Reduced Neural Satiety Responses in Women Affected by Obesity.

Overweight and obesity are major risk factors for a number of chronic diseases, including diabetes, cardiovascular diseases, and cancer. Obesity rates are on the rise worldwide with women more frequently affected than men. Hedonic responses to food seem to play a key role in obesity, but the exact mechanisms and relationships are still poorly understood. In this study, we investigate the perceived pleasantness of food rewards in relation to satiety and calories consumed during an ad libitum meal in women. Using functional magnetic resonance imaging (fMRI) and a milkshake consumption task, we studied how experienced food values are encoded in women with healthy weight, overweight or obesity. Participants rated the pleasantness and intensity of high and low caloric milkshakes in the fMRI scanner during both the fasted and fed states. We found differences in the neural responses and experienced pleasantness of high and low caloric milkshakes depending on satiety and Body Mass Index (BMI). Women with both high ad libitum consumption levels and high BMI reported greater experienced pleasantness for milkshakes. In contrast, among women with low ad libitum consumption levels, greater BMI was associated with less experienced pleasantness. At the neural level, satiety affected women with obesity to a lesser degree than women with healthy weight. Thus, having obesity was associated with altered relationships between food consumption and the hedonic responses to food rewards as well as reduced satiety effects in women.

Ethnic disparities in progression to advanced liver disease and overall survival in patients with chronic hepatitis C: impact of a sustained virological response.

BACKGROUND: Chronic hepatitis C (CHC) can lead to cirrhosis and hepatocellular carcinoma (HCC). A sustained virological response (SVR) is associated with improved outcomes, however, its impact on different ethnic groups is unknown. AIM: To evaluate ethnic differences in the natural history of CHC and the impact of SVR. METHODS: We conducted a cohort study of 8039 consecutive adult CHC patients seen at two medical centres in California between January 1997 and June 2016. Individual chart review confirmed CHC diagnosis. RESULTS: Asian and Hispanic but not African American patients had significantly higher cirrhosis and HCC incidence than Caucasians. On multivariate analysis, Hispanic ethnicity was independently associated with increased cirrhosis (adjusted HR 1.37, CI, confidence interval 1.10-1.71, P=.006) and HCC risk (adjusted HR 1.47, CI 1.13-1.92, P=.004) compared to Caucasian. Asian ethnicity had a significant association with cirrhosis (adjusted HR 1.28, CI 1.02-1.61, P=.034) and HCC risk (adjusted HR 1.29, CI 0.94-1.77, P=.025). In patients who achieved SVR, Hispanic ethnicity was no longer independently associated with cirrhosis (adjusted HR 1.76, CI 0.66-4.71, P=.26) or HCC (adjusted HR 1.05, CI 0.27-4.08, P=.94); nor was Asian ethnicity (adjusted HR 0.62, CI 0.21-1.82, P=.38 for cirrhosis; 2.01, CI 0.63-6.36, P=.24 for HCC). Similar findings were observed with overall survival among the ethnicities by SVR status. CONCLUSION: Hispanic and Asian ethnicity was independently associated with increased cirrhosis and HCC risk. Achieving an SVR eliminates the ethnic disparity in liver disease progression and overall survival between Hispanic and Asian vs Caucasian CHC patients.

Dopamine D2/3- and µ-opioid receptor antagonists reduce cue-induced responding and reward impulsivity in humans.

Increased responding to drug-associated stimuli (cue reactivity) and an inability to tolerate delayed gratification (reward impulsivity) have been implicated in the development and maintenance of drug addiction. Whereas data from animal studies suggest that both the dopamine and opioid system are involved in these two reward-related processes, their role in humans is less clear. Moreover, dopaminergic and opioidergic drugs have not been directly compared with regard to these functions, even though a deeper understanding of the underlying mechanisms might inform the development of specific treatments for elevated cue reactivity and reward impulsivity. In a randomized, double-blind, between-subject design we administered the selective dopamine D2/D3 receptor antagonist amisulpride (400 mg, n=41), the unspecific opioid receptor antagonist naltrexone (50 mg, n=40) or placebo (n=40) to healthy humans and measured cue-induced responding with a Pavlovian-instrumental transfer task and reward impulsivity with a delay discounting task. Mood was assessed using a visual analogue scale. Compared with placebo, amisulpride significantly suppressed cue-induced responding and reward impulsivity. The effects of naltrexone were similar, although less pronounced. Both amisulpride and naltrexone decreased average mood ratings compared with placebo. Our results demonstrate that a selective blockade of dopamine D2/D3 receptors reduces cue-induced responding and reward impulsivity in healthy humans. Antagonizing µ-opioid receptors has similar effects for cue-induced responding and to a lesser extent for reward impulsivity.

