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Study Question: Can additional genetic variants for circulating anti-Müllerian hormone (AMH) levels be identified through a genome-wide association study (GWAS) meta-analysis including a large sample of premenopausal women?Summary Answer: We identified four loci associated with AMH levels at P < 5 × 10-8: the previously reported MCM8 locus and three novel signals in or near AMH, TEX41 and CDCA7.What Is Known Already: AMH is expressed by antral stage ovarian follicles in women, and variation in age-specific circulating AMH levels has been associated with disease outcomes. However, the physiological mechanisms underlying these AMH-disease associations are largely unknown.Study Design, Size, Duration: We performed a GWAS meta-analysis in which we combined summary statistics of a previous AMH GWAS with GWAS data from 3705 additional women from three different cohorts.Participants/materials, Setting, Methods: In total, we included data from 7049 premenopausal female participants of European ancestry. The median age of study participants ranged from 15.3 to 48 years across cohorts. Circulating AMH levels were measured in either serum or plasma samples using different ELISA assays. Study-specific analyses were adjusted for age at blood collection and population stratification, and summary statistics were meta-analysed using a standard error-weighted approach. Subsequently, we functionally annotated GWAS variants that reached genome-wide significance (P < 5 × 10-8). We also performed a gene-based GWAS, pathway analysis and linkage disequilibrium score regression and Mendelian randomization (MR) analyses.Main Results and the Role Of Chance: We identified four loci associated with AMH levels at P < 5 × 10-8: the previously reported MCM8 locus and three novel signals in or near AMH, TEX41 and CDCA7. The strongest signal was a missense variant in the AMH gene (rs10417628). Most prioritized genes at the other three identified loci were involved in cell cycle regulation. Genetic correlation analyses indicated a strong positive correlation among single nucleotide polymorphisms for AMH levels and for age at menopause (rg = 0.82, FDR = 0.003). Exploratory two-sample MR analyses did not support causal effects of AMH on breast cancer or polycystic ovary syndrome risk, but should be interpreted with caution as they may be underpowered and the validity of genetic instruments could not be extensively explored.Large Scale Data: The full AMH GWAS summary statistics will made available after publication through the GWAS catalog (https://www.ebi.ac.uk/gwas/).Limitations, Reasons For Caution: Whilst this study doubled the sample size of the most recent GWAS, the statistical power is still relatively low. As a result, we may still lack power to identify more genetic variants for AMH and to determine causal effects of AMH on, for example, breast cancer. Also, follow-up studies are needed to investigate whether the signal for the AMH gene is caused by reduced AMH detection by certain assays instead of actual lower circulating AMH levels.Wider Implications Of the Findings: Genes mapped to the MCM8, TEX41 and CDCA7 loci are involved in the cell cycle and processes such as DNA replication and apoptosis. The mechanism underlying their associations with AMH may affect the size of the ovarian follicle pool. Altogether, our results provide more insight into the biology of AMH and, accordingly, the biological processes involved in ovarian ageing.Study Funding/competing Interest(s): Nurses' Health Study and Nurses' Health Study II were supported by research grants from the National Institutes of Health (CA172726, CA186107, CA50385, CA87969, CA49449, CA67262, CA178949). The UK Medical Research Council and Wellcome (217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. This publication is the work of the listed authors, who will serve as guarantors for the contents of this article. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). Funding for the collection of genotype and phenotype data used here was provided by the British Heart Foundation (SP/07/008/24066), Wellcome (WT092830M and WT08806) and UK Medical Research Council (G1001357). M.C.B., A.L.G.S. and D.A.L. work in a unit that is funded by the University of Bristol and UK Medical Research Council (MC_UU_00011/6). M.C.B.'s contribution to this work was funded by a UK Medical Research Council Skills Development Fellowship (MR/P014054/1) and D.A.L. is a National Institute of Health Research Senior Investigator (NF-0616-10102). A.L.G.S. was supported by the study of Dynamic longitudinal exposome trajectories in cardiovascular and metabolic non-communicable diseases (H2020-SC1-2019-Single-Stage-RTD, project ID 874739). The Doetinchem Cohort Study was financially supported by the Ministry of Health, Welfare and Sports of the Netherlands. The funder had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Ansh Labs performed the AMH measurements for the Doetinchem Cohort Study free of charge. Ansh Labs was not involved in the data analysis, interpretation or reporting, nor was it financially involved in any aspect of the study. R.M.G.V. was funded by the Honours Track of MSc Epidemiology, University Medical Center Utrecht with a grant from the Netherlands Organization for Scientific Research (NWO) (022.005.021). The Study of Women's Health Across the Nation (SWAN) has grant support from the National Institutes of Health (NIH), DHHS, through the National Institute on Aging (NIA), the National Institute of Nursing Research (NINR) and the NIH Office of Research on Women's Health (ORWH) (U01NR004061; U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, U01AG012495). The SWAN Genomic Analyses and SWAN Legacy have grant support from the NIA (U01AG017719). The Generations Study was funded by Breast Cancer Now and the Institute of Cancer Research (ICR). The ICR acknowledges NHS funding to the NIHR Biomedical Research Centre. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent official views of the funders. The Sister Study was funded by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Environmental Health Sciences (Z01-ES044005 to D.P.S.); the AMH assays were supported by the Avon Foundation (02-2012-065 to H.B. Nichols and D.P.S.). The breast cancer genome-wide association analyses were supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the 'Ministère de l'Économie, de la Science et de l'Innovation du Québec' through Genome Québec and grant PSR-SIIRI-701, The National Institutes of Health (U19 CA148065, X01HG007492), Cancer Research UK (C1287/A10118, C1287/A16563, C1287/A10710) and The European Union (HEALTH-F2-2009-223175 and H2020 633784 and 634935). All studies and funders are listed in Michailidou et al. (Nature, 2017). F.J.M.B. has received fees and grant support from Merck Serono and Ferring BV. D.A.L. has received financial support from several national and international government and charitable funders as well as from Medtronic Ltd and Roche Diagnostics for research that is unrelated to this study. N.S. is scientific consultant for Ansh Laboratories. The other authors declare no competing interests. [ABSTRACT FROM AUTHOR]

Objective: (1) To derive reference values for the Shock Index (heart rate/systolic blood pressure) based on a large emergency department (ED) population of febrile children and (2) to determine the diagnostic value of the Shock Index for serious illness in febrile children.Design/setting: Observational study in 11 European EDs (2017-2018).Patients: Febrile children with measured blood pressure.Main Outcome Measures: Serious bacterial infection (SBI), invasive bacterial infection (IBI), immediate life-saving interventions (ILSIs) and intensive care unit (ICU) admission. The association between high Shock Index (>95th centile) and each outcome was determined by logistic regression adjusted for age, sex, referral, comorbidity and temperature. Additionally, we calculated sensitivity, specificity and negative/positive likelihood ratios (LRs).Results: Of 5622 children, 461 (8.2%) had SBI, 46 (0.8%) had IBI, 203 (3.6%) were treated with ILSI and 69 (1.2%) were ICU admitted. High Shock Index was associated with SBI (adjusted OR (aOR) 1.6 (95% CI 1.3 to 1.9)), ILSI (aOR 2.5 (95% CI 2.0 to 2.9)), ICU admission (aOR 2.2 (95% CI 1.4 to 2.9)) but not with IBI (aOR: 1.5 (95% CI 0.6 to 2.4)). For the different outcomes, sensitivity for high Shock Index ranged from 0.10 to 0.15, specificity ranged from 0.95 to 0.95, negative LRs ranged from 0.90 to 0.95 and positive LRs ranged from 1.8 to 2.8.Conclusions: High Shock Index is associated with serious illness in febrile children. However, its rule-out value is insufficient which suggests that the Shock Index is not valuable as a screening tool for all febrile children at the ED. [ABSTRACT FROM AUTHOR]

Background: Pulse arrival time (PAT) is commonly used to estimate blood pressure response. We hypothesised that PAT response to obstructive respiratory events would be associated with increased cardiovascular risk in people with obstructive sleep apnoea.Methods: PAT, defined as the time interval between electrocardiography R wave and pulse arrival by photoplethysmography, was measured in the Multi-Ethnic Study of Atherosclerosis Sleep study participants. The PAT response to apnoeas/hypopnoeas was defined as the area under the PAT waveform following respiratory events. Cardiovascular outcomes included markers of subclinical cardiovascular disease (CVD): left ventricular mass, carotid plaque burden score and coronary artery calcification (CAC) (cross-sectional) and incident composite CVD events (prospective). Multivariable logistic and Cox proportional hazard regressions were performed.Results: A total of 1407 participants (mean age 68.4 years, female 47.5%) were included. Higher PAT response (per 1 SD increase) was associated with higher left ventricular mass (5.7 g/m2 higher in fourth vs first quartile, p<0.007), higher carotid plaque burden score (0.37 higher in fourth vs first quartile, p=0.02) and trended to greater odds of CAC (1.44, 95% CI 0.98 to 2.15, p=0.06). A total of 65 incident CVD events were observed over the mean of 4.1 (2.6) years follow-up period. Higher PAT response was associated with increased future CVD events (HR: 1.20, 95% CI 1.02 to 1.42, p=0.03).Conclusion: PAT is independently associated with markers of subclinical CVD and incident CVD events. Respiratory-related PAT response is a novel and promising polysomnography metric with cardiovascular implications. [ABSTRACT FROM AUTHOR]

Purpose: Concerns have been expressed about the possibility of high insertion torque (IT) causing necrosis, impaired osseointegration, and crestal bone loss over time. The present study investigated the relationship between primary stability and implant success, including early and late maintenance of crestal bone levels. Materials and Methods: Implants were placed in patients at three study centers. Every effort was made to achieve the highest possible primary stability, which was measured with IT and implant stability quotient (ISQ). The IT and ISQ at insertion and reopening (3 to 4 months), as well as bone levels at several points in time, were recorded. The correlations between IT, ISQ, and immediate and 3-year crestal bone loss were investigated through linear regression analyses. Results: Average IT was 76.1 ± 20.8 Ncm, while the average ISQ score was 80.4 ± 8.4. The implant success rate at 36 months was 98.6%. The crestal bone loss around most implants (41.0%) ranged from 0.05 to 0.5 mm. None of the osseointegrated implants had crestal bone loss greater than 2.5 mm. The linear regression analysis showed no correlation among early or 3-year crestal bone loss and IT, ISQ at surgery, and ISQ at reopening. Conclusion: The implants studied avoided any negative effects deriving from the high IT values (> 50 Ncm) applied during 3 years of follow-up. [ABSTRACT FROM AUTHOR]

