Whey protein rich in alpha-lactalbumin increases the ratio of plasma tryptophan to the sum of the other large neutral amino acids and improves cognitive performance in stress-vulnerable subjects

BACKGROUND: Cognitive performance often declines under chronic stress exposure. The negative effect of chronic stress on performance may be mediated by reduced brain serotonin function. The uptake of the serotonin precursor tryptophan into the brain depends on nutrients that influence the availability of tryptophan by changing the ratio of plasma tryptophan to the sum of the other large neutral amino acids (Trp-LNAA ratio). In addition, a diet-induced increase in tryptophan may increase brain serotonergic activity levels and improve cognitive performance, particularly in high stress-vulnerable subjects. OBJECTIVE: We tested whether alpha-lactalbumin, a whey protein with a high tryptophan content, would increase the plasma Trp-LNAA ratio and improve cognitive performance in high stress- vulnerable subjects. DESIGN: Twenty-three high stress-vulnerable subjects and 29 low stress-vulnerable subjects participated in a double-blind, placebo-controlled, crossover study. All subjects conducted a memory-scanning task after the intake of a diet enriched with either alpha-lactalbumin (alpha-lactalbumin diet) or sodium caseinate (control diet). Blood samples were taken to measure the effect of dietary manipulation on the plasma Trp-LNAA ratio. RESULTS: A significantly greater increase in the plasma Trp-LNAA ratio after consumption of the alpha-lactalbumin diet than after the control diet (P = 0.0001) was observed; memory scanning improved significantly only in the high stress-vulnerable subjects (P = 0.019). CONCLUSION: Because an increase in the plasma Trp-LNAA ratio is considered to be an indirect indication of increased brain serotonin function, the results suggest that dietary protein rich in alpha-lactalbumin improves cognitive performance in stress-vulnerable subjects via increased brain tryptophan and serotonin activities.     

A method for improving acetabular preparation during cemented all-polyethylene acetabular component insertion during total hip arthroplasty

Long-term outcome from cemented acetabular components has been correlated with the presence of radiolucency on early postoperative radiographs. We describe a means for enhancing acetabular bed preparation to decrease blood at the bone-cement interface and to obtain better pressurization of the cement into the cancellous bone of the acetabulum during cemented acetabular component insertion.     

Impact of Polyethylene Thickness on Clinical Outcomes and Survivorship in Medial Mobile-Bearing Unicondylar Knee Arthroplasty

BackgroundThe thickness of the polyethylene bearing in medial unicondylar knee arthroplasty (UKA) is determined by the depth of the tibial resection, degree of correctable deformity, and balance of the knee. The purpose of this study is to evaluate whether polyethylene thickness in medial mobile-bearing UKA impacts clinical outcomes and survivorship.MethodsA retrospective review from 2004 to 2017 identified patients who underwent a primary mobile-bearing medial UKA with 2-year minimum follow-up or revision. A total of 2305 patients (3030 knees) met inclusion criteria. Patients were divided in 2 groups: thin bearing (group 1): 3-mm or 4-mm bearing and thick bearing (group 2): ≥ 5 mm. The thin group consisted of 2640 knees (87%), whereas the thick group had 390 knees (13%). Preoperative and postoperative demographics, range of motion, Knee Society scores, complications, and reoperations were evaluated.ResultsMean follow-up was 5.2 years (range, 0.5 to 12.6). There was no significant difference between groups in postoperative range of motion or Knee Society scores (P > .05). Manipulations were performed in 1.3% of patients and not significantly different between groups. The all-cause revision rate for group 1 was 4.02% and group 2 was 4.58% (P = .6). Revision rates for tibial aseptic loosening were significantly higher in group 2 (1.8%) than those in group 1 (0.7%) (P = .04). There was no significant difference in failure rates between groups for tibial collapse or fracture, femoral aseptic loosening, arthritic progression, bearing dislocation, or other cause of revision.ConclusionThis study demonstrated that thicker bearings in medial UKA increased the risk of tibial aseptic loosening, but not all-cause failures or clinical outcomes.     

