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The human circadian system consists of the master clock in the suprachiasmatic nuclei of the hypothalamus as well as in peripheral molecular clocks located in organs throughout the body. This system plays a major role in the temporal organization of biological and physiological processes, such as body temperature, blood pressure, hormone secretion, gene expression, and immune functions, which all manifest consistent diurnal patterns. Many facets of modern life, such as work schedules, travel, and social activities, can lead to sleep/wake and eating schedules that are misaligned relative to the biological clock. This misalignment can disrupt and impair physiological and psychological parameters that may ultimately put people at higher risk for chronic diseases like cancer, cardiovascular disease, and other metabolic disorders. Understanding the mechanisms that regulate sleep circadian rhythms may ultimately lead to insights on behavioral interventions that can lower the risk of these diseases. On February 25, 2021, experts in sleep, circadian rhythms, and chronobiology met virtually for the Keystone eSymposium "Sleep & Circadian Rhythms: Pillars of Health" to discuss the latest research for understanding the bidirectional relationships between sleep, circadian rhythms, and health and disease., (© 2021 New York Academy of Sciences.)

Background: The amino acid serine is an important substrate for biosynthesis and redox homeostasis. We investigated whether glioblastoma (GBM) cells are dependent on serine for survival under conditions of the tumour microenvironment., Methods: Serine availability in GBM cells was modulated pharmacologically, genetically and by adjusting serine and glycine concentrations in the culture medium. Cells were investigated for regulation of serine metabolism, proliferation, sensitivity to hypoxia-induced cell death and redox homeostasis., Results: Hypoxia-induced expression of phosphoglycerate dehydrogenase (PHGDH) and the mitochondrial serine hydroxymethyltransferase (SHMT2) was observed in three of five tested glioma cell lines. Nuclear factor erythroid 2-related factor (Nrf) 2 activation also induced PHGDH and SHMT2 expression in GBM cells. Low levels of endogenous PHGDH as well as PHGDH gene suppression resulted in serine dependency for cell growth. Pharmacological inhibition of PHGDH with CBR-5884 reduced proliferation and sensitised cells profoundly to hypoxia-induced cell death. This effect was accompanied by an increase in reactive oxygen species and a decrease in the NADPH/NADP + ratio. Similarly, hypoxia-induced cell death was enhanced by PHGDH gene suppression and reduced by PHGDH overexpression., Conclusions: Serine facilitates adaptation of GBM cells to conditions of the tumour microenvironment and its metabolism could be a plausible therapeutic target.

Recent discoveries demonstrate a critical role for circadian rhythms and sleep in immune system homeostasis. Both innate and adaptive immune responses - ranging from leukocyte mobilization, trafficking, and chemotaxis to cytokine release and T cell differentiation -are mediated in a time of day-dependent manner. The National Institutes of Health (NIH) recently sponsored an interdisciplinary workshop, "Sleep Insufficiency, Circadian Misalignment, and the Immune Response," to highlight new research linking sleep and circadian biology to immune function and to identify areas of high translational potential. This Review summarizes topics discussed and highlights immediate opportunities for delineating clinically relevant connections among biological rhythms, sleep, and immune regulation.

Introduction: In a single-center, prospective, randomized clinical trial three different configured wound dressings Biobrane(®), Dressilk(®) and PolyMem(®) were compared with each other regarding objective and subjective healing parameters and cost efficiency., Methods: 28 burn patients received surgical treatment with split-thickness skin grafting, while utilizing Biobrane(®), Dressilk(®) and PolyMem(®) as a single bound donor site wound dressing in all patients. Following a standardized case report form, we monitored several parameters such as pain, transparency of the dressing, active bleeding, exudation and inflammation by using the Verbal Rating Scale 1-10 through out., Results: With regard to re-epithelialization, pain and acute bleeding all three dressings were equivalent. Dressilk(®) and Biobrane(®) presented clearly superior to PolyMem(®) in both wound assessment and in the reduction of mild inflammation and exudation. High subjective satisfaction rates were reported with Dressilk(®) and Biobrane(®) dressings in regard to comfort and mobility. During the continuous monitoring period Biobrane(®) outperformed Dressilk(®) by providing higher wound transparency rates and offering a better level of wound control during the entire study period. Regarding their cost efficiency, PolyMem(®) and Dressilk(®) are clearly superior to Biobrane(®)., Conclusion: The "ideal" wound dressing maximizes patients' comfort while reducing pain and the risk of pulling off migrating epidermal cells from the wound surface. In addition reliable wound status evaluation (minimizing complications), an increase of treatment cost value efficacy, and reduced hospitalization rates should be provided. Dressilk(®) and Biobrane(®) were favored by patients and surgeons for providing an effective and safe healing environment, with overall low complication rates with respect to infection and exudation. Regarding cost-effectiveness PolyMem(®) and Dressilk(®) presented superior to Biobrane(®)., (Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.)

