Hypohydration alters pre-frontal cortex haemodynamics, but does not impair motor learning

It is unknown how hypohydration influences fine motor performance training and motor learning. Here, 30 participants (aged 19-46 years) were randomly assigned to a hypohydration (HYPO) or control (CON) group (both n = 15). Moderate hypohydration (~ 2.4% loss in body mass) was produced in HYPO via active dehydration before a 46 min fluid restricted rest period was undertaken. The conclusion of rest coincided with when CON attended the facilities. Both groups undertook a discrete sequence production task consisting of 6 training blocks, and returned ~ 300 min later to complete a delayed retention and transfer test while euhydrated. Bilateral pre-frontal cortex (PFC) haemodynamics were assessed using functional near-infrared spectroscopy throughout training and delayed learning assessments. Response time improved across training (P P = 0.22). Analysis of training PFC haemodynamics revealed a significant group by block interaction for oxygenated (O2Hb; P P = 0.77). In training block 1, bilateral O2Hb was higher in HYPO (P = 0.02), while bilateral O2Hb increased in CON between blocks 2-3 and 5-6 (both P ≤ 0.03). During the delayed retention and transfer test, no group differences or interactions were found in response time, response error, or PFC haemodynamics (all P ≥ 0.27). Moderate hypohydration does increase PFC activation during motor skill learning, however, this appears to be transient and of little consequence to training or delayed retention or transfer performance

Twinning superlattices in indium phosphide nanowires

Here, we show that we control the crystal structure of indium phosphide (InP) nanowires by impurity dopants. We have found that zinc decreases the activation barrier for 2D nucleation growth of zinc-blende InP and therefore promotes the InP nanowires to crystallise in the zinc blende, instead of the commonly found wurtzite crystal structure. More importantly, we demonstrate that we can, by controlling the crystal structure, induce twinning superlattices with long-range order in InP nanowires. We can tune the spacing of the superlattices by the wire diameter and the zinc concentration and present a model based on the cross-sectional shape of the zinc-blende InP nanowires to quantitatively explain the formation of the periodic twinning.Comment: 18 pages, 4 figure

Generic nano-imprint process for fabrication of nanowire arrays

A generic process has been developed to grow nearly defect free arrays of (heterostructured) InP and GaP nanowires. Soft nanoimprint lithography has been used to pattern gold particle arrays on full 2 inch substrates. After lift-off organic residues remain on the surface, which induce the growth of additional undesired nanowires. We show that cleaning of the samples before growth with piranha solution in combination with a thermal anneal at 550 C for InP and 700 C for GaP results in uniform nanowire arrays with 1% variation in nanowire length, and without undesired extra nanowires. Our chemical cleaning procedure is applicable to other lithographic techniques such as e-beam lithography, and therefore represents a generic process.Comment: 12 pages, 4 figures, 2 table

Sequence Motifs in MADS Transcription Factors Responsible for Specificity and Diversification of Protein-Protein Interaction

Protein sequences encompass tertiary structures and contain information about specific molecular interactions, which in turn determine biological functions of proteins. Knowledge about how protein sequences define interaction specificity is largely missing, in particular for paralogous protein families with high sequence similarity, such as the plant MADS domain transcription factor family. In comparison to the situation in mammalian species, this important family of transcription regulators has expanded enormously in plant species and contains over 100 members in the model plant species Arabidopsis thaliana. Here, we provide insight into the mechanisms that determine protein-protein interaction specificity for the Arabidopsis MADS domain transcription factor family, using an integrated computational and experimental approach. Plant MADS proteins have highly similar amino acid sequences, but their dimerization patterns vary substantially. Our computational analysis uncovered small sequence regions that explain observed differences in dimerization patterns with reasonable accuracy. Furthermore, we show the usefulness of the method for prediction of MADS domain transcription factor interaction networks in other plant species. Introduction of mutations in the predicted interaction motifs demonstrated that single amino acid mutations can have a large effect and lead to loss or gain of specific interactions. In addition, various performed bioinformatics analyses shed light on the way evolution has shaped MADS domain transcription factor interaction specificity. Identified protein-protein interaction motifs appeared to be strongly conserved among orthologs, indicating their evolutionary importance. We also provide evidence that mutations in these motifs can be a source for sub- or neo-functionalization. The analyses presented here take us a step forward in understanding protein-protein interactions and the interplay between protein sequences and network evolution

