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Apolipoprotein ε4 (APOE4) carriers develop brain metabolic dysfunctions decades before the onset of Alzheimer's disease (AD). A goal of the study is to identify if rapamycin, an inhibitor for the mammalian target of rapamycin (mTOR) inhibitor, would enhance synaptic and mitochondrial function in asymptomatic mice with human APOE4 gene (E4FAD) before they showed metabolic deficits. A second goal is to determine whether there may be genetic-dependent responses to rapamycin when compared to mice with human APOE3 alleles (E3FAD), a neutral AD genetic risk factor. We fed asymptomatic E4FAD and E3FAD mice with control or rapamycin diets for 16 weeks from starting from 3 months of age. Neuronal mitochondrial oxidative metabolism and excitatory neurotransmission rates were measured using in vivo 1 H-[ 13 C] proton-observed carbon-edited magnetic resonance spectroscopy, and isolated mitochondrial bioenergetic measurements using Seahorse. We found that rapamycin enhanced neuronal mitochondrial function, glutamate-glutamine cycling, and TCA cycle rates in the asymptomatic E4FAD mice. In contrast, rapamycin enhances glycolysis, non-neuronal activities, and inhibitory neurotransmission of the E3FAD mice. These findings indicate that rapamycin might be able to mitigate the risk for AD by enhancing brain metabolic functions for cognitively intact APOE4 carriers, and the responses to rapamycin are varied by APOE genotypes. Consideration of precision medicine may be needed for future rapamycin therapeutics., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To investigate the therapeutic effect of intra-arterial microguidewire electrocoagulation on intracranial vascular diseases., Methods: Data from 10 patients with cerebral aneurysms between May 2018 and September 2022 were analysed. Patients were treated with endovascular coil embolisation and microguidewire electrocoagulation. XperCT scans were conducted to identify new intracranial haemorrhage, infarction and hydrocephalus. Follow-up examinations were conducted 1, 3, 6 and 12 months after discharge., Results: After the patients received electrocoagulation for different durations, Raymond Grade 1 embolisation was achieved in all 10 patients. No complications, such as haemorrhage, infarction or hydrocephalus, were found during or after surgery. Ten patients were followed up for 6-12 months, and none had any symptoms or new neurological dysfunction 1 month after their operation. Among them, nine were followed up for 12 months, and digital subtraction angiography showed no recurrence of aneurysms or occlusion of parent arteries., Conclusion: Intra-arterial microguidewire electrocoagulation can be used as a supplementary treatment for cerebral aneurysms. In cases of incomplete lesion embolisation and cases where tamponade treatment cannot continue, immediate thrombosis may occur. Thus, intra-arterial microguidewire electrocoagulation can help achieve patients' treatment goals., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To evaluate the risk factors for the development of concurrent or delayed-onset rhegmatogenous retinal detachment (RRD) related to endophthalmitis as well as the anatomic and visual outcomes with subsequent RRD repair. Methods: In this retrospective case study, a 2-tailed t test (continuous) and Fisher exact test were used to determine statistical significance of the observed findings. The relative risk (RR) and 95% CIs were calculated to assess statistical significance. Results: Of the 170 patients included, 22 were found to have a concurrent or subsequent RRD. Initial treatment with pars plana vitrectomy (PPV) (RR, 3.544; 95% CI, 1.650-7.614), aphakia (RR, 4.150; 95% CI, 1.434-12.011), endogenous endophthalmitis (RR, 2.684; 95% CI, 1.065-6.764), and posterior synechiae (RR, 3.026; 95% CI, 1.408-6.505) were statistically significant risk factors for RRD. Anatomically successful repair was achieved in 77.7% of patients. Conclusions: In addition to preexisting risk factors, the initial treatment of endophthalmitis may be a significant risk factor for RRD development, with a higher incidence of subsequent RRD in patients who have PPV as the initial treatment for endophthalmitis., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Introduction: The primary objective of this study was to assess the feasibility of a 6-week internet-delivered Mantram Repetition Program (MRP) for women recently treated for breast cancer. A secondary objective explored changes in perceived stress, psycho-spiritual measures, and cytokines in the treatment group compared to a waitlist. Methods: A feasibility study (ORBIT model Phase IIa) with a randomized controlled trial pilot was conducted. Eligible women recently treated for breast cancer were randomized to the treatment group ( n = 14) or a waitlist group ( n = 12) and participated for 12 weeks. During weeks 1-6, the treatment group received the MRP intervention while the waitlisted group was inactive. During weeks 7-12, the treatment group was inactive while the waitlisted group received the MRP intervention. The primary outcomes were feasibility and acceptability of the internet-delivered MRP intervention protocol. Participants completed pre and post-intervention psycho-spiritual health assessments. A subset of participants provided serum for cytokine analyses at enrollment and week 6, coinciding with the period in which the treatment group receiving the MRP intervention. Results: Overall study attrition was 19.2%. MRP adherence for both groups was 86% at post-intervention and 90% in the treatment group at 6-week follow-up. Pre-to-post-intervention analyses pooling both groups' data demonstrated decreased perceived stress ( p = .045) and increased spiritual well-being ( p =.004). IFN-γ and IL-17A were increased in the waitlisted group and decreased in the treatment group ( p = 0.048). Conclusion: Feasibility of a 6-week, internet-delivered MRP intervention for breast cancer survivors was established. Psycho-spiritual variables and serum cytokines are suitable clinical outcome measures for future MRP studies with breast cancer survivors. Data suggest MRP may reduce perceived stress and support spiritual well-being in women with breast cancer; however, additional studies are needed., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Objectives: Safe and effective management of cancer-related pain is a worldwide challenge. In the search for treatment options, natural products used in Chinese herbal medicines (CHMs) have received attention in clinical studies for their effects on cancer-related pain. The objective of this systematic review is to evaluate the clinical evidence for topically applied CHMs as adjunctive treatments for cancer pain management., Methods: Nine biomedical databases and 4 clinical trial registries were searched for randomized-controlled trials (RCTs) that reported measures of pain and/or quality of life. Risk of bias was assessed using the Cochrane tool. Meta-analysis employed mean difference (MD) with 95% confidence intervals (random effects)., Results: Twenty (20) RCTs (1636 participants) met the inclusion criteria. Meta-analyses were grouped based on the comparisons and outcome measures. For pain intensity, there was a greater reduction in the topical CHM group versus placebo (MD -0.72 [-1.04, -0.40]), no difference when compared to tramadol (MD -0.15 [-0.38, 0.08]), and a greater reduction when topical CHMs were combined with conventional analgesic medications (MD -0.67 [-0.93, -0.40]). Analgesic onset time was reduced in the CHM group compared to tramadol (MD -26.02 [-27.57, -24.47] minutes), and for CHMs combined with conventional medications (MD -19.17 [-21.83, -16.52] minutes). When CHMs were combined with analgesic medications, improvements were found for duration of analgesia (MD 1.65 [0.78, 2.51] hours), analgesic maintenance dose (MD -31.72 [-50.43, -13.01] milligrams/day), and quality of life., Conclusion: Addition of topical CHMs to conventional analgesic medications was associated with improved outcomes for pain intensity, some other pain-related outcomes, and measures of quality of life. Limitations included methodological issues in some studies and considerable heterogeneity in some pooled results., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Chinese herbal medicine (CHM) is widely used in breast cancer, but there is no consensus on the Chinese medicine (CM) syndromes in the different conventional treatment stages (preoperative, postoperative, chemotherapy, radiation therapy and endocrine therapy) of early breast cancer. This Delphi study aimed to achieve expert consensus on the CM syndromes, signs and symptoms, and the Chinese herbal formulae for early breast cancer., Methods: Thirty senior CM clinicians with expertise in managing breast cancer were enrolled. The syndromes selected by ≥50% of experts and the corresponding most common Chinese herbal formulae were considered a consensus. Consensus on signs and symptoms was defined as a median score ≥4 (the item was important or very important) and ≥70% of experts rating the sign or symptom as 4 (important) or 5 (very important) on a 5-point Likert scale., Results: Three survey rounds were conducted from 15 October 2021 to 10 March 2022. Consensus was reached with 3 syndromes confirmed for each treatment stage. Several syndromes, such as dual deficiency of qi and Blood, were considered common to multiple treatment stages. Some important signs and symptoms were presented in multiple treatment stages (eg, shortage of qi in the radiation therapy and endocrine therapy stages)., Conclusions: This Delphi study achieved consensus on the most common CM syndromes, corresponding signs and symptoms, and the most common formulae in each treatment stage of early breast cancer, providing an evidence-based approach for future clinical practice., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Studies regarding the relationship of sclerostin (Scl) with clinical outcomes in patients undergoing maintenance haemodialysis have yielded controversial findings. This meta-analysis was performed to investigate the predictive role of Scl in this patient population., Methods: Several electronic medical databases (e.g. PubMed, Embase, Web of Science and Cochrane Library) were searched for eligible studies through December 20, 2019. Summary hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated based on Scr level (high or low) using a random or fixed effects model., Results: From among 641 initially screened publications, 16 eligible studies were included in this meta-analysis. A high Scl level was not associated with cardiovascular events [HR = 0.8 (95% CI, 0.42-1.35)] or all-cause mortality [HR = 0.93 (95% CI, 0.56-1.54)]. There was high heterogeneity, but no evidence of publication bias. Interestingly, a high Scl level was associated with reduced cardiovascular events [HR = 0.44 (95% CI, 0.29-0.69)] in the subgroup by shorter follow-up period or all-cause mortality [pooled HR = 0.58 (95% CI, 0.36-0.91)] by shorter dialysis vintage., Conclusion: This meta-analysis indicated that a high Scl level did not predict total clinical outcomes in patients undergoing maintenance haemodialysis despite survival benefits in the subgroups. The predictive role of Scl in these patients should be further evaluated in large prospective studies., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2021.)

