Accumulation of Cerebrospinal Fluid Glycerophospholipids and Sphingolipids in Cognitively Healthy Participants With Alzheimer’s Biomarkers Precedes Lipolysis in the Dementia Stage

Insight into lipids’ roles in Alzheimer’s disease (AD) pathophysiology is limited because brain membrane lipids have not been characterized in cognitively healthy (CH) individuals. Since age is a significant risk factor of AD, we hypothesize that aging renders the amyloid precursor protein (APP) more susceptible to abnormal processing because of deteriorating membrane lipids. To reflect brain membranes, we studied their lipid components in cerebrospinal fluid (CSF) and brain-derived CSF nanoparticle membranes. Based on CSF Aβ42/Tau levels established biomarkers of AD, we define a subset of CH participants with normal Aβ42/Tau (CH-NAT) and another group with abnormal or pathological Aβ42/Tau (CH-PAT). We report that glycerophospholipids are differentially metabolized in the CSF supernatant fluid and nanoparticle membrane fractions from CH-NAT, CH-PAT, and AD participants. Phosphatidylcholine molecular species from the supernatant fraction of CH-PAT were higher than in the CH-NAT and AD participants. Sphingomyelin levels in the supernatant fraction were lower in the CH-PAT and AD than in the CH-NAT group. The decrease in sphingomyelin corresponded with an increase in ceramide and dihydroceramide and an increase in the ceramide to sphingomyelin ratio in AD. In contrast to the supernatant fraction, sphingomyelin is higher in the nanoparticle fraction from the CH-PAT group, accompanied by lower ceramide and dihydroceramide and a decrease in the ratio of ceramide to sphingomyelin in CH-PAT compared with CH-NAT. On investigating the mechanism for the lipid changes in AD, we observed that phospholipase A2 (PLA2) activity was higher in the AD group than the CH groups. Paradoxically, acid and neutral sphingomyelinase (SMase) activities were lower in AD compared to the CH groups. Considering external influences on lipids, the clinical groups did not differ in their fasting blood lipids or dietary lipids, consistent with the CSF lipid changes originating from brain pathophysiology. The lipid accumulation in a prodromal AD biomarker positive stage identifies perturbation of lipid metabolism and disturbances in APP/Amyloid beta (Aβ) as early events in AD pathophysiology. Our results identify increased lipid turnover in CH participants with AD biomarkers, switching to a predominantly lipolytic state in dementia. This knowledge may be useful for targeting and testing new AD treatments.

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Interactive contributions of self-regulation deficits and social motivation to psychopathology: Unraveling divergent pathways to aggressive behavior and depressive symptoms

Development and Psychopathology ◽

10.1017/s0954579412001149 ◽

2013 ◽

Vol 25 (2) ◽

pp. 407-418 ◽

Cited By ~ 16

Author(s):

Karen D. Rudolph ◽

Wendy Troop-Gordon ◽

Nicole Llewellyn

Keyword(s):

Depressive Symptoms ◽

Aggressive Behavior ◽

Inhibitory Control ◽

Self Regulation ◽

Significant Risk ◽

Significant Risk Factor ◽

Theoretical Models ◽

Social Approach ◽

Avoidance Motivation ◽

Insight Into

AbstractPoor self-regulation has been implicated as a significant risk factor for the development of multiple forms of psychopathology. This research examined the proposition that self-regulation deficits differentially predict aggressive behavior and depressive symptoms, depending on children's social approach versus avoidance motivation. A prospective, multiple-informant approach was used to test this hypothesis in 419 children (M age = 8.92, SD = 0.36). Parents rated children's inhibitory control. Children completed measures of social approach–avoidance motivation and depressive symptoms. Teachers rated children's aggressive behavior. As anticipated, poor inhibitory control predicted aggressive behavior in boys with high but not low approach motivation and low but not high avoidance motivation, whereas poor inhibitory control predicted depressive symptoms in girls with high but not low avoidance motivation. This research supports several complementary theoretical models of psychopathology and provides insight into the differential contributions of poor self-regulation to maladaptive developmental outcomes. The findings suggest the need for targeted intervention programs that consider heterogeneity among children with self-regulatory deficits.

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Highly multiplexed immune profiling throughout adulthood reveals kinetics of lymphocyte infiltration in the aging mouse prostate

10.1101/2020.06.18.160556 ◽

2020 ◽

Author(s):

Jonathan J. Fox ◽

Takao Hashimoto ◽

Héctor I. Navarro ◽

Alejandro J. Garcia ◽

Benjamin L. Shou ◽

...

