Sexual Dimorphism in Titi Monkeys’ Digit (2D:4D) Ratio is Associated with Maternal Urinary Sex Hormones During Pregnancy

The second-to-fourth digit (2D:4D) ratio is a sexually-dimorphic biomarker for prenatal sex hormone exposure. We investigated whether titi monkeys (Plecturocebus cupreus) exhibit sexually-dimorphic 2D:4D ratio, and whether variation in 2D:4D ratio correlates with maternal testosterone and estrogen levels during early pregnancy. Subjects were 61 adult titi monkeys (32 males, 29 females). For 26 subjects, maternal urine samples were collected approximately 15–20 weeks before birth and assayed for testosterone and estrone conjugate (E₁C). Titi monkeys exhibited a human-like pattern of sexual dimorphism in right-hand 2D:4D ratio, with females exhibiting higher 2D:4D ratio than males (β = −0.29, p = 0.023). For left-hand 2D:4D ratio, high levels of maternal E₁C predicted low offspring 2D:4D ratio (β = −0.48, p = 0.009). For right-hand 2D:4D ratio, high levels of testosterone (β = −0.53, p = 0.005) and testosterone-to-E₁C ratio (β = −0.41, p = 0.028) predicted low offspring 2D:4D ratio. For 2D:4D ratio asymmetry (right-hand – left-hand), high levels of testosterone (β = −0.43, p = 0.03) and testosterone-to-E₁C ratio (β = −0.53, p = 0.003) predicted low (right-biased) asymmetry. This is the first report of sexually-dimorphic 2D:4D ratio in New World monkeys, and the results support a growing literature suggesting prenatal sex hormones may modulate offspring 2D:4D ratio.     

Measurement of cortisol,dehydroepiandrosterone, and testosterone in the hair of children: Preliminary results and promising indications

Hormone analysis is a valuable tool for understanding how physiology and behavior interact. Cortisol in hair has recently been examined as a measure of longer-term hormone output. The aim of this study was to investigate the relationships between other androgens in hair and anthropometric measures. In a child sample (n = 114, mean age: 8.5 years, 66 females) levels of cortisol, dehydroepiandrosterone (DHEA) and testosterone were assayed in the 0–3 cm section proximal to scalp. The 3–6 cm segment within a subsample of female participants (n = 35) was examined and compared. Results showed that testosterone strongly correlated with DHEA, and moderately correlated with cortisol (0–3 cm only). Higher hormone concentrations were present in the 3–6 cm segment. Finally, there was a weak positive association between DHEA and height. The replication of previously identified associations between androgens, particularly testosterone-DHEA, and with developmental measures suggests hair may offer a valid method of hormone measurement for DHEA and testosterone.     

Efficacy of cognitive behavioural therapy for insomnia or sleep disturbance in pregnant women: A systematic review ad meta-analysis

During pregnancy many women may experience negative emotions and sleep disturbances. This systematic review and meta-analysis was conducted to assess the efficacy of cognitive behavioural therapy for insomnia (CBT-I) or sleep disturbance in pregnant women. From the earliest available publications to 15 April 2022, seven electronic literature databases were searched: PubMed, Web of Science, Cochrane Library, Embase, Chinese National Knowledge Infrastructure, Wanfang Data, and VIP Database for Chinese Science and Technology Journal. Randomised controlled trials of CBT-I in pregnant women with insomnia or sleep disorders were included. The methodological bias of the included studies was assessed using the Cochrane risk of bias tool. The meta-analysis was performed using RevMan 5.4 software. Stata Statistical Software: Release 15 was used for sensitivity analysis and publication bias. We included eight randomised controlled trials involving 743 pregnant women. Meta-analysis showed that, compared with the control group, CBT-I significantly improved the Insomnia Severity Index (mean difference [MD] = −4.25, 95% confidence interval [CI, −6.32, −2.19], p < 0.001), The Pittsburgh Sleep Quality Index (MD = −3.30, 95% CI [−4.81, −1.79], p < 0.001), sleep onset latency (standardised mean difference [SMD] = −1.25, 95% CI [−2.01, −0.50], p = 0.001), anxiety (SMD = −0.99, 95% CI [−1.32, −0.67], p < 0.001), and depression (SMD = −0.40, 95% CI [−0.72, −0.07], p = 0.02). No significant differences were found in total sleep time (SMD = 0.31, 95% CI [−0.54, 1.17], p = 0.47) and sleep efficiency (SMD = 0.80, 95% CI [−0.53, 2.13], p = 0.24). CBT-I significantly improved pregnant women's sleep quality, insomnia severity, depression, and anxiety. This meta-analysis provides evidence that CBT-I is valid for insomnia or sleep disturbances during pregnancy.     