Recurrent or chronic oral pain is a great burden for patients. Recently, the links between epithelial barrier loss and disease were extended to include initiation and propagation. To explore the effects of pathohistological changes in oral epithelia on pain, we utilized labial mucosa samples in diagnostic labial gland biopsies from patients with suspected Sjögren's syndrome (SS), because they frequently experience pain and discomfort. In most labial mucosa samples from patients diagnosed with SS, disseminated epithelial cellular edema was prevalent as ballooning degeneration. The disrupted epithelia contained larger numbers of infiltrating macrophages in patients with oral pain than in patients without pain. Immunohistochemistry revealed that edematous areas were distinct from normal areas, with disarranged cell-cell adhesion molecules (filamentous actin, E-cadherin, β-catenin). Furthermore, edematous areas were devoid of immunostaining for transient receptor potential channel vanilloid 4 (TRPV4), a key molecule in adherens junctions. In an investigation on whether impaired TRPV4 affect cell-cell adhesion, calcium stimulation induced intimate cell-cell contacts among oral epithelial cells from wild-type mice, while intercellular spaces were apparent in cells from TRPV4-knockout mice. The present findings highlight the relationship between macrophages and epithelia in oral pain processing, and identify TRPV4-mediated cell-cell contacts as a possible target for pain treatment.

