Phase Marker Research Articles

Диагностические маркеры ранней фазы острого нарушения мозгового кровообращения у лиц с КТ-негативными данными инфаркта

Диагностические маркеры ранней фазы острого нарушения мозгового кровообращения у лиц с КТ-негативными данными инфаркта

Chip-based serum proteomics approach to reveal the potential protein markers in the sub-acute stroke patients receiving the treatment of Ginkgo Diterpene Lactone Meglumine Injection

Ethnopharmacological relevanceGinkgo biloba L. is a kind of traditional Chinese medicinal material with a long history. Its main active ingredients, ginkgolides, can be used for the treatment of stroke and other cardio-cerebrovascular diseases. Ginkgo Diterpene Lactone Meglumine Injection (GDLI), a modernized TCM, has attracted much attention because of its neuroprotective and anti-inflammatory properties.Aim of the study: To uncover the effects of GDLI on ischemic stroke patients, as well as the underlying biomarkers involved in sub-acute stroke. Materials and methodsWe used a state-of-the-art targeted proteomics chip to investigate the association between numerous serum proteins (1101 proteins) and the sub-acute phase post-ischemic stroke. Then, the relative proteins of anti-apoptosis, anticoagulant, and neuroprotection of GDLI were verified in animal models. ResultsCompared with the serum from healthy volunteers, we identified 15 up-regulated proteins and 26 down-regulated proteins (FC ≥ 1.5) involved in inflammatory response, immune response, and nervous system development in the sub-acute ischemic stroke. The pro-inflammatory proteins, such as IL17, MSP-R, G–CSF–R, TLR3, MIP-3β, TNFRSF19, and TNFRSF12, were significantly increased in serum, illustrating that the chronic inflammatory state was evident in the sub-acute stage of ischemic stroke. However, the common pro-inflammatory proteins, such as IL-1β, IL-6, IL-8, TNF-α, IFN-γ, and IL-10, known to be up-regulated in acute stroke, had close or lightly lower levels than healthy humans (FC ≥ 1.5, P > 0.05). And some cytokines (IL3, CCL13, TNFRSF3, IL10 R beta, HLA-A, IL-1 F8/FIL1 eta, TNFRSF8, CCL18) were also markedly down-regulated in the sub-acute phase of stroke. These proteins are highly associated with the onset of stroke-induced immunosuppression and post-stroke infection. Moreover, we noticed that Ginkgo Diterpene Lactone Meglumine Injection (GDLI) treatment for 14 days was helpful to the recovery of patients in the subacute period. After the treatment of GDLI, it was observed that several inflammatory cytokines (i.e. IL-17 and IL-28A), chemokine (i.e. CCL14), and Coagulation Factor III were reduced. Meanwhile, the anti-inflammatory cytokines (IL-10 R alpha, GREMLIN, and Activin C) and neurotrophic factors (Neurturin and IGFBP2) were found to be up-regulated in stroke patients through self-control observation. Finally, we identified the IGFBP2 as a novel marker in the animal models. ConclusionsIn summary, the potential markers in sub-acute stroke patients were highly different from known protein markers in the acute phase of ischemic stroke. The serum protein IGFBP2 could be novel biomarkers for the treatment of GDLI in sub-acute stroke patients. Our present findings provide an innovative insight into the novel treatment of GDLI in ischemic stroke therapy.

Akut Gastroenteritli Çocuklarda Etkenlere Göre Klinik ve Laboratuvar Bulgularının Karşılaştırılması