Effect of maternal HIV infection,BMI and NOx air pollution exposure on birth outcomes in South African pregnant women genotyped for the p53 Pro72Arg (rs1042522)

Tumour suppressor protein, p53, plays a role in modulating innate immune responses, DNA repair, cell cycle arrest, senescence and apoptosis. Maternal nitrogen oxide (NOx) air pollution exposure, body mass index (BMI), human immunodeficiency virus (HIV) infection and p53 Pro72Arg (rs1042522) affect foetal growth. We investigated whether the aforementioned factors influence birth outcomes in a South African population. Pregnant women (n = 300; HIV ?ve = 194 and HIV +ve = 106) were genotyped for the p53 rs1042522 using polymerase chain reaction–restriction fragment length polymorphism (PCR‐RFLP), and further stratified based on HIV status, infants' birthweight (BW; NBW: normal BW [>2,500 g] and LBW: low BW [<2,500 g]) and gestational age (GA; NGA: normal GA [>37 weeks] and PTB: preterm birth [≤37 weeks]). A land use regression model was developed to characterize maternal NOx exposure. Pearson's correlation and multivariate regression analysis statistical tests were used to determine the effect of rs1042522 genotyped pregnant women's BMI and NOx exposure on maternal blood pressure and haemoglobin and iron levels, and infants' anthropometric measurements and Appearance Pulse Grimace Activity and Respiration (APGAR) scores. The prevalence of LBW and PTB was 14.7% and 18.7%, respectively. The LBW group had a higher frequency of the variant Arg‐allele versus NBW group (47.7% vs. 31.4%, p = .0046, OR = 2.0, 95% CI = 1.26–3.17). No association was observed between NGA and PTB groups. A significant association between BMI and systolic blood pressure (r = .50, p = .00; B = 0.76, p = .002) and birth length (r = ?.28, p = .01; B = ?0.107, p = .011), and NOx and birth length (r = ?.26, p = .08; B = ?0.191, p = .046) and birthweight (B = ?8.87, p = .048) was observed in HIV‐infected mothers with the variant Pro/Arg + Arg/Arg genotypes. Mothers from the LBW group with the variant genotypes displayed an association between NOx and diastolic blood pressure (r = .58, p = .04), blood iron levels (r = ?.60, p = .04; B = ?0.204, p = .004), APGAR scores at 1 min (r = ?.86, p = .00; B = ?0.101, p = .003) and 5 min (r = ?.75, p = .01) and birth length (r = ?.61, p = .04), and BMI and diastolic blood pressure (r = .72, p = .01). In the PTB group, maternal variant genotypes and NOx were associated with blood haemoglobin levels (B = ?0.132, p = .045) and APGAR scores at 1 min (B = ?0.161, p = .045) and 5 min (B = ?0.147, p = .043). Maternal rs1042522 Arg‐allele, HIV infection, BMI and NOx exposure collectively play a role in lowering blood iron levels, gestational hypertension and LBW outcomes.     

Time‐efficient measurement of multi‐phase arterial spin labeling MR signal in white matter

White matter (WM) perfusion has great potential as a physiological biomarker in many neurological diseases. Although it has been demonstrated previously that arterial spin labeling magnetic resonance imaging (ASL‐MRI) enables the detection of the perfusion‐weighted signal in most voxels in WM, studies of cerebral blood flow (CBF) in WM by ASL‐MRI are relatively scarce because of its particular challenges, such as significantly lower perfusion and longer arterial transit times relative to gray matter (GM). Recently, ASL with a spectroscopic readout has been proposed to enhance the sensitivity for the measurement of WM perfusion. However, this approach suffers from long acquisition times, especially when acquiring multi‐phase ASL datasets to improve CBF quantification. Furthermore, the potential increase in the signal‐to‐noise ratio (SNR) by spectroscopic readout compared with echo planar imaging (EPI) readout has not been proven experimentally. In this study, we propose the use of time‐encoded pseudo‐continuous ASL (te‐pCASL) with single‐voxel point‐resolved spectroscopy (PRESS) readout to quantify WM cerebral perfusion in a more time‐efficient manner. Results are compared with te‐pCASL with a conventional EPI readout for both WM and GM perfusion measurements. Perfusion measurements by te‐pCASL PRESS and conventional EPI showed no significant difference for quantitative WM CBF values (Student's t‐test, p = 0.19) or temporal SNR (p = 0.33 and p = 0.81 for GM and WM, respectively), whereas GM CBF values (p = 0.016) were higher using PRESS than EPI readout. WM CBF values were found to be 18.2 ± 7.6 mL/100 g/min (PRESS) and 12.5 ± 5.5 mL/100 g/min (EPI), whereas GM CBF values were found to be 77.1 ± 11.2 mL/100 g/min (PRESS) and 53.6 ± 9.6 mL/100 g/min (EPI). This study demonstrates the feasibility of te‐pCASL PRESS for the quantification of WM perfusion changes in a highly time‐efficient manner, but it does not result in improved temporal SNR, as does traditional te‐pCASL EPI, which remains the preferred option because of its flexibility in use.     