The design of an implant-abutment interface may have an impact on the peri-implant soft tissue esthetics. In an ongoing randomized controlled trial (RCT) with 141 participants, the authors evaluated the peri-implant tissue responses around three different implant-abutment interface designs used to replace single teeth in the esthetic zone. The aim of this report is to describe the treatment protocol utilized in this ongoing RCT by (1) demonstrating in detail a clinical case treated under this protocol and (2) reporting peri-implant soft tissue responses in a cohort of 12 representative cases from the RCT at 1-year follow-up. Male and female adults requiring single implants in the anterior maxilla were enrolled in the RCT according to the study protocol. Five months following any required extraction and/or socket bone grafting/ridge augmentation, one of the following three implant-abutment interfaces was placed and immediately provisionalized: (1) conical interface (CI; OsseoSpeed, Dentsply Implants), n = 4; (2) flat-to-flat interface (FI; NobelSpeedy Replace, Nobel Biocare), n = 4; or (3) platform-switch interface (PS; NanoTite Certain Prevail, Biomet 3i), n = 4. Twelve weeks later, definitive crowns were delivered. Throughout the treatment, peri-implant buccal gingival zenith height and mesial/distal papilla height were measured on stereotactic device photographs, and pink esthetic scores (PES) were determined. The demographics of the participants in each of the three implant-abutment interface groups were very similar. All 12 study sites had ideal ridge form with a minimum width of 5.5 mm following implant site development performed according to the described treatment protocol. Using this treatment protocol for single-tooth replacement in the anterior maxilla, the clinicians were able to obtain esthetic peri-implant soft tissue outcomes with all three types of implant-abutment interface designs at 1-year follow-up as shown by the Canfield data and PES. The proposed treatment protocol for single-tooth replacement in the esthetic zone provides a reliable method to obtain and assess the esthetic outcome as a function of implant-abutment interface design and is now in its fifth year of follow-up. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective comparative study.Objective: The aim of this study was to compare cervical sagittal alignment after posterior fusion surgery with lateral mass screw (LMS) and cervical pedicle screw (CPS) fixation.Summary Of Background Data: LMS fixation in the subaxial cervical spine has become the preferred method of posterior cervical fusion. Although CPS has biomechanical benefits, it also has neurovascular risks. Few studies to date have compared sagittal alignment changes after posterior cervical fusion using CPS and LMS fixation.Methods: From 2006 to 2017, 71 consecutive patients underwent posterior cervical fusion using CPS (n = 51) or LMS (n = 20) fixation. Patients who underwent fusion with both types of screws and those who planned to undergo additional anterior fusion surgery were excluded. The minimum follow-up period was 12 months. C2-C7 Cobb angle for cervical lordosis (CL), fusion segmental angle (SA), C2-C7 sagittal vertical axis (SVA), and T1 slope (T1S) were measured.Results: Immediate postoperative SA and SVA differed significantly in patients who underwent CPS and LMS fixation. SA changes were more substantial after CPS fixation, with a significant difference maintained until final follow-up. Over time, CL, SVA, and T1S tended to return to their preoperative states regardless of screw type. Two patients who underwent LMS fixation, but none who underwent CPS fixation, required unplanned or additional anterior fusion surgery for revision.Conclusion: The present study is the first radiologic comparison of LMS and CPS fixation after posterior-only fusion surgery. CPS resulted in more reliable and well-preserved SA correction, whereas CL and SVA did not differ between the two groups over time due to loss of correction.Level of Evidence: 4. [ABSTRACT FROM AUTHOR]

Study Design: Prospective comparative study.Objective: The aim of this study was to compare the spatiotemporal, kinematic, kinetic and electromyographic (EMG) gait variables in patients with adolescent idiopathic scoliosis (AIS) and congenital scoliosis and to compare these gait variables of scoliosis patients with healthy controls.Summary Of Background Data: Earlier studies have solely focussed on the possibility of altered gait patterns in AIS patients; not much light has been shed on the differences in gait patterns in congenital and adolescent scoliosis patients.Methods: Forty scoliosis patients (20 each with AIS and congenital scoliosis) and 20 healthy volunteers were prospectively recruited. After thorough clinical and radiological examination, all patients underwent gait analysis in accordance with standard protocols.The outcome measures included spatiotemporal, kinetic, kinematic and EMG activity. Composite indices for gait analysis-Gait Profile Score (GPS) and Gait Deviation Index (GDI)-were also calculated. Relevant statistical tests were applied to compare the different groups.Results: No significant difference was found between the AIS and congenital scoliosis groups with respect to baseline demographic and radiological parameters. The two subgroups of scoliosis patients (AIS and congenital) did not differ significantly with respect to any of the measured gait analysis parameters. However, when compared to the healthy age-matched control group, the scoliosis patients differed significantly with respect to gait speed, stride length, step length, GDI, GPS and peak EMG activation for erector spinae, biceps femoris, semimembranosus, rectus femoris, gastrocnemious, and tibialis anterior.Conclusion: Our findings confirm the previous findings of literature regarding the alteration in gait patterns in scoliosis patients when compared to normal individuals. However, the lack of difference in gait analysis variables between AIS and congenital scoliosis patients suggests that this alteration in gait is secondary to the existence of the deformity and does not correlate with the onset or etiology of deformity.Level of Evidence: 2. [ABSTRACT FROM AUTHOR]

Background: In patients with peripheral arterial disease and presenting intermittent claudication (PAD-IC), the pain due to ischemia impacts gait parameters, particularly in cases of unilateral disease. Deterioration of gait parameters in a pathological context is frequently associated with increased coactivation (simultaneous activation of agonist and antagonist muscles around a joint).Research Question: Does unilateral PAD-IC affect the coactivation pattern during walking? Does the coactivation pattern change with increasing pain intensity?Method: We evaluated symptomatic and asymptomatic legs in 17 subjects with unilateral PAD-IC and 16 without PAD-IC (control group), during walking. Tibialis anterior (TA) and gastrocnemius medialis (GM) electromyographic activity, and peaks of vertical ground reaction force were recorded in this prospective study. We analyzed the coactivation index (CI(GM/TA)) during three periods (pain-free, pain and maximum pain) and phases of the gait cycle. Statistical analysis was carried out using the ANOVA procedure.Results: During single support, CI(GM/TA) increases in the symptomatic leg during the pain period (+28 %) and in the asymptomatic leg during the maximum pain period (+29 %). During second double support, CI(GM/TA) increases in the symptomatic leg only (+49 %). In these gait phases, pain elicits differences in CI(GM/TA) between legs (p < 0.05). Second peak force decreases in the symptomatic leg only (-9%) and is negatively correlated with CI(GM/TA) during the three periods (r = -0.57; -0.76 and -0.78 respectively, p < 0.05). No difference is found in the control group.Significance: The appearance and development of pain in the lower limbs is associated with a higher level of CI(GM/TA), revealing a compensatory gait pattern in PAD-IC patients. Optimal prevention, rehabilitation and re-training strategies for PAD-IC patients should take into consideration neuromuscular compensatory mechanisms between asymptomatic and symptomatic legs. [ABSTRACT FROM AUTHOR]

Context: Dietary fiber intake may relate to bone health.Objective: To investigate whether dietary fiber intake is associated with bone mineral density (BMD), and the modification effect of genetic variations related to gut microbiota-derived short-chain fatty acids (SCFAs).Design: The associations of dietary fiber intake with estimated BMD derived from heel ultrasound and fractures were assessed in 224 630 and 384 134 participants from the UK Biobank.Setting: UK Biobank.Main Outcome Measures: Estimated BMD derived from heel ultrasound.Results: Higher dietary fiber intake (per standard deviation) was significantly associated with higher heel-BMD (β [standard error] = 0.0047 [0.0003], P = 1.10 × 10-54). Similarly significant associations were observed for all the fiber subtypes including cereal, fruit (dried and raw), and vegetable (cooked and raw) (all P < .05). A positive association was found in both women and men but more marked among men except for dietary fiber in cooked vegetables (all Pinteraction < .05). A protective association was found between dietary fiber intake and hip fracture (hazard ratio, 95% confidence interval: 0.94, 0.89-0.99; P = 3.0 × 10-2). In addition, the association between dietary fiber and heel BMD was modified by genetically determined SCFA propionate production (Pinteraction = 5.1 × 10-3). The protective association between dietary fiber and heel BMD was more pronounced among participants with lower genetically determined propionate production.Conclusions: Our results indicate that greater intakes of total dietary fiber and subtypes from various food sources are associated with higher heel-BMD. Participants with lower genetically determined propionate production may benefit more from taking more dietary fiber. [ABSTRACT FROM AUTHOR]

Migraine is the most common neurological disorder worldwide and it has been shown to have complex polygenic origins with a heritability of estimated 40-70%. Both common and rare genetic variants are believed to underlie the pathophysiology of the prevalent types of migraine, migraine with typical aura and migraine without aura. However, only common variants have been identified so far. Here we identify for the first time a gene module with rare mutations through a systems genetics approach integrating RNA sequencing data from brain and vascular tissues likely to be involved in migraine pathology in combination with whole genome sequencing of 117 migraine families. We found a gene module in the visual cortex, based on single nuclei RNA sequencing data, that had increased rare mutations in the migraine families and replicated this in a second independent cohort of 1930 patients. This module was mainly expressed by interneurons, pyramidal CA1, and pyramidal SS cells, and pathway analysis showed association with hormonal signalling (thyrotropin-releasing hormone receptor and oxytocin receptor signalling pathways), Alzheimer's disease pathway, serotonin receptor pathway and general heterotrimeric G-protein signalling pathways. Our results demonstrate that rare functional gene variants are strongly implicated in the pathophysiology of migraine. Furthermore, we anticipate that the results can be used to explain the critical mechanisms behind migraine and potentially improving the treatment regime for migraine patients. [ABSTRACT FROM AUTHOR]

Background: Mobility aids are commonly prescribed to offload an injured lower extremity. Device selection may impact stance foot loading patterns and foot health in clinical populations at risk of foot ulceration.Research Questions: Two questions motivated this study: How does device selection influence peak plantar and regional (rearfoot, mid foot and forefoot) foot forces on the stance foot? Does device selection influence peak, cumulative, and regional plantar forces within a 200 m walking trial?Methods: Twenty-one older adults walked 200 m at self-selected pace in four randomized conditions for this prospective crossover study. Participants used a walker, crutches, wheeled knee walker (WKW), and no assistive device (control condition). Plantar forces were measured using a wireless in-shoe system (Loadsol, Novel Inc., St. Paul, MN). Repeated measures analyses of variance were used to determine differences in peak and cumulative total and regional forces among walking conditions. Paired sample t-tests compared forces during first and last 30 s epochs of each condition to determine device influence over time.Results: The WKW reduced peak net forces by 0.29 and 0.35 bodyweight (BW) when compared to the walker or control condition with similar trends in all foot regions. Crutch use had similar peak forces as control. There were no differences in the number of steps taken within devices comparing first and last epochs. Crutches had a 0.04 and 0.07 BW increase in peak net and forefoot forces during the last epoch. Walker use had 66.44 BW lower cumulative forefoot forces in the last epoch.Significance: Crutches had similar stance foot loading as normal walking while a walker lowered forefoot forces at the expense of increased steps. A WKW may be the best choice to 'protect' tissues in the stance foot from exposure to peak and cumulative forces in the forefoot region. [ABSTRACT FROM AUTHOR]