Background: After diagnosis, a substantial number of people with HIV disease fall out of care. Effective interventions are needed for this priority population., Methods: The "Peers Keep It Real" study aimed to help adults who were disengaged from HIV treatment. Peers, lay individuals living with HIV, facilitated intervention sessions. Participants were randomized to immediately receive the peer-facilitated intervention or were wait-listed., Results: Considerable attrition occurred in the control group. Pre-/postanalyses showed that among participants (n = 23) who received the intervention, 65% had viral load suppression and 100% remained in care at 12 months postintervention. Impact on viral load was significant ( P = .0326), suggesting that peers are effective change agents who positively impacted outcomes for individuals struggling with adherence to HIV treatment., Conclusion: Future endeavors should consider providing all individuals from this priority population with an active peer intervention from the onset to enhance retention and adherence.

Objectives: To assess the clinical evidence for integrative herbal medicine therapy in the management of chemotherapy-induced peripheral neuropathy (CIPN) and hand-foot syndrome (HFS) resulting from treatments for colorectal cancer (CRC)., Design: Randomized controlled trials (RCTs) were identified from major English and Chinese databases. Participants had been diagnosed with CRC by pathology and had received or were undergoing chemotherapy. Interventions included herbal medicines administered orally or topically. Controls were placebo, supportive care or conventional chemotherapy for CRC. Methods followed the Cochrane handbook. Meta-analyses were grouped by study design, outcome measure, severity, and chemotherapy. Random-effects models with 95% confidence intervals were used. Heterogeneity was assessed as I 2 ., Results: Sixty-three RCTs (4286 participants) were included. Five used a placebo in the control groups. Fifty-eight studies tested oral herbal medicine, and 5 tested topical herbal medicine. Data were available for CIPN (60 studies) and HFS (12 studies). Fifty-seven studies combined orally administered herbal medicine with chemotherapy compared with the same chemotherapy. For CIPN, 33 studies used World Health Organization (WHO) criteria, 7 used Levi's criteria, and 10 used the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). These were analyzed separately. For grades III + IV CIPN, there was a significant reduction in the integrative groups for WHO (relative risk [RR] 0.42 [0.23, 0.77], I 2 = 0%) and Levi's (RR 0.28 [0.11, 0.69], I 2 = 0%) but not NCI-CTCAE (RR 0.65 [0.37, 1.13], I 2 = 26.4%). Hand and foot baths showed no differences for Levi's grades III + IV CIPN but a significant reduction in all grades (RR 0.69 [0.50, 0.95], I 2 = 68.8%). For HFS (all grades) there was a significant reduction in the integrative groups for WHO (RR 0.62 [0.41, 0.96], I 2 = 22%) but not for NCI-CTCAE (RR 0.93 [0.55, 1.55], I 2 = 75.7%). Sensitivity analyses explored sources of heterogeneity., Conclusions: Integrative herbal therapy appeared to reduce CIPN and HFS in people receiving chemotherapy for CRC. However, the strength of the evidence was limited by lack of blinding in most studies, potential for bias, and relatively short study durations.