Keyword(s):

Time Course ◽

Disease Risk ◽

Significant Risk ◽

Significant Risk Factor ◽

Age Related ◽

Mouse Prostate ◽

Kinetics Of ◽

Immune Profiling ◽

Insight Into ◽

Age Related Changes

SUMMARYAging is a significant risk factor for cancer in several tissues, including the prostate. Defining the kinetics of age-related changes in these tissues is critical for identifying regulators of aging and evaluating interventions to slow the aging process and reduce disease risk. An altered microenvironment is characteristic of prostatic aging in mice. Whether features of aging in the prostate emerge predominantly in old age or earlier in adulthood has not previously been established. Using comprehensive immune profiling and time-course analysis, we show that populations of T and B lymphocytes increase in the mouse prostate between 6 and 12 months of age. When comparing the prostate to other urogenital tissues, we found similar features of age-related inflammation in the mouse bladder. In summary, our study offers new insight into the kinetics of prostatic inflammaging and the window when interventions to slow down age-related changes may be most effective.

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Endoscopic Endonasal Repair of Spontaneous Cerebrospinal Fluid Leaks Using Multilayer Composite Graft and Vascularized Pedicled Nasoseptal Flap Technique

Allergy & Rhinology ◽

10.1177/2152656719888622 ◽

2019 ◽

Vol 10 ◽

pp. 215265671988862 ◽

Cited By ~ 3

Author(s):

Natalie Kim-Orden ◽

Jasper Shen ◽

Maya Or ◽

Kevin Hur ◽

Gabriel Zada ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Skull Base ◽

Significant Risk ◽

Significant Risk Factor ◽

Composite Graft ◽

Sinus Surgery ◽

Success Rates ◽

Nasoseptal Flap ◽

Endoscopic Repair ◽

Endoscopic Endonasal

Background Endoscopic repair of cerebrospinal fluid (CSF) fistulas is a fundamental practice in anterior skull base surgery due to high success rates and low morbidity profile. However, spontaneous CSF (sCSF) leaks have the highest recurrence rate compared to other etiologies. The most effective management is undetermined due to variations in graft materials and limited evidence. Objective We present the largest study of a standardized endoscopic repair technique for sCSF leaks. Methods Single-institution retrospective review of patients who underwent endoscopic sCSF leak repair between October 2011 and January 2018. All patients underwent repair using a temporary lumbar drain, intrathecal fluorescein, and multilayer reconstruction using bilayered fascia lata autograft and vascularized nasoseptal flap. Results Twenty patients (100% female, mean age: 53.2 years) with 25 separate sCSF leak sites were included. Obesity was present in 15 of 20 patients (mean body mass index [BMI] = 35.3). No patients had previous sinus surgery. Locations of skull base defects included: cribriform plate (44%), ethmoid (32%), lateral sphenoid (12%), and planum sphenoidale (12%). The mean follow-up was 22.8 months and 92% of the leak sites (23/25) were successfully repaired primarily. There were no neurological complications or cases of meningitis. Two patients (mean BMI = 52) with persistent postoperative CSF leaks and elevated intracranial pressure were successfully managed with ventriculoperitoneal shunt placement. BMI was associated with likelihood of repair failure ( P = .003). Conclusions At our institution, endoscopic repair of sCSF leaks using a composite autograft of fascia and a nasoseptal flap demonstrates high success rates. Elevated BMI was a statistically significant risk factor for revision.

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Ventricular Catheter Tract Hemorrhage as a Risk Factor for Ventriculostomy-Related Infection

Operative Neurosurgery ◽

10.1093/ons/opz148 ◽

2019 ◽

Author(s):

Julie Kim ◽

James Lee ◽

Rui Feng ◽

Alexander Chartrain ◽

Stanislaw Sobotka ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Risk Factor ◽

