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Nature Biotechnology Jul 2023Oxytocin (OT), a peptide hormone and neuromodulator, is involved in diverse physiological and pathophysiological processes in the central nervous system and the...
Oxytocin (OT), a peptide hormone and neuromodulator, is involved in diverse physiological and pathophysiological processes in the central nervous system and the periphery. However, the regulation and functional sequences of spatial OT release in the brain remain poorly understood. We describe a genetically encoded G-protein-coupled receptor activation-based (GRAB) OT sensor called GRAB. In contrast to previous methods, GRAB enables imaging of OT release ex vivo and in vivo with suitable sensitivity, specificity and spatiotemporal resolution. Using this sensor, we visualize stimulation-induced OT release from specific neuronal compartments in mouse brain slices and discover that N-type calcium channels predominantly mediate axonal OT release, whereas L-type calcium channels mediate somatodendritic OT release. We identify differences in the fusion machinery of OT release for axon terminals versus somata and dendrites. Finally, we measure OT dynamics in various brain regions in mice during male courtship behavior. Thus, GRAB provides insights into the role of compartmental OT release in physiological and behavioral functions.
Topics: Male; Mice; Animals; Oxytocin; Neurons; Brain; Signal Transduction; Central Nervous System
PubMed: 36593404
DOI: 10.1038/s41587-022-01561-2 -
Frontiers in Bioengineering and... 2021Lifting up objects from the floor has been identified as a risk factor for low back pain, whereby a flexed spine during lifting is often associated with producing higher...
Lifting up objects from the floor has been identified as a risk factor for low back pain, whereby a flexed spine during lifting is often associated with producing higher loads in the lumbar spine. Even though recent biomechanical studies challenge these assumptions, conclusive evidence is still lacking. This study therefore aimed at comparing lumbar loads among different lifting styles using a comprehensive state-of-the-art motion capture-driven musculoskeletal modeling approach. Thirty healthy pain-free individuals were enrolled in this study and asked to repetitively lift a 15 kg-box by applying 1) a freestyle, 2) a squat and 3) a stoop lifting technique. Whole-body kinematics were recorded using a 16-camera optical motion capture system and used to drive a full-body musculoskeletal model including a detailed thoracolumbar spine. Continuous as well as peak compressive, anterior-posterior shear and total loads (resultant load vector of the compressive and shear load vectors) were calculated based on a static optimization approach and expressed as factor body weight (BW). In addition, lumbar lordosis angles and total lifting time were calculated. All parameters were compared among the lifting styles using a repeated measures design. For each lifting style, loads increased towards the caudal end of the lumbar spine. For all lumbar segments, stoop lifting showed significantly lower compressive and total loads (-0.3 to -1.0BW) when compared to freestyle and squat lifting. Stoop lifting produced higher shear loads (+0.1 to +0.8BW) in the segments T12/L1 to L4/L5, but lower loads in L5/S1 (-0.2 to -0.4BW). Peak compressive and total loads during squat lifting occurred approximately 30% earlier in the lifting cycle compared to stoop lifting. Stoop lifting showed larger lumbar lordosis range of motion (35.9 ± 10.1°) than freestyle (24.2 ± 7.3°) and squat (25.1 ± 8.2°) lifting. Lifting time differed significantly with freestyle being executed the fastest (4.6 ± 0.7 s), followed by squat (4.9 ± 0.7 s) and stoop (5.9 ± 1.1 s). Stoop lifting produced lower total and compressive lumbar loads than squat lifting. Shear loads were generally higher during stoop lifting, except for the L5/S1 segment, where anterior shear loads were higher during squat lifting. Lifting time was identified as another important factor, considering that slower speeds seem to result in lower loads.
PubMed: 34805121
DOI: 10.3389/fbioe.2021.769117 -
Alzheimer's & Dementia : the Journal of... May 2023Direct comparisons of the main blood phosphorylated tau immunoassays in memory clinic populations are needed to understand possible differences.
