Brain structure variation and individual differences in theory of mind among older adults.

The theory of mind (ToM) is not substantially influenced by aging, suggesting the emergence of various compensatory mechanisms. To identify brain regions subserving ToM in older adults, we investigated the associations of individual differences in brain structure with performance on the Reading the Mind in the Eyes Test (RMET), a widely used measure of ToM, using voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS). In contrast to findings obtained from young adults, where multiple cortical regions are implicated in ToM, VBM analysis revealed a significant positive correlation between RMET score and gray matter (GM) volume only in the right middle temporal gyrus, a region implicated in social cognition. Alternatively, TBSS revealed significant positive correlations between RMET score and the fractional anisotropy (FA) values in widespread white matter (WM) tracts, including the bilateral uncinate fasciculus, a region previously linked to RMET performance in young adults. We speculate that individual differences in WM integrity are strong influences on ToM among older adults, whereas the impact of individual differences in GM volumes is relatively limited.

A case of meningoencephalitis caused by multisystem inflammatory syndrome in adult SARS-CoV-2 infection.

A 37-year-old woman was hospitalized with fever and consciousness disturbance. She showed systemic inflammation with stress cardiomyopathy. Brain computed tomography showed diffuse brain edema. Cerebrospinal fluid (CSF) findings revealed markedly elevated cerebrospinal fluid pressure with pleocytosis, elevated protein, and elevated interleukin 6. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nicking enzyme amplification reaction test using a nasopharyngeal swab was positive, and the patient was diagnosed with SARS-CoV-2 infection. From the negative result of the CSF SARS-CoV-2 polymerase chain reaction test and no findings of bacterial or viral infection, we diagnosed meningoencephalitis by multisystem inflammation syndrome in adults (MIS-A). Intravenous methylprednisolone pulse therapy improved her symptoms and brain edema. There have been no cases of MIS-A with meningoencephalitis, and no initial treatment strategy has been established, especially in emergency cases of suspected MIS-A. The present case suggested Early intravenous methylprednisolone pulse with anti-coronaviral therapies after the exclusion of bacterial infection would be useful in suspected MIS-A with emergent meningoencephalitis cases.

Implications of interleukin-17 in psoriatic lesions as Koebner phenomenon caused by recurrent occupational burns.

The Koebner phenomenon (KP) is the emergence of new lesions in an uninvolved skin area caused by different types of stimulations, including mechanical stress, chemical stress, trauma, or injury. KP affects patients with certain skin diseases and is frequently observed in patients with psoriasis. We report the case of a 43-year-old obese male welder who developed psoriatic lesions only in areas of repeated burns due to his occupation. He was repeatedly exposed to mild burns in his anterior neck and the periorbital region as he was welding without shield protection. Subsequently, erythema appeared in the same region. Skin appearance and skin biopsy suggested psoriasis vulgaris (PV), and immunohistochemical analysis of anti-interleukin (IL)-17, a crucial element in the development of PV, showed the positivestained cells. The anti-IL-17 staining was prominent around the thickened epidermis as psoriatic lesions. IL-17 produced by T helper 17 cells stimulates keratinized cells and promotes chemokine secretion involved in neutrophil migration. Our case showed that patients, even without a history of PV, may have a risk of developing KP and PV via the enhanced production of IL- 17 locally in the repeated burn area. No recurrence of skin symptoms was observed when the patient used a fully defensive shield during welding.

Innervation of the human minor salivary glands; immunohistochemical study for neurochemical substances.

