Ein Neues Verfahren zur Messung der Bakteriziden Fähigkeit des Vollblutes

Das oben erwahnte Verfahren hat vor den anderen Methoden besonders die Vorzuge, 1) da&#946; man dadurch zu einem sicheren Resultat gelangen und gleichzeitig auch jedes Datum mit exakten Ziffern zum Ausdruck bringen kann, 2) da&#946; bei diesem Verfahren keineswegs erforderlich ist, eine bestimmte Anzahl von Keimen einschlie&#946;ende Bakterienaufschwemmung herzusteHen und auch Kontrollversuch anzustellen, 3) da&#946; es von den Fehlern des Mischverhaltnisses zwischen der Bakterienlosung und dem Blut nicht so erheblich beeinflu&#946;t wird, und 4) da&#946; man durch dieses Verfahren gleichzeitig mehrere bakterientotende Faktoren untersuchen kann. Ferner hat dieses Verfahren auch den Vorzug, da&#946; es praktisch sehr einfach auszufuhren ist und nur 6 Stunden nach der Blutentnahme bereits das Ergebnis liefert. Es gestattet ferner, die bakterizide Kraft des Blutes gleichzeitig bei 6 - 8 Menschen zu untersuchen, was mich zur Uberzeugung fuhrt, da&#946; es in der Klinik hochgeschatzt werden wird. Auch das Verfahren und die ebenfalls vom mir aufgestellte Formel zur zusammenfassenden Beurteilung kann man nach meinem Erachten durch entsprechende Veranderungen einiger Faktoren ohne jede Schwierigkeiten auch fur andere Bakterienarten anwenden. Man wird wohl gegen eine einzige Lucke dieses Verfahrens, da&#946; die mikroskopische Untersuchung und die Berechnung allzu verwickelt zu sein scheint, Einwand erheben, eine Lucke, zu deren Schlu&#946; jedoch nur eine kurzfristige Ubung erfordert wird, durch welche die mikroskopische Untersuchung innerhalb 30 Minuten, die Berechnung nur in 5 Minuten vollendet werden kann. (Zur Berechnung bedarf es einer Gauss'schen Logarithmentafel.) Obgleich das geschilderte Verfahren noch viele, genauere Prufungen erheischende Punkte in sich einschlie&#946;t, mu&#946; es hier, wenn auch in Grundzugen, jetzt schon angefuhrt werden,. da ich der festen Uberzeugung bin, da&#946; es im Vergleich zu den bisherigen Methoden ein dem wirklichen Wert der Bakterizidie des Vollblutes im lebenden Organismus viel naheres Resultat liefert.</p

Thigh-Derived Inertial Sensor Metrics to Assess the Sit-to-Stand and Stand-to-Sit Transitions in the Timed Up and Go (TUG) Task for Quantifying Mobility Impairment in Multiple Sclerosis

INTRODUCTION: Inertial sensors generate objective and sensitive metrics of movement disability that may indicate fall risk in many clinical conditions including multiple sclerosis (MS). The Timed-Up-And-Go (TUG) task is used to assess patient mobility because it incorporates clinically-relevant submovements during standing. Most sensor-based TUG research has focused on the placement of sensors at the spine, hip or ankles; an examination of thigh activity in TUG in multiple sclerosis is wanting. METHODS: We used validated sensors (x-IMU by x-io) to derive transparent metrics for the sit-to-stand (SI-ST) transition and the stand-to-sit (ST-SI) transition of TUG, and compared effect sizes for metrics from inertial sensors on the thighs to effect sizes for metrics from a sensor placed at the L3 level of the lumbar spine. 23 healthy volunteers were compared to 17 ambulatory persons with MS (PwMS, HAI <= 2). RESULTS: During the SI-ST transition, the metric with the largest effect size comparing healthy volunteers to PwMS was the Area Under the Curve of the thigh angular velocity in the pitch direction -- representing both thigh and knee extension; the peak of the spine pitch angular velocity during SI-ST also had a large effect size, as did some temporal measures of duration of SI-ST, although less so. During the ST-SI transition the metric with the largest effect size in PwMS was the peak of the spine angular velocity curve in the roll direction. A regression was performed. DISCUSSION: We propose for PwMS that the diminished peak angular velocities during SI-ST directly represents extensor weakness, while the increased roll during ST-SI represents diminished postural control. CONCLUSIONS: During the SI-ST transition of TUG, angular velocities can discriminate between healthy volunteers and ambulatory PwMS better than temporal features. Sensor placement on the thighs provides additional discrimination compared to sensor placement at the lumbar spine