Interval Between Staged Bilateral Total Knee Arthroplasties Does Not Affect Early Medical or Surgical Complications

BackgroundThe purpose of this study is to evaluate early postoperative surgical and medical complications in patients undergoing staged bilateral total knee arthroplasty (TKA) and determine if the interval to the second stage influences the risk of complications.MethodsA retrospective review was performed from 2016 through 2018 of all staged bilateral primary TKA procedures, yielding a cohort of 1005 patients (2010 TKAs). Four groups were created based on the timing of the second stage: 3 to 6 weeks, 7 to 12 weeks, 13 to 24 weeks, and >24 weeks. Clinical data compared between groups included demographics, knee range of motion, University of California, Los Angeles (UCLA) activity score, Knee Society pain score, Knee Society clinical score, and Knee Society functional score. Postoperative complications within 90 days were evaluated, with complications after the second knee being the primary outcome.ResultsThe mean follow-up after second stage was 10.7 months (range, 3 to 37 months). No significant differences were found between groups in the range of motion, Knee Society pain, Knee Society clinical score, Knee Society functional score, or University of California Los Angeles activity score in either the first or second knee. After the first knee surgery, medical complications were highest in the >24-week group. After the second knee, there were no significant difference in manipulation (P = .9), wound complications (P = .7), venous thromboembolism (P = .8), or other medical complications (P = 1) based on the interval duration.ConclusionThe interval between staged TKA did not affect early medical or surgical complications after the second stage. Early clinical and function results were not different based on timing of the second surgery.     

Trisomy 17p10-p12 resulting from a supernumerary marker chromosome derived from chromosome 17: molecular analysis and delineation of the phenotype

We report a 5-year-old boy with a small de novo marker chromosome derived from the proximal short arm of chromosome 17. His clinical features include hypotonia, global developmental delay, oval face with large nose and prominent ears, and ligamentous laxity of the fingers. Magnetic resonance imaging of the brain demonstrated mildly delayed myelination. G-band chromosome analysis revealed mosaicism for a small marker chromosome in 85% of the peripheral blood cells analyzed. Fluorescence in situ hybridization and microsatellite polymorphism studies showed that the der(17) was of maternal origin and included genetic material from the 17p10-p12 region, but did not contain the PMP22 gene. One breakpoint mapped within the centromere and the second breakpoint mapped adjacent to the Charcot-Marie-Tooth disease type 1A proximal low-copy repeat (CMT1A-REP). We compare the clinical characteristics of our patient with those previously reported to have a duplication involving the proximal short arm region of chromosome 17 to further delineate the phenotype of trisomy 17pl0-p12.     

Two-lever drug-drug discrimination with the 5-HT1 receptor agonists flesinoxan and eltoprazine

Previous drug discrimination studies with the 5-HT1 receptor agonists flesinoxan and eltoprazine showed a clear 5-HT1A receptor-mediated effect for flesinoxan and the involvement of both 5-HT1A and 5-HT1B receptors in eltoprazine. However, there was no clear antagonism of eltoprazine's cue, possibly due to the compound nature of the eltoprazine stimulus. In the present experiments, in order to create a specific 5-HT1A vs. 5-HT1B receptor-mediated discrimination, rats were trained to discriminate between flesinoxan and eltoprazine. All rats learned the discrimination readily (mean = 41.3 sessions to criterion). With training doses of 1.0 mg/kg, p.o. flesinoxan and 1.5 mg/kg, p.o. eltoprazine, saline administration resulted in 50% of the responses made on both levers. Substitution tests showed that the flesinoxan stimulus was mediated by the 5- HT1A receptor (8-OH-DPAT, buspirone) and the eltoprazine stimulus probably mediated by the 5-HT1B receptor (anpirtoline, TFMPP, RU-24969). The selective 5-HT1A receptor antagonist WAY-100635 antagonized the flesinoxan cue, and the discriminative stimulus of eltoprazine could be completely antagonized with the 5-HT1B/1D receptor antagonist GR-127935. When the training doses of both flesinoxan and eltoprazine were administered concurrently, complete substitution for eltoprazine was obtained. We conclude that rats can learn to discriminate between two serotonergic drugs with overlapping stimulus properties and that the flesinoxan stimulus is mediated by 5-HT1A receptors and the eltoprazine stimulus, under these particular training conditions, by 5-HT1B receptors.     