Amaç: Akut Gastroenteritler (AGE) çocukluk çağının sık görülen enfeksiyonlarındandır. Çalışmamızın amacı AGE tanısıyla kliniğe yatırılan vakaların klinik bulgularını ve laboratuvar değerlerini incelemektir. Gereç ve Yöntem: Çalışmamıza kliniğimizde Ocak 2016 ve Ocak 2019 tarihleri arasında AGE tanısıyla yatan 0-17 yaş aralığında, ishali 14 gün veya daha kısa süreli olan 130 hasta alındı. Hastalar, etkenlere göre paraziter ve viral AGE’li olmak üzere iki gruba ayrıldı. Hastaların demografik, laboratuvar ve klinik verileri hasta dosyalarından elde edildi ve istatistiksel incelemeleri yapıldı. Bulgular: Çalışmaya alınan 130 hastanın 47’si paraziter 83’ü viral AGE grubunda idi. Gruplar arasında cinsiyet farkı yokken viral AGE grubunda yaş ortalaması düşük bulundu (p<0.001). Viral AGE grubunda ishal süresi daha uzun ve kusma daha fazla idi (p=0,031, p=0,02, sırasıyla). Paraziter AGE en çok yaz, viral AGE en çok kış mevsiminde görüldü (p=0,01). İshal süresi yatış gün sayısı ile pozitif yönde korele iken (p<0,001, r=0,656) ortalama platelet hacmi, nötrofil sayısı ve C-reaktif protein ile negatif yönde korele idi (p=0,01, r=-0,21, p=0,02, r=-0,193, p=0,01, r=-0,209, sırasıyla). Sonuç: Viral gastroenteritlerde hastanede yatış süresinin, ishal süresinin ve kusmanın daha fazla olduğunu bulduk. Ayrıca kış aylarında daha çok viral, yaz aylarındaysa paraziter vakaların daha sık olduğunu ve paraziter kökenli vakalarda akut faz belirteçlerinin daha yüksek olduğunu bulduk.

MON-258 Hyperprolactinemia: An Unusual Initial Presenting Manifestation of Multiple Sclerosis

Hyperprolactinemia and multiple sclerosis (MS) have a direct relationship and hyperprolactinemia may precede clinical signs of MS as a heralding manifestation of disease. Prolactin has significant pro-inflammatory effects in addition to its lactotrophic properties and can also lower the body’s immune tolerance, inducing autoimmunity. High levels of prolactin have been thought to contribute to the inflammation of multiple sclerosis. However, elevated levels of prolactin, especially in pregnant women, can be protective for MS patients and induce remission. Prolactin is neuroregenerative and stimulates the precursors for oligodendrocytes, the cells responsible for myelination. Our hypothesis is that an elevated prolactin level detected during an MS flare should not be treated with dopamine agonist, but rather allowed to decrease as the MS improves with treatment.Case PresentationA 24 year old woman with a history of marijuana use is referred to our clinic for elevated prolactin levels associated with galactorrhea for 3 months duration. In addition to marijuana use, patient was also sexually active and having regular menses, with menarche at age 11 years old. On physical exam, the patient was found to have bilateral nipple discharge with stimulation, and visual fields were intact to confrontation. At the time of referral, the patient’s prolactin was 92.3 ng/dL (4.8−23.3 ng/mL) TSH was normal, and pregnancy test negative.An MRI showed multiple areas of enhancement compatible with active demyelination, concerning for multiple sclerosis. The pituitary gland was enlarged, without evidence of adenoma. A follow up prolactin level was 101 ng/dL and upon further discussion, patient also admitted to some “funny feeling” and weakness in her right hand and a feeling of being “off balance” diagnosed as a left ear infection. Patient was advised to seek urgent treatment for multiple sclerosis. She was admitted, where she was seen by neurology and diagnosed with relapsing remitting multiple sclerosis. She was initially treated with a course of IV methylprednisolone. She was discharged after this course and followed with neurology as an outpatient. For a few months our patient went into remission and her prolactin improved to 24 ng/dL. A few months later, she had a significant increase in her prolactin to 71.5 ng/dL accompanied by evidence of disease progression on MRI and symptoms of weakness and falls. Neurologists changed her medication from Copaxone to Tecfidera and patient improved clinically and has not had any further flares. Notably, she never received any dopaminergic agent to treat her prolactin level, which improved significantly.Our case illustrates that prolactin may be a disease marker in the acute phase of MS and can be restorative. Further more it will improve when the MS is treated and we should not use any dopamine agonist.

Circulating CX3CR1+CD163+ M2 monocytes markedly elevated and correlated with cardiac markers in patients with acute myocardial infarction.