INTRODUCTION
Direct comparisons of the main blood phosphorylated tau immunoassays in memory clinic populations are needed to understand possible differences.
METHODS
In the BIODEGMAR study, 197 participants presenting with cognitive complaints were classified into an Alzheimer's disease (AD) or a non-AD cerebrospinal fluid (CSF) profile group, according to their amyloid beta 42/ phosphorylated tau (Aβ42/p-tau) ratio. We performed a head-to-head comparison of nine plasma and nine CSF tau immunoassays and determined their accuracy to discriminate abnormal CSF Aβ42/p-tau ratio.
RESULTS
All studied plasma tau biomarkers were significantly higher in the AD CSF profile group compared to the non-AD CSF profile group and significantly discriminated abnormal CSF Aβ42/p-tau ratio. For plasma p-tau biomarkers, the higher discrimination accuracy was shown by Janssen p-tau217 (r = 0.76; area under the curve [AUC] = 0.96), ADx p-tau181 (r = 0.73; AUC = 0.94), and Lilly p-tau217 (r = 0.73; AUC = 0.94).
DISCUSSION
Several plasma p-tau biomarkers can be used in a specialized memory clinic as a stand-alone biomarker to detect biologically-defined AD.
HIGHLIGHTS
Patients with an Alzheimer's disease cerebrospinal fluid (AD CSF) profile have higher plasma phosphorylated tau (p-tau) levels than the non-AD CSF profile group. All plasma p-tau biomarkers significantly discriminate patients with an AD CSF profile from the non-AD CSF profile group. Janssen p-tau217, ADx p-tau181, and Lilly p-tau217 in plasma show the highest accuracy to detect biologically defined AD. Janssen p-tau217, ADx p-tau181, Lilly p-tau217, Lilly p-tau181, and UGot p-tau231 in plasma show performances that are comparable to their CSF counterparts.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Biomarkers; Cognitive Dysfunction; Enzyme-Linked Immunosorbent Assay; Immunoassay; tau Proteins
PubMed: 36370462
DOI: 10.1002/alz.12841 -
Scandinavian Journal of Medicine &... Mar 2020This randomized controlled trial examined the effects of cold-water immersion (CWI), partial-body cryotherapy (PBC), or a passive control (CON) on physiological and... (Randomized Controlled Trial)
Randomized Controlled Trial
This randomized controlled trial examined the effects of cold-water immersion (CWI), partial-body cryotherapy (PBC), or a passive control (CON) on physiological and recovery variables following exercise-induced muscle damage (EIMD, 5 × 20 drop jumps) in females. Twenty-eight females were allocated to PBC (30 seconds at -60°C, 2 minutes at -135°C), CWI (10 minutes at 10°C), or CON (10 minutes resting). Muscle oxygen saturation (SmO ), cutaneous vascular conductance (CVC), mean arterial pressure (MAP), and local skin temperature were assessed at baseline and through 60 minutes (10-minute intervals), while delayed onset of muscle soreness (DOMS), muscle swelling, maximum voluntary isometric contraction (MVIC), and vertical jump performance (VJP) were assessed up to 72 hours (24-hour intervals) following treatments. SmO was lower in PBC (Δ-2.77 ± 13.08%) and CWI (Δ-5.91 ± 11.80%) compared with CON (Δ18.96 ± 1.46%) throughout the 60-minute follow-up period (P < .001). CVC was lower from PBC (92.7 ± 25.0%, 90.5 ± 23.4%) and CWI (90.3 ± 23.5%, 88.1 ± 22.9%) compared with CON (119.0 ± 5.1 and 116.1 ± 6.6%, respectively) between 20 and 30 minutes (P < .05). Mean skin temperature was lower from CWI vs PBC (between 10 and 40 minutes, P < .05). Mean skin temperature was higher in CON compared with CWI up to 60 minutes and compared with PBC up to 30 minutes (P < .05). DOMS was lower following both PBC and CWI compared with CON through 72-hour (P < .05), with no difference between groups. No main group differences for swelling, MVIC, and VJP were observed. In conclusion, CWI elicited generally greater physiological effects compared with PBC while both interventions were more effective than CON in reducing DOMS in females, but had no effect on functional measures or swelling.
