Regulatory element copy number differences shape primate expression profiles

Gene expression differences are shaped by selective pressures and contribute to phenotypic differences between species. We identified 964 copy number differences (CNDs) of conserved sequences across three primate species and examined their potential effects on gene expression profiles. Samples with copy number different genes had significantly different expression than samples with neutral copy number. Genes encoding regulatory molecules differed in copy number and were associated with significant expression differences. Additionally, we identified 127 CNDs that were processed pseudogenes and some of which were expressed. Furthermore, there were copy number-different regulatory regions such as ultraconserved elements and long intergenic noncoding RNAs with the potential to affect expression. We postulate that CNDs of these conserved sequences fine-tune developmental pathways by altering the levels of RNA.     

Enhanced cellulose degradation by targeted integration of a cohesin-fused β-glucosidase into the Clostridium thermocellum cellulosome

The conversion of recalcitrant plant-derived cellulosic biomass into biofuels is dependent on highly efficient cellulase systems that produce near-quantitative levels of soluble saccharides. Similar to other fungal and bacterial cellulase systems, the multienzyme cellulosome system of the anaerobic, cellulolytic bacterium Clostridium thermocellum is strongly inhibited by the major end product cellobiose. Cellobiose-induced inhibition can be relieved via its cleavage to noninhibitory glucose by the addition of exogenous noncellulosomal enzyme β-glucosidase; however, because the cellulosome is adsorbed to the insoluble substrate only a fraction of β-glucosidase would be available to the cellulosome. Towards this end, we designed a chimeric cohesin-fused β-glucosidase (BglA-CohII) that binds directly to the cellulosome through an unoccupied dockerin module of its major scaffoldin subunit. The β-glucosidase activity is thus focused at the immediate site of cellobiose production by the cellulosomal enzymes. BglA-CohII was shown to retain cellobiase activity and was readily incorporated into the native cellulosome complex. Surprisingly, it was found that the native C. thermocellum cellulosome exists as a homooligomer and the high-affinity interaction of BglA-CohII with the scaffoldin moiety appears to dissociate the oligomeric state of the cellulosome. Complexation of the cellulosome and BglA-CohII resulted in higher overall degradation of microcrystalline cellulose and pretreated switchgrass compared to the native cellulosome alone or in combination with wild-type BglA in solution. These results demonstrate the effect of enzyme targeting and its potential for enhanced degradation of cellulosic biomass.     

Recurrent Hyperparathyroidism Caused by Benign Neoplastic Seeding: Two Cases of Parathyromatosis and a Review of the Literature

Background : Parathyromatosis is defined as small nodules of hyperfunctioning parathyroid tissue scattered in the soft tissues of the neck and/or mediastinum. Parathyromatosis may be primary, it may be aimed for when auto-transplanting parathyroid tissue in secondary hyperparathyroidism, and it may occur after surgery for primary hyperparathyroidism (pHPT). In the latter cases parathyromatosis poses a diagnostic and therapeutic challenge. Methods : To illustrate the clinical problem of parathyromatosis as a rare cause of recurrent disease after an operation for pHPT we describe two patients and performed a review of the literature for contributing factors. Results : Two patients, previously treated for pHPT and having undergone multiple neck explorations had at their final operation numerous small nests of benign parathyroid tissue scattered throughout connective tissue of the neck. These findings concur with various previous cases reported in the reviewed literature.

Conclusions : These cases illustrate that meticulous handling of parathyroid adenomas during surgical excision is of the utmost importance. Regardless of which operating technique is utilised, great emphasis must be placed on precautions towards ensuring the complete and above all the intact removal of the affected gland without capsular rupture. As parathymatosis is caused by seeding, which although extremely rare, it might very well result in the need for extensive reexploration.     

LASIK versus PRK for high astigmatism

Purpose

To compare the refractive outcomes of laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK) for myopic astigmatism of 3 diopters (D) or more.

Study design

Retrospective matched comparative study.

Methods

This study include consecutive myopic patients (SE 0 to –10 D) undergoing LASIK or PRK between 2007 and 2016 with astigmatism of 3 to 6 D, and postoperative follow-up of at least 30 days for LASIK and 60 days for PRK, compared outcomes of LASIK and PRK eyes.

Results

The LASIK and PRK groups comprised 175 eyes of 175 patients each, with median follow-up of 39 and 139 days, respectively (P?<?0.001). Mean preoperative manifest astigmatism was –3.35?±?0.46 and –3.42?±?0.51 D (P?=?0.92), postoperative SE was –0.43?±?0.55 and –0.16?±?0.64 D (P?<?0.001), and arithmetic astigmatism was –0.59?±?0.46 and –0.88?±?0.60 D (P?<?0.001), for the LASIK and PRK groups, respectively. Fifty-seven and 64.0% eyes had postoperative SE within?±?0.5 D of emmetropia (P?=?0.19), and 57.7 and 38.8% eyes were within 0.5 D of attempted astigmatic correction (P?<?0.001) for the LASIK and PRK groups, respectively. More PRK eyes were overtreated regarding both SE and astigmatism than LASIK eyes (P?<?0.001). The efficacy and safety indices were close to 1.0 in both groups. The surgically induced astigmatism, magnitude of error, index of success, correction index and flattening index were all better in the LASIK group.