BackgroundVulnerable plaques have been generally recognized to play a role in the pathogenesis of acute myocardial infarction (AMI), however, the role of circulating CX3CR1+CD163+ M2 monocytes has not been studied properly. We aim to evaluate the features of CX3CR1+CD163+ M2 monocytes and its relationship with cardiac specific markers in AMI patients.MethodsThe circulating M2 monocytes were identified in AMI patients (n=35) and healthy controls (HCs, n=10) by flow cytometry using two staining methods: CD68+CD163+ (cytoplasmic staining) and CX3CR1+CD163+ (surface staining). CX3CR1+ monocytes were purified by magnetic cell sorting. The expression level of peroxisome proliferator-activated receptor γ (PPARγ) and arginase-1 (Arg-1) were measured by real-time quantitative PCR and Western Blot in CX3CR1+ monocytes.ResultsCirculating M2 monocytes extremely expanded in AMI patients compared with HCs (P<0.01). Positive linear correlation was confirmed between CD68+CD163+ and CX3CR1+CD163+ cell populations in AMI patients (r=0.39, P=0.02). The percentage of circulating CX3CR1+CD163+ M2 monocytes positively correlated with cardiac specific markers (cTNT, CK-MB) and acute phase markers (glucose, hs-CRP) (cTNT, r=0.63, P<0.01, CK-MB, r=0.54, P<0.01, glucose, r=0.62, P<0.01, hs-CRP, r=0.58, P<0.01). CX3CR1+ monocytes in AMI patients expressed higher levels of PPARγ and Arg-1 than those in HCs (P<0.01).ConclusionsCirculating M2 monocytes increased in AMI patients and positively correlated with the elevation of both cardiac specific and acute phase markers. CX3CR1+CD163+ M2 monocytes might have application value for the early diagnosis of AMI.

Distinct functions of megalin and cubilin receptors in recovery of normal and nephrotic levels of filtered albumin.

Proximal tubule (PT) cells express a single saturable albumin-binding site whose affinity matches the estimated tubular concentration of albumin; however, albumin uptake capacity is greatly increased under nephrotic conditions. Deciphering the individual contributions of megalin and cubilin to the uptake of normal and nephrotic levels of albumin is impossible in vivo, as knockout of megalin in mice globally disrupts PT endocytic uptake. We quantified concentration-dependent albumin uptake in an optimized opossum kidney cell culture model and fit the kinetic profiles to identify albumin-binding affinities and uptake capacities. Mathematical deconvolution fit best to a three-component model that included saturable high- and low-affinity uptake sites for albumin and underlying nonsaturable uptake consistent with passive uptake of albumin in the fluid phase. Knockdown of cubilin or its chaperone amnionless selectively reduced the binding capacity of the high-affinity site, whereas knockdown of megalin impacted the low-affinity site. Knockdown of disabled-2 decreased the capacities of both binding sites. Additionally, knockdown of megalin or disabled-2 profoundly inhibited the uptake of a fluid phase marker, with cubilin knockdown having a more modest effect. We propose a novel model for albumin retrieval along the PT in which cubilin and megalin receptors have different functions in recovering filtered albumin in proximal tubule cells. Cubilin binding to albumin is tuned to capture normally filtered levels of the protein. In contrast, megalin binding to albumin is of lower affinity, and its expression is also essential for enabling the recovery of high concentrations of albumin in the fluid phase.

Changes in markers of lipid oxidation and thermal treatment in feed-grade fats and oils.

Oxidized feed lipids have been shown to have detrimental effects on food animal growth and metabolism. The present study aimed to measure classes of lipid oxidation products (LOP) in feed-grade oils at temperatures representing production and storage conditions. There were significant oil type × time interactions in the accumulation of primary and secondary LOP. At 22.5 °C, peroxide value (PV), a marker for the primary phase of lipid oxidation, increased most in fish oil (FO), followed by tallow (TL), soybean oil (SO), linseed oil (LO) and modified algae oil (MAO), whereas palm oil (PO) showed no appreciable increase in PV. Secondary LOP, such as p-anisidine value, hexanal, 2,4,-decadienal, polymerized triacylglycerols and total polar compounds, increased only in FO. At 45 °C, FO and SO produced both primary and secondary LOP, whereas MAO, PO and TL had slower rates of PV increase and no secondary LOP. At 90 °C and 180 °C, all oils except for FO accumulated both primary and secondary LOP. Higher polyunsaturated fatty acid:saturated fatty acid oils and higher temperatures produced greater quantities of primary and secondary LOP. However, unrefined TL was more prone to oxidation at 22.5 °C than predicted, whereas LO was more stable than predicted, indicating that pro-oxidant and antioxidant compounds can markedly influence the rate of oxidation. Measuring both primary and secondary LOP will provide better information about the oxidative status of feed oils and provide better information about which classes of LOP are responsible for detrimental health effects in animals. Published 2020. This article is a U.S. Government work and is in the public domain in the USA.

