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Junker Arildsen posted an update 3 months, 2 weeks ago
Decay accelerating factor (DAF), a key complement activation control protein, is a 70 kDa membrane bound glycoprotein which controls extent of formation of the C3 and C5 convertases by accelerating their decay. Using clustered regularly-interspaced short palindromic repeats, (CRISPR)/associated protein 9 (Cas9) genome editing we generated a novel DAF deficient (Daf-/-) rat model. The present study describes the renal and extrarenal phenotype of this model and assesses renal response to complement-dependent injury induced by administration of a complement-fixing antibody (anti-Fx1A) against the glomerular epithelial cell (podocyte). Rats generated were healthy, viable and able to reproduce normally. Complete absence of DAF was documented in renal as well as extra-renal tissues at both protein and mRNA level compared to Daf+/+ rats. Renal histology in Daf-/- rats showed no differences regarding glomerular or tubulointerstitial pathology compared to Daf+/+ rats. Moreover, there was no difference in urine protein excretion (ratio of urine albumin to creatinine) or in serum creatinine and urea levels. In Daf-/- rats, proteinuria was significantly increased following binding of anti-Fx1A antibody to podocytes while increased C3b deposition was observed. The DAF knock-out rat model developed validates the role of this complement cascade regulator in immune-mediated podocyte injury. Given the increasing role of dysregulated complement activation in various forms of kidney disease and the fact that the rat is the preferred animal for renal pathophysiology studies, the rat DAF deficient model may serve as a useful tool to study the role of this complement activation regulator in complement-dependent forms of kidney injury.Soybean has a palaeopolyploid genome with nearly 75% of the genes present in multiple copies. Although the CRISPR/Cas9 system has been employed in soybean to generate site-directed mutagenesis, a systematical assessment of mutation efficiency of the CRISPR/Cas9 system for the multiple-copy genes is still urgently needed. Here, we successfully optimize one sgRNA CRISPR/Cas9 system in soybean by testing the efficiency, pattern, specificity of the mutations at multiple loci of GmFAD2 and GmALS. The results showed that simultaneous site-directed mutagenesis of two homoeologous loci by one sgRNA, the mutation frequency in the T0 generation were 64.71% for GmPDS, 60.0% for GmFAD2 and 42.86% for GmALS, respectively. The chimeric and heterozygous mutations were dominant types. Moreover, association of phenotypes with mutation pattern at target loci of GmPDS11 and GmPDS18 could help us further demonstrate that the CRISPR/Cas9 system can efficiently generate target specific mutations at multiple loci using one sgRNA in soybean, albeit with a relatively low transformation efficiency.
Simple anal fistula is one of the most common causes of proctological surgery and fistulotomy is considered the gold standard. This procedure, however, may cause complications. The aim of this systematic review was to assess the surgical treatment of simple anal fistula with traditional and sphincter-sparing techniques.
A literature research was performed using PubMed, Cochrane, and Google Scholar to identify studies on the surgical treatment of simple anal fistulas. Observational studies and randomized clinical trials were included. We assessed the risk of bias of included studies using the Jadad scale for randomized controlled trials, and the MINORS Scale for the remaining studies.
The search returned 456 records, and 66 studies were found to be eligible. The quality of the studies was generally low. A total of 4883 patients with a simple anal fistula underwent a sphincter-cutting procedure, mainly fistulotomy, with a weighted average healing rate of 93.7%, while any postoperative continence impairment was reported in 12.7% of patients. Sphincter-sparing techniques were adopted to treat 602 patients affected by simple anal fistula, reaching a weighted average success rate of 77.7%, with no study reporting a significant postoperative incontinence rate. The postoperative onset of fecal incontinence and the recurrence of the disease reduced patients’ quality of life and satisfaction.
Surgical treatment of simple anal fistulas with sphincter-cutting procedures provides excellent cure rates, even if postoperative fecal incontinence is not a negligible risk. A sphincter-sparing procedure could be useful in selected patients.
Surgical treatment of simple anal fistulas with sphincter-cutting procedures provides excellent cure rates, even if postoperative fecal incontinence is not a negligible risk. A sphincter-sparing procedure could be useful in selected patients.Erectile dysfunction (ED) in younger men is an increasing concern. In middle aged and older men, ED was related to lower resting heart rate variability (HRV), but research in younger men is lacking. The present study examined, in a nonclinical sample of 105 men between 18 and 39 years, the association of ED with several parameters of resting HRV. Scores of the 5-item version of the International Index of Erectile Function (IIEF-5) below 22 were considered as indicating ED. Eighteen men (17.1%) reported ED (mild in 16, mild to moderate in 2). Welch’s tests revealed that ED was associated with lower low-frequency power (LF), lower high-frequency power (HF), lower standard deviation of interbeat intervals, and lower standard deviation of the heart rate, which is influenced by both sympathetic and parasympathetic activity. After removing outliers, ED was unrelated to HF. Paxalisib In younger men, erections might be facilitated by a combination of higher parasympathetic tone and relatively higher sympathetic tone in the heart, as indicated by LF and greater standard deviation of the heart rate, a largely overlooked parameter in HRV research.Biofeedback (BF) training has been utilized with performers for years. Previous literature highlights the effectiveness of multi-week intervention protocols, but there is a lack of evidence for abbreviated interventions using portable devices and the performer’s preference of these devices. Therefore, we investigated the effects of a brief BF intervention on mental workload, mood, arousal, and movement time and BF device preference. Participants (N = 40) were randomly assigned to one of two heart rate variability (HRV) BF interventions or a control group. Although the brief intervention did not have a significant effect on mood, movement time, or mental workload, it did significantly and positively impact perceived arousal. Overall, 12 participants (48%) preferred the EmWave™ desktop device, eight (32%) preferred the Inner Balance™ device, and five (20%) preferred the EmWave2™ portable device. Results support limited effectiveness of a brief HRV BF protocol, although the dose-response effectiveness should continue to be explored.