Assessment of the microvasculature in poppers maculopathy.

PURPOSE: To investigate a possible microvascular component of poppers maculopathy (PMP) using optical coherence tomography angiography (OCTA). METHODS: Twelve patients suffering from poppers maculopathy were included. Health records, optical coherence tomography (OCT), and OCTA data was gathered and compared to a healthy control group (HC). PMP lesion type was determined by manifestation in OCT. OCTA-based evaluation of retinal vascular plexus and choriocapillaris (CC) was executed. Vessel density (VD) and vessel length density (VLD) in superficial and deep capillary plexus (SCP, DCP), as well as flow deficits (FD), within the foveal avascular zone (FAZ) in CC were assessed. RESULTS: Median age of PMP patients was 40 (min 24; max 64) years, all male. Eleven patients presented with ellipsoid zone-type lesions; one patient showed a vitelliform-type lesion. No qualitative microvascular changes between PMP patients and HC were identified. Quantitative values for VD and VLD of SCP and DCP did not differ in between the two groups. The analysis of FDs in CC showed no deviation from PMP patients to HC. CONCLUSIONS: No vascular anomalies in qualitative and quantitative analysis in OCTA were detected in PMP patients. The constitution of the CC within FAZ of PMP patients does not differ from HC when assessed as FD.

Non-invasive measurement of renal perfusion and oxygen metabolism to predict postoperative acute kidney injury in neonates and infants after cardiopulmonary bypass surgery.

BACKGROUND: The pathophysiology of acute kidney injury (AKI) after cardiopulmonary bypass surgery for congenital heart disease is not completely understood. The aim of this study was to carry out a prospective analysis of the diagnostic value of non-invasive monitoring of renal oxygenation and microcirculation by combining laser Doppler flowmetry and tissue spectrometry. METHODS: In 50 neonates and infants who underwent repair (n = 31) or neonatal palliation (n = 19) of congenital heart disease with cardiopulmonary bypass, renal oxygenation, and microcirculatory flow, the approximate renal metabolic rate of oxygen and Doppler-based renal resistive index were determined after surgery. Correlations between these parameters and the occurrence of AKI according to the Pediatric Risk, Injury, Failure, Loss, End Stage Renal Disease criteria were investigated. RESULTS: Acute kidney injury occurred in 45% of patients after repair and in 32% after palliation. Renal oxygenation was significantly lower and the approximate renal metabolic rate of oxygen significantly higher in patients with AKI (P < 0.05). The microcirculatory flow was significantly higher in patients with AKI after neonatal palliation (P < 0.05), whereas renal resistive index was significantly higher in patients with AKI after repair (P < 0.05). The sensitivity of renal oxygenation, metabolic rate of oxygen, microcirculation, and resistive index in predicting AKI was 78-80, 73-78, 64-83, and 71-74%, respectively, with a specificity of 63-65, 54-75, 64-78, and 46-74% (area under the curve: 0.73-0.75, 0.68-0.83, 0.52-0.68, and 0.60-0.75), respectively. CONCLUSIONS: Monitoring of renal oxygen metabolism allows early prediction of AKI in infants after cardiac surgery. In contrast, renal resistive index does not allow prediction of AKI after neonatal palliation with aortopulmonary shunt establishment.

[Loneliness trends in the second half of life: results from the German Ageing Survey (DEAS)]. / Einsamkeittrends in der zweiten Lebenshälfte : Befunde aus dem Deutschen Alterssurvey (DEAS).

UNLABELLED: BACKGROUND AND RESEARCH QUESTIONS: In the current paper, it is analyzed whether the extent of loneliness of adults in the second half of their lives has changed between 1996 and 2008 in Germany. Because patterns of objective social integration have evolved differently in different birth cohorts (familial integration in earlier birth cohorts more fragile, more solid in later birth cohorts), we expected different trends in the extent of loneliness in different birth cohorts. DESIGN AND METHODS: The three waves of the German Ageing Survey (DEAS) constitute the database for the analysis: 1996 (n = 3,979), 2002 (n = 2,766) and 2008 (n = 4,392). Loneliness was measured with the de Jong Gierveld Loneliness Scale. The German Ageing Survey (DEAS) is a nationwide representative survey of the German population aged 40-85 years. RESULTS: Only a minority of people report being very lonely in the second part of life. Between 1996 and 2008, there is a positive trend in the extent of loneliness in the second half of life, i.e., the prevalence of loneliness decreased during this period of time. From 1996 to 2008, the youngest respondents (40-54 years of age) and the middle aged respondents (55-69 years) demonstrated a decline from 1996 to 2002 followed by an increase in loneliness between 2002 and 2008. The oldest respondents (70-85 years of age) experienced a steady decline in loneliness. Gender differences (men are somewhat lonelier than women) remain stable between 1996 and 2008. DISCUSSION AND CONCLUSION: While people who are currently old are socially well integrated and, hence, experience loneliness only to a small degree, there is a higher risk for persons who are currently in middle adulthood because their social networks have become increasingly more fragile. Further changes have to be observed.