Effects of advanced age and pituitary pars intermedia dysfunction on components of the acute phase reaction in horses

Age, neurodegenerative disorders, and dysfunction of insulin secretion may be correlated with increased systemic concentrations of acute phase markers. Thus, the study aimed to determine the effect of age, pituitary pars intermedia dysfunction (PPID), and insulin dysregulation (ID) associated with PPID, on markers of the acute phase reaction. Twenty-nine mix-breed horses of both sexes were classified into groups: (1) healthy adult controls, (2) healthy non-PPID geriatric horses, (3) PPID ID+ horses, and (4) PPID ID− horses. Whole blood proinflammatory cytokine gene expression and serum concentrations of pro- and anti-inflammatory cytokines and acute phase proteins were measured. The data were analyzed using the Mann–Whitney U-test, and correlations between groups of data were assessed using Spearman's correlation coefficient. The tests were statistically significant if P < 0.05. No differences in the whole blood cytokine gene expression, serum cytokine concentrations, or acute phase proteins were noted between the groups. In the PPID ID group, there was a strong correlation between the ACTH concentration after the administration of thyrotropin-releasing hormone and the expression of IL-8 (r = 0.941; P = 0.0321). In the PPID ID+ group, there was a strong correlation between basal insulin concentrations and serum amyloid A (SAA; r = 0.936; P = 0.0083) as well as between postprandial insulin concentrations and SAA (r = 0.965; P = 0.001). These data suggest that neurodegeneration in horses moderately affects circulating markers of inflammation and that ID in horses with PPID influences acute phase inflammatory markers.

Cigarette smoke inhalation impairs angiogenesis in early bone healing processes and delays fracture union

AimsCigarette smoking has a negative impact on the skeletal system, causes a decrease in bone mass in both young and old patients, and is considered a risk factor for the development of osteoporosis. In addition, it disturbs the bone healing process and prolongs the healing time after fractures. The mechanisms by which cigarette smoking impairs fracture healing are not fully understood. There are few studies reporting the effects of cigarette smoking on new blood vessel formation during the early stage of fracture healing. We tested the hypothesis that cigarette smoke inhalation may suppress angiogenesis and delay fracture healing.MethodsWe established a custom-made chamber with airflow for rats to inhale cigarette smoke continuously, and tested our hypothesis using a femoral osteotomy model, radiograph and microCT imaging, and various biomechanical and biological tests.ResultsIn the smoking group, Western blot analysis and immunohistochemical staining revealed less expression of vascular endothelial growth factor (VEGF) and von Willebrand factor (vWF). The smoking group also had a lower microvessel density than the control group. Image and biochemical analysis also demonstrated delayed bone healing.ConclusionCigarette smoke inhalation was associated with decreased expression of angiogenic markers in the early bone healing phase and with impaired bone healing.Cite this article: Bone Joint Res. 2020;9(3):99–107.

Longitudinal Neuroimaging over 30 Days: Temporal Characteristics of Migraine.

Although migraine is defined by the headache and headache-associated symptoms, the true beginning of a migraine attack lies in the premonitory phase. To understand the generation of attacks, one needs to investigate the phase before headache starts. The premonitory phase of migraine is characterized by a well-described complex of symptoms. Its duration, however, is not clearly defined, and there are no biomarkers to help define when this phase starts. Here, we used functional magnetic resonance imaging (MRI) to elucidate the duration of the premonitory phase in spontaneous human migraine attacks. Because migraine attacks are hardly predictable and thereby the premonitory phase is difficult to catch, we scanned 9 patients daily over a minimum period of 30 days using a well-established paradigm for functional MRI of trigeminal nociception. Seven patients were included in the analysis, thus providing cumulative data of 27 spontaneous human migraine attacks including scans before, during, and after migraine pain as well as interictal scans. As a response to painful trigeminal stimulation, activation of the hypothalamus was present within the last 48 hours before headache onset but not earlier. Using hypothalamic activation as a potential marker for the premonitory phase of migraine in this unique dataset, our data corroborated a duration of 48 hours for the premonitory phase of migraine. We suggest applying this time criterion in future studies when focusing on this phase of the migraine cycle. ANN NEUROL 2020;87:646-651.