External Ventricular Drain ◽

Clinical Signs ◽

Significant Risk ◽

Significant Risk Factor ◽

Hospital Length ◽

Hospital Length Of Stay ◽

Ventricular Catheter ◽

Contributing Factors

Abstract BACKGROUND Ventriculostomy-related infection (VRI) is a feared complication of external ventricular drain (EVD) placement. Although many contributing factors to VRI have been examined, little is known whether there is an association between ventriculostomy-related catheter tract hemorrhage (VCTH) and VRI. OBJECTIVE To evaluate risk factors for VRI and assess possible correlations with VCTH. METHODS We performed a retrospective analysis of patients with EVD placement in a neurocritical care unit between 2011 and 2015. VRI was defined as clinical signs of infection with a positive cerebrospinal fluid gram stain and isolation of cerebrospinal fluid culture. VCTH was diagnosed by computed tomography immediately after EVD insertion. RESULTS A total of 247 patients with EVD were identified during the 5-yr study period. An association between VCTH and gram-negative VRI was identified (P = .02). Ten percent (25 of 247 patients) developed a VRI, and 7% (18 of 247 patients) had a VCTH. Of the 25 patients with VRI, 20% (n = 5) had a VCTH, compared to 6% (n = 13) of 222 patients who had an EVD placed but did not develop VRI. There were no significant differences in demographic and clinical factors except for multiple EVD insertions (P < .00001), EVD duration (P < .001), and hospital length of stay (P < .001). CONCLUSION VCTH is a potentially significant risk factor for VRI. Further analysis will be needed to confirm the strength of this association, and to delineate the possible mechanisms by which tract hemorrhage may serve as a nidus for bacterial penetration into the central nervous system.

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Physical Illness and Suicide Risk in Rural Residents of Contemporary China

Crisis ◽

10.1027/0227-5910/a000271 ◽

2014 ◽

Vol 35 (5) ◽

pp. 330-337 ◽

Cited By ~ 14

Author(s):

Cun-Xian Jia ◽

Lin-Lin Wang ◽

Ai-Qiang Xu ◽

Ai-Ying Dai ◽

Ping Qin

Keyword(s):

Risk Factor ◽

Family Income ◽

Rural China ◽

Significant Risk ◽

Significant Risk Factor ◽

Health Condition ◽

Physical Illness ◽

Rural Residents ◽

Increased Risk ◽

Study Population

Background: Physical illness is linked with an increased risk of suicide; however, evidence from China is limited. Aims: To assess the influence of physical illness on risk of suicide among rural residents of China, and to examine the differences in the characteristics of people completing suicide with physical illness from those without physical illness. Method: In all, 200 suicide cases and 200 control subjects, 1:1 pair-matched on sex and age, were included from 25 townships of three randomly selected counties in Shandong Province, China. One informant for each suicide or control subject was interviewed to collect data on the physical health condition and psychological and sociodemographic status. Results: The prevalence of physical illness in suicide cases (63.0%) was significantly higher than that in paired controls (41.0%; χ2 = 19.39, p < .001). Compared with suicide cases without physical illness, people who were physically ill and completed suicide were generally older, less educated, had lower family income, and reported a mental disorder less often. Physical illness denoted a significant risk factor for suicide with an associated odds ratio of 3.23 (95% CI: 1.85–5.62) after adjusted for important covariates. The elevated risk of suicide increased progressively with the number of comorbid illnesses. Cancer, stroke, and a group of illnesses comprising dementia, hemiplegia, and encephalatrophy had a particularly strong effect among the commonly reported diagnoses in this study population. Conclusion: Physical illness is an important risk factor for suicide in rural residents of China. Efforts for suicide prevention are needed and should be integrated with national strategies of health care in rural China.

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Risk factors of poor prognosis and impairment of activities of daily living in patients with hemorrhagic gastroduodenal ulcers

BMC Gastroenterology ◽

10.1186/s12876-020-01580-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Junya Arai ◽

Jun Kato ◽

Nobuo Toda ◽

Ken Kurokawa ◽

Chikako Shibata ◽

...

Keyword(s):

Risk Factors ◽

Activities Of Daily Living ◽

Daily Living ◽

Poor Prognosis ◽

Significant Risk ◽

Care Facility ◽

Significant Risk Factor ◽

Advanced Age ◽

Gastroduodenal Ulcers ◽

Poor Outcomes

Abstract Background Impairment of activities of daily living (ADL) due to hemorrhagic gastroduodenal ulcers (HGU) has rarely been evaluated. We analyzed the risk factors of poor prognosis, including mortality and impairment of ADL, in patients with HGU. Methods In total, 582 patients diagnosed with HGU were retrospectively analyzed. Admission to a care facility or the need for home adaptations during hospitalization were defined as ADL decline. The clinical factors were evaluated: endoscopic features, need for interventional endoscopic procedures, comorbidities, symptoms, and medications. The risk factors of outcomes were examined with multivariate analysis. Results Advanced age (> 75 years) was a significant predictor of poor prognosis, including impairment of ADL. Additional significant risk factors were renal disease (odds ratio [OR] 3.43; 95% confidence interval [CI] 1.44–8.14) for overall mortality, proton pump inhibitor (PPIs) usage prior to hemorrhage (OR 5.80; 95% CI 2.08–16.2), and heart disease (OR 3.05; 95% CI 1.11–8.43) for the impairment of ADL. Analysis of elderly (> 75 years) subjects alone also revealed that use of PPIs prior to hemorrhage was a significant predictor for the impairment of ADL (OR 8.24; 95% CI 2.36–28.7). Conclusion In addition to advanced age, the presence of comorbidities was a risk of poor outcomes in patients with HGU. PPI use prior to hemorrhage was a significant risk factor for the impairment of ADL, both in overall HGU patients and in elderly patients alone. These findings suggest that the current strategy for PPI use needs reconsideration.

