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Environmental Research Jun 2024Glyphosate is the most widely used herbicide worldwide, both in domestic and industrial settings. Experimental research in animal models has demonstrated changes in...
BACKGROUND
Glyphosate is the most widely used herbicide worldwide, both in domestic and industrial settings. Experimental research in animal models has demonstrated changes in muscle physiology and reduced contractile strength associated with glyphosate exposure, while epidemiological studies have shown associations between glyphosate exposure and adverse health outcomes in critical biological systems affecting muscle function.
METHODS
This study used data from a nationally representative survey of the non-institutionalized U.S. general population (NHANES, n = 2132). Urine glyphosate concentrations were determined by ion chromatography with tandem mass spectrometry. Hand grip strength (HGS) was measured using a Takei Dynamometer, and relative strength estimated as the ratio between HGS in the dominant hand and the appendicular lean mass (ALM) to body mass index (ALMBMI) ratio. Low HGS and low relative HGS were defined as 1 sex-, age- and race-specific SD below the mean. Physical function limitations were identified as significant difficulty or incapacity in various activities.
RESULTS
In fully-adjusted models, the Mean Differences (MD) and 95% confidence intervals [95%CI] per doubling increase in glyphosate concentrations were -0.55 [-1.09, -0.01] kg for HGS in the dominant hand, and -0.90 [-1.58. -0.21] kg for HGS/ALMBMI. The Odds Ratios (OR) [95% CI] for low HGS, low relative HGS and functional limitations by glyphosate concentrations were 1.27 [1.03, 1.57] for low HGS; 1.43 [1.05; 1.94] for low relative HGS; 1.33 [1.08, 1.63] for stooping, crouching or kneeling difficulty; 1.17 [0.91, 1.50] for lifting or carrying items weighting up to 10 pounds difficulty; 1.21 [1.01, 1.40] for standing up from armless chair difficulty; and 1.47 [1.05, 2.29] for ascending ten steps without pause difficulty.
CONCLUSIONS
Glyphosate exposure may be a risk factor for decreased grip strength and increased physical functional limitations. More studies investigating the influence of this and other environmental pollutants on functional aging are needed.
Topics: Glyphosate; Glycine; Humans; Male; Middle Aged; Female; Aged; Herbicides; Hand Strength; Environmental Exposure; Nutrition Surveys
PubMed: 38452917
DOI: 10.1016/j.envres.2024.118547 -
Human Reproduction Open 2024Is pronuclear transfer (PNT) capable of restoring embryo developmental arrest caused by cytoplasmic inferiority of -grown (IVG) mouse oocytes?
STUDY QUESTION
Is pronuclear transfer (PNT) capable of restoring embryo developmental arrest caused by cytoplasmic inferiority of -grown (IVG) mouse oocytes?
SUMMARY ANSWER
PNT to matured cytoplasm significantly improved embryo development of IVG mouse oocytes, leading to living, fertile offspring.
WHAT IS KNOWN ALREADY
follicle culture has been considered as a fertility preservation option for cancer patients. Studies describing the culture of human follicles remain scarce, owing to low availability of tissue. Mouse models have extensively been used to study and optimize follicle culture. Although important achievements have been accomplished, including the production of healthy offspring in mice, IVG oocytes are of inferior quality when compared to -grown oocytes, likely because of cytoplasmic incompetence.
STUDY DESIGN SIZE DURATION
The study was carried out from September 2020 to February 2022. In total, 120 15-day-old B6D2 mice were used to perform secondary follicle culture and assess the quality of IVG oocytes. -grown control oocytes were obtained from 85 8- to 12-week-old B6D2 mice, following ovarian stimulation. For sperm collection, four B6D2 males between 10 and 14 weeks old were used. For embryo transfer, 14 8- to 12-week-old CD1 females served as surrogate mothers and 10 CD1 vasectomized males 10-24 weeks old were used to generate pseudo-pregnant females. Finally, for mating, four B6D2 female mice aged 8-10 weeks and two B6D2 male mice aged 10 weeks old were used to confirm the fertility of nuclear transfer (NT)-derived pups.