Circadian Phase Advances in Response to Weekend Morning Light in Adolescents With Short Sleep and Late Bedtimes on School Nights.

Many adolescents fall asleep too late to get enough sleep (8–10 h) on school nights. Morning bright light advances circadian rhythms and could help adolescents fall asleep earlier. Morning bright light treatment before school, however, is difficult to fit into their morning schedule; weekends are more feasible. We examined phase advances in response to morning light treatment delivered over one weekend. Thirty-seven adolescents (16 males; 14.7–18.0 years) who reported short school-night sleep (≤7 h) and late bedtimes (school-nights ≥23:00; weekend/non-school nights ≥24:00) slept as usual at home for ∼2 weeks (“baseline”) and then kept a fixed sleep schedule (baseline school-night bed and wake-up times ±30 min) for ∼1 week before living in the lab for one weekend. Sleep behavior was measured with wrist actigraphy and sleep diary. On Saturday morning, we woke each participant 1 h after his/her midpoint of baseline weekend/non-school night sleep and 1 h earlier on Sunday. They remained in dim room light (∼20 lux) or received 1.5 or 2.5 h of intermittent morning bright light (∼6000 lux) on both mornings. The dim light melatonin onset (DLMO), a phase marker of the circadian timing system, was measured on Friday and Sunday evenings to compute the weekend circadian phase shift. The dim room light and 1.5-h bright light groups advanced the same amount (0.6 ± 0.4 and 0.6 ± 0.5 h). The 2.5-h bright light group advanced 1.0 ± 0.4 h, which was significantly more than the other groups. These data suggest that it is possible to phase advance the circadian clock of adolescents who have late bedtimes and short school-night sleep in one weekend using light that begins shortly after their sleep midpoint.

Cereal dietary fibres influence retention time of digesta solid and liquid phases along the gastrointestinal tract

Nutrient digestion kinetics are determined by gastric emptying (GE) in the stomach and apparent mean retention time (aMRT) along the small and large intestine. This study aimed to evaluate the effects of cereal dietary fibres (DF), either as intrinsic components of plant foods or added ingredients, on the retention of solid and liquid phases of digesta along the gastrointestinal (GI) tract. Thirty pigs were fed one of five diets containing whole wheat (WW), wheat starch (WS) or wheat starch partially replaced by wheat arabinoxylan (AX) or oat β-glucan (βG), or in combination (WSAXβG). Indigestible solid and liquid phase markers were added to each diet and fed at i) constant and ii) pulse dose intervals. Constant markers (acid insoluble ash and chromium) provided aMRT along 11 sections of the GI tract, while pulse dose markers (cerium, ytterbium and cobalt), fed 2–6 h before anaesthesia, provided a GE time. aMRT was slowest in the caecum and large intestine (LI, 15.4h), followed by the small intestine (SI, 3.4h) and stomach (2.6h) with liquid phases moving faster compared to solid phases. Between DF, AX but not βG, delayed GE of solid and liquid contents and showed longer retention time in SI and LI. In the absence of isolated soluble fibres, WS and WW diets showed similar flow characteristics of solid and liquid phases. The aMRT was shown to be dependent on the structure and swellability of added DF.