Background: Even in mild unilateral cerebral palsy increased internal hip rotation can be noted on physical- and gait examination. The influence of spasticity on femoral growth in the transverse plane is not clear. These deviations and asymmetry in movement pattern may negatively affect efficiency of gait and cause psychological concerns about appearance.Research Question: Is increased internal hip rotation on the involved side in mild unilateral CP common and is there compensatory external pelvic rotation to keep foot progression symmetrical?Methods: This prospective study included 45 individuals with unilateral cerebral palsy, mean age 17.7 (13.0-24.0) years. All were Gross Motor Function Classification Level I. Physical examination, three-dimensional gait analysis and magnetic resonance imaging for assessment of rotational alignment was performed.Results: On physical examination internal hip rotation was mean 50.6 (SD 10.4) degrees on the involved side and 44.3 (SD 10.3) on the non-involved side, p = 0.001. In gait analysis calculating the whole gait cycle, internal hip rotation was mean 2.3 (6.2) degrees on the involved side, and on the non-involved side external 1.8 (7.6) degrees, p = 0.004. Increased external pelvic rotation was noted on the involved side, mean 2.0 (4.3) degrees with corresponding internal rotation on the non-involved side, mean 3.6 (4.4), p = 0.001. There was no difference in foot progression, p = 0.067, with mean 5.1 (8.6) and 3.9 (6.4) external respectively. Magnetic resonance imaging revealed femoral torsion on the involved side mean 17.3 (11.3) degrees compared to 11.4 (10.8) on the non-involved side, p = 0.001.Significance: Transverse plane asymmetry in the femur was noted in mild unilateral cerebral palsy. Increased anatomical and dynamic internal rotation was compensated for by external pelvic rotation. Rotational malalignment may contribute to gait deviations in this mild group and should be part of the overall assessment. [ABSTRACT FROM AUTHOR]

Background: We aimed to compare the intraocular pressure (IOP) measurements by a dynamic Scheimpflug analyzer (Corvis ST), a non-contact tonometer, and an ocular response analyzer after hyperopic small-incision lenticule extraction (SMILE).Methods: Thirteen patients who underwent hyperopic SMILE in one eye were enrolled prospectively. IOP and corneal biomechanical parameters were measured preoperatively and at 1 week, 1 month, and 3 months postoperatively with a non-contact tonometer (IOPNCT), Corvis ST (biomechanical corrected IOP [bIOP]), and ocular response analyzer (Goldmann-correlated intraocular pressure [IOPg] and cornea compensated IOP [IOPcc]). A linear mixed model was used to compare the IOPs and biomechanical values among methods at each time point.Results: IOPNCT, IOPg, and IOPcc dropped significantly after surgery, with the amplitude being 3.15 ± 0.48 mmHg, 5.49 ± 0.94 mmHg, and 4.34 ± 0.97 mmHg, respectively, at the last follow-up visit. IOPNCT decreased by 0.11 ± 0.06 mmHg per μm of excised central corneal thickness. bIOP did not change significantly after surgery. Preoperatively, no difference was found among the four measurements (P > 0.05). Postoperatively, IOPNCT and bIOP were higher than IOPg and IOPcc. bIOP was independent of cornea thickness at last follow-up visit, whereas it correlated significantly with corneal biomechanics similar to the other three IOP values.Conclusion: bIOP is a relative accurate measure of IOP after hyperopic SMILE. [ABSTRACT FROM AUTHOR]

Objective: High-flow nasal cannula (HFNC) therapy is increasingly used in preterm infants despite a paucity of physiological studies. We aimed to investigate the effects of HFNC on respiratory physiology.Study Design: A prospective randomised crossover study was performed enrolling clinically stable preterm infants receiving either HFNC or nasal continuous positive airway pressure (nCPAP). Infants in three current weight groups were studied: <1000 g, 1000-1500 g and >1500 g. Infants were randomised to either first receive HFNC flows 8-2 L/min and then nCPAP 6 cm H2O or nCPAP first and then HFNC flows 8-2 L/min. Nasopharyngeal end-expiratory airway pressure (pEEP), tidal volume, dead space washout by nasopharyngeal end-expiratory CO2 (pEECO2), oxygen saturation and vital signs were measured.Results: A total of 44 preterm infants, birth weights 500-1900 g, were studied. Increasing flows from 2 to 8 L/min significantly increased pEEP (mean 2.3-6.1 cm H2O) and reduced pEECO2 (mean 2.3%-0.9%). Tidal volume and transcutaneous CO2 were unchanged. Significant differences were seen between pEEP generated in open and closed mouth states across all HFNC flows (difference 0.6-2.3 cm H2O). Infants weighing <1000 g received higher pEEP at the same HFNC flow than infants weighing >1000 g. Variability of pEEP generated at HFNC flows of 6-8 L/min was greater than nCPAP (2.4-13.5 vs 3.5-9.9 cm H2O).Conclusions: HFNC therapy produces clinically significant pEEP with large variability at higher flow rates. Highest pressures were observed in infants weighing <1000 g. Flow, weight and mouth position are all important determinants of pressures generated. Reductions in pEECO2 support HFNC's role in dead space washout. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluated the pretreatment influence of occlusal splints and relines on mandibular movements (MM) and vertical dimension of occlusion (VDO) in longstanding complete denture wearers.Materials and Methods: A total of 30 volunteers were randomly assigned to three groups (n = 10): control (C), relining of old denture (RD), and occlusal splints (OS). Individual extent of MM was assessed via intraoral Gothic arch tracings and the VDO using posed frontal images taken at three time points.Results: The OS group showed statistically significant differences when compared with the other groups (P < .05).Conclusion: Both MM and VDO were significantly improved by use of occlusal splints pretreatment. [ABSTRACT FROM AUTHOR]

Introduction: The understanding of the temporal pattern of individuals can add a wider perspective to interventions. Therefore, the present study is aimed toward analysis of the temporal activity pattern of individuals with stroke compared to healthy adults. Method: This study is a prospective, case–control, analytic research study. The study sample comprised 50 individuals with stroke and 50 individuals without disease, for 80% power with a 5% type 1 error. The Modified Occupational Questionnaire was administered to assess the temporal activity pattern. Individuals identified the activities performed at each hour of the day and data was analyzed. Results: The temporal activity pattern of individuals with stroke differed from healthy controls; education and play activities were not part of stroke participants' daily routines. Also, participation in work, leisure and social participation activities was significantly different for people with stroke compared to healthy controls (p < 0.01). The study group assigned very low values to the activities; the value perceived by individuals differed significantly between groups (p < 0.01). Conclusion: Clinicians are in a position to enable individuals' time use and help to engage them in meaningful activity. Individuals with stroke may benefit from a program focusing on the temporal aspect of activities. [ABSTRACT FROM AUTHOR]

Novel wide array blood biomarkers of multisystem dysregulation, compared to conventional clinical and blood biomarkers, are potentially able to provide more accurate prognostic information of long-term mortality risks. We identified biomarker signatures of all-cause and disease-specific mortality from a comprehensive range of analytes related to six major physiological functions: cytokine, chemokine, and growth factors; glucose metabolism regulators and adipokines; adhesion molecules; acute phase response; pathogen-specific antibodies; and bone remodeling. A total of 144 elderly were prospectively followed up on mortality for median 136 months. Plasma levels of 93 biomarkers measured by enzyme-linked immunosorbent assay, Luminex, FlowCytomix, DNA quantification, and recombinant DNA technology at baseline were compared among deceased and surviving elderly and in a referent group of 72 healthy young adults. The elderly, and especially deceased elderly, exhibited differential profiles of the composite index of each physiological function from young adults. In Cox regression, we identified and validated in an independent cohort of 357 elderly the specific and common biomarkers predicting all-cause, cardiovascular disease-related, neoplasm-related, and respiratory disease-related mortalities after controlling age, sex, and major comorbidities. These biomarkers had 74.3% correct classification for deceased elderly from surviving elderly. We reported for the first time, stem cell growth factor-β and gastric inhibitory polypeptide as specific biomarkers of mortality risk. [ABSTRACT FROM AUTHOR]

Study Design: This was a prospective simulator study with 16 healthy male subjects.Objective: The aim of this study was to compare the relative efficacy of immobilization systems in limiting involuntary movements of the cervical spine using a dynamic simulation model.Summary Of Background Data: Relatively few studies have tested the efficacy of immobilization methods for limiting involuntary cervical movement, and only one of these studies used a dynamic simulation system to do so.Methods: Immobilization configurations tested were cot alone, cot with cervical collar, long spine board (LSB) with cervical collar and head blocks, and vacuum mattress (VM) with cervical collar. A motion platform reproduced shocks and vibrations from ambulance and helicopter field rides, as well as more severe shocks and vibrations that might be encountered on rougher terrain and in inclement weather (designated as an "augmented" ride). Motion capture technology quantitated involuntary cervical rotation, flexion/extension, and lateral bend. The mean and 95% confidence interval of the mean were calculated for the root mean square of angular changes from the starting position and for the maximum range of motion.Results: All configurations tested decreased cervical rotation and flexion/extension relative to the cot alone. However, the LSB and VM were significantly more effective in decreasing cervical rotation than the cervical collar, and the LSB decreased rotation more than the VM in augmented rides. The LSB and VM, but not the cervical collar, significantly limited cervical lateral bend relative to the cot alone.Conclusion: Under the study conditions, the LSB and the VM were more effective in limiting cervical movement than the cervical collar. Under some conditions, the LSB decreased repetitive and acute movements more than the VM. Further studies using simulation and other approaches will be essential for determining the safest, most effective configuration should providers choose to immobilize patients with suspected spinal injuries.Level Of Evidence: 3. [ABSTRACT FROM AUTHOR]