Background: Electroacupuncture (EA) is a modern form of acupuncture therapy where stainless steel acupuncture needles are used as percutaneous electrodes to apply electrical stimulation. The concern about electrolytic corrosion of needles during EA has not been conclusively addressed., Aim: To examine whether corrosion of stainless steel acupuncture needles occurs after EA to establish the safety profile of this therapy., Methods: The study comprised four EA sessions on healthy participants mimicking a common clinical practice, with needle surface examinations conducted immediately after each session. Used acupuncture needles that did not undergo electrical stimulation and unused needles taken from the original package were also examined as control comparisons. Two commonly used types of single-use, silicone-coated, stainless steel needles were selected for the experiment. The ES-160 digital acupunctoscope (a charge-balanced electric stimulator) was used to deliver electrical stimulation, and an oscilloscope was used to record the waveforms and electric currents. All needles were sterilised before examination by a scanning electron microscope (SEM), where images of needle tips and shafts were taken for further analysis., Results and Conclusions: 32 needles were examined under the SEM. As the main findings, the SEM images showed the surface finish, burr attachments and surface characteristics of needle samples. No evidence of electrolytic corrosion was detected on any needle that underwent electrical stimulation for 30 min delivered by a charge-balanced acupunctoscope in healthy participants. The choice of a charge-balanced acupunctoscope is recommended to avoid any potential corrosion of needles in EA clinical practice., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: An ideal placebo design in clinical research should resemble the intervention under investigation to facilitate blinding, yet remain clinically inert. With regard to physical interventions such as acupuncture, a true placebo device has not been developed and validated. Since 1998, researchers have designed several placebo acupuncture devices (PADs). The three most widely used PADs are the Streitberger, the Park and the Takakura device., Aim: This review focuses on evaluating studies of these devices, in the context of credibility of blinding (COB), assessment of penetrating pain or sensation, and de qi sensation., Methods: Electronic database searches were conducted in four English and two Chinese databases from their inception until November 2016. All studies included in the review were conducted on healthy participants and compared verum manual acupuncture with any of the aforementioned PADs with respect to one or more of the above three outcomes related to blinding effect., Results: The synthesised analyses of the 15 included studies showed that the Streitberger and Park placebo devices may not blind participants successfully when tested at a sensitive acupuncture point (LI4). In terms of penetrating sensation, there were significant differences between these two placebo devices and verum acupuncture when applied at this point. The Takakura device was the only PAD that had the potential to blind the acupuncturist. However, the blinding analyses of all outcome measures were inconsistent., Conclusion: Overall, there were insufficient data to confirm the blinding effects of these skin-contact PADs as each device was associated with limitations that warrant further design improvements., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