Topics: Adult; Cold Temperature; Cryotherapy; Female; Humans; Immersion; Isometric Contraction; Muscle, Skeletal; Myalgia; Skin Temperature; Water; Young Adult
PubMed: 31677292
DOI: 10.1111/sms.13593 -
Alzheimer's Research & Therapy Dec 2021Studies using different assays and technologies showed highly promising diagnostic value of plasma phosphorylated (P-)tau levels for Alzheimer's disease (AD). We aimed...
INTRODUCTION
Studies using different assays and technologies showed highly promising diagnostic value of plasma phosphorylated (P-)tau levels for Alzheimer's disease (AD). We aimed to compare six P-tau Simoa assays, including three P-tau181 (Eli Lilly, ADx, Quanterix), one P-tau217 (Eli Lilly), and two P-tau231 (ADx, Gothenburg).
METHODS
We studied the analytical (sensitivity, precision, parallelism, dilution linearity, and recovery) and clinical (40 AD dementia patients, age 66±8years, 50%F; 40 age- and sex-matched controls) performance of the assays.
RESULTS
All assays showed robust analytical performance, and particularly P-tau217 Eli Lilly; P-tau231 Gothenburg and all P-tau181 assays showed robust clinical performance to differentiate AD from controls, with AUCs 0.936-0.995 (P-tau231 ADx: AUC = 0.719). Results obtained with all P-tau181 assays, P-tau217 Eli Lilly assay, and P-tau231 Gothenburg assay strongly correlated (Spearman's rho > 0.86), while correlations with P-tau231 ADx results were moderate (rho < 0.65).
DISCUSSION
P-tau isoforms can be measured robustly by several novel high-sensitive Simoa assays.
Topics: Aged; Alzheimer Disease; Amyloid beta-Peptides; Biomarkers; Humans; Middle Aged; Phosphorylation; Protein Isoforms; tau Proteins
PubMed: 34863295
DOI: 10.1186/s13195-021-00939-9 -
Human Reproduction (Oxford, England) Jul 2022Does ovarian stimulation with the addition of tamoxifen or letrozole affect the number of cumulus-oocyte complexes (COCs) retrieved compared to standard ovarian... (Randomized Controlled Trial)
Randomized Controlled Trial
STUDY QUESTION
Does ovarian stimulation with the addition of tamoxifen or letrozole affect the number of cumulus-oocyte complexes (COCs) retrieved compared to standard ovarian stimulation in women with breast cancer who undergo fertility preservation?
SUMMARY ANSWER
Alternative ovarian stimulation protocols with tamoxifen or letrozole did not affect the number of COCs retrieved at follicle aspiration in women with breast cancer.
WHAT IS KNOWN ALREADY
Alternative ovarian stimulation protocols have been introduced for women with breast cancer who opt for fertility preservation by means of banking of oocytes or embryos. How these ovarian stimulation protocols compare to standard ovarian stimulation in terms of COC yield is unknown.
STUDY DESIGN, SIZE, DURATION
This multicentre, open-label randomized controlled superiority trial was carried out in 10 hospitals in the Netherlands and 1 hospital in Belgium between January 2014 and December 2018. We randomly assigned women with breast cancer, aged 18-43 years, who opted for banking of oocytes or embryos to one of three study arms; ovarian stimulation plus tamoxifen, ovarian stimulation plus letrozole or standard ovarian stimulation. Standard ovarian stimulation included GnRH antagonist, recombinant FSH and GnRH agonist trigger. Randomization was performed with a web-based system in a 1:1:1 ratio, stratified for oral contraception usage at start of ovarian stimulation, positive estrogen receptor (ER) status and positive lymph nodes. Patients and caregivers were not blinded to the assigned treatment. The primary outcome was number of COCs retrieved at follicle aspiration.