Objective: The prevalence of heart failure (HF) among adult patients with congenital heart disease (ACHD) is rising. Right ventricle (RV) exercise reserve and its relationship to outcomes have not been characterised. We aim to evaluate the prognostic impact of impaired RV reserve in an ACHD population referred for cardiopulmonary exercise testing (CPET).Methods: This retrospective study evaluates patients with ACHD who underwent CPET (n=147) with first-pass radionuclide ventriculography at a single tertiary care centre. RV reserve was categorised as normal, mild to moderately or severely impaired. The primary composite clinical outcome included clinical right HF, arrhythmia, transplantation or death.Results: Patients were median age 41±13 years, 50% were female and median follow-up was 1.1 (IQR: 0.7-2.0) years. Exercise RV reserve was impaired in 103 patients (70%), of whom 32% were asymptomatic. Resting RV systolic function poorly predicted RV reserve, with 52% of patients with severe impairment having a qualitatively normal echocardiographic assessment. The severely impaired reserve group had lower peak oxygen consumption (VO2)(17.2 vs 22.5 mL/kg/min, p<0.0001) compared with the normal reserve group, and was more likely to develop the composite outcome (48% vs 9%, log-rank p<0.001). Severely impaired RV reserve predicted event-free survival after adjusting for peak VO2, age, sex, RV pathology, QRS duration, New York Heart Association class, resting RV ejection fraction and RV dilation by echocardiography or MRI (HR 3.7, 95% CI 1.1 to 13.0, p=0.039).Conclusion: Impaired RV reserve, occurred in asymptomatic patients, was not well predicted by resting systolic function assessment, and strongly predicted adverse cardiovascular outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To assess the impact of computed tomography-derived fractional flow reserve (FFRCT) on reader confidence and reader time for interpretation of coronary computed tomography angiography (CCTA).Material and Methods: This IRB-approved, HIPAA-compliant, consent waivered, quality-improvement study included 50 patients (23 women, age 67 ± 12years, body mass index 28.7 ± 5.3 kg/m2). CCTA was acquired on 2nd and 3rd generation dual-source MDCT with use of beta-blockers and nitroglycerin, and FFRCT was calculated (HeartFlow,Redwood City,CA). Two readers with experience level COCATS2 (Core- Cardiology-Training-Symposium) and two with COCATS3 assessed severity of epicardial coronary artery disease (CAD) using CCTA alone and CCTA with FFRCT. Reader confidence for CAD and hemodynamically significant stenosis (HS) was rated on a 4-point Likert-scale (1=high, 2=good, 3=limited, 4=none) for the four major epicardial coronary artery (CA) vessels. Time to interpret was recorded.Results: The severity of CAD in the cohort population was CAD-RADS1 (Coronary-Artery-Disease Reporting-and-Data-System) n = 15, CAD-RADS2 n = 8, CAD-RADS3 n = 11, and CAD-RADS4A n = 16. Sixty-three CA in 30 patients had minimal FFRCT values  ≤0.8. Reader confidence when using FFRCT increased for CAD and HS (p = 0.0001) with a reduction of "non-confident" patient reads (rank 3&4) by 27% and 75%, respectively. The change in confidence was not associated with CAD-RADS (p = 0.1) but correlated with reader experience (p < 0.001). The median time-to-read a CCTA study decreased by 5 min when FFRCT was available (p < 0.001).Conclusion: Interpretation of CCTA in conjunction with FFRCT improved reader for assessment of severity of CAD and HS with reduction of "non-confident" reads and decreased the median time-to-interpretation of a CCTA. [ABSTRACT FROM AUTHOR]

Objectives: Hyponatraemia is a well-known predictor of clinical outcomes in heart failure (HF). However, the mechanism remains poorly understood. Previous reports suggest that hyponatraemia is related to right HF. We sought to evaluate the association between right ventricular (RV) dysfunction and hyponatraemia, and the impact of this relationship on the prognosis of patients with acute heart failure (AHF).Methods: This is a nested case-control study of the Korean Acute Heart Failure registry. Among 2935 AHF patients enrolled prospectively and consecutively at four tertiary hospitals in Korea from 2011 to 2014, 116 patients with severe persistent hyponatraemia, defined as serum sodium level <130 mmol/L at admission and <135 mmol/L before discharge, were matched with 232 controls, based on propensity scores for hyponatraemia. RV function was assessed with fractional area change (FAC) by echocardiography.Results: RV dysfunction (FAC <35%) was more prevalent in patients with severe persistent hyponatraemia than in those without (81.0% vs 33.6%, p<0.001). Hyponatraemia was strongly associated with RV dysfunction (adjusted OR 8.00, 95% CI 4.50 to 14.22, p<0.001), but not with left ventricular dysfunction (adjusted OR 1.21, 95% CI 0.74 to 1.50, p=0.308). RV dysfunction was an independent predictor of all-cause mortality, after adjustment for hyponatraemia (adjusted HR 2.20, 95% CI 1.53 to 3.15, p<0.001), while hyponatraemia was not (adjusted HR 1.33, 95% CI 0.94 to 1.87, p=0.108).Conclusions: In patients with AHF, hyponatraemia was more common with RV dysfunction. RV dysfunction, rather than hyponatraemia, was more significantly related with patients' prognosis. Thus, the utility of RV dysfunction instead of hyponatraemia per se should be considered in HF risk models.Trial Registration Number: Korean Acute Heart Failure registry NCT01389843; Results. [ABSTRACT FROM AUTHOR]

Background: There are few data concerning the association between season and cognition and its neurobiological correlates in older persons-effects with important translational and therapeutic implications for the diagnosis and treatment of Alzheimer disease (AD). We aimed to measure these effects.Methods and Findings: We analyzed data from 3,353 participants from 3 observational community-based cohort studies of older persons (the Rush Memory and Aging Project [MAP], the Religious Orders Study [ROS], and the Minority Aging Research Study [MARS]) and 2 observational memory-clinic-based cohort studies (Centre de Neurologie Cognitive [CNC] study at Lariboisière Hospital and the Sunnybrook Dementia Study [SDS]). We performed neuropsychological testing and, in subsets of participants, evaluated cerebrospinal fluid AD biomarkers, standardized structured autopsy measures, and/or prefrontal cortex gene expression by RNA sequencing. We examined the association between season and these variables using nested multiple linear and logistic regression models. There was a robust association between season and cognition that was replicated in multiple cohorts (amplitude = 0.14 SD [a measure of the magnitude of seasonal variation relative to overall variability; 95% CI 0.07-0.23], p = 0.007, in the combined MAP, ROS, and MARS cohorts; amplitude = 0.50 SD [95% CI 0.07-0.66], p = 0.017, in the SDS cohort). Average composite global cognitive function was higher in the summer and fall compared to winter and spring, with the difference equivalent in cognitive effect to 4.8 years' difference in age (95% CI 2.1-8.4, p = 0.002). Further, the odds of meeting criteria for mild cognitive impairment or dementia were higher in the winter and spring (odds ratio 1.31 [95% CI 1.10-1.57], p = 0.003). These results were robust against multiple potential confounders including depressive symptoms, sleep, physical activity, and thyroid status and persisted in cases with AD pathology. Moreover, season had a marked effect on cerebrospinal fluid Aβ 42 level (amplitude 0.30 SD [95% CI 0.10-0.64], p = 0.003), which peaked in the summer, and on the brain expression of 4 cognition-associated modules of co-expressed genes (m6: amplitude = 0.44 SD [95% CI 0.21-0.65], p = 0.0021; m13: amplitude = 0.46 SD [95% CI 0.27-0.76], p = 0.0009; m109: amplitude = 0.43 SD [95% CI 0.24-0.67], p = 0.0021; and m122: amplitude 0.46 SD [95% CI 0.20-0.71], p = 0.0012), which were in phase or anti-phase to the rhythms of cognition and which were in turn associated with binding sites for several seasonally rhythmic transcription factors including BCL11A, CTCF, EGR1, MEF2C, and THAP1. Limitations include the evaluation of each participant or sample once per annual cycle, reliance on self-report for measurement of environmental and behavioral factors, and potentially limited generalizability to individuals in equatorial regions or in the southern hemisphere.Conclusions: Season has a clinically significant association with cognition and its neurobiological correlates in older adults with and without AD pathology. There may be value in increasing dementia-related clinical resources in the winter and early spring, when symptoms are likely to be most pronounced. Moreover, the persistence of robust seasonal plasticity in cognition and its neurobiological correlates, even in the context of concomitant AD pathology, suggests that targeting environmental or behavioral drivers of seasonal cognitive plasticity, or the key transcription factors and genes identified in this study as potentially mediating these effects, may allow us to substantially improve cognition in adults with and without AD. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to quantify the extent to which apparent movements of the posterior superior iliac spine and sacral base areas Gillet sacroiliac motion testing were related to (a) degree of hip flexion and (b) the examiner's palpatory pressure. Methods: A preliminary exploratory study quantified relative PSIS/S2 displacements in 10 sacroiliac joints among 5 asymptomatic subjects at 10° increments of hip flexion from 0-90°. A comprehensive follow-up asymptomatic study quantified PSIS/S2 displacements at 0° vs. 30° vs. 90° hip flexion, and for light vs. firm pressure at 30° hip flexion. Displacements measured in pixels on digital photographs were transformed to mm. Mean differences for the various test conditions were evaluated for statistical significance using paired t-testing and Wilcoxon signed rank test. Results: With light pressure, the left PSIS moved caudal for hip flexion ≤30° during right-legged stance, whereas the right PSIS moved cephalad relative to the sacral base. For hip flexion =90°, both PSISs moved cephalad. The use of firm palpatory pressure abolished the initial caudal movement of the left PSIS, as well as differences in the amount of cephalad PSIS movement at 30° vs. 90° hip flexion. Conclusions: The results are consistent with there being left-right differences in gluteus medius and biceps femoris activation among asymptomatic individuals that result in different balancing strategies during one-legged stance. This may create the appearance of relative PSIS/SB displacement, even though the results of Gillet testing can be wholly or partially explained by pelvic obliquity owing to muscle function asymmetry. This study questions the validity of the upright Gillet test for sacroiliac motion. [ABSTRACT FROM AUTHOR]

Objective: To determine whether the freeze-all policy ensures a higher efficacy in terms of cumulative live birth rate (CLBR) in comparison with a conventional fresh/frozen embryo transfer (ET) approach in patients with normal ovarian response.Design: Retrospective, matched, multicenter cohort study.Setting: Private IVF centers.Patient(s): This study analyzed 564 completed IVF cycles in which an average of 12-18 oocytes were retrieved. In 435 cycles the conventional strategy was applied, with initial ET followed by frozen embryo replacements, whereas in 129 cycles the freeze-all policy was performed, with elective cryopreservation and deferred use of all viable embryos.Intervention(s): None.Main Outcome Measure(s): The primary endpoint was CLBR. The secondary endpoint was cumulative clinical pregnancy rate.Result(s): Overall, statistically comparable CLBRs were achieved in the fresh/frozen and freeze-all groups (45.5% vs. 53.5%). Stratification of data for age and number of retrieved oocytes confirmed the absence of differences between the two groups. In a subanalysis in which the day of ET and cryopreservation were taken into account, a similar outcome was achieved in cleavage-stage groups (45.6% vs. 46.4%), whereas when ET was performed at the blastocyst stage the CLBR was significantly higher in the freeze-all group (45.3% vs. 66.7%).Conclusion(s): Our CLBR analysis indicates that clinical performance of the freeze-all policy is equivalent to that of the conventional strategy when ET is carried out at the cleavage stage. However, it seems to be superior if associated with cryopreservation and transfer at the blastocyst stage. [ABSTRACT FROM AUTHOR]