To investigate whether the soluble Klotho (s-Klotho) level in patients with chronic kidney disease (CKD) is related to kidney function and whether a low s-Klotho level can predict adverse renal outcomes or CKD progression in patients with advanced CKD. 112 patients with CKD stages 3-5 and 30 healthy volunteers were enrolled. Blood samples were collected to measure serum creatinine, calcium, phosphorus, intact parathyroid hormone, and hemoglobin. s-Klotho and fibroblast growth factor 23 (FGF23) were determined by ELISA. We first conducted a cross-sectional study to investigate correlations between s-Klotho and estimated glomerular filtration rate (eGFR) and other parameters. Patients were then followed prospectively for 20.1±10.1 months according to s-Klotho median level until serum creatinine doubled, or initiation of renal replacement therapy, or death. s-Klotho levels inpatients with CKD were significantly lower than that in the control group. For patients with CKD, there were no differences in age distribution among subgroups. However, s-Klotho level differed significantly across CKD stages, and it was lower in the advanced CKD group compared with the moderate CKD group. Correlation analysis revealed that s-Klotho was positively associated with eGFR, but inversely associated with FGF23. During the follow-up of 20.1±10.1 months, patients with higher s-Klotho levels showed a reduced risk of kidney adverse outcomes, including serum creatinine doubling and initiation of renal replacement therapy. Cox regression analysis revealed that low s-Klotho was an independent risk factor for CKD progression. s-Klotho level was closely correlated with kidney function, further, low s-Klotho level could predict adverse kidney disease outcomes in patients with progressive CKD., Competing Interests: Competing interests: None declared., (© American Federation for Medical Research (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

We recently showed that mTOR attenuation blocks progression and abrogates established cognitive deficits in Alzheimer's disease (AD) mouse models. These outcomes were associated with the restoration of cerebral blood flow (CBF) and brain vascular density (BVD) resulting from relief of mTOR inhibition of NO release. Recent reports suggested a role of mTOR in atherosclerosis. Because mTOR drives aging and vascular dysfunction is a universal feature of aging, we hypothesized that mTOR may contribute to brain vascular and cognitive dysfunction associated with atherosclerosis. We measured CBF, BVD, cognitive function, markers of inflammation, and parameters of cardiovascular disease in LDLR -/- mice fed maintenance or high-fat diet ± rapamycin. Cardiovascular pathologies were proportional to severity of brain vascular dysfunction. Aortic atheromas were reduced, CBF and BVD were restored, and cognitive dysfunction was attenuated potentially through reduction in systemic and brain inflammation following chronic mTOR attenuation. Our studies suggest that mTOR regulates vascular integrity and function and that mTOR attenuation may restore neurovascular function and cardiovascular health. Together with our previous studies in AD models, our data suggest mTOR-driven vascular damage may be a mechanism shared by age-associated neurological diseases. Therefore, mTOR attenuation may have promise for treatment of cognitive impairment in atherosclerosis.

Management of the behavioural and psychological symptoms of dementia remains a challenge worldwide. Herbal medicines may play a role in the development of new interventions. To determine effects of herbal medicines for management of the behavioural and psychological symptoms of dementia, meta-analysis was conducted of 31 controlled trials (3613 participants). Frequently tested herbal medicines were the Ginkgo biloba leaf extract EGb 761 (seven studies) and the multi-ingredient formula Yokukansan (eight studies). Sixteen studies tested other herbal medicines. Improvements were detected in Neuropsychiatric Inventory scores in EGb 761 groups compared to placebo (MD -3.46 [-5.94, -0.98]; I 2 = 93%; n = 1757) and Yokukansan groups compared to no treatment (SMD -0.53 [-0.86, -0.21]; I 2 = 0%; n = 150). Cognitive scores were improved in EGb 761 groups while Yokukansan did not appear to affect cognitive function. Of the other herbal medicines, there were improvements in the behavioural and psychological symptoms of dementia and cognitive outcomes in two of four placebo-controlled studies. EGb 761 and Yokukansan appeared safe and well tolerated. Adverse effects and dropouts were not reported consistently for the other herbal medicines. Weaknesses of these included short durations, small sample sizes, lack of blinding and other risks of bias. Well-designed studies are needed to further investigate the reported effects of these interventions on the behavioural and psychological symptoms of dementia.

Neurologic complications of cancer are common and are frequently life-threatening events. Certain neurologic emergencies occur more frequently in the cancer population, specifically elevated intracranial pressure, epidural cord compression, status epilepticus, ischemic and hemorrhagic stroke, central nervous system infection, and treatment-associated neurologic dysfunction. These emergencies require early diagnosis and prompt treatment to ensure the best possible outcome and are best managed in the intensive care unit. This article reviews the presentation, pathophysiology, and management of the most common causes of acute neurologic decompensation in the patient with cancer.