Major theories on the neural basis of schizophrenic core symptoms highlight aberrant salience network activity (insula and anterior cingulate cortex), prefrontal hypoactivation, sensory processing deficits as well as an impaired connectivity between temporal and prefrontal cortices. The mismatch negativity is a potential biomarker of schizophrenia and its reduction might be a consequence of each of these mechanisms. In contrast to the previous electroencephalographic studies, functional magnetic resonance imaging may disentangle the involved brain networks at high spatial resolution and determine contributions from localized brain responses and functional connectivity to the schizophrenic impairments. Twenty-four patients and 24 matched control subjects underwent functional magnetic resonance imaging during an optimized auditory mismatch task. Haemodynamic responses and functional connectivity were compared between groups. These data sets further entered a diagnostic classification analysis to assess impairments on the individual patient level. In the control group, mismatch responses were detected in the auditory cortex, prefrontal cortex and the salience network (insula and anterior cingulate cortex). Furthermore, mismatch processing was associated with a deactivation of the visual system and the dorsal attention network indicating a shift of resources from the visual to the auditory domain. The patients exhibited reduced activation in all of the respective systems (right auditory cortex, prefrontal cortex, and the salience network) as well as reduced deactivation of the visual system and the dorsal attention network. Group differences were most prominent in the anterior cingulate cortex and adjacent prefrontal areas. The latter regions also exhibited a reduced functional connectivity with the auditory cortex in the patients. In the classification analysis, haemodynamic responses yielded a maximal accuracy of 83% based on four features; functional connectivity data performed similarly or worse for up to about 10 features. However, connectivity data yielded a better performance when including more than 10 features yielding up to 90% accuracy. Among others, the most discriminating features represented functional connections between the auditory cortex and the anterior cingulate cortex as well as adjacent prefrontal areas. Auditory mismatch impairments incorporate major neural dysfunctions in schizophrenia. Our data suggest synergistic effects of sensory processing deficits, aberrant salience attribution, prefrontal hypoactivation as well as a disrupted connectivity between temporal and prefrontal cortices. These deficits are associated with subsequent disturbances in modality-specific resource allocation. Capturing different schizophrenic core dysfunctions, functional magnetic resonance imaging during this optimized mismatch paradigm reveals processing impairments on the individual patient level, rendering it a potential biomarker of schizophrenia., (© The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Patients transferred to Plastic Surgery Departments for sternum osteomyelitis have a high morbidity of about 3%. Despite several known options for sternal wound coverage and salvage operations, wound dehiscence or wound necrosis can occur, increasing patient morbidity., Patients and Methods: One hundred thirty-five patients admitted between January 2007 and December 2010 were evaluated in a retrospective study for wound dehiscence after salvage wound coverage at our institution. Various flaps were applied, such as pectoralis major myocutaneous pedicled flaps, pectoralis major muscle pedicled flaps, latissimus dorsi pedicled flaps, greater omental flaps, and vertical rectus abdominis muscle and transverse rectus abdominis muscle flaps. Inclusion criteria were sternal wound infection, bacterial wound infection, previous wound debridement outside our institution, vacuum-assisted closure device wound treatment at our institution, and secondary flap closure of the sternal defect at our institution. A multivariate regression analysis was performed., Results: One hundred thirty patients met the inclusion criteria. In all patients, bacterial wound colonization was shown. Forty patients showed wound dehiscence after closure at our institution. Reasons for wound dehiscence were attributed to wound size, >4 different species of bacteria colonizing the wound, gram-negative bacteria, Candida albicans, intensive care unit stay, and female gender. Interestingly, wound dehiscence was not significant correlated to obesity, smoking, atherosclerosis, renal insufficiency or type of closure influenced significantly, or necrosis., Conclusions: Female patients after CABG, with large sternal wounds infected with gram-negative bacteria and candida, have an 85% risk of wound dehiscence after flap coverage for sternal wound infection.