PARTICIPANTS/MATERIALS SETTING METHODS
Secondary follicles from 15-day-old B6D2 mice were isolated from the ovaries and cultured for 9 days, before a maturation stimulus was given. Following 16-18 h of maturation, oocytes were collected and evaluated on maturation rate, oocyte diameter, activation rate, spindle morphology, calcium-releasing ability, and mitochondrial membrane potential. For every experiment, -grown oocytes were used as a control for comparison. When cytoplasmic immaturity and poor embryo development were confirmed in IVG oocytes, PNT was performed. For this, the pronuclei from IVG oocytes, created following parthenogenetic activation and IVF, were transferred to the cytoplasm of fertilized, -grown oocytes. Genetic analysis and embryo transfer of the generated embryos were implemented to confirm the safety of the technique.
MAIN RESULTS AND THE ROLE OF CHANCE
Following 9 days of follicle culture, 703 oocytes were collected, of which 76% showed maturation to the metaphase II stage. Oocyte diameters were significantly lower in IVG oocytes, measuring 67.4 μm versus 73.1 μm in controls ( < 0.001). Spindle morphology did not differ significantly between IVG and control oocytes, but calcium-releasing ability was compromised in the IVG group. An average calcium release of 1.62 arbitrary units was observed in IVG oocytes, significantly lower than 5.74 in control oocytes ( < 0.001). Finally, mitochondrial membrane potential was inferior in IVG compared to the control group, reaching an average value of 0.95 versus 2.27 ( < 0.001). Developmental potential of IVG oocytes was assessed following parthenogenetic activation with strontium chloride (SrCl). Only 59.4% of IVG oocytes cleaved to two cells and 36.3% reached the blastocyst stage, significantly lower than 89.5% and 88.2% in control oocytes, respectively ( < 0.001 and 0.001). Both PNT and spindle transfer (ST) were explored in pilot experiments with parthenogenetically activated oocytes, as a means to overcome poor embryo development. After the added value of NT was confirmed, we continued with the generation of biparental embryos by PNT. For this purpose, IVG and control oocytes first underwent IVF. Only 15.5% of IVG oocytes were normally fertilized, in contrast to 45.5% in controls ( < 0.001), with resulting failure of blastocyst formation in the IVG group (0 versus 86.2%, < 0.001). When the pronuclei of IVG zygotes were transferred to the cytoplasm of control zygotes, the blastocyst rate was restored to 86.9%, a similar level as the control. Genetic analysis of PNT embryos revealed a normal chromosomal profile, to a rate of 80%. Finally, the generation of living, fertile offspring from PNT was possible following embryo transfer to surrogate mothers.
LARGE-SCALE DATA
N/A.
LIMITATIONS REASONS FOR CAUTION
Genetic profiles of analysed embryos from PNT originate from groups that are too small to draw concrete conclusions, whilst ST, which would be the preferred NT approach, could not be used for the generation of biparental embryos owing to technical limitations. Even though promising, the use of PNT should be considered as experimental. Furthermore, results were acquired in a mouse model, so validation of the technique in human IVG oocytes needs to be performed to evaluate the clinical relevance of the technology. The genetic profiles from IVG oocytes, which would be the ultimate characterization for chromosomal abnormalities, were not analysed owing to limitations in the reliable analysis of single cells.
WIDER IMPLICATIONS OF THE FINDINGS
PNT has the ability to overcome the poor cytoplasmic quality of IVG mouse oocytes. Considering the low maturation efficiency of human IVG oocytes and potential detrimental effects following long-term culture, NT could be applied to rescue embryo development and could lead to an increased availability of good quality embryos for transfer.