PARTICIPANTS/MATERIALS, SETTING, METHODS
During the study period, 162 women were randomly assigned to one of three interventions. Fifty-four underwent ovarian stimulation plus tamoxifen, 53 ovarian stimulation plus letrozole and 55 standard ovarian stimulation. Analysis was according to intention-to-treat principle.
MAIN RESULTS AND THE ROLE OF CHANCE
No differences among groups were observed in the mean (±SD) number of COCs retrieved: 12.5 (10.4) after ovarian stimulation plus tamoxifen, 14.2 (9.4) after ovarian stimulation plus letrozole and 13.6 (11.6) after standard ovarian stimulation (mean difference -1.13, 95% CI -5.70 to 3.43 for tamoxifen versus standard ovarian stimulation and 0.58, 95% CI -4.03 to 5.20 for letrozole versus standard ovarian stimulation). After adjusting for oral contraception usage at the start of ovarian stimulation, positive ER status and positive lymph nodes, the mean difference was -1.11 (95% CI -5.58 to 3.35) after ovarian stimulation plus tamoxifen versus standard ovarian stimulation and 0.30 (95% CI -4.19 to 4.78) after ovarian stimulation plus letrozole versus standard ovarian stimulation. There were also no differences in the number of oocytes or embryos banked. There was one serious adverse event after standard ovarian stimulation: one woman was admitted to the hospital because of ovarian hyperstimulation syndrome.
LIMITATIONS, REASONS FOR CAUTION
The available literature on which we based our hypothesis, power analysis and sample size calculation was scarce and studies were of low quality. Our study did not have sufficient power to perform subgroup analysis on follicular, luteal or random start of ovarian stimulation.
WIDER IMPLICATIONS OF THE FINDINGS
Our study showed that adding tamoxifen or letrozole to a standard ovarian stimulation protocol in women with breast cancer does not impact the effectiveness of fertility preservation and paves the way for high-quality long-term follow-up on breast cancer treatment outcomes and women's future pregnancy outcomes. Our study also highlights the need for high-quality studies for all women opting for fertility preservation, as alternative ovarian stimulation protocols have been introduced to clinical practice without proper evidence.
STUDY FUNDING/COMPETING INTEREST(S)
The study was supported by a grant (2011.WO23.C129) of 'Stichting Pink Ribbon', a breast cancer fundraising charity organization in the Netherlands. M.G., C.B.L. and R.S. declared that the Center for Reproductive Medicine, Amsterdam UMC (location VUMC) has received unconditional research and educational grants from Guerbet, Merck and Ferring, not related to the presented work. C.B.L. declared a speakers fee for Inmed and Yingming. S.C.L. reports grants and non-financial support from Agendia, grants, non-financial support and other from AstraZeneca, grants from Eurocept-pharmaceuticals, grants and non-financial support from Genentech/Roche and Novartis, grants from Pfizer, grants and non-financial support from Tesaro and Immunomedics, other from Cergentis, IBM, Bayer, and Daiichi-Sankyo, outside the submitted work; In addition, S.C.L. has a patent UN23A01/P-EP pending that is unrelated to the present work. J.M.J.S. reported payments and travel grants from Merck and Ferring. C.C.M.B. reports her role as unpaid president of the National guideline committee on Fertility Preservation in women with cancer. K.F. received unrestricted grants from Merck Serono, Good Life and Ferring not related to present work. K.F. declared paid lectures for Ferring. D.S. declared former employment from Merck Sharp & Dohme (MSD). K.F. declared paid lectures for Ferring. D.S. reports grants from MSD, Gedeon Richter and Ferring paid to his institution; consulting fee payments from MSD and Merck Serono paid to his institution; speaker honoraria from MSD, Gedeon Richter, Ferring Pharmaceuticals and Merck Serono paid to his institution. D.S. has also received travel and meeting support from MSD, Gedeon Richter, Ferring Pharmaceuticals and Merck Serono. No payments are related to present work.