Risk factors of unmet needs among women with breast cancer in the post-treatment phase

OBJECTIVE: Unmet health care needs require additional care resources to achieve optimal patient well-being. In this nationwide study we examined associations between a number of risk factors and unmet needs after treatment among women with breast cancer, while taking into account their health care practices. We expected that more care use would be associated with lower levels of unmet needs. METHODS: A multicenter, prospective, observational design was employed. Women with primary breast cancer completed questionnaires 6 and 15 months post-diagnosis. Medical data were retrieved from medical records. Direct and indirect associations between sociodemographic and clinical risk factors, distress, care use, and unmet needs were investigated with structural equation modeling. RESULTS: Seven hundred forty-six participants completed both questionnaires (response rate 73.7%). The care services received were not negatively associated with the reported levels of unmet needs after treatment. Comorbidity was associated with higher physical and daily living needs. Higher age was associated with higher health system-related and informational needs. Having had chemotherapy and a mastectomy were associated with higher sexuality needs and breast cancer-specific issues, respectively. A higher level of distress was associated with higher levels of unmet need in all domains. CONCLUSIONS: Clinicians may use these results to timely identify which women are at risk of developing specific unmet needs after treatment. Evidence-based, cost-effective (online) interventions that target distress, the most influential risk factor, should be further implemented and disseminated among patients and clinicians

Maternal and neonatal antibody levels on pertussis vaccination in pregnant women on immune-modulating therapy for rheumatic disease

OBJECTIVES: While protection against pertussis following maternal tetanus-diphtheria-and-acellular-pertussis (Tdap) vaccination was demonstrated in healthy term-born infants, no evidence is available on Tdap vaccination in combination with immune-modulating therapy during pregnancy. In this pilot study, we explored whether treatment with tumour necrosis factor alpha inhibitors (TNFis) in pregnant patients with rheumatic disease interferes with Tdap vaccine responses and affects maternal anti-pertussis IgG antibody levels in newborns. METHODS: Patients were included by a rheumatologist during pregnancy in case they received maternal Tdap vaccination in the late-second or early-third trimester of pregnancy. Blood samples were obtained from mothers during the first pregnancy trimester, 3 months after delivery and from the umbilical cord. IgG antibody levels against Tdap-included antigens were measured using a bead-based multiplex immunoassay. Findings on patients exposed to TNFis were compared with those from TNFi-unexposed patients and with data from a historical comparator study among healthy Tdap vaccinated mother-infant pairs (n=53). RESULTS: 66 patients (46 exposed and 20 unexposed to TNFIs) were enrolled. No major differences in IgG antibody levels were observed between TNFi-exposed and unexposed mothers before maternal Tdap vaccination and 3 months after delivery. In cord sera, however, antibody levels against pertussis toxin were significantly lower after TNFi-treatment (35.94 IU/mL, 95% CI 20.68 to 62.45) compared with no TNFi-treatment of mothers with rheumatic disease (94.61 IU/mL, 95% CI 48.89 to 183.07) and lower compared with a cohort of healthy mothers (125.12 IU/mL, 95% CI 90.75 to 172.50). We observed similar differences for filamentous haemagglutinin, pertactin, tetanus toxoid and diphtheria toxoid. CONCLUSION: These preliminary data indicate no major differences in IgG antibody levels on maternal Tdap vaccination in pregnant women with or without immune-modulating treatment, although our findings suggest that TNFis during pregnancy induce lower maternal anti-pertussis-specific protective antibody levels in newborns

Risk factors of unmet needs among women with breast cancer in the post-treatment phase