STUDY FUNDING/COMPETING INTERESTS
A.C. is a holder of FWO (Fonds voor Wetenschappelijk Onderzoek) grants (1S80220N and 1S80222N). B.H. and A.V.S. have been awarded with a special BOF (Bijzonder Onderzoeksfonds), GOA (Geconcerteerde onderzoeksacties) 2018000504 (GOA030-18 BOF) funding. B.H. has been receiving unrestricted educational funding from Ferring Pharmaceuticals (Aalst, Belgium). The authors declare that they have no conflict of interest.
PubMed: 38425578
DOI: 10.1093/hropen/hoae009 -
Ergonomics Feb 2024Back support exosuits aim to reduce tissue demands and thereby risk of injury and pain. However, biomechanical analyses of soft active exosuit designs have been limited....
Back support exosuits aim to reduce tissue demands and thereby risk of injury and pain. However, biomechanical analyses of soft active exosuit designs have been limited. The objective of this study was to evaluate the effect of a soft active back support exosuit on trunk motion and thoracolumbar spine loading in participants performing stoop and squat lifts of 6 and 10 kg crates, using participant-specific musculoskeletal models. The exosuit did not change overall trunk motion but affected lumbo-pelvic motion slightly, and reduced peak compressive and shear vertebral loads at some levels, although shear increased slightly at others. This study indicates that soft active exosuits have limited kinematic effects during lifting, and can reduce spinal loading depending on the vertebral level. These results support the hypothesis that a soft exosuit can assist without limiting trunk movement or negatively impacting skeletal loading and have implications for future design and ergonomic intervention efforts.
PubMed: 38389220
DOI: 10.1080/00140139.2024.2320355 -
The British Journal of Surgery Jan 2024This study evaluated the association of pathological tumour response (tumour regression grade, TRG) and a novel scoring system, combining both TRG and nodal status...
BACKGROUND
This study evaluated the association of pathological tumour response (tumour regression grade, TRG) and a novel scoring system, combining both TRG and nodal status (TRG-ypN score; TRG1-ypN0, TRG>1-ypN0, TRG1-ypN+ and TRG>1-ypN+), with recurrence patterns and survival after multimodal treatment of oesophageal adenocarcinoma.
METHODS
This Dutch nationwide cohort study included patients treated with neoadjuvant chemoradiotherapy followed by oesophagectomy for distal oesophageal or gastro-oesophageal junctional adenocarcinoma between 2007 and 2016. The primary endpoint was the association of Mandard score and TRG-ypN score with recurrence patterns (rate, location, and time to recurrence). The secondary endpoint was overall survival.
RESULTS
Among 2746 inclusions, recurrence rates increased with higher Mandard scores (TRG1 30.6%, TRG2 44.9%, TRG3 52.9%, TRG4 61.4%, TRG5 58.2%; P < 0.001). Among patients with recurrent disease, the distribution (locoregional versus distant) was the same for the different TRG groups. Patients with TRG1 developed more brain recurrences (17.7 versus 9.8%; P = 0.001) and had a longer mean overall survival (44 versus 35 months; P < 0.001) than those with TRG>1. The TRG>1-ypN+ group had the highest recurrence rate (64.9%) and worst overall survival (mean 27 months). Compared with the TRG>1-ypN0 group, patients with TRG1-ypN+ had a higher risk of recurrence (51.9 versus 39.6%; P < 0.001) and worse mean overall survival (33 versus 41 months; P < 0.001).
CONCLUSION
Improved tumour response to neoadjuvant therapy was associated with lower recurrence rates and higher overall survival rates. Among patients with recurrent disease, TRG1 was associated with a higher incidence of brain recurrence than TRG>1. Residual nodal disease influenced prognosis more negatively than residual disease at the primary tumour site.
