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t of mandatory FA fortification, our data indicate that higher-than-recommended FA doses are unwarranted, with the exception of individuals at higher risk for NTDs. Ideally, prenatal supplements would contain 400 rather than 1000 µg FA, thereby enabling the consumption of optimal and safe FA doses.

Thrombocytopenia is a serious complication of myelodysplastic syndromes (MDS) associated with an increased bleeding risk and worse prognosis. Eltrombopag (ELT), a thrombopoietin receptor agonist, can increase platelet counts and reverse anti-megakaryopoietic effects of lenalidomide (LEN) in preclinical studies. We hypothesized ELT would reduce the incidence of thrombocytopenia in MDS.

We conducted a Phase II multicenter trial of ELT and LEN in adult patients with low- or intermediate-1-risk MDS with symptomatic or transfusion-dependent anemia or thrombocytopenia (NCT01772420). Thrombocytopenic patients were started on ELT and subsequently treated with LEN after platelets were increased. Patients without thrombocytopenia were started on LEN monotherapy and treated with ELT if they became thrombocytopenic.

Fifty-two patients were enrolled; mean age was 71 years (range 34-93). selleck chemicals Overall response rate (ORR) in the intention-to-treat population was 35% (18/52). ELT monotherapy led to ORR of 33.3% (7/21), 29% achieving hematologic improvement (HI)-Platelets, and 24% bilineage responses. LEN monotherapy had 38% ORR (6/16) with all responders achieving HI-Erythroid. Fifteen patients received both ELT and LEN with ORR of 33.3%, 20% achieved HI-Erythroid, and 20% HI-Platelets with 13% bilineage responses. Median duration of response was 40 weeks for ELT (range 8-ongoing), 41 weeks (25-ongoing) for LEN, and 88 weeks (8.3-ongoing) for ELT/LEN. Non-hematologic grade 3-4 treatment-related adverse events were infrequent. Among patients on ELT, 2 had major bleeding events, 1 had a reversible increase in peripheral blasts, and 1 developed marrow fibrosis after 6 years on ELT.

ELT and LEN are well tolerated and effective in achieving hematologic improvement in patients with low-/intermediate-risk MDS.

ELT and LEN are well tolerated and effective in achieving hematologic improvement in patients with low-/intermediate-risk MDS.

A retrospective cross-sectional study.

To assess the association between spinal muscle morphology and spinopelvic parameters in lumbar fusion patients, with a special emphasis on lumbar lordosis (LL).

Maintenance of sagittal alignment relies on muscle forces, but the basic association between spinal muscles and spinopelvic parameters is poorly understood.

Patients operated between 2014 and 2017 who had both lumbar magnetic resonance imaging scan and standing whole-spine radiographs within six months before surgery were included. Muscle measurements were conducted on axial T2-weighted magnetic resonance images at the superior endplate L3-L5 for the psoas and L3-S1 for combined multifidus and erector spinae (paraspinal) muscles. A pixel intensity threshold method was used to calculate the total cross-sectional area (TCSA) and the functional cross-sectional area (FCSA). Spinopelvic parameters were measured on lateral standing whole-spine radiographs and included LL, pelvic incidence (PI), PI-LL mismatch,ndicate that psoas and lumbar spine extensor muscles interact differently on LL among men and women, creating a unique mechanical environment.

Level 4.

Level 4.

A retrospective database study.

The purpose of our study was to compare the perioperative complications and reoperation rates after anterior cervical discectomy and fusion (ACDF), cervical disk arthroplasty (CDA), and posterior cervical foraminotomy (PCF) in patients treated for cervical radiculopathy.

Cervical radiculopathy results from compression or irritation of nerve roots in the cervical spine. While most cervical radiculopathy is treated nonoperatively, ACDF, CDA, and PCF are the techniques most commonly used if operative intervention is indicated. There is limited research evaluating the perioperative complications of these surgical techniques.

A retrospective review was performed using the PearlDiver Patient Record Database to identify cases of cervical radiculopathy that underwent ACDF, CDA, or PCF at one or two levels from 2007 to 2016. Perioperative complications and reoperations following each of the procedures were assessed.

During the study period, 25,051 patients underwent ACDF, 522 underwent CDA, and 3986 underwent PCF. After propensity score matching, each of the three groups consisted of 507 patients. Surgical site infection rates were highest after PCF (2.17%) compared with ACDF (0.20%) and CDA (0.59%) at 30 days and three months ( P =0.003, P <0.001), respectively. New-onset cervicalgia was highest following ACDF (34.32%) and lowest after PCF (22.88%) at three and six months ( P <0.001 and P =0.003), respectively. Revision surgeries were highest among those who underwent CDA (6.90%) versus ACDF (3.16%) and PCF (3.55%) at six months ( P =0.007). Limb paralysis was significantly higher after PCF compared with CDA and ACDF at six months ( P <0.017).

The rate of surgical site infection was higher in PCF compared with ACDF and CDA. New-onset cervicalgia was higher after ACDF compared with PCF and CDA at short-term follow-up. Revision surgeries were highest among those undergoing CDA and lowest in those undergoing ACDF.

3.