Purpose: This randomized, open-label trial was conducted to investigate the optimal duration of bed rest after intrathecal chemotherapy to reduce the incidence of complications without increasing patients' tolerance to long-term bed rest.Methods: A total of 390 patients receiving intrathecal chemotherapy were randomly assigned 1:1:1 to undergo bed rest for 6, 8, or 10 h after intrathecal chemotherapy. The primary outcome was the rate of complications after intrathecal chemotherapy. The analysis was per protocol.Results: A total of 359 patients among the 390 patients in our study completed follow-up with 120 patients in the 6-h group, 120 in the 8-h group, and 119 in the 10-h group. The complications among the three groups differed significantly (P = 0.005). The 6-h group had significantly more complications than the 8- (50, 41.7% vs 29, 24.2%, P = 0.004) and 10-h groups (50, 41.7% vs 31, 26.1%, P = 0.011), whereas the difference between the 8- and 10-h groups was not significant (29, 24.2% vs 31, 26.1%, P = 0.737).Conclusions: The overall results support that the optimal time interval for bed rest in the supine position after intrathecal chemotherapy is 8 h. This trial is registered with the Chinese Clinical Trial Registry (number ChiCTR-IOR-17011671). [ABSTRACT FROM AUTHOR]

Cognitive decline is common in multiple sclerosis and strongly affects overall quality of life. Despite the identification of cross-sectional MRI correlates of cognitive impairment, predictors of future cognitive decline remain unclear. The objective of this study was to identify which MRI measures of structural damage, demographic and/or clinical measures at baseline best predict cognitive decline, during a 5-year follow-up period. A total of 234 patients with clinically definite multiple sclerosis and 60 healthy control subjects were examined twice, with a 5-year interval (mean = 4.9 years, standard deviation = 0.9). An extensive neuropsychological evaluation was performed at both time points and the reliable change index was computed to evaluate cognitive decline. Both whole-brain and regional MRI (3 T) measures were assessed at baseline, including white matter lesion volume, diffusion-based white matter integrity, cortical and deep grey matter volume. Logistic regression analyses were performed to determine which baseline measures best predicted cognitive decline in the entire sample as well as in early relapsing-remitting (symptom duration <10 years), late relapsing-remitting (symptom duration ≥10 years) and progressive phenotypes. At baseline, patients with multiple sclerosis had a mean disease duration of 14.8 (standard deviation = 8.4) years and 96/234 patients (41%) were classified as cognitively impaired. A total of 66/234 patients (28%) demonstrated cognitive decline during follow-up, with higher frequencies in progressive compared to relapsing-remitting patients: 18/33 secondary progressive patients (55%), 10/19 primary progressive patients (53%) and 38/182 relapsing-remitting patients (21%). A prediction model that included only whole-brain MRI measures (Nagelkerke R2 = 0.22, P < 0.001) showed cortical grey matter volume as the only significant MRI predictor of cognitive decline, while a prediction model that assessed regional MRI measures (Nagelkerke R2 = 0.35, P < 0.001) indicated integrity loss of the anterior thalamic radiation, lesions in the superior longitudinal fasciculus and temporal atrophy as significant MRI predictors for cognitive decline. Disease stage specific regressions showed that cognitive decline in early relapsing-remitting multiple sclerosis was predicted by white matter integrity damage, while cognitive decline in late relapsing-remitting and progressive multiple sclerosis was predicted by cortical atrophy. These results indicate that patients with more severe structural damage at baseline, and especially cortical atrophy, are more prone to suffer from cognitive decline. New studies now need to further elucidate the underlying mechanisms leading to cortical atrophy, evaluate the value of including cortical atrophy as a possible outcome marker in clinical trials as well as study its potential use in individual patient management. [ABSTRACT FROM AUTHOR]

Aims To evaluate the association of cumulative blood pressure (BP) from young adulthood to middle age with left atrial (LA) structure/function as assessed by three-dimensional echocardiography (3DE) in a large longitudinal bi-racial population study. Methods and results We conducted a prospective post hoc analysis of individuals enrolled at the Coronary Artery Risk Development in Young Adults, which is a multi-centre bi-racial cohort with 30 years of follow-up. Cumulative systolic and diastolic BP levels were defined by summing the product of average millimetres of mercury and the years between each two consecutive clinic visits over 30 years of follow-up. Multivariable linear regression analyses were used to assess the relationship between cumulative systolic and diastolic BP with 3DE LA structure and function, adjusting for demographics and traditional cardiovascular risk factors. A total of 1033 participants were included, mean age was 55.4 ± 3.5 years, 55.2% women, 43.9% blacks. Cumulative systolic BP had stronger correlations than cumulative diastolic BP. Higher cumulative systolic BP was independently associated with higher 3D LA volumes: maximum (β  = 1.74, P  = 0.004), pre-atrial contraction (β  = 1.87, P  < 0.001), minimum (β  = 0.76, P  = 0.04), total emptying (β  = 0.98, P  = 0.006), active emptying (β  = 1.12, P  < 0.001), and lower magnitude 3D LA early diastolic strain rate (β  = 0.05, P  = 0.02). Higher cumulative diastolic BP was independently associated with higher 3D LA active emptying volume (β  = 0.66, P  = 0.002), lower magnitude 3D LA early diastolic strain rate (β  = 0.05, P  = 0.004), and higher magnitude 3D LA late diastolic strain rate (β  = −0.04, P  = 0.05). Conclusion Higher cumulative BP from early adulthood throughout middle age was associated with adverse LA remodelling evaluated by 3D echocardiography. [ABSTRACT FROM AUTHOR]

Objectives: The ratio of mitral peak early diastolic filling to early diastolic mitral annular velocity (E/e') reflects diastolic cardiac function in adults. Dual-gate Doppler (DD) enables measurements of E/e' in the same heart beat. This study was designed to assess the utility of the DD method for measurement of fetal E/e' and determine reference ranges for normal fetuses.Methods: This prospective study comprised normal singleton pregnancies undergoing fetal echocardiography between 16 and 36 weeks of gestation. According to the DD method, E-wave velocity on pulsed-wave Doppler and e'-wave on tissue Doppler imaging were measured simultaneously on an apical or basal four-chamber view, and fetal E/e' was calculated. Spearman's correlation coefficient was used to assess the relationship between gestational age (GA) and E-wave and e'-wave velocities and E/e'.Results: A total of 133 pregnancies were included in this study and all E/e' measurements were successful. Significant correlation was observed between GA and both left ventricular (LV) E/e' (r s  = -0.666, P < 0.001) and right ventricular (RV) E/e' (r s  = -0.607, P < 0.001). The regression equations for bilateral E/e' were: LV-E/e' = 17.341 - 0.631GA + 0.008 × GA2 (mean ± SD, R 2  = 0.440 ± 1.333); and RV-E/e' = 19.156 - 0.794GA + 0.012GA2 (R 2  = 0.419 ± 1.329).Conclusions: Bilateral E/e' of normal fetuses, measured using the DD method, decreased with GA, which is considered to be related to myocardial maturity. DD is a useful and convenient method for evaluating fetal E/e' in order to assess diastolic function in the prenatal period. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Background: Cross-sectional studies suggest that coffee drinking is associated with better renal function. However, to our knowledge, no prospective study has examined its relation with the risk of end-stage renal disease (ESRD).Objective: We examined the relations between coffee, tea, soda, and total caffeine consumption and the risk of ESRD among middle-aged and older Chinese in Singapore.Methods: We used data from the Singapore Chinese Health Study, a prospective cohort of 63,257 men and women aged 45-74 y at recruitment from 1993 to 1998. Baseline information on the consumption of caffeinated coffee and other caffeinated beverages (tea and sodas), habitual diet, medical history, and lifestyle factors was obtained via in-person interviews. The standard serving size of 1 cup was assigned as 237 mL in the questionnaire. Incident ESRD cases were identified via linkage with the nationwide registry. We used multivariable Cox regression models to estimate HRs and 95% CIs of ESRD risk associated with the consumption of caffeinated beverages, with adjustment for potential confounders.Results: After a mean follow-up of 16.8 y, 1143 cohort subjects developed ESRD. Compared with those who drank coffee less than daily, the HR (95% CI) was 0.91 (0.79, 1.05) for those who drank 1 cup of coffee/d and 0.82 (0.71, 0.96) for those who drank ≥2 cups/d (P-trend = 0.012). When stratified by sex, this association was observed in men but not in women. Compared with those who drank less than daily, the HR (95% CI) for drinking ≥2 cups/d was 0.71 (0.57, 0.87) among men and 0.97 (0.78, 1.19) among women (P-interaction = 0.03). Conversely, intakes of tea, soda, or total caffeine were not associated with the risk of ESRD in multivariable models.Conclusion: The consumption of ≥2 cups of coffee/d may reduce the risk of ESRD in the general population, especially among men. This study was registered at http://www.clinicaltrials.gov as NCT03356340. [ABSTRACT FROM AUTHOR]

Laser-assisted new attachment procedure (LANAP) is a new protocol that has been proposed for the treatment of periodontitis. However, there is little evidence regarding the rate of revascularization and the clinical efficacy of LANAP over conventional periodontal therapies. Hence, this study is done to evaluate and compare the clinical efficacy of LANAP vs Excisional new attachment procedure (ENAP) and also to assess the blood flow in both the techniques using ultrasound Doppler flowmetry. A split-mouth double-blinded controlled clinical trial was carried out in 15 subjects with chronic periodontitis. In every patient, 2 quadrants were treated with ENAP and the other 2 quadrants with LANAP. Clinical parameters like plaque index (PI), gingival index (GI), pocket depth (PD), clinical attachment level (CAL), and radiographic measurements (RBL) were recorded at baseline and 6, 9, and 12 months, postoperatively. Gingival blood flow assessment was done at baseline and on the ninth day postoperatively. Both the groups showed statistically significant reduction in all the clinical parameters when compared from baseline to subsequent follow-up visits. There was greater reduction in all the parameters in LANAP group than that of ENAP group. The rate of revascularization was higher in ENAP group than that of LANAP group when compared from baseline to the ninth day postoperatively. Although there is a delay in the rate of revascularization in the LANAP group, there was significant improvement in all the clinical and radiographic parameters than that of the ENAP group when compared from baseline to follow-up visits. [ABSTRACT FROM AUTHOR]