Objective: Unmet health care needs require additional care resources to achieve optimal patient well-being. In this nationwide study we examined associations between a number of risk factors and unmet needs after treatment among women with breast cancer, while taking into account their health care practices. We expected that more care use would be associated with lower levels of unmet needs. Methods: A multicenter, prospective, observational design was employed. Women with primary breast cancer completed questionnaires 6 and 15 months post-diagnosis. Medical data were retrieved from medical records. Direct and indirect associations between sociodemographic and clinical risk factors, distress, care use, and unmet needs were investigated with structural equation modeling. Results: Seven hundred forty-six participants completed both questionnaires (response rate 73.7%). The care services received were not negatively associated with the reported levels of unmet needs after treatment. Comorbidity was associated with higher physical and daily living needs. Higher age was associated with higher health system-related and informational needs. Having had chemotherapy and a mastectomy were associated with higher sexuality needs and breast cancer-specific issues, respectively. A higher level of distress was associated with higher levels of unmet need in all domains. Conclusions: Clinicians may use these results to timely identify which women are at risk of developing specific unmet needs after treatment. Evidence-based, cost-effective (online) interventions that target distress, the most influential risk factor, should be further implemented and disseminated among patients and clinicians

Sensitive Detection of p65 Homodimers Using Red-Shifted and Fluorescent Protein-Based FRET Couples

BACKGROUND: Fluorescence Resonance Energy Transfer (FRET) between the green fluorescent protein (GFP) variants CFP and YFP is widely used for the detection of protein-protein interactions. Nowadays, several monomeric red-shifted fluorescent proteins are available that potentially improve the efficiency of FRET. METHODOLOGY/PRINCIPAL FINDINGS: To allow side-by-side comparison of several fluorescent protein combinations for detection of FRET, yellow or orange fluorescent proteins were directly fused to red fluorescent proteins. FRET from yellow fluorescent proteins to red fluorescent proteins was detected by both FLIM and donor dequenching upon acceptor photobleaching, showing that mCherry and mStrawberry were more efficient acceptors than mRFP1. Circular permutated yellow fluorescent protein variants revealed that in the tandem constructs the orientation of the transition dipole moment influences the FRET efficiency. In addition, it was demonstrated that the orange fluorescent proteins mKO and mOrange are both suitable as donor for FRET studies. The most favorable orange-red FRET pair was mKO-mCherry, which was used to detect homodimerization of the NF-kappaB subunit p65 in single living cells, with a threefold higher lifetime contrast and a twofold higher FRET efficiency than for CFP-YFP. CONCLUSIONS/SIGNIFICANCE: The observed high FRET efficiency of red-shifted couples is in accordance with increased Förster radii of up to 64 A, being significantly higher than the Förster radius of the commonly used CFP-YFP pair. Thus, red-shifted FRET pairs are preferable for detecting protein-protein interactions by donor-based FRET methods in single living cells

Hyperbaric oxygen therapy for late radiation-induced tissue toxicity: Prospectively patient-reported outcome measures in breast cancer patients

__Introduction:__ This study examines patient reported outcome measures of women undergoing hyperbaric oxygen treatment (HBOT) after breast-conserving therapy. __Method:__ Included were 57 women treated with HBOT for late radiation-induced tissue toxicity (LRITT) referred in the period January 2014-December 2015. HBOT consisted of (on average) 47 sessions. In total, 80 min of 100 % O2 was administered under increased pressure of 2.4 ATA. Quality of life was assessed before and after treatment using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-BR23, and a NRS pain score. __Results:__ Fifty-seven women were available for evaluation before and after treatment. Before HBOT, patients had severe complaints of pain in the arm/shoulder (46 %), swollen arm/hand (14 %), difficulty to raise arm or move it sideways (45 %), pain in the area of the affected breast (67 %), swollen area of the affected breast (45 %), oversensitivity of the affected breast (54 %), and skin problems on/in the area of the affected breast (32 %); post HBOT, severe complaints were still experienced in 17, 7, 22, 15, 13, 15, and 11 % of the women, respectively. Differences were all significant. The NRS pain score improved at least 1 point (range 0-10) in 81 % of the patients (p < 0.05). __Conclusion:__ In these breast cancer patients treated with HBOT for LRITT, the patient-reported outcomes were positive and improvements were observed. HBOT was a well-tolerated treatment for LRITT and its side-effects were both minimal and reversible