Apolipoprotein E ɛ4 allele is a common susceptibility gene for late-onset Alzheimer's disease. Brain vascular and metabolic deficits can occur in cognitively normal apolipoprotein E ɛ4 carriers decades before the onset of Alzheimer's disease. The goal of this study was to determine whether early intervention using rapamycin could restore neurovascular and neurometabolic functions, and thus impede pathological progression of Alzheimer's disease-like symptoms in pre-symptomatic Apolipoprotein E ɛ4 transgenic mice. Using in vivo, multimodal neuroimaging, we found that apolipoprotein E ɛ4 mice treated with rapamycin had restored cerebral blood flow, blood-brain barrier integrity and glucose metabolism, compared to age- and gender-matched wild-type controls. The preserved vasculature and metabolism were associated with amelioration of incipient learning deficits. We also found that rapamycin restored the levels of the proinflammatory cyclophilin A in vasculature, which may contribute to the preservation of cerebrovascular function in the apolipoprotein E ɛ4 transgenics. Our results show that rapamycin improves functional outcomes in this mouse model and may have potential as an effective intervention to block progression of vascular, metabolic and early cognitive deficits in human Apolipoprotein E ɛ4 carriers. As rapamycin is FDA-approved and neuroimaging is readily used in humans, the results of the present study may provide the basis for future Alzheimer's disease intervention studies in human subjects., (© The Author(s) 2015.)

Risk factors and cognitive sequelae of brain arteriolosclerosis pathology are not fully understood. To address this, we used multimodal data from the National Alzheimer's Coordinating Center and Alzheimer's Disease Neuroimaging Initiative data sets. Previous studies showed evidence of distinct neurodegenerative disease outcomes and clinical-pathological correlations in the "oldest-old" compared to younger cohorts. Therefore, using the National Alzheimer's Coordinating Center data set, we analyzed clinical and neuropathological data from two groups according to ages at death: < 80 years (n = 1008) and ≥80 years (n = 1382). In both age groups, severe brain arteriolosclerosis was associated with worse performances on global cognition tests. Hypertension (but not diabetes) was a brain arteriolosclerosis risk factor in the younger group. In the ≥ 80 years age at death group, an ABCC9 gene variant (rs704180), previously associated with aging-related hippocampal sclerosis, was also associated with brain arteriolosclerosis. A post-hoc arterial spin labeling neuroimaging experiment indicated that ABCC9 genotype is associated with cerebral blood flow impairment; in a convenience sample from Alzheimer's Disease Neuroimaging Initiative (n = 15, homozygous individuals), non-risk genotype carriers showed higher global cerebral blood flow compared to risk genotype carriers. We conclude that brain arteriolosclerosis is associated with altered cognitive status and a novel vascular genetic risk factor., (© The Author(s) 2016.)

Females currently make up 15% of U.S. military service members. Minimal attention has been paid to families of female National Guard members who have been deployed and their subsequent reintegration challenges. This cross-sectional Internet-based survey of female members of four National Guard units compared those who were and were not deployed. Instruments, guided by the variables of the Family Resilience Model, measured individual, family, and deployment-related factors. Bivariate analysis and ordinal logistic regression were done to assess differences between the groups. Of the 239 National Guard members surveyed, deployed women (n = 164) had significantly higher levels of posttraumatic stress disorder (PTSD; p < .001) and lower coping skills (p = .003) than non-deployed women (n = 75). Perceptions of overall family functioning were higher among deployed when compared with never deployed women. Results indicate community interventions that focus on strengthening coping skills of female Guard members would be useful for this population., (© The Author(s) 2016.)

Background: Non-adherence to antiretroviral (ART) treatment remains a prevalent problem even among the segment of the U.S. HIV population that is 'linked' to medical care., Methods: Controlled pilot feasibility study with ART experienced adult patients (n = 20) linked to HIV medical care without suppressed viral load. Patients were randomized to a peer-led HIV medication adherence intervention named `Ready' or a time equivalent `healthy eating' control arm. Lay individuals living with HIV were trained to facilitate `Ready'., Results: Patients had been prescribed a mean of three prior ART regimens. The group randomized to `Ready' had significantly improved adherence. MEMS and pharmacy refill data correlated with viral load log drop. Higher readiness for healthful behavior change correlated with viral load drop and approached significance., Conclusion: A peer-led medication adherence intervention had a positive impact among adults who had experienced repeated non-adherence to HIV treatment. A larger study is needed to examine intervention dissemination and efficacy., (© The Author(s) 2014.)