Objective: Methylglyoxal (MGO) is a reactive dicarbonyl compound and a potential key player in diabetic cardiovascular disease (CVD). Whether plasma MGO levels are associated with CVD in type 2 diabetes is unknown.Research Design and Methods: We included 1,003 individuals (mean ± SD age 59.1 ± 10.5 years, 69.3% male, and 61.6% with prior CVD) with type 2 diabetes from the Second Manifestations of ARTerial disease cohort (SMART). We measured plasma MGO levels and two other dicarbonyls (glyoxal [GO] and 3-deoxyglucosone [3-DG]) at baseline with mass spectrometry. Median follow-up of CVD events was 8.6 years. Data were analyzed with Cox regression with adjustment for sex, age, smoking, systolic blood pressure, total cholesterol, HbA1c, BMI, prior CVD, and medication use. Hazard ratios are expressed per SD Ln-transformed dicarbonyl.Results: A total of 287 individuals suffered from at least one CVD event (n = 194 fatal events, n = 146 myocardial infarctions, and n = 72 strokes); 346 individuals died, and 60 individuals underwent an amputation. Higher MGO levels were associated with total (hazard ratio 1.26 [95% CI 1.11-1.42]) and fatal (1.49 [1.30-1.71]) CVD and with all-cause mortality (1.25 [1.11-1.40]), myocardial infarction (1.22 [1.02-1.45]), and amputations (1.36 [1.05-1.76]). MGO levels were not apparently associated with stroke (1.03 [0.79-1.35]). Higher GO levels were significantly associated with fatal CVD (1.17 [1.00-1.37]) but not with other outcomes. 3-DG was not significantly associated with any of the outcomes.Conclusions: Plasma MGO and GO levels are associated with cardiovascular mortality in individuals with type 2 diabetes. Influencing dicaronyl levels may therefore be a target to reduce CVD in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: In many regions globally, buildings designed for harnessing heat during the cold exacerbate thermal exposures during heat waves (HWs) by maintaining elevated indoor temperatures even when high ambient temperatures have subdued. While previous experimental studies have documented the effects of ambient temperatures on cognitive function, few have observed HW effects on indoor temperatures following subjects' habitual conditions. The objective was to evaluate the differential impact of having air conditioning (AC) on cognitive function during a HW among residents of AC and non-AC buildings using a prospective observational cohort study.Methods: We followed 44 students (mean age = 20.2 years; SD = 1.8 years) from a university in the Greater Boston area, Massachusetts in the United States living in AC (n = 24) and non-AC (n = 20) buildings before, during, and after a HW. Two cognition tests were self-administered daily for a period of 12 days (July 9-July 20, 2016), the Stroop color-word test (STROOP) to assess selective attention/processing speed and a 2-digit, visual addition/subtraction test (ADD) to evaluate cognitive speed and working memory. The effect of the HW on cognitive function was evaluated using difference-in-differences (DiD) modelling.Findings: Mean indoor temperatures in the non-AC group (mean = 26.3°C; SD = 2.5°C; range = 19.6-30.4°C) were significantly higher (p < 0.001) than in the AC group (mean = 21.4°C; SD = 1.9°C; range = 17.5-25.0°C). DiD estimates show an increase in reaction time (STROOP = 13.4%, p < 0001; ADD = 13.3%, p < 0.001) and reduction in throughput (STROOP = -9.9%, p < 0.001; ADD = -6.3%, p = 0.08) during HWs among non-AC residents relative to AC residents at baseline. While ADD showed a linear relationship with indoor temperatures, STROOP was described by a U-shaped curve with linear effects below and above an optimum range (indoor temperature = 22°C-23°C), with an increase in reaction time of 16 ms/°C and 24 ms/°C for STROOP and ADD, respectively. Cognitive tests occurred right after waking, so the study is limited in that it cannot assess whether the observed effects extended during the rest of the day. Although the range of students' ages also represents a limitation of the study, the consistent findings in this young, healthy population might indicate that greater portions of the population are susceptible to the effects of extreme heat.Conclusions: Cognitive function deficits resulting from indoor thermal conditions during HWs extend beyond vulnerable populations. Our findings highlight the importance of incorporating sustainable adaptation measures in buildings to preserve educational attainment, economic productivity, and safety in light of a changing climate. [ABSTRACT FROM AUTHOR]

This study investigated developmental changes and differences in upper-limb movement organization from 4 to 8 years of age in children born preterm (PT) and fullterm (FT). Kinematic recordings of precision-demanding unimanual movements and lateral assessments were carried out in 37 children (18 PT). All children, particularly children born PT, displayed considerable gain in movement kinematics. Contrary to controls, children born PT displayed persistently less-evident side preference. Gestational age (GA) contributed significantly to kinematic differences shown, with larger upper-limb deviances in the lowest GAs, in agreement with cross-sectional findings of altered hemispheric connections and delayed side-specialization among children born very PT. [ABSTRACT FROM AUTHOR]

Background: The pediatric patient's response to hemorrhage as a function of young age is not well understood. As a result, there is no consensus on optimal resuscitation strategies for hemorrhagic shock in pediatric patients, or on the identification of clinical triggers to prompt implementation. The study objective was to develop a model of pediatric hemorrhage using young pigs to simulate school-aged children, and determine clinical and laboratory indicators for significant hemorrhage.Materials and Methods: 29 non-splenectomized female pigs, aged 3 months, weighing 30-40 kg, were randomized into groups with varying degrees of hemorrhage. Bleeding occurred intermittently over 5 h while the animals were anesthetized but spontaneously breathing. Various physiologic and biochemical markers were used to monitor the piglets during hemorrhage.Results: Swine experiencing up to 50% hemorrhage survived without exception throughout the course of hemorrhage. 80% (4/5) of the animals in the 60% hemorrhage group survived. Need for respiratory support was universal when blood loss reached 50% of estimated blood volume. Blood pressure was not useful in classifying the degree of shock. Heart rate was helpful in differentiating between the extremes of blood loss examined. Arterial pCO2, pH, lactate, HCO3 and creatinine levels, as well as urine output, changed significantly with increasing blood loss.Conclusions: Young swine are resilient against hemorrhage, although hemorrhage of 50% or greater universally require respiratory support. In this animal model, with the exception of heart rate, vital signs were minimally helpful in identification of shock. However, change in select laboratory values from baseline was significant with increasing blood loss.Level Of Evidence: This was a level II prospective comparative study. [ABSTRACT FROM AUTHOR]

Background: While current research is largely consistent as to the harms of heavy drinking in terms of both cancer incidence and mortality, there are disparate messages regarding the safety of light-moderate alcohol consumption, which may confuse public health messages. We aimed to evaluate the association between average lifetime alcohol intakes and risk of both cancer incidence and mortality.Methods and Findings: We report a population-based cohort study using data from 99,654 adults (68.7% female), aged 55-74 years, participating in the U.S. Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Cox proportional hazards models assessed the risk of overall and cause-specific mortality, cancer incidence (excluding nonmelanoma skin cancer), and combined risk of cancer and death across categories of self-reported average lifetime alcohol intakes, with adjustment for potential confounders. During 836,740 person-years of follow-up (median 8.9 years), 9,599 deaths and 12,763 primary cancers occurred. Positive linear associations were observed between lifetime alcohol consumption and cancer-related mortality and total cancer incidence. J-shaped associations were observed between average lifetime alcohol consumption and overall mortality, cardiovascular-related mortality, and combined risk of death or cancer. In comparison to lifetime light alcohol drinkers (1-3 drinks per week), lifetime never or infrequent drinkers (<1 drink/week), as well as heavy (2-<3 drinks/day) and very heavy drinkers (3+ drinks/day) had increased overall mortality and combined risk of cancer or death. Corresponding hazard ratios (HRs) and 95% confidence intervals (CIs) for combined risk of cancer or death, respectively, were 1.09 (1.01-1.13) for never drinkers, 1.08 (1.03-1.13) for infrequent drinkers, 1.10 (1.02-1.18) for heavy drinkers, and 1.21 (1.13-1.30) for very heavy drinkers. This analysis is limited to older adults, and residual confounding by socioeconomic factors is possible.Conclusions: The study supports a J-shaped association between alcohol and mortality in older adults, which remains after adjustment for cancer risk. The results indicate that intakes below 1 drink per day were associated with the lowest risk of death.Trial Registration: NCT00339495 (ClinicalTrials.gov). [ABSTRACT FROM AUTHOR]

Background: Observational studies have shown inverse associations among fitness, physical activity, and cardiovascular disease. However, little is known about these associations in individuals with elevated genetic susceptibility for these diseases.Methods: We estimated associations of grip strength, objective and subjective physical activity, and cardiorespiratory fitness with cardiovascular events and all-cause death in a large cohort of 502 635 individuals from the UK Biobank (median follow-up, 6.1 years; interquartile range, 5.4-6.8 years). Then we further examined these associations in individuals with different genetic burden by stratifying individuals based on their genetic risk scores for coronary heart disease and atrial fibrillation. We compared disease risk among individuals in different tertiles of fitness, physical activity, and genetic risk using lowest tertiles as reference.Results: Grip strength, physical activity, and cardiorespiratory fitness showed inverse associations with incident cardiovascular events (coronary heart disease: hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.77-0.81; HR, 0.95; 95% CI, 0.93-0.97; and HR, 0.68; 95% CI, 0.63-0.74, per SD change, respectively; atrial fibrillation: HR, 0.75; 95% CI, 0.73-0.76; HR, 0.93; 95% CI, 0.91-0.95; and HR, 0.60; 95% CI, 0.56-0.65, per SD change, respectively). Higher grip strength and cardiorespiratory fitness were associated with lower risk of incident coronary heart disease and atrial fibrillation in each genetic risk score group (Ptrend <0.001 in each genetic risk category). In particular, high levels of cardiorespiratory fitness were associated with 49% lower risk for coronary heart disease (HR, 0.51; 95% CI, 0.38-0.69) and 60% lower risk for atrial fibrillation (HR, 0.40; 95%, CI 0.30-0.55) among individuals at high genetic risk for these diseases.Conclusions: Fitness and physical activity demonstrated inverse associations with incident cardiovascular disease in the general population, as well as in individuals with elevated genetic risk for these diseases. [ABSTRACT FROM AUTHOR]