Perfusion has no effect on the in vivo CEST effect from Cr (CrCEST) in skeletal muscle

Creatine, a key component of muscle energy metabolism, exhibits a chemical exchange saturation transfer (CEST) effect between its amine group and bulk water, which has been exploited to spatially and temporally map creatine changes in skeletal muscle before and after exercise. In addition, exercise leads to an increase in muscle perfusion. In this work, we determined the effects of perfused blood on the CEST effects from creatine in skeletal muscle. Experiments were performed on healthy human subjects (n = 5) on a whole‐body Siemens 7T magnetic resonance imaging (MRI) scanner with a 28‐channel radiofrequency (RF) coil. Reactive hyperemia, induced by inflation and subsequent deflation of a pressure cuff secured around the thigh, was used to increase tissue perfusion whilst maintaining the levels of creatine kinase metabolites. CEST, arterial spin labeling (ASL) and ³¹P MRS data were acquired at baseline and for 6 min after cuff deflation. Reactive hyperemia resulted in substantial increases in perfusion in human skeletal muscle of the lower leg as measured by the ASL mean percentage difference. However, no significant changes in CrCEST asymmetry (CrCEST_asym) or ³¹P MRS‐derived PCr levels of skeletal muscle were observed following cuff deflation. This work demonstrates that perfusion changes do not have a major confounding effect on CrCEST measurements.     

Restless legs syndrome and health‐related quality of life in adults with multiple sclerosis

Restless legs syndrome (RLS) is a sleep disorder that may exacerbate many of the symptoms and consequences of multiple sclerosis (MS), and may have further implications for health‐related quality of life (HRQOL). The present study examined the relationships among RLS, symptoms and HRQOL in people with MS. Participants with MS (n = 275) completed the Cambridge‐Hopkins Restless Legs Syndrome Questionnaire, the International Restless Legs Syndrome Study Group Scale, the Multiple Sclerosis Impact Scale, the Pittsburgh Sleep Quality Index, the Fatigue Severity Scale, the Hospital Anxiety and Depression Scale and the Patient Determined Disease Steps. There were 74 (26.9%) persons with MS who had RLS (MS + RLS). The MS + RLS group reported worse physical and psychological HRQOL (p = 0.020 and p = 0.017, respectively) and greater perceived fatigue (p = 0.006) and anxiety symptoms (p = 0.042) than the MS‐only group. Within the MS + RLS group, RLS severity was associated with physical (r = 0.43) and psychological (r = 0.46) HRQOL, sleep quality (r = 0.38), perceived fatigue (r = 0.28), depression (r = 0.38) and anxiety (r = 0.28). The relationships between RLS severity and the domains of HRQOL were attenuated when accounting for fatigue, depression and/or anxiety. Worse RLS severity was associated with reduced HRQOL, which was accounted for by fatigue, depression and anxiety.     

A dimensional examination of eating disorder symptoms in relation to cognitive processing: An event‐related potentials study

Identifying neurocognitive mechanisms involved in individuals experiencing eating disorder (ED) symptoms may be important for preventing EDs and improving rates of recovery. The present pilot study assessed how cognitive functioning may be associated with ED symptoms in college students (N = 41). Cognitive functioning was examined using electroencephalography during an auditory response inhibition task to measure the P3 component of event‐related potentials. Multiple regression analysis revealed that longer P3 latencies in the frontal region of the cortex were significantly and linearly associated with greater ED symptoms F(3, 37) = 13.62, p < .001, R² = 0.525, Adj. R² = 0.486. These pilot findings build upon prior work in clinical samples in that they indicate that functional brain differences are observable across a wide span of ED symptoms, not just in those with diagnosed ED. The present findings provide support for further exploration of changes in P3 latencies among individuals with ED symptoms to enhance our understanding of neural mechanisms that may pertain to the dimensional aspects of disordered eating attitudes and behaviors.     