Distributions of choline acetyltransferase (ChAT), vasoactive intestinal polypeptide (VIP), dopamine ß-hydroxylase (DBH), tyrosine hydroxylase (TH), neuropeptide Y (NPY) and the transient receptor potential cation channel subfamily V member 2 (TRPV2) were examined in the human minor salivary glands. ChAT-, VIP- and DBH-immunoreactive (-IR) nerve fibers were detected within nerve bundles and close to blood vessels and ducts in the salivary glands. Periacinar nerve fibers were commonly immunoreactive for ChAT in the Ebner's gland but infrequently in other salivary glands. Periacinar VIP-IR nerve fibers were numerous in the palatal gland, moderate in the lingual gland and relatively rare in the labial and Ebner's glands. Some TH-, NPY- and TRPV2-IR nerve fibers were also present around blood vessels and glandular acini in the palatal, lingual and Ebner's glands. Neuronal cells in the vicinity of Ebner's and lingual glands were immunoreactive for ChAT, VIP, TH and TRPV2. By confocal laser scanning microscopy, VIP- and ChAT-IR varicosities were located in the vicinity of myoepithelial and acinar cells in the minor salivary glands. The human minor salivary glands are probably innervated by parasympathetic and sympathetic nerves. Neurotransmitters including neuropeptides in these nerves are thought to be correlated to vasodilation and/or salivary secretion. Acetylcholine and VIP may regulate secretion of the saliva and its components in the salivary glands.

The role of executive functions in older adults' affective theory of mind.

PURPOSE: Executive function (EF) has three subsystems: inhibition, updating, and shifting. Of these three, only inhibition is considered to be involved in affective theory of mind (ToM). This study investigated whether inhibition remains the sole driver for affective ToM in the three EF subsystems in older adults as well as in young people without functional reorganization via aging within EF. MATERIALS AND METHODS: Through hierarchical multiple regression analysis, we examined how these three subsystems affect older participants' performance in the Reading the Mind in the Eyes Test (RMET), a measure of affective ToM, after determining the effect of domain-specific cognitive (nonverbal and verbal) abilities. RESULTS: We found that only inhibition influenced the participants' performance in the RMET, with effects from nonverbal (fluid) ability but not from verbal ability. CONCLUSIONS: Results showed that inhibition continues to be essential for affective ToM after aging decline, and functional reorganization via aging is less likely to occur within EF.

Examination of the Antimicrobial Peptide Myticalin A6 Active Site.

In 2017, Leoni et al. reported myticalins as novel cationic linear antimicrobial peptides obtained from marine mussels. The authors focused on myticalin A6 (29 amino acids), which has a relatively short chain length among myticalins and contains a repeating X-proline(Pro)-arginine (Arg) sequence in its structure. We investigated the antimicrobial activity of myticalin A6 against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus (S. aureus). Fragment derivatives of myticalin A6 were synthesized, and the site required for expression of antimicrobial activity was examined. To investigate the structure-antimicrobial activity relationship of myticalin A6, short-chain derivatives and partially substituted derivatives were synthesized, and the antimicrobial activity was measured. Furthermore, some cyclized derivatives were synthesized and examined for antimicrobial activity. Circular dichroism (CD) spectroscopy of myticalin A6 and its derivatives was carried out to evaluate the secondary structure. Myticalin A6 exhibited an antimicrobial activity of 1.9 µM against S. aureus. Myticalin A6 (3-23)-OH (21 amino acids) exhibited an antimicrobial activity of 2.4 µM against S. aureus, suggesting that the X-Pro-Arg repeat sequence is important for antimicrobial activity. Derivatives with different CD measurement results from myticalin A6 (3-23)-OH exhibited decreased activity. The myticalin A6 (3-23)-OH derivative in which all Arg residues were replaced with lysine (Lys) residues exhibited reduced antimicrobial activity against S. aureus. We succeeded in synthesizing cyclic derivatives using 9-fluorenylmethoxycarbonyl (Fmoc)-aspartic acid (Asp)(Wang resin)-[2-phenylisopropyl ester (OPis)], but the yield of derivatives with 21 amino acids was decreased. The myticalin derivatives synthesized in this study did not exhibit any enhancement in antimicrobial activity due to cyclization.

Video-based evaluation of infant crawling toward quantitative assessment of motor development.