TRIAL REGISTRATION NUMBER
NTR4108.
TRIAL REGISTRATION DATE
6 August 2013.
DATE OF FIRST PATIENT’S ENROLMENT
30 January 2014.
Topics: Breast Neoplasms; Female; Fertility Preservation; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Letrozole; Multicenter Studies as Topic; Ovulation Induction; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Sperm Injections, Intracytoplasmic; Tamoxifen
PubMed: 35776109
DOI: 10.1093/humrep/deac145 -
Military Psychology : the Official... 2023The reported that 39.1% of the civilian workforce in the United States performs physically demanding jobs that require lifting, carrying, pushing/pulling, kneeling,... (Review)
Review
The reported that 39.1% of the civilian workforce in the United States performs physically demanding jobs that require lifting, carrying, pushing/pulling, kneeling, stooping, crawling, and climbing activities in varied environmental conditions. United States military occupations are similar to those in the civilian sector involving equipment installation, emergency rescues, and maintenance, along with combat arms occupations. This article provides an overview of the types of criterion measures used to assess the physical domain and approaches for designing and evaluating the criteria. It also includes a method for generating criterion measures that are applicable across multiple jobs.
Topics: Humans; Military Personnel; Occupations; Posture; United States; Workforce
PubMed: 37352446
DOI: 10.1080/08995605.2022.2063008 -
Clinics in Orthopedic Surgery Feb 2023Corrective osteotomy is an effective surgery for correcting posture in patients with ankylosing spondylitis (AS). Despite satisfactory correction, some patients...
BACKGROUND
Corrective osteotomy is an effective surgery for correcting posture in patients with ankylosing spondylitis (AS). Despite satisfactory correction, some patients experience re-stooping during follow-up. However, there have been no studies on re-stooping in AS. We aimed to analyze the factors that affect re-stooping.
METHODS
Fifty patients (50 cases) who underwent thoracolumbar corrective osteotomy for AS from March 2006 to April 2018 were analyzed. We defined re-stooping as global kyphosis that recurs after corrective osteotomy. The patients were divided into two groups based on the ratio of correction loss: non-re-stooping group (N group) and re-stooping group (R group). We analyzed the demographic data and radiological parameters, such as modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), sagittal vertical axis, and various angles. We also investigated the factors affecting re-stooping by analyzing the correlation between the ratio of correction loss and various factors.
RESULTS
A significant difference was seen in the change in the mSASSS from before surgery to the last follow-up between the N group (2.87 ± 3.08) and the R group (9.20 ± 5.44). In multivariate analysis, only the change in the mSASSS from before surgery to the last follow-up was significantly correlated with the ratio of correction loss.
CONCLUSIONS
Thoracolumbar corrective osteotomy seems to provide high satisfaction among patients with AS but can lead to re-stooping during follow-up. The change in mSASSS was related with re-stooping in the current study. We recommend active rehabilitative exercises and appropriate medication depending on the patient's condition, which may help delay the postoperative progression of AS.
Topics: Humans; Spondylitis, Ankylosing; Treatment Outcome; Spine; Kyphosis; Osteotomy; Phenolphthalein; Lumbar Vertebrae; Thoracic Vertebrae; Retrospective Studies
PubMed: 36778985
DOI: 10.4055/cios22075 -
Tidsskrift For Den Norske Laegeforening... May 2017
Topics: Female; Humans; Magnetic Resonance Imaging; Middle Aged; Multiple System Atrophy; Neck Muscles; Parkinson Disease; Posture
PubMed: 28468480
DOI: 10.4045/tidsskr.16.0993