The free extended lateral arm flap (ELAF) has gained increasing popularity thank to its slimness and versatility, longer neurovascular pedicle, and greater flap size when compared with the original flap design. The aim of this study was to assess the donor-site morbidity associated with this extended procedure. A retrospective study of 25 consecutive patients analyzing postoperative complications using a visual analogue scale questionnaire revealed high patients satisfaction and negligible donor-site morbidity of the ELAF. Scar visibility was the commonest negative outcome. Impaired mobility of the elbow had the highest correlation with patient dissatisfaction. Sensory deficits or paresthetic disorders did not affect patient satisfaction. The extension of the lateral arm flap and positioning over the lateral humeral epicondyle is a safe and well-accepted procedure with minimal donor-site morbidity. To optimize outcomes, a maximal flap width of 6 or 7 cm and intensive postoperative mobilization therapy is advisable., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Attentional deficits are prominent in schizophrenia, affecting nearly all cognitive functions. Human attention comprises three essential components: alerting, orienting and executive control. For the assessment of these functions, the attention network test (ANT) has been proposed and used in healthy controls and patients. In schizophrenia, the ANT has revealed behavioral deficits; however, the corresponding neural correlates have not been examined. In the present study, neural correlates of attention were investigated in 17 schizophrenia patients and 17 healthy controls using the ANT with fMRI. Behavioral deficits emerged in the alertness system with a reduced efficiency for temporal cues. In fMRI, changes were observed for all three domains-alerting, orienting and conflict-and revealed hyper- as well as hypoactivation in patients. Affected regions during alerting comprised a broad fronto-temporo-parieto-occipito-cerebellar network, while differences during orienting mainly tapped fronto-parietal regions and during conflict processing a thalamo-frontal-temporal occipital network including the postcentral regions. In general, hyperactivations were positively correlated with more severe psychopathologial symptoms.

Thrombasthenia Glanzmann, named after the Swiss paediatrician Eduard Glanzmann (1887-1959), is a rare disease of platelet dysfunction. This disease is characterized by a deficiency or defect of the fibrinogen receptor (GPIIb-IIIa) on the platelet surface. The GPIIb-IIIa receptor has an essential function in the adhesion and aggregation of the platelets. The platelets of these patients cannot bind fibrinogen and aggregation does not occur. Patients have a severe lifelong risk of bleeding, especially during surgical procedures. These patients require a special perioperative regimen for an adequate function of the coagulation system to prevent intraoperative and postoperative bleeding. In this study, we present the perioperative management of a patient with thrombasthenia Glanzmann during elective inguinal hernia repair.

The direct visualization of systemic microcirculation using intravitalmicroscopy permits the classification of proinflammatory and ischemic microvascular alterations during normothermic and hypothermic cardiopulmonary bypass in neonates. We used seven newborn piglets, on average aged 9 days, and weighing 3200g, as a control group. In addition, we studied nine piglets subjected to 60 minutes of constant nonpulsatile flow using hypothermic extracorporeal circulation at 28 degrees C, and five piglets using normothermic conditions at 37 degrees C. The microvascular network of the greater omentum and the subcutaneous tissue was directly visualized using intravitalmicroscopy. We analysed interactions between leukocytes and endothelial cells, microvascular morphology, and microrheological conditions, focussing on signs of ischemic and proinflammatory alterations. During normothermic cardiopulmonary bypass, the numbers of activated leukocytes were elevated compared to hypothermic cardiopulmonary bypass (p > 0.05). Arteriolar diameter decreased during hypothermia. Capillaries were markedly dilated during normothermia. Patterns of microvascular perfusion, for both types of cardiopulmonary bypass, showed signs of ischemic damage, revealed by a reduced functional capillary density. Perfusion dependent levels of lactate were higher during normothermic cardiopulmonary bypass (p > 0.05). This new experimental approach revealed that non-pulsatile cardiopulmonary bypass, independent of temperature, induces a proinflammatory and ischemic response compared to an unaltered control group. The markedly elevated numbers of activated adherent leukocytes, the reduced capillary density, and the high lactate levels in those undergoing bypass in normothermic conditions indicate a more pronounced inflammatory stimulus and tissue hypoperfusion compared to the possible protective effect of hypothermia for children undergoing cardiopulmonary bypass.

We adopted a multidimensional approach to the study of the social support convoys of older adults. We distinguished between age and gender differences in four specific dimensions of the social support convoy: (a) existence versus functioning of relationships in the convoy, (b) kinds of relationships (i.e., those with children, siblings, and friends), (c) types of social support (i.e., emotional support, respect, and health support), and (d) receipt versus provision of support. Using a national survey of 718 adults, multivariate and univariate analyses of variance were performed to determine age and gender differences in these four dimensions of social support. The multidimensional approach was useful in pinpointing those aspects of the social support convoy affected by aging. We anticipated that the social support convoy would be devastated by aging. Instead, we found that older people received less support (i.e., emotional and health support) in the absence of sibling relationships. Otherwise, the effects of aging had more to do with what the older person contributed to the convoy than with what he or she received. Women had better social support resources than men, particularly within their friendships. We found no evidence, however, that women's social support advantage counterbalanced the effects of aging on the convoy.