Oxidative stress, inflammation, and muscle soreness in an 894-km relay trail run

We describe the effects of multi-day relay trail running on muscle soreness and damage, and systemic immune, inflammatory, and oxidative responses. 16 male and 4 female athletes ran 894 km in 47 stages over 95 h, with mean (SD) 6.4 (1.0) stages per athlete and 19.0 (1.7) km per stage. We observed post–pre run increases in serum creatine kinase (qualified effect size extremely large, p = 0.002), IL-6 (extremely large, p < 0.001), urinary 8–isoprostane/creatinine (extremely large, p = 0.04), TNF-α (large, p = 0.002), leukocyte count (very large, p < 0.0001) and neutrophil fraction (very large, p < 0.001); and reductions in hemoglobin (moderate, p < 0.001), hematocrit (moderate, p < 0.001), and lymphocyte fraction (trivial, p < 0.001). An increase in ORAC total antioxidant capacity (TAC, small, p = 0.3) and decrease in urinary 8-OHdG/creatinine (small, p = 0.1) were not statistically significant. During the run, muscle soreness was most frequent in the quadriceps. The threshold for muscle pain (pain-pressure algometry) in the vastus lateralis and gastrocnemius was lower post-run (small, p = 0.04 and 0.03). Average running speed was correlated with algometer pain and leukocyte count (large, r = 0.52), and TAC was correlated with IL-6 (very large, r = 0.76) and 8-isoprostane/creatinine (very large, r = −0.72). Multi-day stage-racing increases inflammation, lipid peroxidation, muscle damage and soreness without oxidative DNA damage. High TAC is associated with reduced exercise-induced lipid peroxidation, but is not related to immune response or muscle damage.     

Serum testosterone in Nigerian men with type 2 diabetes mellitus and its relationship with insulin sensitivity and glycemic control

BackgroundThere is increasing evidence that testosterone deficiency has key associations with insulin sensitivity and glycemic control. Its presence may therefore contribute to and/or exacerbate clinical disease in men with type 2 diabetes mellitus (T2DM). This study sought to determine the frequency of low free testosterone and explore its relationship with, insulin sensitivity and glycemic control among Nigerian men with T2DM.MethodsOne hundred and four men with type 2 DM and one hundred and one apparently healthy non-diabetic men matched for age, were recruited into the study Socio-demographic data, anthropometric measurements and blood samples were obtained for measurement of serum total testosterone (TT), sex hormone binding globulin (SHBG), fasting plasma insulin, fasting plasma glucose (FPG), glycated hemoglobin (HbA1c) and fasting lipid profile in all the subjects. Insulin sensitivity (%IS) and free testosterone (CFT) were then calculated.ResultsThe median CFT for men with T2DM was significantly lower than that of non-diabetic controls (0.17 nmol/L vs 0.58 nmol/L respectively; P < 0.001). 52.9% of men with T2DM had low CFT, as compared with 21.4% amongst the non-diabetic controls; P < 0.001.Among men with T2DM, those with lower CFT had significantly lower median % S and higher mean HbA1c than those with normal CFT (37.0% versus 63.0%; P = 0.021 and 7.79 (2.03) % versus 7.02 (1.94) %; P = 0.038 respectively]. HbA1c had significant negative correlations with both CFT (correlation coefficient: ?0.239 (P < 0.05) and TT (correlation coefficient: 0.354; P < 0.01.There was no significant difference in serum lipids when T2DM men with low serum CFT were compared with T2DM men with normal serum CFT levels.ConclusionWe conclude that low serum testosterone is common among men with T2DM and has a significant association with glycemic control (HbA1c) and insulin sensitivity.     