This study proposes a quantitative evaluation support system for infant motor development and uses the system to analyze hands-and-knees creeping and belly crawling. This system measures movements using two video cameras and extracts movement features via background and inter-frame subtractions of original images. Eight evaluation indices for each crawling cycle are calculated, enabling markerless movement analysis of infants. Cross-sectional analysis of 16 10-month-olds confirmed significant differences between hands-and-knees creeping and belly crawling in five of the eight indices, demonstrating the system capability to quantitatively differentiate between creeping and crawling. Longitudinal analysis of one infant (aged 7-10 months) also suggested that the proposed quantitative indices can follow changes in crawling characteristics and evaluate infants' motor development process. The results from the experiments suggest that the proposed system may enable diagnosis support in clinical practice.

Plasma Levels of Presepsin (Soluble CD14-subtype) as a Novel Prognostic Marker for Hemophagocytic Syndrome in Hematological Malignancies.

Objective Recent studies suggest that presepsin (soluble CD14-subtype) is a useful diagnostic and prognostic marker for sepsis, with secretion by activated macrophages potentially dependent on phagocytosis of microorganisms. As "hemophagocytosis" is one of the major characteristics in patients with hemophagocytic syndrome (HPS), we hypothesized that presepsin may reflect the phagocytic activity and be a useful prognostic marker for HPS. Therefore, we aimed to assess the prognostic potential of presepsin in secondary HPS in adult patients with hematological malignancies. Methods Between April 2006 and August 2014, we retrospectively examined consecutive patients with HPS whose blood samples were available at our institution and compared the prognostic value of the following in HPS, singly and in combination: plasma presepsin, serum soluble interleukin (IL)-2 receptor (sIL-2R), ferritin, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-6 and IL-10. Results A total of 14 patients were enrolled. The median age of the patients was 46.5 years (range, 22-65). In univariable Cox models, there were no significant variables associated with the prognosis. However, in 12 evaluable patients, only the combination of higher median values of presepsin (>1,935 pg/mL) and sIL-2R (>4,585 U/mL) at the onset of HPS was significantly associated with the 90-day mortality (hazard ratio 14.5; 95% CI, 1.47-143.36; p=0.02). Conclusion These results suggest that a composite model of plasma presepsin and serum sIL-2R levels at the onset of HPS might be a novel predictor of the prognosis of patients with hematological malignancies and secondary HPS.

SPARCL1-containing neurons in the human brainstem and sensory ganglion.

Secreted protein, acidic and rich in cysteine-like 1 (SPARCL1) is a member of the osteonectin family of proteins. In this study, immunohistochemistry for SPARCL1 was performed to obtain its distribution in the human brainstem, cervical spinal cord, and sensory ganglion. SPARCL1-immunoreactivity was detected in neuronal cell bodies including perikarya and proximal dendrites, and the neuropil. The motor nuclei of the IIIrd, Vth, VIth, VIIth, IXth, Xth, XIth, and XIIth cranial nerves and spinal nerves contained many SPARCL1-immunoreactive (-IR) neurons with medium-sized to large cell bodies. Small and medium-sized SPARCL1-IR neurons were distributed in sensory nuclei of the Vth, VIIth, VIIIth, IXth, and Xth cranial nerves. In the medulla oblongata, the dorsal column nuclei also had small to medium-sized SPARCL1-IR neurons. In addition, SPARCL1-IR neurons were detected in the nucleus of the trapezoid body and pontine nucleus within the pons and the arcuate nucleus in the medulla oblongata. In the cervical spinal cord, the ventral horn contained some SPARCL1-IR neurons with large cell bodies. These findings suggest that SPARCL1-containing neurons function to relay and regulate motor and sensory signals in the human brainstem. In the dorsal root (DRG) and trigeminal ganglia (TG), primary sensory neurons contained SPARCL1-immunoreactivity. The proportion of SPARCL1-IR neurons in the TG (mean ± SD, 39.9 ± 2.4%) was higher than in the DRG (30.6 ± 2.1%). SPARCL1-IR neurons were mostly medium-sized to large (mean ± SD, 1494.5 ± 708.3 µm(2); range, 320.4-4353.4 µm(2)) in the DRG, whereas such neurons were of various cell body sizes in the TG (mean ± SD, 1291.2 ± 532.8 µm(2); range, 209.3-4326.4 µm(2)). There appears to be a SPARCL1-containing sensory pathway in the ganglion and brainstem of the spinal and trigeminal nervous systems.

