this study was to assess the effects of CO versus EVOO intake on fasting lipoprotein and subfraction cholesterol levels, apolipoprotein (apo) A1, apo B, and low-density lipoprotein particle concentrations in men and women. SUBJECTS/METHODS: As part of a weight maintenance diet, men and women were provided with food items prepared with 54 g per day of CO or EVOO (21-day treatment, 21-day washout) in a randomized, double-blind, controlled-feeding, crossover trial. Fasting lipoprotein cholesterol and related variables were determined with density gradient ultracentrifugation. RESULTS: Among the 54 completers, CO reduced total cholesterol, low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apo B and LDL particle concentration to a greater extent compared with EVOO intake. Changes in LDL-C and VLDL-C contributed to the larger reduction in non-HDL-C with CO compared with EVOO intake (-0.39 mmol/l vs -0.04 mmol/l; P<0.001). The larger reduction in LDL-C by CO intake was attributable to changes (P<0.05) caused by CO vs EVOO in large LDL1+2-C (-0.22 mmol/l) and intermediate-density lipoprotein cholesterol (-0.12 mmol/l). HDL-C responses did not differ between treatments, but apo A1 increased more with EVOO compared with CO intake (4.6 versus 0.7 mg/dl, respectively, P=0.016). CONCLUSIONS: CO intake reduced atherogenic lipoprotein cholesterol and particle concentrations to a larger extent than did EVOO, which may have implications for cardiovascular disease risk.

A link between vascular damage and cognitive deficits after whole-brain radiation therapy for cancer: A clue to other types of dementia?

Whole brain radiation therapy for the treatment of tumors can sometimes cause cognitive impairment. Memory deficits were noted in up to 50% of treated patients over a short period of several months. In addition, an increased rate of dementia in young patients has been noted over the longer term, i.e. years. A deficit in neurogenesis after irradiation has been postulated to be the main cause of cognitive decline in patients, but recent data on irradiation therapy for limited parts of the brain appear to indicate other possibilities. Irradiation can directly damage various types of cells other than neuronal stem cells. However, this paper will focus on injury to brain vasculature leading to cognitive decline since vessels represent a better therapeutic target for drug development than other cells in the brain because of the blood-brain barrier.

Angiogenesis in refractory depression: A possible phenotypic target to avoid the blood brain barrier.

Major depressive syndrome (so-called depression) is a common but serious mental disease that causes low mood. Most patients are treatable, mainly because of high response rates for medicines such as selective serotonin-reuptake inhibitors (SSRIs). However, there are still a considerable number of patients with refractory or drug-resistant depression. On the other hand, recent findings suggest that angiogenesis, i.e., making new blood vessels, could have an important role in the recovery from depressive disorders, at least in part. It has been reported that the brain capillaries are physiologically capable of undergoing angiogenesis upon stimuli such as exercise and SSRIs seem to accelerate brain angiogenesis. Drugs targeting angiogenesis may possibly be another good concept. In addition, the blood brain barrier (BBB), which is a major obstacle for drug development for the central nervous system, would be circumvented. Here I summarize the reports that relate angiogenesis to a cure for major depression and discuss some of the potential molecular targets.

Safety and lipid-altering efficacy of a new omega-3 fatty acid and antioxidant-containing medical food in men and women with elevated triacylglycerols.

This randomized, double-blind, placebo-controlled multi-center trial investigated the lipid-altering effects of a medical food (PDL-0101) providing 1.8 g/d eicosapentaenoic acid; 12 mg/d astaxanthin, a marine algae-derived carotenoid; and 100 mg/d tocopherol-free gamma/delta tocotrienols enriched with geranylgeraniol, extracted from annatto, on triacylglycerols (TAG), other lipoprotein lipids, and oxidized low-density lipoprotein (LDL) in 102 subjects with TAG 150-499 mg/dL (1.69-5.63 mmol/L) and LDL cholesterol (LDL-C) ≥70 mg/dL (1.81 mmol/L). Compared to placebo, after eight weeks of treatment, PDL-0101 significantly reduced median TAG (-9.5% vs. 10.6%, p<0.001), while not significantly altering mean LDL-C (-3.0% vs. -8.0% for PDL-0101 and placebo, respectively, p=0.071), mean high-density lipoprotein cholesterol (~3% decrease in both groups, p=0.732), or median oxidized LDL concentrations (5% vs. -5% for PDL-0101 and placebo, respectively, p=0.112). These results demonstrate that PDL-0101 is an effective medical food for the management of elevated TAG.