Using wearable inertial sensors to compare different versions of the dual task paradigm during walking

The dual task paradigm (DTP), where performance of a walking task co-occurs with a cognitive task to assess performance decrement, has been controversially mooted as a more suitable task to test safety from falls in outdoor and urban environments than simple walking in a hospital corridor. There are a variety of different cognitive tasks that have been used in the DTP, and we wanted to assess the use of a secondary task that requires mental tracking (the alternate letter alphabet task) against a more automatic working memory task (counting backward by ones). In this study we validated the x-io x-IMU wearable inertial sensors, used them to record healthy walking, and then used dynamic time warping to assess the elements of the gait cycle. In the timed 25 foot walk (T25FW) the alternate letter alphabet task lengthened the stride time significantly compared to ordinary walking, while counting backward did not. We conclude that adding a mental tracking task in a DTP will elicit performance decrement in healthy volunteers

Lingering delays in a go/no-go task: mind wandering delays thought probes reliably but not reaction times

BACKGROUND: In a go/no-go task, changes to the inter-trial interval (ITI) or the press percentage (PP) are known to have decelerating effects on both reaction time and on thought probe response time. The mental causes of these delays remain obscure. AIMS: To see whether the delaying effects of ITI and PP are additive, and to determine whether these timing effects are linked with mental states detectable by subjective ratings. METHODS: An 18-minute online experiment with 60 participants who each performed 8 versions of the ToVA with different ITIs and PPs. At the end of each block were mind wandering (MW) thought probes and rating scales for subjective effort and awareness. RESULTS: The decelerating effects of long ITIs, low PPs, and MW seem to be synergistic, but the effects of individual factors on thought probes seem brittle. A version of the ToVA with zero no-go-stimuli spontaneously and implicitly accelerated mean reaction time significantly. That version also quickened three subsequent response times for rating tasks by hundreds of milliseconds, which suggests that the basis of this effect is a lingering mental state (or substrate). None of the subjective ratings measured were strongly related to the reaction time delay, although MW seems to delay the thought probe response. CONCLUSION: The strategic effect on both the reaction time and the thought probe response time is presumably a change in the speed-accuracy trade-off in which the participant adopts a mental strategy that speeds up thinking by reducing caution, so caution needs to be subjectively measured

Intentional mind wandering is objectively linked to low effort and tasks with high predictability

BACKGROUND: Intentional Mind Wandering (IMW) is proposed to be a low executive control state in response to boredom, to distinguish it from unintentional mind wandering (UMW), which may be a low arousal state in response to exhaustion of resources. AIMS: To demonstrate that the objective differences between IMW and UMW reflect the subjective difference that IMW is linked to a low effort and high predictability strategy. METHODS: The metronome response task (MRT) requires participants to predict when the next tone in a regular series will occur. Inter-Trial Interval (ITI) variants of the MRT were presented in blocks of ∼ 90 seconds. RESULTS: The most predictable version of MRT resulted in the percentage of reported IMW doubling, whereas UMW remained similar in all three versions of the MRT. IMW necessitates subjective effort to be low (capped at 5 on a 1-9 scale). IMW in easy and predictable versions of the task resulted in normal performance, whereas IMW during difficult tasks that required sustained attention led to poor performance and occasional errors. IMW during the least predictable MRT led to a significantly higher rate of omission errors (compared to on-task or UMW), and also to a higher maximum-in-block reaction time, as predicted by the worst performance rule. Conscientiousness was linked to reduced IMW (but not reduced UMW), higher on-task probes, increased effort, and improved prediction accuracy. CONCLUSIONS: Subjective assessment of task difficulty predisposes IMW, with transient increases of both omission errors and slow lapses due to diminished allocation of cognitive resources

Randomized Dose-Ranging Controlled Trial of AQ-13, a Candidate Antimalarial, and Chloroquine in Healthy Volunteers