Objective: To detect if removing the cervical mucus before performing intrauterine insemination (IUI) could improve pregnancy outcomes in patients with unexplained infertility.Design: Prospective randomized study.Setting: An Egyptian University Hospital.Population: Seven hundred and fourteen couples with unexplained infertility who underwent intrauterine insemination (IUI) with or without cervical mucus removal.Methods: Using computer-generated numbers, patients were randomly allocated to cervical-mucus-removal (removed from both internal and external os) or non-mucus-removal groups. Only participants were blinded as to group assignment.Main Outcome Measures: The clinical pregnancy rate.Results: Of 714 IUI patients between November 2014 and March 2017, 361 were in the mucus removal group, and 353 in the non-mucus-removal group. Difficult catheterization was encountered in 17 cases out of 666 (2.6%) 12 in the cervical-mucus-removal group and five in the non-mucus-removal group). A total of 666 IUI cycles were completed while 48 were either cancelled or lost in their follow-up. The clinical pregnancy rate was significantly higher in the mucus-removal group [31.0% (n = 112)] than in the non-mucus-removal group [21.8% (n = 77); P = 0.005]. Ovarian hyperstimulation developed in 33 (4.6%) cases: 18 cervical mucus-removal and 15 non-mucus-removal. All except one were mild and managed with outpatient care.Conclusions: Cervical mucus removal before IUI could improve pregnancy outcomes in women with unexplained infertility.Tweetable Abstract: Cervical mucus removal before IUI can improve pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Objective: To investigate the pregnancy outcomes in a cohort of women who failed to obtain a result in non-invasive prenatal testing (NIPT).Design: Historical cohort study.Setting: A multicentre private practice in Sydney, Australia.Population: Women who failed to obtain a result from NIPT (n = 131).Methods: The maternal characteristics, antenatal investigations and pregnancy outcomes for these women were compared with those who obtained a result at the same practice and to the general Australian obstetric population.Main Outcome Measures: Antenatal investigations: pregnancy-associated plasma protein-A (PAPP-A), free β-human chorionic gonadotrophin (β-hCG), placental growth factor (PlGF), uterine artery pulsatility index (PI), mean arterial pressure (MAP). Pregnancy outcomes: chromosomal abnormality, pre-eclampsia, gestational diabetes, small-for-gestational-age (SGA), preterm delivery.Results: Only 1.1% of NIPT samples failed to return a result. This cohort was significantly older and had significantly increased weight compared with the general Australian obstetric population. Pregnancy outcomes were available for 94% of the cohort. There were significantly higher rates of chromosomal aneuploidies (6.5% versus 0.2%, P < 0.0001), pre-eclampsia (11% versus 1.5%, P < 0.0001) and gestational diabetes (23% versus 7.5%, P < 0.0001) compared with the general obstetric population. Rates of preterm delivery and SGA were elevated but did not reach significance. Antenatal investigations demonstrated decreased PAPP-A MoM (0.75 versus 1.14, P < 0.0001), decreased free β-hCG (0.71 versus 1.01, P < 0.0001) and increased uterine artery PI (1.79 versus 1.65, P = 0.02).Conclusion: Women who fail to obtain a result from NIPT are at increased risk of adverse pregnancy outcomes, in particular chromosomal aneuploidy, gestational diabetes and pre-eclampsia.Funding: None received.Tweetable Abstract: Women who fail to obtain a result from cell-free DNA NIPT are at increased risk of adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Background: Compensatory pelvis, hip- and knee movements are reported after stroke to overcome insufficient foot-clearance. Ankle-foot orthoses (AFOs) are often used to improve foot-clearance, but the optimal timing of AFO-provision post-stroke is unknown. Early AFO-provision to prevent foot-drop might decrease the development of compensatory movements, but it is unknown whether timing of AFO-provision affects post-stroke kinematics.Research Questions: 1) To compare the effect of AFO-provision at two different points in time (early versus delayed) on frontal pelvis and hip, and sagittal hip and knee kinematics in patients with sub-acute stroke. Effects were assessed after 26 weeks; 2) To study whether possible changes in kinematics or walking speed during the 26-weeks follow-up period differed between both groups.Method: An explorative randomized controlled trial was performed, including unilateral hemiparetic patients maximal six weeks post-stroke with indication for AFO-use. Subjects were randomly assigned to AFO-provision early (at inclusion) or delayed (eight weeks later). 3D gait-analysis with and without AFO was performed in randomized order. Measurements were performed in study-week 1, 9, 17 and 26.Results: Twenty-six subjects (15 early, 11 delayed) were analyzed. After 26 weeks, no differences in kinematics were found between both groups for any of the joint angles, both for the without and with AFO-condition. Changes in kinematics during the 26-weeks follow-up period did not differ between both groups for any of the joint angles during walking without AFO. Significant differences in changes in walking speed during the 26-weeks follow-up were found (p = 0.034), corresponding to the first eight weeks after AFO-provision.Significance: Results indicate that early or delayed AFO-use post-stroke does not influence pelvis, hip and knee movements after 26 weeks, despite that AFO-use properly corrected drop-foot. AFOs should be provided to improve drop-foot post-stroke, but not with the intention to influence development of compensatory patterns around pelvis and hip. [ABSTRACT FROM AUTHOR]

Background: Pain is a cardinal symptom of knee osteoarthritis (OA) and although conservative treatments such as exercise and diet related interventions can reduce pain, effects are modest and can be improved. Frontal plane knee joint motion has been associated with knee pain, and is suggested as a patient-specific characteristic on which to tailor interventions.Research Question: Does the association between baseline frontal plane knee joint kinematics and pain-relief differ among overweight and obese people with knee OA who underwent an intervention from the Intensive Diet and Exercise for Arthritis (IDEA) clinical trial: diet-only, exercise-only, and combined diet and exercise intervention?Methods: 323 participants with knee OA were included in the analysis (77% females; 66 ± 6 years; 33.5 ± 3.7 kg/m2). At baseline, frontal plane knee joint kinematics during walking were measured using 3-dimensional gait analysis and characterised as peak varus-valgus knee angle, peak varus-valgus excursion, and peak varus angular velocity. Pain was assessed at baseline and 18-month follow-up using the Western Ontario and McMaster Universities Osteoarthritis Index pain subscale. Linear regressions were performed unadjusted and adjusted for covariates to determine if the associations between baseline frontal plane knee joint kinematics and 18-month change in pain differed according to intervention.Results: The interaction terms between the intervention and measures of frontal plane knee joint kinematics were not statistically significant (all P ≥ 0.05).Significance: We found no evidence to suggest that 18-months of either exercise, diet, or a combination of diet and exercise could be more effective than the other to improve pain based on frontal plane measures of knee kinematics. [ABSTRACT FROM AUTHOR]

Little is known about the repertoire dynamics and persistence of pathogenic T cells in HLA-associated disorders. In celiac disease, a disorder with a strong association with certain HLA-DQ allotypes, presumed pathogenic T cells can be visualized and isolated with HLA-DQ:gluten tetramers, thereby enabling further characterization. Single and bulk populations of HLA-DQ:gluten tetramer-sorted CD4+ T cells were analyzed by high-throughput DNA sequencing of rearranged TCR-α and -β genes. Blood and gut biopsy samples from 21 celiac disease patients, taken at various stages of disease and in intervals of weeks to decades apart, were examined. Persistence of the same clonotypes was seen in both compartments over decades, with up to 53% overlap between samples obtained 16 to 28 years apart. Further, we observed that the recall response following oral gluten challenge was dominated by preexisting CD4+ T cell clonotypes. Public features were frequent among gluten-specific T cells, as 10% of TCR-α, TCR-β, or paired TCR-αβ amino acid sequences of total 1813 TCRs generated from 17 patients were observed in 2 or more patients. In established celiac disease, the T cell clonotypes that recognize gluten are persistent for decades, making up fixed repertoires that prevalently exhibit public features. These T cells represent an attractive therapeutic target. [ABSTRACT FROM AUTHOR]

Background: Higher physical activity (PA) is associated with lower heart failure (HF) risk; however, the effect of changes in PA on HF risk is unknown.Methods: We evaluated 11 351 ARIC study (Atherosclerosis Risk in Communities) participants (mean age 60 years) who attended visit 3 (1993-1995) and did not have a history of cardiovascular disease. Exercise PA was assessed using a modified Baecke questionnaire and categorized according to American Heart Association guidelines as recommended, intermediate, or poor. We used Cox regression models to characterize the association of 6-year changes in PA between the first (1987-1989) and third ARIC visits and HF risk.Results: During a median of 19 years of follow-up, 1750 HF events occurred. Compared with those with poor activity at both visits, the lowest HF risk was seen for those with persistently recommended activity (hazard ratio, 0.69; 95% confidence interval, 0.60-0.80). However, those whose PA increased from poor to recommended also had reduced HF risk (hazard ratio, 0.77; 95% confidence interval 0.63-0.93). Among participants with poor baseline activity, each 1 SD higher PA at 6 years (512.5 METS*minutes/week, corresponding to ≈30 minutes of brisk walking 4 times per week) was associated with significantly lower future HF risk (hazard ratio, 0.89, 95% confidence interval, 0.82-0.96).Conclusions: Although maintaining recommended activity levels is associated with the lowest HF risk, initiating and increasing PA, even in late middle age, are also linked to lower HF risk. Augmenting PA may be an important component of strategies to prevent HF. [ABSTRACT FROM AUTHOR]

Child maltreatment is linked to distinct neurophysiological patterns and social-emotional vulnerability. Relations among maltreatment, relative resting frontal alpha asymmetry, shyness, and psychopathology were examined prospectively. Adolescent girls (age 14-16) who experienced child maltreatment (N = 55) were compared to nonmaltreated controls (N = 25), and returned for 6- and 12-month follow-ups. Among participants exhibiting relative right frontal asymmetry, maltreated adolescents reported higher shyness than controls at Time 1. Low-stable and high-stable shyness trajectories were observed for maltreated participants. Compared to low shy, participants in high-shy trajectory reported at Time 3: higher neuroticism and generalized anxiety; and lower extraversion if they also exhibited relative right frontal asymmetry. Thus, right frontal brain activity and shyness are involved in social-emotional vulnerability of adolescents who experienced child maltreatment. [ABSTRACT FROM AUTHOR]

It was examined how ventral striatum responses to rewards develop across adolescence and early adulthood and how individual differences in state- and trait-level reward sensitivity are related to these changes. Participants (aged 8-29 years) were tested across three waves separated by 2 years (693 functional MRI scans) in an accelerated longitudinal design. The results confirmed an adolescent peak in reward-related ventral striatum, specifically nucleus accumbens, activity. In early to mid-adolescence, increases in reward activation were related to trait-level reward drive. In mid-adolescence to early adulthood decreases in reward activation were related to decreases in state-level hedonic reward pleasure. This study demonstrates that state- and trait-level reward sensitivity account for reward-related ventral striatum activity in different phases of adolescence and early adulthood. [ABSTRACT FROM AUTHOR]