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Neurodevelopmental outcome of healthy term newborn with serum bilirubin >15 mg/dl at one year

Journal of Neonatal-Perinatal Medicine ◽

10.3233/npm-200511 ◽

2020 ◽

pp. 1-6

Author(s):

P. Dubey ◽

J. Shrivastava ◽

B.P. Choubey ◽

A. Agrawal ◽

V. Thakur

Keyword(s):

Serum Bilirubin ◽

Tertiary Care ◽

Neurodevelopmental Outcome ◽

Significant Risk ◽

Central India ◽

Significant Risk Factor ◽

Motor Domain ◽

Medical Emergency ◽

One Year ◽

Group 1

BACKGROUND: Neonatal hyperbilirubinemia is a common medical emergency in early neonatal period. Unconjugated bilirubin is neurotoxic and can lead to lifelong neurological sequelae in survivors. OBJECTIVE: To find out the association between serum bilirubin and neurodevelopmental outcome at 1 year of age using Development Assessment Scale for Indian Infants (DASII). METHODS: A prospective cohort study was conducted in the Department of Pediatrics of a tertiary care institution of Central India between January 2018 and August 2019. Total 108 term healthy neonates, with at least one serum bilirubin value of >15 mg/dl, were included. Subjects were divided into three groups based on the serum bilirubin; group 1: (15–20 mg/dl) –85(78.7%) cases, group 2: (20–25 mg/dl) –17(15.7%), and group 3: (>25 mg/dl) –6(5.5%). Developmental assessment was done using DASII at 3, 6, 9, 12 months of age. RESULTS: Out of 108 cases, 101(93.5%) received phototherapy, and 7(6.5%) received double volume exchange transfusion. Severe delay was observed in 5(4.6%) and mild delay in 2(1.9%) cases in the motor domain of DASII at one year. Severe delay in the motor domain was associated with mean TSB of 27.940±2.89 mg/dl and mild delay with mean TSB of 22.75±1.76 mg/dl (p = 0.001). On cluster analysis, delay was observed in locomotion 1 score in 11(13%) cases (p = 0.003) and manipulation score in 6(7.1%) cases in group 1. CONCLUSION: Increased serum bilirubin was a significant risk factor for the delayed neurodevelopment in babies with neonatal jaundice. Even a moderate level of bilirubin significantly affects the developmental outcome.

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Higher premature atrial complex burden from the Holter examination predicts poor cardiovascular outcome

Scientific Reports ◽

10.1038/s41598-021-91800-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ting-Chun Huang ◽

Po-Tseng Lee ◽

Mu-Shiang Huang ◽

Pei-Fang Su ◽

Ping-Yen Liu

Keyword(s):

Risk Factor ◽

Dose Response ◽

Cox Model ◽

Significant Risk ◽

Significant Risk Factor ◽

Cardiovascular Death ◽

Specific Model ◽

Distribution Model ◽

All Cause Mortality ◽

Quartile Group

AbstractPremature atrial complexes (PACs) have been suggested to increase the risk of adverse events. The distribution of PAC burden and its dose–response effects on all-cause mortality and cardiovascular death had not been elucidated clearly. We analyzed 15,893 patients in a medical referral center from July 1st, 2011, to December 31st, 2018. Multivariate regression driven by ln PAC (beats per 24 h plus 1) or quartiles of PAC burden were examined. Older group had higher PAC burden than younger group (p for trend < 0.001), and both genders shared similar PACs distribution. In Cox model, ln PAC remained an independent risk factor for all-cause mortality (hazard ratio (HR) = 1.09 per ln PAC increase, 95% CI = 1.06‒1.12, p < 0.001). PACs were a significant risk factor in cause-specific model (HR = 1.13, 95% CI = 1.05‒1.22, p = 0.001) or sub-distribution model (HR = 1.12, 95% CI = 1.04‒1.21, p = 0.004). In ordinal PAC model, 4th quartile group had significantly higher risk of all-cause mortality than those in 1st quartile group (HR = 1.47, 95% CI = 1.13‒1.94, p = 0.005), but no difference in cardiovascular death were found in competing risk analysis. In subgroup analysis, the risk of high PAC burden was consistently higher than in low-burden group across pre-specified subgroups. In conclusion, PAC burden has a dose response effect on all-cause mortality and cardiovascular death.