Topics: Humans; Prognosis; Cohort Studies; Disease-Free Survival; Combined Modality Therapy; Esophageal Neoplasms; Adenocarcinoma
PubMed: 38387083
DOI: 10.1093/bjs/znae034 -
Psychopharmacology Jun 2024Understanding mechanisms of drug use decisions will inform the development of treatments for opioid use disorder (OUD). Decision-making experiments using neurobehavioral...
A dose-ranging study of the physiological and self-reported effects of repeated, rapid infusion of remifentanil in people with opioid use disorder and physical dependence on fentanyl.
RATIONALE
Understanding mechanisms of drug use decisions will inform the development of treatments for opioid use disorder (OUD). Decision-making experiments using neurobehavioral approaches require many trials or events of interest for statistical analysis, but the pharmacokinetics of most opioids limit dosing in humans.
OBJECTIVES
This experiment characterized the effects of repeated infusions of the ultra-short acting opioid remifentanil in people with OUD and physical opioid dependence.
METHODS
An inpatient study using a within-subjects, single-blind, escalating, within-session, pre-post design was conducted. Seven (3 female) subjects were maintained on oral oxycodone (40-60 mg, 4x/day = 160-240 total mg/day) for seven days prior to the dose-ranging session. Subjects received infusions of three ascending remifentanil doses (0.03, 0.1, 0.3 mcg/kg/infusion in 2 subjects; 0.1, 0.3, 1.0 mcg/kg/infusion in 5 subjects) every minute for 40 min per dose, with infusions administered over 5 s to model naturalistic delivery rates. End tidal carbon dioxide, respiration rate, oxygen saturation (SpO) and heart rate were measured continuously. Blood pressure (BP), pupil diameter and self-reported drug effects were measured every 5 min.
RESULTS
Pupil diameter, SpO and systolic BP decreased, and ratings on prototypic subjective effects questionnaire items increased, as a function of remifentanil dose. The number of infusions held because of sedation or physiological parameters exceeding predetermined cutoffs also increased with dose.
CONCLUSIONS
This experiment established doses and procedures for the safe delivery of rapid, repeated remifentanil infusions to individuals with OUD and physical fentanyl dependence, which can be applied to the mechanistic study of opioid use decisions.
Topics: Humans; Remifentanil; Female; Male; Adult; Opioid-Related Disorders; Fentanyl; Dose-Response Relationship, Drug; Analgesics, Opioid; Piperidines; Single-Blind Method; Heart Rate; Blood Pressure; Infusions, Intravenous; Middle Aged; Self Report; Young Adult; Oxycodone
PubMed: 38383903
DOI: 10.1007/s00213-024-06557-1 -
Systematic review on management of high-output enterostomy in children: An urgent call for evidence.Journal of Pediatric Gastroenterology... Feb 2024High-output stoma is one of the most common major morbidities in young children with an enterostomy that could lead to intestinal failure. Management of high-output... (Review)
Review
OBJECTIVES/BACKGROUND
High-output stoma is one of the most common major morbidities in young children with an enterostomy that could lead to intestinal failure. Management of high-output enterostomy in children is mostly based on personal experience. This systematic review aims to clarify the evidence-based therapeutic approach of high-output enterostomy in children.
METHODS
A systematic review was performed using Pubmed, Embase (Ovid), and Cochrane Library to identify studies published until March 20, 2023, following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. The study population comprised children (i.e., age <18 years) with high-output enterostomy (i.e., jejuno-, ileo-, and/or colostomy), regardless of underlying aetiology. Interventions comprised any (non)pharmacological and/or surgical treatment. Interventions were compared with each other, placebos, and/or no interventions. Primary outcome was reduction of enterostomy output. Secondary outcomes were morbidity, mortality, quality of life, associated healthcare costs, and adverse events.
RESULTS
The literature search identified 4278 original articles of which 366 were screened on full text, revealing that none of the articles met the inclusion criteria.