3.The complex process by which a single-celled zygote develops into a viable embryo is nothing short of a miraculous wonder of the natural world. Elucidating how this process is orchestrated in humans has long eluded the grasp of scientists due to ethical and practical limitations. Thankfully, pluripotent stem cells that resemble early developmental cell types possess the ability to mimic specific embryonic events. As such, murine and human stem cells have been leveraged by scientists to create in vitro models that aim to recapitulate different stages of early mammalian development. Here, we examine the wide variety of stem cell-based embryo models that have been developed to recapitulate and study embryonic events, from pre-implantation development through to early organogenesis. We discuss the applications of these models, key considerations regarding their importance within the field, and how such models are expected to grow and evolve to achieve exciting new milestones in the future.In June 2022, the second meeting on 'Engineering Multicellular Systems', organized by the European Molecular Biology Laboratory and the Institute of Bioengineering of Catalonia, took place in Barcelona. Stem cell and systems biologists, physicists and engineers from all over the world gathered to discuss how recent breakthroughs in organoid technologies, engineering and mechanobiology are boosting our understanding of early morphogenesis, organogenesis and organ function with applications in tissue engineering, disease modeling and drug screening. The meeting was organized with sustainability in mind, and included an ethics session and an outreach public activity.Interrogating the impact of metabolism during development is important for understanding cellular and tissue formation, organ and systemic homeostasis, and dysregulation in disease states. To evaluate the vital functions metabolism coordinates during human brain development and disease, pluripotent stem cell-derived models, such as organoids, provide tractable access to neurodevelopmental processes. Despite many strengths of neural organoid models, the extent of their replication of endogenous metabolic programs is currently unclear and requires direct investigation. Studies in intestinal and cancer organoids that functionally evaluate dynamic bioenergetic changes provide a framework that can be adapted for the study of neural metabolism. Validation of in vitro models remains a significant challenge; investigation using in vivo models and primary tissue samples is required to improve our in vitro model systems and, concomitantly, improve our understanding of human development.

To investigate the association of retinal sensitivity with microstructural features in optical coherence tomography (OCT) of high myopic eyes.

This cross-sectional study included 78 eyes (78 patients). Microstructural features on spectral-domain OCT, such as the integrity of the retinal pigment epithelium (RPE), ellipsoid zone (EZ), and external limiting membrane (ELM) and outer retinoschisis, were evaluated at each retinal location corresponding to microperimetric testing points.

For all testing points, retinal sensitivity was significantly associated with the integrity of the RPE, EZ, and ELM (all P < 0.001) based on OCT but not with outer retinoschisis (P = 0.183). A higher category of myopic maculopathy according to the Meta-Analysis of Pathologic Myopia classification was associated with lower mean retinal sensitivity (P < 0.001). In eyes with patchy atrophy (PA), mean retinal sensitivity of testing points adjacent to the PA lesion (15.7 ± 6.8 dB) was greater than points within or at the PA border (2.6 ± 5.2 dB; P < 0.001) but lower than distant points (19.6 ± 4.3 dB; P < 0.001). Microstructural features in OCT were well correlated with the differences in retinal sensitivity according to myopic maculopathy severity and proximity to the PA lesion.

In highly myopic eyes, retinal sensitivity on microperimetry was strongly associated with microstructural features in OCT. Both retinal sensitivity and microstructure were affected by the severity of myopic degeneration and proximity to the PA lesion.

In highly myopic eyes, retinal sensitivity on microperimetry was strongly associated with microstructural features in OCT. Both retinal sensitivity and microstructure were affected by the severity of myopic degeneration and proximity to the PA lesion.

The laminar region of the optic nerve head (ONH), thought to be the site of damage to the retinal ganglion cell axons in glaucoma, is continuously loaded on its anterior and posterior surfaces by dynamic intraocular pressure (IOP) and orbital cerebrospinal fluid pressure (CSFP), respectively. Thus, translaminar pressure (TLP; TLP = IOP-CSFP) has been proposed as a glaucoma risk factor.

Three eye-specific finite element models of the posterior human eye were constructed, including full 3D microstructures of the load-bearing lamina cribrosa (LC) with interspersed laminar neural tissues (NTs), and heterogeneous, anisotropic, hyperelastic material formulations for the surrounding peripapillary sclera and adjacent pia. ONH biomechanical responses were simulated using three combinations of IOP and CSFP loadings consistent with posture change from sitting to supine.

Results show that tensile, compressive, and shear stresses and strains in the ONH were higher in the supine position compared to the sitting position (P < 0.05). In addition, LC beams bear three to five times more TLP-driven stress than interspersed laminar NT, whereas laminar NT exhibit three to five times greater strain than supporting LC (P < 0.05). Compared with CSFP, IOP drove approximately four times greater stress and strain in the LC, NT, and peripapillary sclera, normalized per mm Hg pressure change. In addition, IOP drove approximately three-fold greater scleral canal expansion and anterior-posterior laminar deformation than CSFP per mm Hg (P < 0.05).

Whereas TLP has been hypothesized to play a prominent role in ONH biomechanics, the IOP and CSFP effects are not equivalent, as IOP-driven stress, strain, and deformation play a more dominant role than CSFP effects.

Whereas TLP has been hypothesized to play a prominent role in ONH biomechanics, the IOP and CSFP effects are not equivalent, as IOP-driven stress, strain, and deformation play a more dominant role than CSFP effects.