Aims/hypothesis Glucagon-like peptide-1 (GLP-1) has various extra-pancreatic actions, in addition to its enhancement of insulin secretion from pancreatic beta cells. The GLP-1 receptor is produced in ...kidney tissue. However, the direct effect of GLP-1 on diabetic nephropathy remains unclear. Here we demonstrate that a GLP-1 receptor agonist, exendin-4, exerts renoprotective effects through its anti-inflammatory action via the GLP-1 receptor without lowering blood glucose. Methods We administered exendin-4 at 10 μg/kg body weight daily for 8 weeks to a streptozotocin-induced rat model of type 1 diabetes and evaluated their urinary albumin excretion, metabolic data, histology and morphometry. We also examined the direct effects of exendin-4 on glomerular endothelial cells and macrophages in vitro. Results Exendin-4 ameliorated albuminuria, glomerular hyperfiltration, glomerular hypertrophy and mesangial matrix expansion in the diabetic rats without changing blood pressure or body weight. Exendin-4 also prevented macrophage infiltration, and decreased protein levels of intercellular adhesion molecule-1 (ICAM-1) and type IV collagen, as well as decreasing oxidative stress and nuclear factor-κB activation in kidney tissue. In addition, we found that the GLP-1 receptor was produced on monocytes/macrophages and glomerular endothelial cells. We demonstrated that in vitro exendin-4 acted directly on the GLP-1 receptor, and attenuated release of pro-inflammatory cytokines from macrophages and ICAM-1 production on glomerular endothelial cells. Conclusions/interpretation These results indicate that GLP-1 receptor agonists may prevent disease progression in the early stage of diabetic nephropathy through direct effects on the GLP-1 receptor in kidney tissue.
Summary
Periodontitis is an inflammatory disease caused by periodontal bacteria in subgingival plaque. These bacteria are able to colonize the periodontal region by evading the host immune response. ...Neutrophils, the host's first line of defense against infection, use various strategies to kill invading pathogens, including neutrophil extracellular traps (NETs). These are extracellular net‐like fibers comprising DNA and antimicrobial components such as histones, LL‐37, defensins, myeloperoxidase, and neutrophil elastase from neutrophils that disarm and kill bacteria extracellularly. Bacterial nuclease degrades the NETs to escape NET killing. It has now been shown that extracellular nucleases enable bacteria to evade this host antimicrobial mechanism, leading to increased pathogenicity. Here, we compared the DNA degradation activity of major Gram‐negative periodontopathogenic bacteria, Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, and Aggregatibacter actinomycetemcomitans. We found that Pr. intermedia showed the highest DNA degradation activity. A genome search of Pr. intermedia revealed the presence of two genes, nucA and nucD, putatively encoding secreted nucleases, although their enzymatic and biological activities are unknown. We cloned nucA‐ and nucD‐encoding nucleases from Pr. intermedia ATCC 25611 and characterized their gene products. Recombinant NucA and NucD digested DNA and RNA, which required both Mg2+ and Ca2+ for optimal activity. In addition, NucA and NucD were able to degrade the DNA matrix comprising NETs.
A simple and sensitive automated method, consisting of in-tube solid-phase microextraction (SPME) coupled with high-performance liquid chromatography-fluorescence detection (HPLC-FLD), was developed ...for the determination of 15 polycyclic aromatic hydrocarbons (PAHs) in food samples. PAHs were separated within 15
min by HPLC using a Zorbax Eclipse PAH column with a water/acetonitrile gradient elution program as the mobile phase. The optimum in-tube SPME conditions were 20
draw/eject cycles of 40
μL of sample using a CP-Sil 19CB capillary column as an extraction device. Low- and high-molecular weight PAHs were extracted effectively onto the capillary coating from 5% and 30% methanol solutions, respectively. The extracted PAHs were readily desorbed from the capillary by passage of the mobile phase, and no carryover was observed. Using the in-tube SPME HPLC-FLD method, good linearity of the calibration curve (
r
>
0.9972) was obtained in the concentration range of 0.05–2.0
ng/mL, and the detection limits (
S/
N
=
3) of PAHs were 0.32–4.63
pg/mL. The in-tube SPME method showed 18–47 fold higher sensitivity than the direct injection method. The intra-day and inter-day precision (relative standard deviations) for a 1
ng/mL PAH mixture were below 5.1% and 7.6% (
n
=
5), respectively. This method was applied successfully to the analysis of tea products and dried food samples without interference peaks, and the recoveries of PAHs spiked into the tea samples were >70%. Low-molecular weight PAHs such as naphthalene and pyrene were detected in many foods, and carcinogenic benzo
apyrene, at relatively high concentrations, was also detected in some black tea samples. This method was also utilized to assess the release of PAHs from tea leaves into the liquor.
Purpose of Review
We review recent community interventions to promote mental health and social equity. We define community interventions as those that involve multi-sector partnerships, emphasize ...community members as integral to the intervention, and/or deliver services in community settings. We examine literature in seven topic areas: collaborative care, early psychosis, school-based interventions, homelessness, criminal justice, global mental health, and mental health promotion/prevention. We adapt the social-ecological model for health promotion and provide a framework for understanding the actions of community interventions.