This study describes an evaluation of a community-based psychoeducational intervention, called The Family Series Workshop, for caregivers of community-dwelling persons with Alzheimer's disease or related dementias (ADRD). In a one-group pretest-posttest design, participants (n = 35) attended six weekly sessions. Caregiver stress, coping, and caregiving competence were evaluated along with demographic characteristics of participants. There was a significant improvement found for caregiving competence, and a marginally significant increase in coping with humor. Using regression analysis we also found that coping with humor, along with stress, were significant predictors of caregiving competence. These findings indicate that it is possible to increase caregiving competence utilizing a "grassroots" approach and that it is feasible to hold educational, group discussions on a plethora of challenging caregiving topics., (© The Author(s) 2015.)

Chronic cough is a significant health burden. Patients experience variable benefits from over the counter and prescribed products, but there is an unmet need to provide more effective treatments. Natural products have been used to treat cough and some plant compounds such as pseudoephedrine from ephedra and codeine from opium poppy have been developed into drugs. Text mining historical literature may offer new insight for future therapeutic development. We identified natural products used in the East Asian historical literature to treat chronic cough. Evaluation of the historical literature revealed 331 natural products used to treat chronic cough. Products included plants, minerals and animal substances. These natural products were found in 75 different books published between AD 363 and 1911. Of the 331 products, the 10 most frequently and continually used products were examined, taking into consideration findings from contemporary experimental studies. The natural products identified are promising and offer new directions in therapeutic development for treating chronic cough., (© The Author(s) 2015.)

Alzheimer's disease (AD) is characterized by age-dependent biochemical, metabolic, and physiologic changes. These age-dependent changes ultimately converge to impair cognitive functions. This study was carried out to examine the metabolic changes by probing glucose and tricarboxylic acid cycle metabolism in a 7-month-old triple transgenic mouse model of AD (3xTg-AD). The effect of lipoic acid, an insulin-mimetic agent, was also investigated to examine its ability in modulating age-dependent metabolic changes. Seven-month-old 3xTg-AD mice were given intravenous infusion of [1-(13)C]glucose followed by an ex vivo (13)C nuclear magnetic resonance to determine the concentrations of (13)C-labeled isotopomers of glutamate, glutamine, aspartate, gamma aminobutyric acid, and N-acetylaspartate. An intravenous infusion of [1-(13)C]glucose+[1,2-(13)C]acetate was given for different periods of time to distinguish neuronal and astrocytic metabolism. Enrichments of glutamate, glutamine, and aspartate were calculated after quantifying the total ((12)C+(13)C) concentrations by high-performance liquid chromatography. A hypermetabolic state was clearly evident in 7-month-old 3xTg-AD mice in contrast to the hypometabolic state reported earlier in 13-month-old mice. Hypermetabolism was evidenced by prominent increase of (13)C labeling and enrichment in the 3xTg-AD mice. Lipoic acid feeding to the hypermetabolic 3xTg-AD mice brought the metabolic parameters to the levels of nonTg mice.

Caloric restriction (CR) prolongs lifespan and retards many detrimental effects of aging, but its effect on brain mitochondrial function and neuronal activity--especially in healthy aging--remains unexplored. Here we measured rates of neuronal glucose oxidation and glutamate-glutamine neurotransmitter cycling in young control, old control (i.e., healthy aging), and old CR rats using in vivo nuclear magnetic resonance spectroscopy. We found that, compared with the young control, neuronal energy production and neurotransmission rates were significantly reduced in healthy aging, but were preserved in old CR rats. The results suggest that CR mitigated the age-related deceleration of brain physiology.

Unlabelled: Loss of muscle strength, flexibility, and balance are strong predictors of falls in the elderly., Objectives: The goal of this research was to investigate the effectiveness of a 10-week, strength-based exercise program delivered by Extension professionals., Methods: Matched pair t tests were used to compare differences in five measures of fitness collected from 808 participants (mean age = 65.4 years) at the start and finish of the exercise program., Results: Following programming, participants significantly improved strength, flexibility, and balance., Discussion: Results indicate that an evidence-based program can be translated into a community Extension program that is able to improve the fitness level of seniors.