Plasma TNF-α and IL-10 Level-Based Prognostic Model Predicts Outcome of Patients with Diffuse Large B-Cell Lymphoma in Different Risk Groups Defined by the International Prognostic Index

Tumor necrosis factor (TNF)-α and interleukin (IL)-10 are key cytokines involved in lymphoma development. Their pretreatment plasma levels were reported to influence the clinical course of non-Hodgkin’s lymphoma. In this study the impact of combined elevation of TNF-α and IL-10 on disease features and outcome of patients with diffuse large B-cell lymphoma (DLBCL) were investigated. Plasma TNF-α and IL-10 levels were determined at the time of diagnosis in a group of 106 DLBCL patients uniformly treated with anthracycline-based regimens. Three risk groups depending on the pretreatment levels of the cytokines were identified: low-, intermediate-, and high-risk groups. In univariate analysis, the cytokine intermediate- and high-risk groups were associated with lower probability of achieving a complete remission (odds ratio [OR] = 0.2, 95% confidence interval [CI] 0.06–0.6, p = 0.006 and OR = 0.05, 95% CI 0.01–0.2, p < 0.0001, respectively) and shorter progression-free survival (PFS) (OR = 4.4, 95% CI 1.9–10.2, p < 0.001 and OR = 9.7, 95% CI 4.1–23.0, p < 0.0001, respectively) and overall survival (OS) (OR = 4.2, 95% CI 1.7–10.1, p = 0.002 and OR = 11.2, 95% CI 4.4–28.4, p < 0.0001, respectively) in comparison with the cytokine low-risk group. In multivariate analysis, the cytokine intermediate- and high-risk groups also correlated with shorter PFS (relative risk [RR] = 4.5, 95% CI 1.9–10.9, p = 0.001 and RR = 5.8, 95% CI 2.2–15.3, p < 0.0001, respectively) and OS (RR = 4.6, 95% CI 1.8–12.0, p = 0.001 and RR = 7.5, 95% CI 2.7–20.9, p < 0.0001, respectively) regardless of the International Prognostic Index (IPI) scoring system. The TNF-α and IL-10 level-based index may work as an additional model to the IPI for predicting the survival of DLBCL patients. This model may help to identify patients in a given IPI risk group for whom more accurate and risk-adapted treatment could be advised.     

Rhythmic Oscillations of Human Penile Bioimpedance in Healthy Individuals and in Patients with Vascular Erectile Dysfunction

Small variations of electric impedance (bioimpedance) of human penis were examined in healthy volunteers and in patients with vascular erectile dysfunction (ED). The harmonic analysis revealed rhythmic oscillations of penile bioimpedance at frequencies corresponding to the heart and respiration rates and Mayer wave (0.1 Hz) and to multiple frequencies (harmonics) of the respiratory and cardiac oscillations. In normal penile bioimpedance spectrum, the Mayer and respiratory peaks were several times higher than the first cardiac (pulsatile) harmonic indicating neurogenic origin of rhythmic bioimpedance variations in the whole penis. The most of healthy individuals (78%) demonstrated the cardiac harmonics at the frequency range of 4–7 Hz that violated the monotone decrement of the pulsatile harmonic series suggesting the resonant character of oscillations of the penile arteries at this “near” frequency range. In contrast to stable 1–4 cardiac harmonics, the amplitudes of the near-range resonant harmonics could vary during few minutes suggesting a causal relation of the corresponding bioimpedance oscillations with the varying vascular tone in penile arteries. The most patients (89%) with vascular ED demonstrated not only the first 1–4 monotonically decrementing harmonics and the near-resonant ones, but also the stable cardiac harmonics at the “far” frequency range of 8–14 Hz that also disturbed the monotonic character of the cardiac harmonic series indicating the sclerotic alterations in regional arteries. In ED patients, insignificant decrease of the initial cardiac harmonics C1-C3 in comparison with the norm was accompanied by pronounced and significant decrease of the respiratory R1 and Mayer M1 peaks. The study showed that the far-frequency bioimpedance resonances at the range of 8–14 Hz and dramatic drop of Mayer and respiratory peaks are the diagnostic signs of vascular ED independent on the accompanying hormonal or neurogenic disorders.     