Introduction: Gay and bisexual men (GBM) often use illicit drugs to enhance sexual pleasure, commonly referred to as 'chemsex' or 'party n play'. In particular, the use of methamphetamine and Viagra™, and other erectile dysfunction medications, both together and separately are strongly predictive of subsequent HIV infection. Truvada™, as pre-exposure prophylaxis (PrEP), virtually eliminates HIV transmission during condomless anal intercourse (CLAI). HIV-negative GBM in intensive sex partying networks may be adding PrEP to their drug regimen to actively reduce the possibility of HIV transmission during chemsex.Aim: We describe the prevalence and context of concurrent use of methamphetamine, Truvada™ (or its generic formulations), and Viagra™ or other erectile dysfunction medication (collectively, MTV).Method: The Following Lives Undergoing Change study is an online prospective observational study of licit and illicit drug use among Australian GBM. Between January and July 2017, 1831 GBM provided details about their use of MTV. Binary logistic multiple regression analysis were used to estimate adjusted odds ratios (aOR) and associated 95% confidence intervals (95%CI).Results: Concurrent MTV use was reported by 6.0% of participants; 3.1% used methamphetamine and Viagra™ or other erectile dysfunction medication ('MV only') and 11.2% used Truvada™ as PrEP ('T only'). In multivariate analysis, compared to use of 'MV only', MTV was independently associated with CLAI with casual partners (aOR = 6.78;95%CI = 1.42-32.34) and 'fuckbuddies' (aOR = 3.47;95%CI = 1.41-8.56) in the previous six months. Compared to use of 'T only', MTV was independently associated with being older (aOR = 3.95;95%CI = 1.55-10.03) and engaging in group sex (aOR = 3.31;95%CI = 1.82-6.00). Greater social engagement with other gay men (aOR = 1.44;95%CI = 1.18-1.76) and having more sexual partners (aOR = 2.30;95%CI = 1.10-4.82) were independently associated with use of MTV compared to use of 'MV only' or 'T only'.Conclusion: GBM in intensive sex partying networks are increasingly adding PrEP alongside other drugs they use to enhance sexual experiences. Interventions that promote the use of PrEP during chemsex could mitigate HIV risk. [ABSTRACT FROM AUTHOR]

Background: There is a need to increase access to surgical treatments in African countries, but perioperative complications represent a major global health-care burden. There are few studies describing surgical outcomes in Africa.Methods: We did a 7-day, international, prospective, observational cohort study of patients aged 18 years and older undergoing any inpatient surgery in 25 countries in Africa (the African Surgical Outcomes Study). We aimed to recruit as many hospitals as possible using a convenience sampling survey, and required data from at least ten hospitals per country (or half the surgical centres if there were fewer than ten hospitals) and data for at least 90% of eligible patients from each site. Each country selected one recruitment week between February and May, 2016. The primary outcome was in-hospital postoperative complications, assessed according to predefined criteria and graded as mild, moderate, or severe. Data were presented as median (IQR), mean (SD), or n (%), and compared using t tests. This study is registered on the South African National Health Research Database (KZ_2015RP7_22) and ClinicalTrials.gov (NCT03044899).Findings: We recruited 11 422 patients (median 29 [IQR 10-70]) from 247 hospitals during the national cohort weeks. Hospitals served a median population of 810 000 people (IQR 200 000-2 000 000), with a combined number of specialist surgeons, obstetricians, and anaesthetists totalling 0·7 (0·2-1·9) per 100 000 population. Hospitals did a median of 212 (IQR 65-578) surgical procedures per 100 000 population each year. Patients were younger (mean age 38·5 years [SD 16·1]), with a lower risk profile (American Society of Anesthesiologists median score 1 [IQR 1-2]) than reported in high-income countries. 1253 (11%) patients were infected with HIV, 6504 procedures (57%) were urgent or emergent, and the most common procedure was caesarean delivery (3792 patients, 33%). Postoperative complications occurred in 1977 (18·2%, 95% CI 17·4-18·9]) of 10 885 patients. 239 (2·1%) of 11 193 patients died, 225 (94·1%) after the day of surgery. Infection was the most common complication (1156 [10·2%] of 10 970 patients), of whom 112 (9·7%) died.Interpretation: Despite a low-risk profile and few postoperative complications, patients in Africa were twice as likely to die after surgery when compared with the global average for postoperative deaths. Initiatives to increase access to surgical treatments in Africa therefore should be coupled with improved surveillance for deteriorating physiology in patients who develop postoperative complications, and the resources necessary to achieve this objective.Funding: Medical Research Council of South Africa. [ABSTRACT FROM AUTHOR]

Background: Recent studies suggest that ambient air pollution exposure during pregnancy is associated with stillbirth occurrence. However, the results on the associations between ambient air pollutants and stillbirths are inconsistent and little is known about the gestational timing of sensitive periods for the effects of ambient air pollutants exposure on stillbirth.Objective: This study aimed to examine whether exposure to high levels of ambient air pollutants in a Chinese population is associated with an increased risk of stillbirth, and determine the gestational period when the fetus is most susceptible.Methods: We conducted a population-based cohort study in Wuhan, China, involving 95,354 births between June 10, 2011 and June 9, 2013. The exposure assessments were based on the daily mean concentrations of air pollutants obtained from the exposure monitor nearest to the pregnant women's residence. Logistic regression analyses were performed to determine the associations between stillbirths and exposure to each of the air pollutants at different pregnancy periods with adjustment for confounding factors.Results: Stillbirth increased with a 10 μg/m3 increase in particulate matter 2.5 (PM2.5) in each stage of pregnancy, and a significant association between carbon monoxide (CO) exposure and stillbirth was found during the third trimester (adjusted odds ratio (aOR): 1.01, 95% confidence interval (CI): 1.00-1.01) and in the entire pregnancy (aOR: 1.18, 95% CI: 1.04-1.34). Furthermore, an increased risk of stillbirth in the third trimester was associated with a 10 μg/m3 increase in PM10 (aOR: 1.08, 95% CI: 1.04-1.11), nitrogen dioxide (NO2) (aOR: 1.13, 95% CI: 1.07-1.21) and sulfur dioxide (SO2) (aOR: 1.26, 95% CI: 1.16-1.35). However, no positive association was observed between ozone exposure and stillbirth. In the two-pollutant models, PM2.5 and CO exposures were found to be consistently associated with stillbirth.Conclusions: Our study revealed that exposure to high levels of PM2.5, PM10, SO2, NO2 and CO increases the risk of stillbirth and the most susceptible gestational period to ambient air pollution exposure was in the third trimester. Further toxicological and prospective cohort studies with improved exposure assessments are needed to confirm the causal link between air pollutants and stillbirth. [ABSTRACT FROM AUTHOR]

Aims: To correlate the dynamics of platelet activation with the development of thromboembolic events in patients with continuous-flow left ventricular assist device (cf-LVAD).Methods and Results: The platelet activity state (PAS) assay was utilized to evaluate platelet activation in 68 cf-LVAD patients implanted with the HeartMate II (n = 15, 22%), HeartMate 3 (n = 15, 22%), or HeartWare HVAD (n = 38, 56%). PAS was measured preoperatively, early post-implant, and at long-term follow-up (1, 3, 6, 12, 18, and 24 months post-implant). PAS was also measured at the occurrence of adverse events in patients who developed thrombotic complications. Data on patient demographics, medical history, antithrombotic therapy, and coagulation parameters were also analysed. Over a median follow-up of 602 (234-942) days, PAS values did not increase over time in the overall population (P = 0.15). However, PAS measured at event was 15-fold higher in the six patients (9%) who suffered pump thrombosis (n = 2) or ischaemic stroke (n = 4) vs. the rest of the population [6.67% (5.59%-11.98%) vs. 0.45% (0.33%-0.75%); P = 0.012], despite comparable coagulation profile. Pre-implant PAS values were 4.5-fold higher in these patients [1.90% (1.24%-3.17%) vs. 0.42% (0.32%-0.72%); P = 0.006]. Neither preoperative variables nor the type of the pump or the antiplatelet strategy were associated with a higher risk of complications.Conclusions: Thrombotic events are associated with altered PAS values. Moreover, baseline elevated PAS values in patients who developed thrombotic events suggest patient-specific tendency to post-implant thromboembolic complications. Prospectively, systematic monitoring of PAS might guide the development of refined patient-tailored antithrombotic strategies and the technological improvement of LVAD design. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the current study is to investigate the diagnostic role of shear-wave elastography and diffusion tensor imaging in patients with carpal tunnel syndrome.Material and Methods: The study included a total of 77 wrists; 18 normal, 35 wrists with mild, 9 wrists with moderate and 15 wrists with severe carpal tunnel syndrome. Elastography of the median nerve was performed by defining the boundaries of a segment of the nerve at sagittal plane at the level of proximal carpal row. Additionally, the cross-sectional area of the median nerve was evaluated. Fractional anisotropy and apparent diffusion coefficient measurements were carried out by placing region-of-interest at three levels: at pisiform bone (carpal tunnel inlet), mid carpal tunnel, and hook of hamate (carpal tunnel outlet).Results: Patients with carpal tunnel syndrome had higher elasticity values of median nerve (53.0 kPa; IQR 40.8-77.0 kPa) compared to control subjects. (36.8 kPa; IQR 31.0-39.9 kPa) Patients with moderate-severe carpal tunnel syndrome had higher elasticity values (82 kPa; IQR 64.0-95.5 kPa) compared to patients with mild carpal tunnel syndrome. (44 kPa; IQR 32.5-59.5 kPa) Patients with carpal tunnel syndrome had lower fractional anisotropy at mid-carpal level (0.382; IQR 0.330-0.495) compared to the control group. (0.494; IQR 0.434-0.537) Patients with moderate-severe carpal tunnel syndrome had lower fractional anisotropy values (0.366; IQR 0.331-0.407) and higher apparent diffusion coefficient values (1.509 mm2/s; IQR 1.374-1.733 mm2/s) compared to patients with mild carpal tunnel syndrome. (0,423; IQR 0.324-0.526 and 1.293 mm2/s; IQR 0.967-1.514 mm2/s) CONCLUSION: Shear-wave elastography and diffusion tensor imaging are helpful imaging modalities in diagnosing carpal tunnel syndrome and assessing its severity. [ABSTRACT FROM AUTHOR]

Objective: Fear of falling (FOF) is a major health problem for older adults, present not just in fallers, but also nonfallers. This study examined the impact of FOF and fall history on disability incidence among community-dwelling older adults from a prospective cohort study.Methods: A total of 5104 older adults living in community settings participated in baseline assessment and were followed up for about 4 years (median 52 mo, range 49-55 mo). At baseline, participants were assessed the presence of FOF and their fall history, and divided into 4 groups: Fall (-) FOF (-), Fall (+) FOF (-), Fall (-) FOF (+), and Fall (+) FOF (+). Disability incidence was defined as national long-term care insurance certification for personal support or care.Results: During the follow-up period, 429 participants (9.9%) were newly certified as having a disability and needing personal support for long-term care insurance. Fall (-) FOF (+) group and Fall (+) FOF (+) group showed a significantly higher risk of disability incidence than Fall (-) FOF (-) group even after adjusting for covariates (Fall (-) FOF (+): hazard ratio 1.28, 95% confidence interval, 1.01-1.62, Fall (+) FOF (+): hazard ratio 1.44, 95% confidence interval, 1.05-1.98).Conclusions: Fear of falling could be a simple and useful predictor of disability incidence in community-dwelling older adults. Identifying and decreasing fall risk factors may prevent fall-related injuries, but excessive FOF may be associated with increased risk of disability incidence. [ABSTRACT FROM AUTHOR]