[Very old age in an ageing society. Theoretical challenges, empirical problems and sociopolitical responsibilities]. / Hochaltrigkeit in der Gesellschaft des langen Lebens. Theoretische Herausforderung, empirisches Problem und sozialpolitische Aufgabe.

This paper focuses on very old age as a challenge for ageing theory, as an empirical problem and as a scope for social policy and it introduces the contributions of the special issue "Very old age in an ageing society". Especially the need for (re-)integration of the life-phases of young and old age is discussed from the position of social and behavioural ageing research. While reaching very old age is an increasingly normal life-event, and thus there is an increasing need for knowledge, there is currently only limited knowledge about it. It is particularly the diversity and inequality within old and very old age and the pathways into latest life that needs to be targeted. Finally, normative patterns and biographical outlines of this increasingly important phase of life need to be developed.

A Novel Quantitative Assessment Method of Disease Activity in Susac's Syndrome Based on Ultra-Wide Field Imaging.

PURPOSE: Susac's syndrome (ScS) is a rare, potentially life-threatening auto-immune disease. Ophthalmic imaging can depict characteristic branch retinal arteriolar occlusions (BRAO) and arterial wall hyperfluorescences that form one of the three diagnostic pillars of this condition. We aim to demonstrate that ophthalmological ultrawide-field (UWF) imaging allows for a qualitative and quantitative assessment in ScS, with application in diagnostics, monitoring of treatment response, and titration of therapy. METHODS: In seven ScS patients (♀:♂ = 2:5), with a median age of 36 years, range 18 to 57 years, serial ultrawide-field fluoresceine angiography (UWF-FA) studies were performed, with adjunctive wide-field optical coherence tomography angiography analyses (WF-OCTA) in five patients. Mean follow-up was 12.5 months, range 1 to 46 months. RESULTS: In all seven patients, BRAO and arterial wall hyperfluorescences were present in UWF-FA and calculated as a quantitative score of disease activity in fluorescein angiography (DA-FA) during follow-up visits. Treatment response was accessible in follow-up imaging as partial reperfusion of retinal vessels, resolution of arterial wall hyperfluorescences and consequently, in reduction of DA-FA score. While qualitative analysis of WF-OCTA provided further information about retinal micro-perfusion, quantitative analysis did not demonstrate a vectored treatment response as it was accessible in FA. CONCLUSION: DA-FA score, as a comprehensive disease activity parameter in ScS has potential to facilitate optimal communication between subspecialties and thereby treatment success.

[Theories on aging and health: what do aging and old age mean and what constitutes a good life in old age?]. / Theorien zu Alter(n) und Gesundheit: Was bedeuten Alterwerden und Altsein und was macht ein gutes Leben im Alter aus?

The present paper starts by introducing different perspectives of the aging process and includes biological, psychological, and sociological theories in its scope. The article addresses the issue of when "old age" begins and why a distinction is made between the third and fourth age. With increasing age, it becomes more and more difficult to differentiate between health-related losses due to illnesses or to aging. However, this can be important with respect to health behavior and health care. Having the best possible health in old age is an important factor for a good life in old age. Over their whole lives, from childhood to old age, people can actively contribute to their health in old age. But health is not the sole criterion for a good life in old age. Having interests and aims are just as important as being integrated in a social network. In old age, people often differ greatly and this is why there is such variety in what people consider to constitute a good life for themselves in old age.

Functional annotation of genomic data with metabolic inference.