CONCLUSION
This first systematic review on management of high-output enterostomy in children revealed that any evidence on the primary and secondary outcomes is lacking. There is an urgent need for evidence on conservative treatment strategies including fluid restrictions, dietary advices, oral rehydration solution, chyme re-infusion, and pharmacological and surgical treatments of high-output enterostomy in children, aiming to reduce the risk for short- and long-term complications. Till more evidence is available, a systematic and multidisciplinary step-up approach is needed. Therefore, a therapeutic work-up is proposed that could guide the care.
Topics: Child; Humans; Child, Preschool; Adolescent; Quality of Life; Surgical Stomas; Enterostomy
PubMed: 38374570
DOI: 10.1002/jpn3.12043 -
Journal of Neurochemistry Feb 2024Brain amyloid-β (Aβ) deposits are key pathological hallmarks of both cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD). Microvascular deposits in CAA...
Brain amyloid-β (Aβ) deposits are key pathological hallmarks of both cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD). Microvascular deposits in CAA mainly consist of the Aβ peptide, whereas Aβ is the predominant variant in parenchymal plaques in AD. The relevance in pathogenesis and diagnostic accuracy of various other Aβ isoforms in CAA remain understudied. We aimed to investigate the biomarker potential of various Aβ isoforms in cerebrospinal fluid (CSF) to differentiate CAA from AD pathology. We included 25 patients with probable CAA, 50 subjects with a CSF profile indicative of AD pathology (AD-like), and 23 age- and sex-matched controls. CSF levels of Aβ , Aβ , Aβ , Aβ , Aβ , and Aβ were quantified by liquid chromatography mass spectrometry. Lower CSF levels of all six Aβ peptides were observed in CAA patients compared with controls (p = 0.0005-0.03). Except for Aβ (p = 1.0), all peptides were decreased in CAA compared with AD-like subjects (p = 0.007-0.03). Besides Aβ , none of the Aβ peptides were decreased in AD-like subjects compared with controls. All Aβ peptides combined differentiated CAA from AD-like subjects better (area under the curve [AUC] 0.84) than individual peptide levels (AUC 0.51-0.75). Without Aβ in the model (since decreased Aβ served as AD-like selection criterion), the AUC was 0.78 for distinguishing CAA from AD-like subjects. CAA patients and AD-like subjects showed distinct disease-specific CSF Aβ profiles. Peptides shorter than Aβ were decreased in CAA patients, but not AD-like subjects, which could suggest different pathological mechanisms between vascular and parenchymal Aβ accumulation. This study supports the potential use of this panel of CSF Aβ peptides to indicate presence of CAA pathology with high accuracy.
PubMed: 38362804
DOI: 10.1111/jnc.16074 -
BMJ Case Reports Feb 2024A woman in her 70s with a medical history of recurrent ovarian carcinoma was referred to the gastroenterologist because of rectal blood loss. Colonoscopy revealed a...
A woman in her 70s with a medical history of recurrent ovarian carcinoma was referred to the gastroenterologist because of rectal blood loss. Colonoscopy revealed a spontaneously bleeding lesion, which was not a typical colorectal carcinoma by optical diagnosis. Biopsies confirmed the diagnosis of recurrence of the former ovarian carcinoma. The patient was not eligible for surgical resection due to former abdominal surgery and she declined chemotherapy due to severe side effects earlier. After a multidisciplinary team consultation, she was treated with endoscopic full-thickness resection (eFTR). This is a minimally invasive resection technique for removal of challenging colorectal lesions. The patient has recovered well and 2 years after the metastasis resection with eFTR there still have been no signs of recurrent malignancy.
Topics: Female; Humans; Carcinoma; Carcinoma, Ovarian Epithelial; Colonoscopy; Colorectal Neoplasms; Endoscopic Mucosal Resection; Neoplasm Recurrence, Local; Ovarian Neoplasms; Retrospective Studies; Treatment Outcome; Aged
PubMed: 38355211
DOI: 10.1136/bcr-2023-256466 -
IEEE Transactions on Bio-medical... Jul 2024Lumbar exoskeleton is an assistive robot, which can reduce the risk of injury and pain in low back muscles when lifting heavy objects. An important challenge it faces...