17α-estradiol is generated locally in the male rat brain and can regulate GAD65 expression and anxiety.

Increasing evidence suggests that 17ß-estradiol, a sex hormone, is synthesized by neurons. In addition, 17α-estradiol, the stereoisomer of 17ß-estradiol, is reported to be the dominant form in the male mouse brain. However, probably because the method to detect these isomers requires unusual and precise experimental design, the presence of this endogenous 17α-estradiol has not been reported subsequently and the actual role is therefore not well elucidated. We first quantified the estradiol level in hippocampal extracts using gas chromatography/mass spectrometry. As a result, 17α-estradiol was found in all of the male rats tested, while that of 17ß-estradiol was detected only in a certain subset. The estrogen-biosynthesis inhibitor letrozole decreased the expression of the major presynaptic GABA synthesizing enzyme GAD65 in cultured neurons and the effect was abrogated by exogenously supplied 17α-estradiol. Next, injection of the inhibitor into the brain reduced the 17α-estradiol level, indicating its biogenesis in the brain. Under the same conditions, immuno-staining of GAD65 was also decreased. Furthermore, the inhibitor treatment increased anxiety index of rats in the open field and this was ameliorated by the addition of 17α-estradiol. We showed that 17α-estradiol was generated in the brain and acted as a regulator of inhibitory neurotransmission as well as behavior. These results may have implications for a variety of diseases, such as the menopausal depression and Alzheimer's disease that have been reported to be related to estrogen levels.

Differences in the developmental origins of the periosteum may influence bone healing.

BACKGROUND AND OBJECTIVE: The jaw bone, unlike most other bones, is derived from neural crest stem cells, so we hypothesized that it may have different characteristics to bones from other parts of the body, especially in the nature of its periosteum. The periosteum exhibits osteogenic potential and has received considerable attention as a grafting material for the repair of bone and joint defects. MATERIAL AND METHODS: Gene expression profiles of jaw bone and periosteum were evaluated by DNA microarray and real-time polymerase chain reaction. Furthermore, we perforated an area 2 mm in diameter on mouse frontal and parietal bones. Bone regeneration of these calvarial defects was evaluated using microcomputed tomography and histological analysis. RESULTS: The DNA microarray data revealed close homology between the gene expression profiles within the ilium and femur. The gene expression of Wnt-1, SOX10, nestin, and musashi-1 were significantly higher in the jaw bone than in other locations. Microcomputed tomography and histological analysis revealed that the jaw bone had superior bone regenerative abilities than other bones. CONCLUSION: Jaw bone periosteum exhibits a unique gene expression profile that is associated with neural crest cells and has a positive influence on bone regeneration when used as a graft material to repair bone defects. A full investigation of the biological and mechanical properties of jaw bone as an alternative graft material for jaw reconstructive surgery is recommended.

The skeletal maturation status estimated by statistical shape analysis: axial images of Japanese cervical vertebra.

OBJECTIVES: To evaluate axial cervical vertebral (ACV) shape quantitatively and to build a prediction model for skeletal maturation level using statistical shape analysis for Japanese individuals. METHODS: The sample included 24 female and 19 male patients with hand-wrist radiographs and CBCT images. Through generalized Procrustes analysis and principal components (PCs) analysis, the meaningful PCs were extracted from each ACV shape and analysed for the estimation regression model. RESULTS: Each ACV shape had meaningful PCs, except for the second axial cervical vertebra. Based on these models, the smallest prediction intervals (PIs) were from the combination of the shape space PCs, age and gender. Overall, the PIs of the male group were smaller than those of the female group. There was no significant correlation between centroid size as a size factor and skeletal maturation level. CONCLUSIONS: Our findings suggest that the ACV maturation method, which was applied by statistical shape analysis, could confirm information about skeletal maturation in Japanese individuals as an available quantifier of skeletal maturation and could be as useful a quantitative method as the skeletal maturation index.