Ruthenocene-Type Complexes of N-Fused Porphyrins.

Ruthenocene-type hybrid complexes with N-fused porphyrinato ligands, [Ru(NFp)Cp] (NFp=N-fused porphyrin, Cp=cyclopentadienyl), have been prepared and characterized by NMR and UV/Vis/NIR spectroscopy, cyclovoltammetry, and X-ray crystallography. [Ru(NFp)Cp] is a common low-spin ruthenium(II) complex and shows strong aromaticity. The Ru-Cp distance (1.833 Å) in [Ru(NFp)Cp] is comparable to that in [RuCp2 ] (1.840 Å). DFT calculations on [Ru(NFp)Cp] showed the unequivocal contribution of the RuCp moiety as well as the NFp moiety to both the HOMO and LUMO, constructing a three-dimensional d-π conjugated system. The HOMO-LUMO gaps of [Ru(NFp)Cp] are insensitive to the substituents on the NFp ligand, which is illustrated spectroscopically as well as theoretically. This is in sharp contrast to the ligand precursor, the N-fused porphyrin, in which the HOMO-LUMO gap is affected by substituents in a similar manner to standard porphyrins and related macrocycles.

Diagnostic value of levels of presepsin (soluble CD14-subtype) in febrile neutropenia in patients with hematological disorders.

BACKGROUND: Whether presepsin (soluble CD14-subtype) is better than other markers including procalcitonin (PCT), has not been adequately investigated in febrile neutropenia (FN). METHODS: We prospectively examined the utility of presepsin in FN in Cohort 1 (C1) and 2 (C2), between November 2010 and February 2012, and between November 2013 and January 2014, respectively. The purpose of this study was to investigate 1) the relative value of serum presepsin over serum PCT in C1, and 2) the relative value of plasma presepsin as compared with serum PCT, C-reactive protein, interleukin-6 and interleukin-8 with frequent, repeated sampling in C2. RESULTS: Seventy-nine FN episodes (C1, 75; C2, 4) were evaluable. In C1, when compared with control values, presepsin was significantly higher at onset of FN (P = 0.004), while PCT was not significantly higher (P = 0.54). The median value of serum presepsin within 72 h of onset of FN in subjects with fever of unknown origin, local infection, bacteremia and septic shock was 680 (reference 314) pg/ml, 763, 782 and 1359, respectively. In C2, the mean levels of plasma presepsin from onset of FN to 72 h were classified as negative in the two patients with no suspected site of infection, and those of the remaining two patients with clinically probable infections were positive (175, 131, 346 and 329 pg/ml, respectively). In contrast, the other markers did not discriminate between this two groups. CONCLUSIONS: In FN, presepsin may be an earlier and more sensitive indicator of bacterial infection than PCT.

Prevention of cognitive and physical decline by enjoyable walking-habituation program based on brain-activating rehabilitation.

AIM: Evaluating effects of an enjoyable walking-habituation program. METHODS: We carried out a 12-week intervention, consisting of an enjoyable walking-habituation program based on five principles of brain-activating rehabilitation: pleasant atmosphere, interactive communication, social roles, praising each other and errorless support. The program, once a week for 90 min, was carried out in small groups. Participants were 71 community-dwelling people (72.2 ± 4.3) without dementia. Cognitive function was evaluated in five cognitive domains: memory, executive function, word fluency, visuospatial abilities and sustained attention. Additionally, quality of life, depressive state, functional capacity, range of activities, social network and subjective memory complaints were assessed using questionnaires. Motor function was also evaluated. Measurement was carried out before the observation period, after observation and after intervention. RESULTS: A total of 63 participants were included in the analysis. Daily steps, executive function, subjective memory complaints, functional capacity and 5-m maximum walking time significantly improved during the intervention period (after observation to after intervention) compared with the observation period (before the observation period to after observation). No significant differences were seen in other evaluations. At 6 months after the intervention, 52 of 63 participants (82.5%) continued to walk once a week or more, and all of them were confident about continuing to walk in the future. Furthermore, all participants were satisfied with our walking-habituation program and all replied that they felt delighted. CONCLUSION: The intervention program, based on the five principles of brain-activating rehabilitation, resulted in improvement of some cognitive and physical functions, as well as a high walking-habituation rate at 6 months' follow up. Geriatr Gerontol Int 2015; ●●: ●●-●●.