Conclusion

Both LASIK and PRK achieve good outcomes in high astigmatism. LASIK achieved mild superiority over PRK.

     

Evaluation of hip flexion strength following lateral lumbar interbody fusion

Background context

Lateral interbody fusion (LIF) is a minimally invasive procedure that is designed to achieve a solid interbody fusion while minimizing the damage to the surrounding soft tissue. Although short-term results have been promising, few data have been published to date regarding its risks and complication rate.

Purpose

The aim was to evaluate the extent of injury to the psoas muscle after the LIF procedure by measuring hip flexion strength.

Study design

A prospective case series was used in the study.

Method

Hip flexion strength was measured using a handheld digital dynamometer while the patient was seated on a chair; the examiner held the device against the patient’s attempt to flex the hip. Both sides were measured to compare the operated and nonoperated psoas muscles. Each side was measured three times and the average amount (in pounds) was recorded. Measurements were done before and after surgery on Day 2-3, at 2 weeks, 6 weeks, and at 3 and 6 months.

Results

Thirty-three patients were recruited for this study. Mean preoperative hip flexion strength values were 20.7±3.47 lb and 21.3±4.31 lb for operated and nonoperated legs, respectively, with no significant difference (p=.85). With a mean of 11.2±2.24 lb postoperative measurements on Day 2, the operated side showed statistically significant reduction of strength (p=.0001). The nonoperated side was also weaker postoperatively, but not significantly (mean=19.12±1.74 lb; p=.097). From the first follow-up visit at 2 weeks, the values on the operated leg had returned to baseline values (20.6, p=.97) and were not significantly different from preoperative values on either side.

Discussion

Hip flexion was weakened immediately after the LIF procedure, which may be attributed to psoas muscle injury during the procedure. However, this damage was temporary, with almost complete return to baseline values by 2 weeks.     

Frequency of hand movements as a possible diagnostic tool for parkinsonian bradykinesia. Proposal of a simple bedside test

Neurological Sciences - Bradykinesia, dysrhythmia, and decrement in hand movements (HM) are core symptoms of Parkinson’s disease (PD). The maximal rate of repetitive rhythm-preserving HM can...     

Alvimopan Accelerates Gastrointestinal Recovery After Radical Cystectomy: A Multicenter Randomized Placebo-Controlled Trial

Background

Radical cystectomy (RC) for bladder cancer is frequently associated with delayed gastrointestinal (GI) recovery that prolongs hospital length of stay (LOS).

Objective

To assess the efficacy of alvimopan to accelerate GI recovery after RC.

Design, setting, and participants

We conducted a randomized double-blind placebo-controlled trial in patients undergoing RC and receiving postoperative intravenous patient-controlled opioid analgesics.

Intervention

Oral alvimopan 12 mg (maximum: 15 inpatient doses) versus placebo.

Outcome measurements and statistical analysis

The two-component primary end point was time to upper (first tolerance of solid food) and lower (first bowel movement) GI recovery (GI-2). Time to discharge order written, postoperative LOS, postoperative ileus (POI)-related morbidity, opioid consumption, and adverse events (AEs) were evaluated. An independent adjudication of cardiovascular AEs was performed.

Results and limitations

Patients were randomized to alvimopan (n = 143) or placebo (n = 137); 277 patients were included in the modified intention-to-treat population. The alvimopan cohort experienced quicker GI-2 recovery (5.5 vs 6.8 d; hazard ratio: 1.8; p < 0.0001), shorter mean LOS (7.4 vs 10.1 d; p = 0.0051), and fewer episodes of POI-related morbidity (8.4% vs 29.1%; p < 0.001). The incidence of opioid consumption and AEs or serious AEs (SAEs) was comparable except for POI, which was lower in the alvimopan group (AEs: 7% vs 26%; SAEs: 5% vs 20%, respectively). Cardiovascular AEs occurred in 8.4% (alvimopan) and 15.3% (placebo) of patients (p = 0.09). Generalizability may be limited due to the exclusion of epidural analgesia and the inclusion of mostly high-volume centers utilizing open laparotomy.

Conclusions

Alvimopan is a useful addition to a standardized care pathway in patients undergoing RC by accelerating GI recovery and shortening LOS, with a safety profile similar to placebo.

Patient summary

This study examined the effects of alvimopan on bowel recovery in patients undergoing radical cystectomy for bladder cancer. Patients receiving alvimopan experienced quicker bowel recovery and had a shorter hospital stay compared with those who received placebo, with comparable safety.

Trial registration

ClinicalTrials.gov identifier NCT00708201