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The Role of Past Suicidal Behavior on Current Suicidality: A Retrospective Study in the Israeli Military

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18020649 ◽

2021 ◽

Vol 18 (2) ◽

pp. 649

Author(s):

Leah Shelef ◽

Jessica M Rabbany ◽

Peter M Gutierrez ◽

Ron Kedem ◽

Ariel Ben Yehuda ◽

...

Keyword(s):

Suicide Attempt ◽

Suicidal Behavior ◽

Military Service ◽

Suicide Ideation ◽

Rating Scale ◽

Suicide Attempts ◽

Significant Risk ◽

Significant Risk Factor ◽

Severity Rating ◽

Significant Difference

Past suicide attempts are a significant risk factor for future suicidality. Therefore, the present military-based study examined the past suicidal behavior of soldiers who recently made a severe suicide attempt. Our sample consisted of 65 active-duty soldiers (61.5% males), between the ages of 18 and 28 years old (M = 20.4, SD ± 1.3). The inclusion criterion was a recent severe suicide attempt, requiring at least a 24 h hospitalization. This sample was divided into two groups, according to previous suicidal behavior, namely whether their first suicide attempt was before or after enlistment (n = 25; 38.5% and n = 40; 61.5%, respectively). We then examined the lethality and intent of the recent event in regard to this division. Four measures were used to assess the subjects’ suicidal characteristics: the Columbia Suicide Severity Rating Scale, the Self-Harm Behavior Questionnaire, the Suicidal Behaviors Questionnaire-Revised, and the Beck Scale for Suicide Ideation. No significant difference in the severity of the suicide attempts (either actual or potential severity) were found between those who had suicide attempts before enlistment and those who had their first attempt in the service. As a matter of fact, most of the suicide attempts that occurred for the first time during military service had used a violent method (58.3%, n = 21). Finally, using multivariate analyses, we found that current thoughts and behavior, rather than past suicidality, was the strongest predictor for the lethality of suicide attempts.

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Comparison of plasma and cerebrospinal fluid proteomes identifies gene products guiding adult neurogenesis and neural differentiation in birds

Scientific Reports ◽

10.1038/s41598-021-84274-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Eleni Voukali ◽

Nithya Kuttiyarthu Veetil ◽

Pavel Němec ◽

Pavel Stopka ◽

Michal Vinkler

Keyword(s):

Cerebrospinal Fluid ◽

Adult Neurogenesis ◽

Neural Development ◽

Neural Differentiation ◽

Csf Proteins ◽

Nymphicus Hollandicus ◽

Liquid Chromatography Tandem Mass ◽

Genome Information ◽

Insight Into ◽

Brain Homeostasis

AbstractCerebrospinal fluid (CSF) proteins regulate neurogenesis, brain homeostasis and participate in signalling during neuroinflammation. Even though birds represent valuable models for constitutive adult neurogenesis, current proteomic studies of the avian CSF are limited to chicken embryos. Here we use liquid chromatography–tandem mass spectrometry (nLC-MS/MS) to explore the proteomic composition of CSF and plasma in adult chickens (Gallus gallus) and evolutionarily derived parrots: budgerigar (Melopsittacus undulatus) and cockatiel (Nymphicus hollandicus). Because cockatiel lacks a complete genome information, we compared the cross-species protein identifications using the reference proteomes of three model avian species: chicken, budgerigar and zebra finch (Taeniopygia guttata) and found the highest identification rates when mapping against the phylogenetically closest species, the budgerigar. In total, we identified 483, 641 and 458 unique proteins consistently represented in the CSF and plasma of all chicken, budgerigar and cockatiel conspecifics, respectively. Comparative pathways analyses of CSF and blood plasma then indicated clusters of proteins involved in neurogenesis, neural development and neural differentiation overrepresented in CSF in each species. This study provides the first insight into the proteomics of adult avian CSF and plasma and brings novel evidence supporting the adult neurogenesis in birds.

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