Potential for drug interactions mediated by polymorphic flavin-containing monooxygenase 3 in human livers.

Human flavin-containing monooxygenase 3 (FMO3) in the liver catalyzes a variety of oxygenations of nitrogen- and sulfur-containing medicines and xenobiotic substances. Because of growing interest in drug interactions mediated by polymorphic FMO3, benzydamine N-oxygenation by human FMO3 was investigated as a model reaction. Among the 41 compounds tested, trimethylamine, methimazole, itopride, and tozasertib (50 µM) suppressed benzydamine N-oxygenation at a substrate concentration of 50 µM by approximately 50% after co-incubation. Suppression of N-oxygenation of benzydamine, trimethylamine, itopride, and tozasertib and S-oxygenation of methimazole and sulindac sulfide after co-incubation with the other five of these six substrates was compared using FMO3 proteins recombinantly expressed in bacterial membranes. Apparent competitive inhibition by methimazole (0-50 µM) of sulindac sulfide S-oxygenation was observed with FMO3 proteins. Sulindac sulfide S-oxygenation activity of Arg205Cys variant FMO3 protein was likely to be suppressed more by methimazole than wild-type or Val257Met variant FMO3 protein was. These results suggest that genetic polymorphism in the human FMO3 gene may lead to changes of drug interactions for N- or S-oxygenations of xenobiotics and endogenous substances and that a probe battery system of benzydamine N-oxygenation and sulindac sulfide S-oxygenation activities is recommended to clarify the drug interactions mediated by FMO3.

Dienogest inhibits nerve growth factor expression induced by tumor necrosis factor-α or interleukin-1ß.

OBJECTIVE: Dienogest (DNG), a selective P receptor (PR) agonist, is used to treat endometriosis. To investigate whether DNG affects nerve growth factor (NGF) expression, we stimulated human endometrial epithelial cells (hEECs) with inflammatory cytokines. DESIGN: Prospective basic research study using immortalized hEEC lines. SETTING: Development Research, Mochida Pharmaceutical Co., Ltd., Japan. PATIENT(S): None. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): In immortalized hEECs, NGF production induced by tumor necrosis factor-α (TNF-α) or interleukin-1ß (IL-1ß) was evaluated in the presence or absence of the synthetic progestin DNG or endogenous P. The NGF messenger RNA (mRNA) and protein were measured using real-time reverse transcriptase-polymerase chain reaction (PCR) and ELISA, respectively. The NGF bioactivity in the culture medium was measured by assaying neurite outgrowth of PC-12 cells. RESULT(S): Tumor necrosis factor-α and IL-1ß induced NGF mRNA and protein and increased NGF bioactivity in the culture medium. These activities were inhibited by DNG in a hEEC line that stably expresses PR. In contrast, in an hEEC line that constitutively expresses faint levels of PR, no inhibitory effect of DNG on NGF mRNA was detected. The NGF mRNA was also inhibited in hEEC lines that express only PR-A or only PR-B. CONCLUSION(S): Nerve growth factor is one of the key mediators that generates the pain associated with endometriosis. Dienogest inhibits NGF expression through PR-A and PR-B in hEEC, which may contribute to the pharmacological mechanisms of how DNG relieves pain in endometriosis.

Synthesis and isomerization of N-fused tetraphenylporphyrin ruthenium(II) complexes.