The Burn Wound Inflammatory Response Is Influenced by Midazolam

Burn patients requiring hospitalization are often treated for anxiety with benzodiazepines (BDZs). Benzodiazepines are reported to influence immune system function. Immune system alterations are a major cause of burn-induced mortality. We wanted to determine whether the BDZ, midazolam given daily at an anxiolytic dose, had any influence on the burn injury-induced inflammatory response in the blood and wound. Mice received a 15% total body surface area flame burn and received either midazolam 1 mg/kg i.p. or saline 0.1 ml daily. Blood and skin wounds were harvested 24 h after injection on post-burn day 2, 3, 7, or 8. Mice treated with midazolam had significantly lower serum IL-1β (p = 0.002), TNF-α (p = 0.002), IL-6 (p = 0.016), IL-10 (p = 0.009), and TGF-β (p = 0.004) than saline-treated mice, with little impact on serum chemokine levels. In the wound, TNF-α and IL-10 were the only cytokines significantly influenced by the drug, being lower (p = 0.018) and higher (p = 0.006), respectively. The chemokines in the wound influenced significantly by midazolam were MIP-1α, MIP-1β, and MIP-2 while MCP-1 and KC were not. There were more inflammatory cells at the burn wound margin in midazolam-treated mice on post-burn day 3. Although serum nitrate/nitrite was significantly increased by midazolam (p = 0.03), both eNOS and iNOS mRNA expression in the wound were similar to the saline group. We found that midazolam given daily after burn injury significantly influenced the inflammatory response. The clinical implications of these findings on wound healing and shock following burn injury, especially larger burns, deserve further investigation.     

Simultaneous Quantification of Perfusion and Permeability in the Prostate Using Dynamic Contrast-Enhanced Magnetic Resonance Imaging with an Inversion-Prepared Dual-Contrast Sequence

The aim of the present study was to quantify both perfusion and extravasation in the prostate to discriminate tumor from healthy tissue, which might be achieved by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using a nonspecific low-molecular-weight contrast medium (CM). To determine extravasation as well as tissue perfusion an inversion-prepared dual-contrast sequence employing a parallel acquisition technique (PAT) was designed for interleaved acquisition of T ₁-weighted images for extravasation measurement and T2-weighted images for determination of the highly concentrated bolus with a sufficiently high temporal and spatial resolution at an acceptable signal-to-noise ratio. Thirteen patients with proven prostate cancer were examined with the sequence using a combined body-array prostate coil. Before pharmacokinetic evaluation the images were intensity-corrected and, if required, motion-corrected. The pharmacokinetic model used to calculate perfusion, permeability, blood volume, interstitial volume, transit time, and vessel size index included two compartments and a correction of delay and dispersion of the arterial input function. The information provided by the dual-contrast sequence allowed application of a more elaborate model for evaluation and enabled quantification of all parameters. Peripheral prostate tumors were found to differ from peripheral healthy prostate tissue in perfusion (1.38 mL/(min cm³) vs. 0.23 mL/(min cm³), p = 0.004), mean transit time (2.88 vs. 4.88 s, p = 0.039), and blood volume (1.9  vs. 0.7%, p = 0.019). A inversion-prepared dual-contrast sequence acquiring T ₁- and -weighted images with sufficient temporal resolution and signal-to-noise ratio was successfully applied in patients with prostate cancer to quantify all pharmacokinetic parameters of inflow and extravasation of a low-molecular-weight inert tracer.     

Advanced emergency braking system reduces the risk of motor vehicle collisions caused by falling asleep while driving in patients with untreated obstructive sleep apnea

Obstructive sleep apnea leads to excessive daytime sleepiness and cognitive dysfunction, which are risk factors for motor vehicle collisions. We aimed to clarify if vehicles with an advanced emergency braking system could reduce motor vehicle collisions caused by falling asleep while driving among patients with untreated obstructive sleep apnea. We enrolled patients with untreated obstructive sleep apnea who underwent polysomnography. The questionnaires included the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, history of drowsy driving accidents, and use of an advanced emergency braking system. Multivariate analysis was performed, and odds ratios and 95% confidence intervals were calculated. This study included 1097 patients (mean age, 51.2 ± 12.9 years). Collisions caused by falling asleep while driving were recorded in 59 (5.4%) patients, and were more frequently observed in vehicles without an advanced emergency braking system (p = 0.045). Multivariate analysis showed that these collisions were associated with use of an advanced emergency braking system (odds ratio [95% confidence interval]: 0.39 [0.16–0.97], p = 0.04), length of driving (2.79 [1.19–6.50], p = 0.02), total sleep time (2.40 [1.62–3.55], p < 0.0001), sleep efficiency (0.94 [0.90–0.98], p = 0.003) and periodic limb movement index (1.02 [1.01–1.03], p = 0.004). The collision risk caused by falling asleep while driving in vehicles with an advanced emergency braking system was significantly lower. This study indicates that advanced emergency braking systems may be a preventive measure to reduce motor vehicle collisions among patients with untreated obstructive sleep apnea.     