OBJECTIVES: To determine: (1) the pharmacokinetics and safety of an investigational aminoquinoline active against multidrug–resistant malaria parasites (AQ-13), including its effects on the QT interval, and (2) whether it has pharmacokinetic and safety profiles similar to chloroquine (CQ) in humans. DESIGN: Phase I double-blind, randomized controlled trials to compare AQ-13 and CQ in healthy volunteers. Randomizations were performed at each step after completion of the previous dose. SETTING: Tulane–Louisiana State University–Charity Hospital General Clinical Research Center in New Orleans. PARTICIPANTS: 126 healthy adults 21–45 years of age. INTERVENTIONS: 10, 100, 300, 600, and 1,500 mg oral doses of CQ base in comparison with equivalent doses of AQ-13. OUTCOME MEASURES: Clinical and laboratory adverse events (AEs), pharmacokinetic parameters, and QT prolongation. RESULTS: No hematologic, hepatic, renal, or other organ toxicity was observed with AQ-13 or CQ at any dose tested. Headache, lightheadedness/dizziness, and gastrointestinal (GI) tract–related symptoms were the most common AEs. Although symptoms were more frequent with AQ-13, the numbers of volunteers who experienced symptoms with AQ-13 and CQ were similar (for AQ-13 and CQ, respectively: headache, 17/63 and 10/63, p = 0.2; lightheadedness/dizziness, 11/63 and 8/63, p = 0.6; GI symptoms, 14/63 and 13/63; p = 0.9). Both AQ-13 and CQ exhibited linear pharmacokinetics. However, AQ-13 was cleared more rapidly than CQ (respectively, median oral clearance 14.0–14.7 l/h versus 9.5–11.3 l/h; p ≤ 0.03). QTc prolongation was greater with CQ than AQ-13 (CQ: mean increase of 28 ms; 95% confidence interval [CI], 18 to 38 ms, versus AQ-13: mean increase of 10 ms; 95% CI, 2 to 17 ms; p = 0.01). There were no arrhythmias or other cardiac AEs with either AQ-13 or CQ. CONCLUSIONS: These studies revealed minimal differences in toxicity between AQ-13 and CQ, and similar linear pharmacokinetics

Mutations involving the SRY-related gene SOX8 are associated with a spectrum of human reproductive anomalies

SOX8 is an HMG-box transcription factor closely related to SRY and SOX9. Deletion of the gene encoding Sox8 in mice causes reproductive dysfunction but the role of SOX8 in humans is unknown. Here, we show that SOX8 is expressed in the somatic cells of the early developing gonad in the human and influences human sex-determination. We identified two individuals with 46,XY disorders/differences in sex development (DSD) and chromosomal rearrangements encompassing the SOX8 locus and a third individual with 46,XY DSD and a missense mutation in the HMG-box of SOX8. In-vitro functional assays indicate that this mutation alters the biological activity of the protein. As an emerging body of evidence suggests that DSDs and infertility can have common etiologies, we also analyzed SOX8 in a cohort of infertile men (n = 274) and two independent cohorts of women with primary ovarian insufficiency (POI; n = 153 and n = 104). SOX8 mutations were found at increased frequency in oligozoospermic men (3.5%; p<0.05) and POI (5.06%; p=4.5x10-5) as compared to fertile/normospermic control populations (0.74%). The mutant proteins identified altered SOX8 biological activity as compared to the wild-type protein. These data demonstrate that SOX8 plays an important role in human reproduction and SOX8 mutations contribute to a spectrum of phenotypes including 46,XY DSD, male infertility and 46,XX POI

Mutations involving the SRY-related gene SOX8 are associated with a spectrum of human reproductive anomalies.

© The Author(s) 2018. Published by Oxford University Press. All rights reserved. SOX8 is an HMG-box transcription factor closely related to SRY and SOX9. Deletion of the gene encoding Sox8 in mice causes reproductive dysfunction but the role of SOX8 in humans is unknown. Here, we show that SOX8 is expressed in the somatic cells of the early developing gonad in the human and influences human sex determination. We identified two individuals with 46, XY disorders/differences in sex development (DSD) and chromosomal rearrangements encompassing the SOX8 locus and a third individual with 46, XY DSD and a missense mutation in the HMG-box of SOX8. In vitro functional assays indicate that this mutation alters the biological activity of the protein. As an emerging body of evidence suggests that DSDs and infertility can have common etiologies, we also analysed SOX8 in a cohort of infertile men (n=274) and two independent cohorts of women with primary ovarian insufficiency (POI; n=153 and n=104). SOX8 mutations were found at increased frequency in oligozoospermic men (3.5%; P < 0.05) and POI (5.06%; P=4.5×10 -5 ) as compared with fertile/normospermic control populations (0.74%). The mutant proteins identified altered SOX8 biological activity as compared with the wild-type protein. These data demonstrate that SOX8 plays an important role in human reproduction and SOX8 mutations contribute to a spectrum of phenotypes including 46, XY DSD, male infertility and 46, XX POI.Link_to_subscribed_fulltex