Notes

A singular inhibitor saves cerebellar disorders in the zebrafish model of Down syndrome-associated kinase Dyrk1A overexpression.
This research demonstrated that pumpkin seed extracts could be a candidate in the prevention of thrombotic events.The study aimed to evaluate the effect of powdered coconut water-based diluent (ACP-101c) associated with extra virgin coconut oil (CO) as an external cryoprotectant in the conservation of cryopreserved buck sperm. For cryopreservation, the ejaculates from four bucks were pooled and divided into three aliquots and diluted at 37°C for treatments T1 (ACP-101c + 2.5% egg yolk +7% glycerol), T2 (ACP-101c + 2.5% CO +7% glycerol), and T3 (ACP-101c + 5% CO +7% glycerol). Then, the samples were packaged and cooled at a rate of 1.07°C/min decrease. Upon reaching 4°C, the samples were stored in a refrigerator at 4°C for 30 minutes for stabilization. After this period, the straws were frozen in nitrogen vapor for 15 minutes and then immersed and stored in liquid nitrogen at -196°C. After thawing, the samples were evaluated for sperm kinetics, plasma membrane integrity, acrosomal integrity, membrane functionality, mitochondrial activity (MA), and sperm morphology. In this study, no statistically significant differences were observed between the three treatments regarding the kinetic parameters (p > 0.05; Table 1). However, in relation to the velocities, a reduction was observed beyond the expected. There were no statistically significant differences between the diluents T1, T2, and T3 for the three velocities (curvilinear velocity [VCL], linear velocity [VSL], average path velocity [VAP]). Furthermore, no statistically significant differences were observed (p > 0.05) among treatments regarding the evaluation of membrane integrity, the functional membrane, MA, and sperm morphology after thawing. In conclusion, the use of CO in concentrations of 2.5% and 5.0% is effective in maintaining goat sperm quality, presenting itself as an alternative diluent for international programs of artificial insemination and embryo transfers.
Retrospective cohort.

To compare outcomes of minimally invasive surgery (MIS) vs open surgery (OPEN) for lumbar spinal stenosis (LSS) in patients with diabetes.

Patients with diabetes who underwent spinal decompression alone or with fusion for LSS within the Canadian Spine Outcomes and Research Network (CSORN) database were included. MIS vs OPEN outcomes were compared for 2 cohorts (1) patients with diabetes who underwent decompression alone (N = 116; MIS n = 58 and OPEN n = 58), (2) patients with diabetes who underwent decompression with fusion (N = 108; MIS n = 54 and OPEN n = 54). Modified Oswestry Disability Index (mODI) and back and leg pain were compared at baseline, 6-18weeks, and 1-year post-operation. The number of patients meeting minimum clinically important difference (MCID) or minimum pain/disability at 1-year was compared.

MIS approaches had less blood loss (decompression alone difference 100mL,
= .002; with fusion difference 244mL,
< .001) and shorter length of stay (LOS) (decompression alone difference 1.2days,
= .008; with fusion difference 1.2days,
= .026). MIS compared to OPEN decompression with fusion had less patients experiencing adverse events (AEs) (difference 13 patients,
= .007). The MIS decompression with fusion group had lower 1-year mODI (difference 14.5, 95% CI [7.5, 21.0],
< .001) and back pain (difference 1.6, 95% CI [.6, 2.7],
= .002) compared to OPEN. More patients in the MIS decompression with fusion group exceeded MCID at 1-year for mODI (MIS 75.9% vs OPEN 53.7%,
= .028) and back pain (MIS 85.2% vs OPEN 70.4%,
= .017).