IL-2 −330 T/G SNP and serum values—potential new tumor markers in neuroendocrine tumors of the gastrointestinal tract and pancreas (GEP-NETs)

Cytokines participate in tumorigenesis of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Single nucleotide polymorphisms (SNPs) in cytokine genes influence expression of proteins and are evaluated in cancer susceptibility. The aim of this study was to evaluate IL-2 −330 T/G SNP and susceptibility to GEP-NETs, and analyze the correlation between G-allele and IL-2 serum values in GEP-NET patients. Moreover we assessed the value of IL-2 as a tumor serum marker. IL-2 −330 T/G SNP was examined in 101 patients and 150 healthy volunteers and IL-2 serum levels in patients and 20 controls. Patients’ IL-2 serum levels were compared to IL-2 −330 T/G genotypes and tumor functional status and finally with known markers such as chromogranin A (CgA) and 5-hydroxyindolacetic acid (5-HIAA). There was a significant difference in genotype distribution of the IL-2 −330 polymorphisms between GEP-NET and control group (p = 0.0006) as well as in the frequency of G-allele (p = 0.010). G-allele correlated with higher IL-2 serum levels (p = 0.028) and elevated in all patients, being highest in patients with functional tumors (p = 0.039). Compared to CgA and 5-HIAA, IL-2 was more specific in detecting GEP-NET patients (p < 0.0001 and p < 0.0001, respectively). Our results indicate importance of IL-2 in GEP-NET development and biochemical diagnosis.     

HLA class II eplet mismatch load improves prediction of dnDSA development after living donor kidney transplantation

HLA donor‐specific antibodies developed de novo after transplant remain a major cause of chronic allograft dysfunction. Our study main purpose was to determine whether HLA MM, assessed traditionally and by HLA total and AbVer eplet mismatch load (EptMM and EpvMM) assessed with HLAMatchMaker, had impact on dnDSA development after living donor kidney transplantation (LDKT). We retrospectively analysed a cohort of 96 LDKT between 2008 and 2017 performed in Hospital Santo António. Seven patients developed dnDSA‐II and EpvMM and EptMM were greater in dnDSA‐II group compared to the no dnDSA‐II (18.0 ± 8.7 versus 9.9 ± 7.9, p = .041 and 41.3 ± 18.9 versus 23.1 ± 16.7, p = .018), which is not observed for AgMM (2.29 versus 1.56; p = .09). In a multivariate analysis, we found that preformed DSA (HR = 7.983; p = .023), living unrelated donors (HR = 8.052; p = .024) and retransplantation (HR = 14.393; p = .009) were predictors for dnDSA‐II (AUC = 0.801; 0.622–0.981). HLA‐II EpvMM (HR = 1.105; p = .028; AUC = 0.856) showed to be a superior predictor of dnDSA‐II, when compared to AgMM (HR = 1.740; p = .113; AUC = 0.783), when adjusted for these clinical variables. Graft survival was significantly lower within dnDSA‐II patient group (36% versus 88%, p < .001). HLA molecular mismatch analysis is extremely important to minimize risk for HLA‐II dnDSA development improving outcome and increasing chance of retransplant lowering allosensitization.     

A 7‐year follow‐up study of the Mindfulness‐Based Program for Infertility: Are there long‐term effects?

The Mindfulness‐Based Program for Infertility (MBPI) was developed for people facing infertility and proved effective in cultivating mindfulness skills, improving infertility self‐efficacy, and decreasing depression, shame, entrapment, and defeat feelings. Fifty‐five women attended the MBPI sessions and completed self‐report measures of depression, anxiety, mindfulness, and experiential avoidance at post‐MBPI (T1), 6‐month follow‐up (T2), and 7‐year follow‐up (T3). There were significant direct time effects regarding experiential avoidance (F = 3.81; p < 0.033; η_p² = 0.08), the mindfulness facets describing (F = 3.54; p = 0.037; η_p² = 0.13), acting with awareness (F = 6.87; p = 0.002; η_p² = 0.22), nonjudging of inner experience (F = 10.66; p < 0.001; η_p² = 0.31), and depressive symptoms (F = 4.85; p = 0.020; η_p² = 0.10). There was an increase in the describing facet from T1 to T3 (p = 0.036). The act with awareness facet increased from T1 to T2 (p = 0.010) and from T1 to T3 (p = 0.007), as well as the nonjudging of inner experience facet (T1 to T2 [p = 0.030] and T1 to T3 [p = 0.002]). Experiential avoidance decreased from T1 to T3 (p = 0.022) and depressive symptoms from T1 to T2 (p = 0.019). Post‐MBPI scores were maintained at T2 and T3 concerning anxiety symptoms and the observing and no‐reactivity mindfulness facets. There were long‐term effects of MBPI on mindfulness and experiential avoidance. Moreover, therapeutic gains were maintained regarding depression and anxiety symptoms, independently of the reproductive outcome.     