Recent studies have challenged the prevailing view that reduced mitochondrial function and increased oxidative stress are correlated with reduced longevity. Mice carrying a homozygous knockout (KO) of the Surf1 gene showed a significant decrease in mitochondrial electron transport chain Complex IV activity, yet displayed increased lifespan and reduced brain damage after excitotoxic insults. In the present study, we examined brain metabolism, brain hemodynamics, and memory of Surf1 KO mice using in vitro measures of mitochondrial function, in vivo neuroimaging, and behavioral testing. We show that decreased respiration and increased generation of hydrogen peroxide in isolated Surf1 KO brain mitochondria are associated with increased brain glucose metabolism, cerebral blood flow, and lactate levels, and with enhanced memory in Surf1 KO mice. These metabolic and functional changes in Surf1 KO brains were accompanied by higher levels of hypoxia-inducible factor 1 alpha, and by increases in the activated form of cyclic AMP response element-binding factor, which is integral to memory formation. These findings suggest that Surf1 deficiency-induced metabolic alterations may have positive effects on brain function. Exploring the relationship between mitochondrial activity, oxidative stress, and brain function will enhance our understanding of cognitive aging and of age-related neurologic disorders.

Vascular pathology is a major feature of Alzheimer's disease (AD) and other dementias. We recently showed that chronic administration of the target-of-rapamycin (TOR) inhibitor rapamycin, which extends lifespan and delays aging, halts the progression of AD-like disease in transgenic human (h)APP mice modeling AD when administered before disease onset. Here we demonstrate that chronic reduction of TOR activity by rapamycin treatment started after disease onset restored cerebral blood flow (CBF) and brain vascular density, reduced cerebral amyloid angiopathy and microhemorrhages, decreased amyloid burden, and improved cognitive function in symptomatic hAPP (AD) mice. Like acetylcholine (ACh), a potent vasodilator, acute rapamycin treatment induced the phosphorylation of endothelial nitric oxide (NO) synthase (eNOS) and NO release in brain endothelium. Administration of the NOS inhibitor L-NG-Nitroarginine methyl ester reversed vasodilation as well as the protective effects of rapamycin on CBF and vasculature integrity, indicating that rapamycin preserves vascular density and CBF in AD mouse brains through NOS activation. Taken together, our data suggest that chronic reduction of TOR activity by rapamycin blocked the progression of AD-like cognitive and histopathological deficits by preserving brain vascular integrity and function. Drugs that inhibit the TOR pathway may have promise as a therapy for AD and possibly for vascular dementias.

Students in an undergraduate legal and ethical issues course continually told the authors that they did not have time to study for the course because they were busy studying for their clinical courses. Faculty became concerned that students were failing to realize the value of legal and ethical concepts as applicable to clinical practice. This led the authors to implement a transformational learning experience in which students applied legal and ethical course content in a high-fidelity human simulation (HFHS) scenario. A preliminary evaluation compared the new HFHS experience with in-person and online student groups using the same case. Based on both student and faculty perceptions, the HFHS was identified as the best of the three approaches for providing a transformational learning experience regarding legal and ethical content.

African American women are less physically active than White women and have a higher prevalence of inactivity-related diseases. Increased physical activity is known to reduce the risks for many chronic diseases. Positive health behavior changes have resulted from health promotion interventions conducted in African American churches. Eighteen midlife African American women participated in the Heart and Soul Physical Activity Program (HSPAP), a church-based physical activity intervention conceptualized in appraisal, belonging, tangible, and self-esteem domains of social support. Feasibility of the HSPAP was tested by determining changes in time and intensity of physical activity and social support for physical activity from baseline to 6 weeks. Data analyses were conducted utilizing paired t tests. Significant increases in time spent in physical activity from a mean of 412 min/week at baseline to 552 min/week at 6 weeks were noted. Participants reported increases in social support for physical activity in the 6-week study.

This article outlines the development and feasibility of an HIV and IPV prevention intervention. Researchers formed a partnership with a group of women representative of the population that the intervention was intended to reach using methods derived from participatory action research. The use of health protective behaviors changed from pre- to postintervention in the clinically desirable direction. Results indicated that intervention delivery was feasible in the novel setting of a large urban day care center. This intervention has promise as a strategy to reduce HIV among low-income women; however, a controlled study is indicated to further examine intervention efficacy.

The purpose of this study is to explore the prevalence and associated behaviors of dating violence among a population of girls in the juvenile justice system. A sample of 590 girls from an urban juvenile justice system completed a questionnaire assessing attitudes and self-efficacy about and occurrence of dating violence. The analysis developed a random effect model to determine a risk profile for dating violence. The strongest predictors of dating violence were (a) initial sexual experience at age 13 or earlier, (b) unwillingness of initial sexual experience, (c) drug use, and (d) low self-efficacy about preventing dating violence. The high prevalence of dating violence and associated behaviors among participants suggests the importance of implementing primary prevention programs to assist preteen girls in delaying initial sexual intercourse and in learning techniques to prevent dating violence.