Recent Findings
There are recent examples of effective interventions in each topic area. The majority of interventions focus on individual, family/interpersonal, and program/institutional social-ecological levels, with few intervening on whole communities or involving multiple non-healthcare sectors. Findings from many studies reinforce the interplay among mental health, interpersonal relationships, and social determinants of health.
Summary
There is evidence for the effectiveness of community interventions for improving mental health and some social outcomes across social-ecological levels. Studies indicate the importance of ongoing resources and training to maintain long-term outcomes, explicit attention to ethics and processes to foster equitable partnerships, and policy reform to support sustainable healthcare-community collaborations.
Policy discussions regarding the mental health needs of children and adolescents emphasize a lack of use of mental health services among youth, but few national estimates are available. The authors ...use three national data sets and examine ethnic disparities in unmet need (defined as having a need for mental health evaluation but not using any services in a 1-year period) to provide such estimates.
The authors conducted secondary data analyses in three nationally representative household surveys fielded in 1996-1998: the National Health Interview Survey, the National Survey of American Families, and the Community Tracking Survey. They determined rates of mental health service use by children and adolescents 3-17 years of age and differences by ethnicity and insurance status. Among the children defined as in need of mental health services, defined by an estimator of mental health problems (selected items from the Child Behavior Checklist), they examined the association of unmet need with ethnicity and insurance status.
In a 12-month period, 2%-3% of children 3-5 years old and 6%-9% of children and adolescents 6-17 years old used mental health services. Of children and adolescents 6-17 years old who were defined as needing mental health services, nearly 80% did not receive mental health care. Controlling for other factors, the authors determined that the rate of unmet need was greater among Latino than white children and among uninsured than publicly insured children.
These findings reveal that most children who need a mental health evaluation do not receive services and that Latinos and the uninsured have especially high rates of unmet need relative to other children. Rates of use of mental health services are extremely low among preschool children. Research clarifying the reasons for high rates of unmet need in specific groups can help inform policy and clinical programs.
•We proposed the efficacy of DRIAs and dietary supplement on endometriosis.•DRIAs inhibit cell proliferation in human endometriotic stromal cells.•DRIAs reduce inflammatory cytokines and exhibit ...ERβ-mediated activity.•DRIAs reduce the extent of endometriosis-like lesions in a mouse model.•DRIAs might be a potential therapeutic option for management of endometriosis.
Endometriosis is an estrogen-dependent disease, and isoflavones interact with estrogen receptors. The purposes of this study are to investigate the in vitro and in vivo effects of daidzein-rich isoflavone aglycones (DRIAs), dietary supplements, on cellular proliferation in endometriosis. Stromal cells isolated from ovarian endometrioma (OESCs) and normal endometrium (NESCs) were cultured with DRIAs, i.e., each of the DRIA components (daidzein, genistein, or glycitein), or isoflavone glycosides (IG; DRIA precursors). A mouse model of endometriosis was established by transplanting donor-mouse uterine fragments into recipient mice. Our results showed that DRIAs (0.2–20 μM) inhibited the proliferation of OESCs (P < 0.05 for 0.2 μM; P < 0.01 for 2 and 20 μM) but not of NESCs. However, daidzein, genistein, glycitein, and IG did not inhibit their proliferation. DRIA-induced suppression was reversed by inhibition of the estrogen receptor (ER)β by an antagonist, PHTPP, or by ERβ siRNA (P < 0.05), but not by MPP, an ERα antagonist. In OESCs, DRIAs led to reduced expression of IL-6, IL-8, COX-2, and aromatase, as well as reduced aromatase activity, serum glucocorticoid-regulated kinase levels, and PGE2 levels (P < 0.05). Western blot and immunofluorescence assays revealed that DRIAs inhibited TNF-α-induced IκB phosphorylation and p65 uptake into the nuclei of OESCs. In the mouse model, a DRIA-containing feed significantly decreased the number, weight, and Ki-67 proliferative activity of endometriosis-like lesions compared to in mice fed with an IG-containing feed and the control feed (P < 0.01). In conclusion, DRIAs inhibit cellular proliferation in endometriosis, thus representing a potential therapeutic option for the management of endometriosis.
CFD (computational fluid dynamics) is being increasingly applied to the prediction of the wind environment around actual high-rise buildings. Despite this increasing use, the prediction accuracy and ...many factors that might affect simulation results are not yet thoroughly understood. In order to clarify ambiguities and make a guideline for CFD prediction of the wind environment, a working group was organized by the Architectural Institute of Japan. This group has carried out various comparative studies as follows.
•
First stage: Flow fields around two types of single high-rise buildings.
•
Second stage: Flow field around a high-rise building located in a city.
•
Last stage: Flow fields around two types of Building Complexes in actual urban areas.
This paper describes some of the results of the investigation by the working group, and discusses the influences of various calculation conditions on CFD results, and also on the present status and the problems in CFD prediction of the wind environment.