High Remission Rate with Infliximab and Plant-Based Diet as First-Line (IPF) Therapy for Severe Ulcerative Colitis: Single-Group Trial

About one-third of patients with severe ulcerative colitis (UC) do not respond to corticosteroid therapy and receive rescue therapy with infliximab or cyclosporine. Up to 20% of such patients fail to respond to rescue therapy and undergo colectomy. We investigated the outcomes of infliximab and a plant-based diet (PBD) as first-line therapy for severe UC. Patients with severe UC defined by the Truelove and Witts criteria were admitted and given standard induction therapy with infliximab (5.0 mg/kg-7.5 mg/kg) at 0, 2, and 6 weeks. Additionally, they received a PBD. The primary endpoint was remission or colectomy in the induction phase and 1 year after discharge. Secondary endpoints were changes in inflammatory markers in the induction phase and the PBD score at baseline and follow-up. A higher PBD score indicates greater adherence to a PBD. Infliximab and PBD as first-line therapy was administered in 17 cases. The remission rate was 76% (13/17), and the colectomy rate was 6% (1/17) in the induction phase. C-reactive protein values and the erythrocyte sedimentation rate significantly decreased at week 6 from 9.42 mg/dL to 0.33 mg/dL and from 59 to 17 mm/h, respectively (p < 0.0001). At 1-year follow-up, the cumulative relapse rate was 25%, and there were no additional colectomy cases. Mean PBD scores of 27.7 at 1 year and 23.8 at 4 years were significantly higher than baseline scores of 8.3 and 9.9, respectively (p < 0.0001 and p = 0.0391). This new first-line therapy for severe UC demonstrated a higher remission rate and lower colectomy rate than with the current modality.

An Easy-to-Use Multi-Source Recording and Synchronization Software for Experimental Trials

A typical routine in many scientific studies consists of recording data from devices and identifying which segment of data corresponds with an experimental interval. However, many current applications have been designed to obtain and save data from one single device, and synchronizing data with the markers that delimit the test phases can be difficult. To address this issue, we have developed LSLRec, which is based on Lab-Streaming Layer, a C++ library that allows data synchronization. LSLRec is an easy-to-use, open-source, multi-platform, recording system developed on Java that can save data from several devices at the same time, while maintaining synchronization with the experimental phase markers. It supports three explicit sync methods: the first uses one-integer-channel input Lab-Streaming Layer streams. The others use TCP/UDP socket messages and allow any existing software that generates sync markers through TCP/UDP messages to be used under the same conditions. In LSLRec, the markers are saved together with input data, facilitating the process of linking data with test stages. A prerequisite for recording software is to guarantee suitable timing performance, with no data loss and an easy user interface. These features were assessed for LSLRec, with no data loss detected for 20 hours (25 sessions). We evaluated performance by measuring timestamp deviations for sync marker and input data. The sync methods exhibited an average of deviations of around -34μs (which is more than acceptable, e.g., in studies involving living beings), whereas the absolute value of deviation for one-channel data was lower than 40μs. Finally, we assessed the system's usability with the technology acceptance model 3 survey (6 volunteers). Subjects saw the software as useful, and intended to use it in the future. In conclusion, LSLRec is a useful tool for those who need to record data from multiple sources, and maintain synchronization with experimental phases with low delay.

Investigation of Positivity Rates in Urine Culture and Its Relationship with Acute Phase Markers in Children with Pyuria in the Emergency Department

Investigation of Positivity Rates in Urine Culture and Its Relationship with Acute Phase Markers in Children with Pyuria in the Emergency Department

The Alpha-1 Antitrypsin Polymer Load Correlates With Hepatocyte Senescence, Fibrosis Stage and Liver-Related Mortality.

Alpha-1 antitrypsin deficiency (AATD) is an important, inherited cause of chronic liver disease. Marked variation in fibrosis stages in patients with homozygous deficiency and those factors that determine whether heterozygous carriers develop liver fibrosis, remain unexplained. Murine studies implicate polymerized alpha-1 antitrypsin (AAT) within hepatocytes as pathogenic. The relationship between the quantity of polymerized AAT within hepatocytes (polymer load), stage of hepatic fibrosis and liver-related clinical outcomes (death, evolution to hepatocellular carcinoma, or need for liver transplantation) were investigated using liver tissue from 92 patients at first presentation with either homozygous or heterozygous AATD. Further tissue-based studies were undertaken to determine if polymerized AAT was associated with failure of cell cycle progression, accelerated aging or hepatocyte senescence by immunohistochemical analysis. The AAT polymer load correlated closely with hepatic fibrosis stage and long-term clinical outcome, independent of homozygous or heterozygous status. AAT polymers within hepatocytes correlated closely with failure of cell cycle progression assessed using cell cycle phase markers, accelerated aging manifest as shortened telomeres and other markers consistent with hepatocyte senescence manifest as the presence of nuclear p21 expression and enlarged nuclei. The proportion of p21 positive hepatocytes or hepatocytes with enlarged nuclei correlated with hepatic fibrosis stage and the long-term clinical outcome. These data suggest that accumulation of AAT polymers within hepatocytes drives senescence. Quantitation of both the AAT polymer load or hepatocyte senescence markers correlated with hepatic fibrosis stage and the long-term clinical outcome. Either or both could be considered markers of disease severity and treatment response in clinical trials.