Metabolomics is an appealing new approach in systems biology aimed at enabling an improved understanding of the dynamic biochemical composition of living systems. Biological systems are remarkably complex. Importantly, metabolites are the end products of cellular regulatory processes, and their concentrations reflect the ultimate response of a biological system to genetic or environmental changes. In this article, we describe the components of lipid metabolomics and then use them to investigate the metabolic basis for increased abdominal adiposity in 2 strains of divergently selected chickens. Lipid metabolomics were chosen due to the availability of well-developed analytical platforms and the pervasive physiological importance of lipids in metabolism. The analysis suggests that metabolic shifts that result in increased abdominal adiposity are not universal and vary with genetic background. Metabolomics can be used to reverse engineer selection programs through superior metabolic descriptions that can then be associated with specific gene networks and transcriptional profiles.

Long-term changes of markers of alcoholism after orthotopic liver transplantation (OLT).

Both physical rehabilitation and the course of the alcoholism improve after orthotopic liver transplantation (OLT) in patients with end-stage alcoholic liver cirrhosis. In the present study including 17 alcoholics and 14 nonalcoholics, after OLT, three of the alcoholic patients resumed their pre-OLT alcohol drinking habits, 4 consumed alcohol occasionally, 10 remained abstinent over the observation period of 13 to 36 months. The laboratory parameters before OLT did not discriminate alcoholics from nonalcoholic patients. Furthermore, the blood levels of two so-called alcogens (harman and norharman) were determined to investigate whether they discriminate between the two groups. Alcogens are natural compounds that are presumed to induce alcohol abuse in predisposed individuals. Both alcogens measured were elevated in plasma from nonalcoholics and alcoholics before OLT, suggesting a disturbance in inactivation in end-stage liver disease. Following OLT, the alcogens normalized but in the alcoholics this process was slower with respect to harman. The present exploratory study suggests that the normalized metabolic capacity of the liver after OLT causes a normalization of the levels of alcogens, for which harman and norharman are representative. These changes could contribute to the observed benefit to the outcome in alcoholics with respect to the alcohol dependence.

Motor unit recruitment when neuromuscular electrical stimulation is applied over a nerve trunk compared with a muscle belly: quadriceps femoris.

Neuromuscular electrical stimulation (NMES) can be delivered over a nerve trunk or muscle belly and both can generate contractions through peripheral and central pathways. Generating contractions through peripheral pathways is associated with a nonphysiological motor unit recruitment order, which may limit the efficacy of NMES rehabilitation. Presently, we compared recruitment through peripheral and central pathways for contractions of the knee extensors evoked by NMES applied over the femoral nerve vs. the quadriceps muscle. NMES was delivered to evoke 10 and 20% of maximum voluntary isometric contraction torque 2-3 s into the NMES (time(1)) in two patterns: 1) constant frequency (15 Hz for 8 s); and 2) step frequency (15-100-15 Hz and 25-100-25 Hz for 3-2-3 s, respectively). Torque and electromyographic activity recorded from vastus lateralis and medialis were quantified at the beginning (time(1)) and end (time(2); 6-7 s into the NMES) of each pattern. M-waves (peripheral pathway), H-reflexes, and asynchronous activity (central pathways) during NMES were quantified. Torque did not differ regardless of NMES location, pattern, or time. For both muscles, M-waves were ∼7-10 times smaller and H-reflexes ∼8-9 times larger during NMES over the nerve compared with over the muscle. However, unlike muscles studied previously, neither torque nor activity through central pathways were augmented following 100 Hz NMES, nor was any asynchronous activity evoked during NMES at either location. The coefficient of variation was also quantified at time(2) to determine the consistency of each dependent measure between three consecutive contractions. Torque, M-waves, and H-reflexes were most variable during NMES over the nerve. In summary, NMES over the nerve produced contractions with the greatest recruitment through central pathways; however, considering some of the limitations of NMES over the femoral nerve, it may be considered a good complement to, as opposed to a replacement for, NMES over the quadriceps muscle for maintaining muscle quality and reducing contraction fatigue during NMES rehabilitation.

Plasma fatty acid profiles in autism: a case-control study.