Lumbar exoskeleton is an assistive robot, which can reduce the risk of injury and pain in low back muscles when lifting heavy objects. An important challenge it faces involves enhancing assistance with minimal muscle energy consumption. One of the viable solutions is to adjust the force or torque of assistance in response to changes in the load on the low back muscles. It requires accurate loading recognition, which has yet to yield satisfactory outcomes due to the limitations of available measurement tools and load classification methods. This study aimed to precisely identify muscle loading using a multi-channel surface electromyographic (sEMG) electrode array on the low back muscles, combined with a participant-specific load classification method. Ten healthy participants performed a stoop lifting task with objects of varying weights, while sEMG data was collected from the low back muscles using a 3x7 electrode array. Nineteen time segments of the lifting phase were identified, and time-domain sEMG features were extracted from each segment. Participant-specific classifiers were built using four classification algorithms to determine the object weight in each time segment, and the classification performance was evaluated using a 5-fold cross-validation method. The artificial neural network classifier achieved an impressive accuracy of up to 96%, consistently improving as the lifting phase progressed, peaking towards the end of the lifting movement. This study successfully achieves accurate recognition of load on low back muscles during the object lifting task. The obtained results hold significant potential in effectively reducing muscle energy consumption when wearing a lumbar exoskeleton.
Topics: Humans; Electromyography; Male; Exoskeleton Device; Adult; Young Adult; Back Muscles; Female; Signal Processing, Computer-Assisted; Algorithms; Weight-Bearing; Muscle, Skeletal
PubMed: 38324444
DOI: 10.1109/TBME.2024.3363212 -
Journal of Biomechanics Feb 2024Whole-body lifting strategies could be derived from conventional video recordings using the Stoop-Squat-Index, which quantifies the ratio between trunk forward lean and...
Conventional video recordings dependably quantify whole-body lifting strategy using the Stoop-Squat-Index: A methods comparison against motion capture and a reliability study.
Whole-body lifting strategies could be derived from conventional video recordings using the Stoop-Squat-Index, which quantifies the ratio between trunk forward lean and lower extremity joint flexion from 0 (full squat) to 100 (full stoop). The purpose of this study was to compare Stoop-Squat-Indices derived from conventional video recordings to those from a three-dimensional marker-based motion capture system and to evaluate interrater and intrarater reliability of the video-based approach. Thirty healthy participants lifted a 5-kg box under different conditions (freestyle, squat, stoop). Kinematic data were recorded using a Vicon motion capture system (serving as reference standard) and an iPad camera. Stoop-Squat-Indices over the entire lifting cycle were derived separately from both approaches. Agreement was assessed using mean differences (video minus motion capture) and limits of agreement. Reliability was investigated by calculating intraclass correlation coefficients (ICC) and minimal detectable changes (MDC) over the course of the lifting cycle. Systematic errors were identified with Statistical Parametric Mapping-based T-tests. Systematic errors between the video-based and the motion capture-based approach were observed among all conditions. Mean differences in Stoop-Squat-Indices over the lifting cycle ranged from -6.9 to 3.2 (freestyle), from -1.8 to 5.3 (squat) and from -2.8 to -1.1 (stoop). Limits of agreement were lower when the box was close to the floor, and higher towards upright standing. Reliability of the video-based approach was excellent for most of the lifting cycle, with ICC above 0.995 and MDC below 3.5. These findings support using a video-based assessment of Stoop-Squat-Indices to quantify whole-body lifting strategy in field.
Topics: Humans; Lifting; Motion Capture; Reproducibility of Results; Joints; Video Recording; Biomechanical Phenomena
PubMed: 38320342
DOI: 10.1016/j.jbiomech.2024.111975