The location of intracerebral hemorrhage in Moyamoya disease is a prognostic factor for rebleeding and the degree of preventive effects obtainable with bypass surgery. We evaluated whether the ...bleeding point and responsible vessel were detectable using fusion images of SWI and time-of-flight MRA performed during chronic-phase hemorrhage.
We retrospectively enrolled 42 patients with hemorrhagic Moyamoya disease (48 hemorrhagic events). Fusion images of SWI and MRA were made using workstations, and we defined the bleeding point as the point at which the signal of an abnormally extended artery on MRA overlapped the hypointense area on SWI. Two independent raters identified the bleeding point, and classified the location and responsible vessels.
The bleeding point was detectable at a frequency of 79.2% by rater 1. Agreement for the presence of a bleeding point was high (interrater κ = 0.83; 95% CI, 0.65-1; intrarater κ = 0.86; 95% CI, 0.68-1). The frequency of a periventricular location of the bleeding point was 65.8% by rater 1, and agreement on the location was again high (interrater κ = 0.92; 95% CI, 0.82-1; intrarater κ = 0.85; 95% CI, 0.72-0.99). The choroidal artery was the most frequent responsible vessel (57.9% by rater 1), and agreement on the responsible vessel was high (interrater κ = 0.84; 95% CI, 0.69-1; intrarater κ = 0.90; 95% CI, 0.78-1).
Detection of the bleeding point in hemorrhagic Moyamoya disease using SWI and MRA fusion images offers highly reproducible results.
Radiation-induced changes can occur after stereotactic radiosurgery for brain AVMs, potentially causing symptomatic complications. We evaluated the incidence of such changes and the efficacy of ...repeat gamma knife radiosurgery for incompletely obliterated AVMs.
We retrospectively evaluated 150 patients who underwent gamma knife radiosurgery for AVMs between 2002 and 2020; twenty-five underwent further radiosurgical procedures for incompletely obliterated AVMs. We recorded the median margin doses at the first (median, 20 Gy; range, 12-23 Gy; AVM volume, 0.026-31.3 mL) and subsequent procedures (median, 18 Gy; range, 12-23 Gy; AVM volume, 0.048-9.2 mL).
After the first treatment, radiologic radiation-induced changes developed in 48 (32%) patients, eight of whom had symptomatic changes. After repeat gamma knife radiosurgery, 16 of 25 patients achieved complete AVM obliteration (64%). The development of radiation-induced changes after the first treatment was significantly associated with successful obliteration by subsequent radiosurgery (OR = 24.0, 95% CI 1.20-483,
= .007). Radiation-induced changes occurred in only 5 (20%) patients who underwent a second gamma knife radiosurgery, one of whom experienced transient neurologic deficits. Between the first and repeat gamma knife radiosurgery procedures, there was no significant difference in radiologic and symptomatic radiation-induced changes (
= .35 and
= 1.0, respectively).
Radiation-induced changes after the first gamma knife radiosurgery were associated with AVM obliteration after a repeat procedure. The risk of symptomatic radiation-induced changes did not increase with retreatment. When the first procedure fails to achieve complete AVM obliteration, a favorable outcome can be achieved by a repeat gamma knife radiosurgery, even if radiation-induced changes occur after the first treatment.
A simple and sensitive automated method for determination of aflatoxins (B1, B2, G1, and G2) in nuts, cereals, dried fruits, and spices was developed consisting of in-tube solid-phase microextraction ...(SPME) coupled with liquid chromatography–mass spectrometry (LC–MS). Aflatoxins were separated within 8
min by high-performance liquid chromatography using a Zorbax Eclipse XDB-C8 column with methanol/acetonitrile (60/40, v/v): 5
mM ammonium formate (45:55) as the mobile phase. Electrospray ionization conditions in the positive ion mode were optimized for MS detection of aflatoxins. The pseudo-molecular ions M+H
+ were used to detect aflatoxins in selected ion monitoring (SIM) mode. The optimum in-tube SPME conditions were 25
draw/eject cycles of 40
μL of sample using a Supel-Q PLOT capillary column as an extraction device. The extracted aflatoxins were readily desorbed from the capillary by passage of the mobile phase, and no carryover was observed. Using the in-tube SPME LC–MS with SIM method, good linearity of the calibration curve (
r
>
0.9994) was obtained in the concentration range of 0.05–2.0
ng/mL using aflatoxin M1 as an internal standard, and the detection limits (S/N
=
3) of aflatoxins were 2.1–2.8
pg/mL. The in-tube SPME method showed >23-fold higher sensitivity than the direct injection method (10
μL injection volume). The within-day and between-day precision (relative standard deviations) at the concentration of 1
ng/mL aflatoxin mixture were below 3.3% and 7.7% (
n
=
5), respectively. This method was applied successfully to analysis of food samples without interference peaks. The recoveries of aflatoxins spiked into nuts and cereals were >80%, and the relative standard deviations were <11.2%. Aflatoxins were detected at <10
ng/g in several commercial food samples.
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