Increasing evidence is mounting in support of fatty acid metabolism playing a role in neurodevelopmental disorders such as autism. In order to definitely determine whether fatty acid concentrations were associated with autism, we quantitatively measured 30 fatty acids from seven lipid classes in plasma from a large subset of subjects enrolled in the Childhood Autism Risk from Genetics and the Environment (CHARGE) study. The CHARGE study is a large, population-based case-control study on children aged 2-5 born in California. Our subset consisted of 153 children with autism and 97 developmentally normal controls. Results showed that docosahexaenoic acid (DHA, 22:6n-3) was significantly decreased in phosphatidylethanolamine. Dimethyl acetals were significantly decreased in phosphatidylethanolamine and phosphatidylcholine as well. These results are consistent with the only other study to measure dimethyl acetals in children with autism, and suggest that the function of peroxisomes and the enzymes of the peroxisome involved with fatty acid metabolism may be affected in autism.

Extracellular calcium depletion as a mechanism of short-term synaptic depression.

Recent experiments have demonstrated that normal neural activity can cause significant decrements in external calcium levels, and that these decrements mediate a form of short-term synaptic depression. These findings raise the possibility that certain forms of short-term synaptic depression at glutamatergic synapses throughout the mammalian CNS may be influenced by similar changes in external calcium. We use a computational model of the extracellular space, combined with experimental data on calcium consumption, to show that such short-term depression can be accounted for by changes in calcium just outside active synapses, provided that external calcium diffusion is restricted. Remarkably, the model suggests the novel possibility that synapses may possess private pools of external calcium that enforce some forms of short-term depression in a synapse-specific manner.

Dendritic spikes and their influence on extracellular calcium signaling.

Extracellular calcium is critical for many neural functions, including neurotransmission, cell adhesion, and neural plasticity. Experiments have shown that normal neural activity is associated with changes in extracellular calcium, which has motivated recent computational work that employs such fluctuations in an information-bearing role. This possibility suggests that a new style of computing is taking place in the mammalian brain in addition to current 'circuit' models that use only neurons and connections. Previous computational models of rapid external calcium changes used only rough approximations of calcium channel dynamics to compute the expected calcium decrements in the extracellular space. Using realistic calcium channel models, experimentally measured back-propagating action potentials, and a model of the extracellular space, we computed the fluctuations in external calcium that accrue during neural activity. In this realistic setting, we showed that rapid, significant changes in local external calcium can occur when dendrites are invaded by back-propagating spikes, even in the presence of an extracellular calcium buffer. We further showed how different geometric arrangements of calcium channels or dendrites prolong or amplify these fluctuations. Finally, we computed the influence of experimentally measured synaptic input on peridendritic calcium fluctuations. Remarkably, appropriately timed synaptic input can amplify significantly the decrement in external calcium. The model shows that the extracellular space and the calcium channels that access it provide a medium that naturally integrates coincident spike activity from different dendrites that intersect the same tissue volume.

Impact of hypertension guideline implementation on blood pressure control and drug use in primary care clinics.

BACKGROUND: A worsening of blood pressure control has occurred in the 1990s despite the availability of sophisticated technologic, pharmacologic, and educational advances applicable to hypertension care. Clinical guidelines that are intended to improve hypertension care by making specific recommendations on drug use, frequency of follow-up care, and target levels of blood pressure have been developed. METHODS: The Institute for Clinical Systems Integration's (ICSI's; Minneapolis) Hypertension Treatment Guideline was developed in 1994 and is updated annually. This study employed a quasi-experimental, before-and-after design at two medical groups to assess changes in the care provided to patients 18 years of age and older with identified hypertension (International Classification of Diseases-9 codes 401.0, 401.1, or 401.9). RESULTS: Among adults with hypertension, the proportion meeting the blood pressure goal of < 140/90 mm Hg increased from 36.8% (of 685 patients) preguideline to 50.3% (of 928 patients) postguideline (chi-square = 29.4, p < 0.001); the mean arterial pressure decreased from 102.7 mm Hg to 99.4 mm Hg (t = 5.45, p < 0.001). Cohort analysis of patients enrolled at both points in time confirmed these findings and showed an increase in the number of office visits from 5.4 to 6.7 visits per patient per year after guideline implementation (F = 10.9, p = 0.001). The use of a guideline-recommended medication for treatment of blood pressure was 35.9% preguideline and 36.2% postguideline. CONCLUSIONS: Implementation of a hypertension treatment guideline in primary care clinics was related to significantly improved hypertension control. Identification, tracking, and active outreach to patients with hypertension were used by all clinics.