MIS approaches were associated with more favorable outcomes for patients with diabetes undergoing decompression with fusion for LSS.
MIS approaches were associated with more favorable outcomes for patients with diabetes undergoing decompression with fusion for LSS.Hantaan virus infection may cause severe lethal hemorrhagic fever with renal syndrome (HFRS) in humans. The chemokine fractalkine (CX3CL1) acts as a proinflammatory cytokine, and it is elevated in several infectious diseases. However, little is known about the contributions of CX3CL1 to HFRS pathogenesis. Present study detected plasma CX3CL1 levels and expression of the receptor CX3CR1 in HFRS patients and discussed the possible effects of CX3CL1 on pathogenesis of HFRS. Plasma CX3CL1 in acute phase and Critical/Severe groups of HFRS patients were significantly increased compared to that in normal controls (p  less then  0.001 and p  less then  0.01, respectively). High plasma CX3CL1 was negatively correlated with platelet count (r = -0.5844, p  less then  0.0001) and positively correlated with blood urea nitrogen (r = 0.3668, p = 0.0039), creatinine (r = 0.42, p = 0.0008), and white blood cells (r = 0.2646, p = 0.0411). check details Expression of CX3CR1 on nonclassical and intermediate monocytes was also increased in the acute phase (p  less then  0.01 for both the cells) and Critical/Severe groups (p  less then  0.05 and p  less then  0.01, respectively) of HFRS patients compared to that in normal controls. Taken together, elevation of plasma CX3CL1 in HFRS patients and expression of CX3CR1 on nonclassical and intermediate monocyte subsets might provide new insights into the potential role of CX3CL1/CX3CR1 in pathogenesis of HFRS.Time spent in jail can provide opportunities to deliver comprehensive medical care, including screening and treatment for HIV; however, engagement in HIV care postrelease is often fragmented. Identifying ways to improve the transition of care from jail to community for people with HIV (PWH) may help with engagement in HIV care postrelease. We evaluated the current HIV care transition processes of one jail in Massachusetts and identified change ideas to facilitate improving the transition of care from the jail to the community for PWH. We conducted qualitative interviews in 2018-2019 with incarcerated men with HIV (n = 17), jail staff (n = 7), and community providers (n = 6) to understand the processes of HIV care prerelease from the jail and engagement in care on release. Data from these interviews and quality improvement tools were used to identify ways to improve the release process for PWH, such as using a release planning checklist, to help ensure that a 30-day supply of HIV medication and an appointment with a community provider within 30 days of release were provided. We identified communication process inefficiencies related to knowing release dates between the HIV care team and case managers that prevented providing HIV medications on release. We worked with jail administrators to find ways to improve the prerelease planning process, which is vital to the continuity of successful HIV care. The use of quality improvement methods generated a list of testable change ideas to improve the release planning process to better align with the Centers for Disease Control and Prevention guidelines, which has implications for PWH and public health.Aim To assess concordance between HER2 status measured by traditional methods and ERBB2 amplification measured by next-generation sequencing and its association with first-line trastuzumab clinical benefit in patients with advanced esophagogastric cancer. Methods Retrospective analysis of HER2/ERBB2 concordance using a deidentified USA-based clinicogenomic database. Clinical outcomes were assessed for patients with HER2+ advanced esophagogastric cancer who received first-line trastuzumab. Results Overall HER2/ERBB2 concordance was 87.5%. Among patients who received first-line trastuzumab, concordant HER2/ERBB2 was associated with longer time to treatment discontinuation (adjusted hazard ratio [aHR] 0.63; 95% CI 0.43-0.90) and overall survival (aHR 0.51; 95% CI 0.33-0.79). ERBB2 copy number ≥25 (median) was associated with longer time to treatment discontinuation (aHR 0.56; 95% CI 0.35-0.88) and overall survival (aHR 0.52; 95% CI 0.30-0.91). Conclusion HER2/ERBB2 concordance and higher ERBB2 copy number predicted clinical benefit from trastuzumab.
Polygenic risk scores (PRS) may enhance risk stratification for coronary heart disease among young adults. Whether a coronary heart disease PRS improves prediction beyond modifiable risk factors in this population is not known.

Genotyped adults aged 18 to 35 years were selected from the CARDIA study (Coronary Artery Risk Development in Young Adults; n=1132) and FOS (Framingham Offspring Study; n=663). Systolic blood pressure, total and HDL (high-density lipoprotein) cholesterol, triglycerides, smoking, and waist circumference or body mass index were measured at the visit 1 exam of each study, and coronary artery calcium, a measure of coronary atherosclerosis, was assessed at year 15 (CARDIA) or year 30 (FOS). A previously validated PRS for coronary heart disease was computed for each subject. The C statistic and integrated discrimination improvement were used to compare Improvements in prediction of elevated coronary artery calcium between models containing the PRS, risk factors, or both.

There were 62 (5%) and 93 (14%) participants with a coronary artery calcium score >20 (CARDIA) and >300 (FOS), respectively. At these thresholds, the C statistic changes of adding the PRS to a risk factor-based model were 0.015 (0.004-0.028) and 0.020 (0.001-0.039) in CARDIA and FOS, respectively. When adding risk factors to a PRS-based model, the respective changes were 0.070 (0.033-0.109) and 0.051 (0.017-0.079). The integrated discrimination improvement, when adding the PRS to a risk factor model, was 0.027 (-0.006 to 0.054) in CARDIA and 0.039 (0.0005-0.072) in FOS.

Among young adults, a PRS improved model discrimination for coronary atherosclerosis, but improvements were smaller than those associated with modifiable risk factors.
Among young adults, a PRS improved model discrimination for coronary atherosclerosis, but improvements were smaller than those associated with modifiable risk factors.Mass spectrometry (MS) is a powerful technique for protein identification, quantification and characterization that is widely applied in biochemical studies, and which can provide data on the quantity, structural integrity and post-translational modifications of proteins. It is therefore a versatile and widely used analytic tool for quality control of biopharmaceuticals, especially in quantifying host-cell protein impurities, identifying post-translation modifications and structural characterization of biopharmaceutical proteins. Here, we summarize recent advances in MS-based analyses of these key quality attributes of the biopharmaceutical development and manufacturing processes.Coronaviruses (CoVs) are a class of viruses that cause respiratory tract infections in birds and mammals. Severe acute respiratory syndrome and Middle East respiratory syndrome are pathogenic human viruses. The ongoing coronavirus causing a pandemic of COVID-19 is a recently identified virus from this group. The first step in the control of spreading the disease is to detect and quarantine infected subjects. Consequently, the introduction of rapid and reliable detection methods for CoVs is crucial. To date, several methods were reported for the detection of coronaviruses. Nanoparticles play an important role in detection tools, thanks to their high surface-to-volume ratio and exclusive optical property enables the development of susceptible analytical nanoparticle-based sensors. The studies performed on using nanoparticles-based (mainly gold) sensors to detect CoVs in two categories of optical and electrochemical were reviewed here. Details of each reported sensor and its relevant analytical parameters are carefully provided and explained.
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