Mosaicism in a patient with Down syndrome reveals post-fertilization formation of a Robertsonian translocation and isochromosome

Metaphyseal chondrodysplasias (MCD) are skeletal disorders characterized by metaphyseal irregularities and, usually, by short stature. In MCD, wide heterogeneity exists with regard to clinical and radiological changes. We report on a patient with clinical and radiological findings of MCD who had coxa valga and normal height with metaphyseal involvement of the long bones. The short radii and ulnae showed a very severe change in their distal metaphyses, leading to mesomelic shortening confined to the upper limbs. Hematological, ophthalmological, and hearing examinations were normal. This type of MCD appears to represent a yet undescribed syndrome.     

Interferon-beta-1a for the treatment of steroid-refractory ulcerative colitis: a randomized, double-blind, placebo-controlled trial.

BACKGROUND & AIMS: We performed a randomized, double-blind, placebo-controlled, multicenter trial to investigate the efficacy and safety of recombinant interferon-beta-1a (rIFN-beta-1a) in outpatients with active steroid-refractory ulcerative colitis. METHODS: Ninety-one randomized patients subcutaneously received 3 MIU rIFN-beta-1a (group A, n = 32), 1 MIU rIFN-beta-1a (group B, n = 30), or placebo (group C, n = 29) 3 times a week over a period of 8 weeks in addition to standard therapy. An intention-to-treat analysis was performed to evaluate the efficacy and safety of treatment. Results: In all 3 groups, the median prestudy clinical activity index (CAI) was 10. In 18 of 32 patients (56%) in group A, in 11 of 30 patients (36%) in group B, and in 10 of 29 patients (34%) in group C, a reduction of the CAI of 6 points or greater (response) was achieved (differences were not statistically significant). Complete response (reduction of CAI to < or =4) was achieved in 56%, 30%, and 38% of patients in groups A, B, and C, respectively. Compared with baseline, the median endoscopic index had been reduced by 5, 3, and 4 points in groups A, B, and C, respectively. Steroid reduction was 12 mg in group A, 6 mg in group B, and 10 mg in group C. Identical side effects occurred in all 3 groups. Seven serious adverse events were reported (1 in group A and 6 in group C). All were unrelated to therapy as judged by the investigating physicians. CONCLUSIONS: rIFN-beta-1a was safe but not significant, at the dosage and/or duration of treatment used, in steroid-refractory ulcerative colitis. Further studies are indicated.     

Detecting Neuroimaging Biomarkers for Schizophrenia: A Meta-Analysis of Multivariate Pattern Recognition Studies

Multivariate pattern recognition approaches have recently facilitated the search for reliable neuroimaging-based biomarkers in psychiatric disorders such as schizophrenia. By taking into account the multivariate nature of brain functional and structural changes as well as their distributed localization across the whole brain, they overcome drawbacks of traditional univariate approaches. To evaluate the overall reliability of neuroimaging-based biomarkers, we conducted a comprehensive literature search to identify all studies that used multivariate pattern recognition to identify patterns of brain alterations that differentiate patients with schizophrenia from healthy controls. A bivariate random-effects meta-analytic model was implemented to investigate the sensitivity and specificity across studies as well as to assess the robustness to potentially confounding variables. In the total sample of n=38 studies (1602 patients and 1637 healthy controls), patients were differentiated from controls with a sensitivity of 80.3% (95% CI: 76.7–83.5%) and a specificity of 80.3% (95% CI: 76.9–83.3%). Analysis of neuroimaging modality indicated higher sensitivity (84.46%, 95% CI: 79.9–88.2%) and similar specificity (76.9%, 95% CI: 71.3–81.6%) of rsfMRI studies as compared with structural MRI studies (sensitivity: 76.4%, 95% CI: 71.9–80.4%, specificity of 79.0%, 95% CI: 74.6–82.8%). Moderator analysis identified significant effects of age (p=0.029), imaging modality (p=0.019), and disease stage (p=0.025) on sensitivity as well as of positive-to-negative symptom ratio (p=0.022) and antipsychotic medication (p=0.016) on specificity. Our results underline the utility of multivariate pattern recognition approaches for the identification of reliable neuroimaging-based biomarkers. Despite the clinical heterogeneity of the schizophrenia phenotype, brain functional and structural alterations differentiate schizophrenic patients from healthy controls with 80% sensitivity and specificity.