The µMCTQ: An Ultra-Short Version of the Munich ChronoType Questionnaire.

Individuals vary in how their circadian system synchronizes with the cyclic environment (zeitgeber). Assessing these differences in "phase of entrainment"-often referred to as chronotype-is an important procedure in laboratory experiments and epidemiological studies but is also increasingly applied in circadian medicine, both in diagnosis and therapy. While biochemical measurements (e.g., dim-light melatonin onset [DLMO]) of internal time are still the gold standard, they are laborious, expensive, and mostly rely on special conditions (e.g., dim light). Chronotype estimation in the form of questionnaires is useful in approximating the timing of an individual's circadian clock. They are simple, inexpensive, and location independent (e.g., administrable on- and offline) and can therefore be easily administered to many individuals. The Munich ChronoType Questionnaire (MCTQ) is an established instrument to assess chronotype by asking subjects about their sleep-wake-behavior. Here we present a shortened version of the MCTQ, the µMCTQ, for use in situations in which instrument length is critical, such as in large cohort studies. The µMCTQ contains only the core chronotype module of the standard MCTQ (stdMCTQ), which was shortened and adapted from 17 to 6 essential questions, allowing for a quick assessment of chronotype and other related parameters such as social jetlag and sleep duration. µMCTQ results correspond well to the ones collected by the stdMCTQ and are externally validated by actimetry and DLMO, assessed at home (no measure of compliance). Sleep onset, midpoint of sleep, and the µMCTQ-derived marker of chronotype showed slight deviations toward earlier times in the µMCTQ when compared with the stdMCTQ (<35 min). The µMCTQ assessment of chronotype showed good test-retest reliability and correlated significantly with phase markers from actimetry and melatonin (DLMO), especially with measurements taken on work-free days. Because of its brevity, the µMCTQ represents an ideal tool to estimate individual internal time in time-critical contexts, from large cohort studies to individualized medicine.

Superfluid 3He in Squeezed Nematic Aerogel

We present results of nuclear magnetic resonance (NMR) experiments in superfluid 3He in two samples of nematic aerogel consisting of nearly parallel mullite strands. The samples were cut from the same piece of the aerogel, but one of them was squeezed by 30% in the direction transverse to the strands. In both samples the superfluid transition of 3He occurred into the polar phase, where no qualitative difference between NMR properties of 3He in these samples was found. The difference, however, has appeared on further cooling, after the transition to the polar-distorted A phase (PdA phase) with the orbital part of the order parameter in the 2D Larkin-Imry-Ma (LIM) state. In the squeezed sample the 2D LIM state is anisotropic that results in changes in the NMR, which can be used as an additional marker of the PdA phase and have allowed us to measure the value of the anisotropy.

Тест генерации тромбина в оценке адаптационных возможностей системы гемокоагуляции у пациентов с дегенеративно-дистрофическими заболеваниями суставов