Three possible isomers of N-fused tetraphenylporphyrin ruthenium complexes, Ru(NFTPp)Cl(CO)2 (2a-c), were isolated and fully characterized by NMR, IR, CV, UV-vis-NIR absorption, and X-ray crystallographic analyses. Each isomer was stable at ambient conditions and isomerization among 2a-c occurred at elevated temperature both in solution and in a solid state, through the intramolecular rotational pathways. Electronic structures of 2a-c were analyzed in detail by DFT study to reveal appreciable differences in the interaction between the NFTPp ligand and the Ru-Cl moiety.

[A case of stage IVb vulvar cancer effectively treated by concurrent chemoradiotherapy with cisplatin].

A 72-year-old woman was hospitalized because of a 10 cm tumor in her right inguinal area. Furthermore, a 6 cm tumor mass was observed in her right vulva. Computed tomography revealed multiple swollen lymph nodes in the para-aortic and pelvic areas. On the basis of these findings, the patient was diagnosed with stage IVb squamous cell carcinoma of the vulva. Radiation therapy of 67.4 Gy/33 Fr was administered to the pelvis, inguinal area and vulva. Four courses of chemotherapy with cisplatin (40 mg/m(2)) were concurrently administered every week during radiation therapy. The response to chemoradiotherapy was assessed to be complete. The patient has been doing well without any recurrence for 24 months.

Antiobesity effect of eicosapentaenoic acid in high-fat/high-sucrose diet-induced obesity: importance of hepatic lipogenesis.

OBJECTIVE: Given the pleiotropic effect of eicosapentaenoic acid (EPA), it is interesting to know whether EPA is capable of improving obesity. Here we examined the anti-obesity effect of EPA in mice with two distinct models of obesity. RESEARCH DESIGN AND METHODS: Male C57BL/6J mice were fed a high-fat/high-sucrose diet (25.0% [w/w] fat, 32.5% [w/w] sucrose) (HF/HS group) or a high-fat diet (38.1% [w/w] fat, 8.5% [w/w] sucrose) (HF group) for 4-20 weeks. A total of 5% EPA was administered by partially substituting EPA for fat in the HF/HS + EPA and HF + EPA groups. RESULTS: Both the HF/HS and HF groups similarly developed obesity. EPA treatment strongly suppresses body weight gain and obesity-related hyperglycemia and hyperinsulinemia in HF/HS-fed mice (HF/HS + EPA group), where hepatic triglyceride content and lipogenic enzymes are increased. There is no appreciable effect of EPA on body weight in HF-fed mice (HF + EPA group) without enhanced expression of hepatic lipogenic enzymes. Moreover, EPA is capable of reducing hepatic triglyceride secretion and changing VLDL fatty acid composition in the HF/HS group. By indirect calorimetry analysis, we also found that EPA is capable of increasing energy consumption in the HF/HS + EPA group. CONCLUSIONS: This study is the first demonstration that the anti-obesity effect of EPA in HF/HS-induced obesity is associated with the suppression of hepatic lipogenesis and steatosis. Because the metabolic syndrome is often associated with hepatic lipogenesis and steatosis, the data suggest that EPA is suited for treatment of the metabolic syndrome.

Cide-a and Cide-c are induced in the progression of hepatic steatosis and inhibited by eicosapentaenoic acid.

Cide-a and Cide-c belong to the cell death-inducing DNA fragmentation factor-alpha-like effector family. Recent evidences suggest that these proteins may be involved in lipid accumulation in liver and adipose tissues. We confirmed that in the high-fat/high-sucrose diet-induced murine model of hepatic steatosis, the expression levels of the Cide-a and Cide-c genes were markedly and time-dependently increased, but returned to normal levels following improvement of hepatic steatosis by eicosapentaenoic acid (EPA) administration. Levels of expression of the Cide-a and Cide-c genes correlated well with plasma ALT. EPA inhibited the promoter activity of the Cide-a gene in vitro. Sterol regulatory element-binding protein-1 (SREBP-1) markedly enhanced the promoter activity of Cide-a, and EPA inhibited the expression of Cide-a mRNA. SREBP-1 and EPA did not affect those of Cide-c. These findings indicate that Cide-a and Cide-c are closely involved in the progression of hepatic steatosis, and that EPA inhibits Cide-a gene expression through SREBP-1 regulation.