Human leucocyte antigen‐G 14‐bp InDel polymorphism and oral squamous cell carcinoma risk in Chinese Han population: A case–control study

Human leucocyte antigen‐G (HLA‐G) is a nonclassical HLA class I molecule involved in tumour immune escape. The purpose of this study was to investigate the association between the 14‐bp insertion/deletion (InDel) polymorphism in the 3′ untranslated region (3′‐UTR) of HLA‐G gene and oral squamous cell carcinoma (OSCC) risk in Chinese Han population (216 cases and 193 healthy controls), and furthermore, to evaluate serum soluble HLA‐G (sHLA‐G) levels in the OSCC patients. Our results demonstrated that the Ins allele was significantly less frequent in the OSCC patients than that in the healthy controls (odds ratio [OR] = 0.75; 95% confidence interval [CI]: 0.57–0.99; p = 0.040). Distribution of the 14‐bp genotypes in the OSCC patients and the healthy controls revealed that the Ins/Ins genotype was associated with decreased OSCC risk in both the codominant model (Ins/Ins versus Del/Del; OR = 0.57; 95% CI = 0.33–0.99; p = 0.044) and the log‐additive model (OR = 0.76; 95% CI: 0.58–0.99; p = 0.044). The serum sHLA‐G level was significantly higher in the OSCC patients than those in the healthy controls (p < 0.001). Receiver operating characteristic (ROC) curve revealed the valuable diagnostic value of sHLA‐G for OSCC detection, with an area under the ROC curve (AUC) of 0.891 (95% CI: 0.856–0.925, p < 0.001). The OSCC patients with Ins/Ins genotype had lower serum sHLA‐G levels than those with Ins/Del and Del/Del genotypes (p = 0.015). Furthermore, serum sHLA‐G levels were significantly increased with the increasing TNM stages of the OSCC patients (p = 0.017). Our findings revealed that the HLA‐G 14‐bp InDel polymorphism might be a genetic risk factor for OSCC susceptibility, and the serum sHLA‐G may act as a promising biomarker for noninvasive diagnosis of OSCC.     

Gender differences in clinical,laboratory and polysomnographic features of restless legs syndrome

Restless legs syndrome is a common neurological disorder with a clear female predominance. This study aims to evaluate gender differences in clinical, laboratory and polysomnographic features in patients with restless legs syndrome. For this retrospective analysis, 42 women and 42 men from the Innsbruck RLS database matched by age and therapy were included. Demographic data as well as different severity scales (IRLS, RLS‐6 and CGI) were evaluated. Laboratory parameters included several indicators of serum iron status. In all patients, polysomnography was performed according to the AASM guidelines, and periodic leg movements during sleep were scored according to the AASM criteria. IRLS, RLS‐6 and CGI revealed more severe symptoms in women (IRLS median [range]: 17.5 [0–35] versus 13.5 [0–32], p = 0.028; RLS‐6 median [range]: 18 [0–39] versus 12 [1–42], p = 0.014). Women had lower serum ferritin levels than men (median [range] in μg L^?1: 74 [9–346] versus 167 [15–389], p < 0.001). Twenty‐two women and eight men (53.7% versus 22.2%, p = 0.003) had ferritin values below 75 μg L^?1. Periodic leg movements during sleep indices were significantly lower in women than in men (median [range] in number per hr: 11.4 [0–62.5] versus 40 [0–154], p = 0.004, and 12.6 [0–58.5] versus 40 [0.5–208], p = 0.002, for night I and night II, respectively). Restless legs syndrome severity as measured by validated scales was worse in women, while periodic leg movements during sleep indices were higher in men. These results suggest a possible gender difference in phenotypical presentation of restless legs syndrome, manifesting with predominantly sensory symptoms in women and predominantly motor symptoms in men.