Введение. Поиски методов оценки функционального состояния системы гемокоагуляции у пациентов, которые ожидают выполнения эндопротезирования крупных суставов нижних конечностей, обоснованы высокой частотой встречаемости у них тромбоэмболических осложнений. Цель исследования: изучение теста генерации тромбина (ТГТ) с позиции оценки адаптационных возможностей системы гемокоагуляции у больных с дегенеративнодистрофическими заболеваниями крупных суставов нижних конечностей. Материалы и методы. Обследован 141 больной с дегенеративнодистрофическими поражениями тазобедренных и коленных суставов (35 мужчин, 106 женщин), средний возраст 62,6 9,9 лет. Контрольную группу составили 30 условно здоровых доноров, средний возраст 49,7 6,5 лет. Исследовали коагуляционные свой ства крови рутинными методами и регистрировали кривую процесса тромбинообразования в ТГТ, анализируя параметры: tlag латентное время тромбинообразования, ttpeak время достижения максимума тромбина, peak максимальное количество тромбина, VI индекс скорости тромбинообразования, AUC площадь под кривой. Больные были разделены на 2 группы в зависимости от характера изменения временных параметров ТГТ в ответ на инициацию тромбиногенеза активаторами с концентрацией тканевого фактора 2 пмоль/мл (активатор RB) и 5 пмоль/мл (активатор RClow). Результаты. В 1й группе значения параметров tlag и ttpeak в ответ на действие активатора RClow были меньше, чем на действие активатора RB, реакцию системы гемокоагуляции расценивали как адекватную. Во 2й группе значения tlag и ttpeak при использовании активатора RClow превышали величины аналогичных параметров при инициации тромбообразования активатором RB, а корреляционный анализ отразил ослабление связей между параметрами ТГТ, что свидетельствовало об адаптационной перестройке системы на фоне высокого тромбогенного потенциала и повышенном риске развития гемокоагуляционных осложнений у больных 2й группы. Заключение. ТГТ с использованием активаторов RB и RClow ерспективный инструмент выявления больных с высоким риском развития послеоперационных гемокоагуляционных осложнений. Introduction. The search of methods for assessing of hemocoagulation functional state in patients that are waiting endoprosthesis replacement of large joints of lower extremities is justified by the high incidence of thromboembolic complications. Aim: to study thrombin generation assay (TGA) for assessment of hemocoagulation adaptive potential in patients with degenerativedystrophic diseases of the large joints of lower extremities. Materials and methods. We examined 141 patients with degenerativedystrophic lesions of hip and knee joints (35 men, 106 women), average age was 62.6 9.9 years. Control group consisted of 30 relatively healthy donors, average age was 49.7 6.5 years. We investigated blood coagulation properties by routine methods and recorded the curve of thrombin formation by TGA. We analyzed next parameters: tlag is the latent time of thrombin formation, ttpeak is the time to reach the maximum of thrombin, peak is the maximum amount of thrombin, VI is the index of thrombin formation speed, AUC is the area under the curve. Patients were divided into 2 groups according TGA parameters in response to thrombinogenesis initiation by activators with different tissue factor concentrations 2 pmol/ml (RB activator) and 5 pmol/ml (RClow activator). Results. In the 1st group, tlag and ttpeak values in TGA with RClow activator were less than with RB activator, the hemocoagulation response was regarded as adequate. In the 2nd group, tlag and ttpeak values with RClow activator were higher than with RB activator and correlation analysis revealed the weakening of the relationships between TGA parameters. This indicated about system adaptation at a time of high thrombogenic potential and about increased risk of developing hemocoagulation complications in patients of the 2nd group. Conclusion. TGA with RB and RClow activators is a promising tool for identifying patients with a high risk of postoperative hemocoagulation complications.

Assessing Chronotypes by Ambulatory Circadian Monitoring.

In order to develop objective indexes for chronotype identification by means of direct measurement of circadian rhythms, 159 undergraduate students were recruited as volunteers and instructed to wear ambulatory circadian monitoring (ACM) sensors that continuously gathered information on the individual’s environmental light and temperature exposure, wrist temperature, body position, activity, and the integrated TAP (temperature, activity, and position) variable for 7 consecutive days under regular free-living conditions. Among all the proposed indexes, the night phase marker (NPM) of the TAP variable was the best suited to discriminate among chronotypes, due to its relationship with the Munich ChronoType Questionnaire (β = 0.531; p < 0.001). The NPM of TAP allowed subjects to be classified as early- (E-type, 20%), neither- (N-type, 60%), and late-types (L-type, 20%), each of which had its own characteristics. In terms of light exposure, while all subjects had short exposure times to bright light (>100 lux), with a daily average of 93.84 ± 5.72 min, the earlier chronotypes were exposed to brighter days and darker nights compared to the later chronotypes. Furthermore, the earlier chronotypes were associated with higher stability and day–night contrast, along with an earlier phase, which could be the cause or consequence of the light exposure habits. Overall, these data support the use of ACM for chronotype identification and for evaluation under free living conditions, using objective markers.