Arthroscopic debridement and acromioplasty versus mini-open repair in the treatment of significant partial-thickness rotator cuff tears.

Partial tears of the rotator cuff, especially of the articular side, have received attention only with the recent ability of magnetic resonance imaging (MRI) and arthroscopy to diagnose these lesions. Several early reports showed nearly 100% success in managing these lesions with arthroscopic debridement with or without acromioplasty. This series compares 32 patients with significant partial-thickness rotator cuff tears treated with debridement and acromioplasty versus 33 patients with mini-open repair. Follow-up was from 2 to 7 years. Preoperative MRI was not useful; when positive, preoperative arthrography was useful for articular side tears. Of the tears, 12% were bursal side tears and the remainder were articular side tears; all were at least 50% or more of the thickness of the tendon. A significant number of the arthroscopic group had fair results by UCLA score criteria. Three patients reruptured the remaining cuff later despite adequate acromioplasty. Healing of the partial tear was never observed at second-look arthroscopy. Although postoperative pain was significantly greater and recovery slower with open repair, no patient was reoperated on and rerupture of the repair did not occur. The outstanding results of prior studies of cuff debridement were not duplicated in this series of cuff debridements with long-term follow-up. Adequate acromioplasty alone does not prophylactically prevent rotator cuff tear progression. Recognition and repair of these significant partial tears may be advisable for the long-term function of the shoulder despite short-term improvement in morbidity with arthroscopic treatment.

Arthroscopic debridement and acromioplasty versus mini-open repair in the management of significant partial-thickness tears of the rotator cuff.

Treatment options for partial-thickness rotator cuff tears have included debridement and acromioplasty or open repair. The outcome of these two treatments has been difficult to assess from the literature. The results of a retrospective review of arthroscopic versus open treatment are reviewed with recommendations for a treatment algorithm.

A novel yeast expression/secretion system for the recombinant plant thiol endoprotease propapain.

A new high-yield yeast expression/secretion system has been adapted for the plant thiol endoprotease papain. The propapain gene, obtained from Carica papaya fruit, is expressed in the yeast Saccharomyces cerevisiae. The gene was cloned into a FLAG epitope-tagging expression vector downstream of the yeast alpha mating factor (alpha-factor) secretion signal sequence. Expression of the heterologous propapain in yeast is controlled by the glucose-repressible alcohol dehydrogenase isoenzyme II promoter (ADH2). Glycosylated FLAG-tagged propapain is secreted by a so-called 'super secretor' strain, pmr1 (ssc1), into the culture supernatant where it accumulates to approximately 1.7 mg/l. The proregion contains three consensus N-linked glycosylation sites, whereas there are only two such sites in previously reported cDNA sequences. Removal of this third N-linked glycosylation site results in a drastic reduction in the level of protease activity present in the culture supernatant. Two different types of affinity chromatography were used to purify either propapain or papain. The propapain precursor is autoproteolytically activated to mature papain (M(r) = 24 kDa) using conditions reported previously. The kinetic parameters obtained agree well with the literature values. The yields of active papain are 10-fold higher than those previously reported for propapain in other yeast or bacterial expression systems. This, together with the ease with which mutant proteins can be made, makes this yeast advantageous for a structure-function analysis of recombinant wild-type and mutant papain, and possibly for other related cysteine proteases as well.

Gene disruption with PCR products in Saccharomyces cerevisiae.

We describe here the generation of gene disruption constructs using PCR amplification of selectable markers with primers that provide homology to the target gene of interest. We find that regions of homology as short as 38 to 50 bp suffice to mediate homologous recombination in yeast. We describe applications of this technology to three specific yeast genes that would have been difficult to disrupt with current methods. By dispensing with the need to either clone the gene of interest or engineer a standard disruption construct, this method should facilitate analysis of sequenced genes of unknown function, which will soon include the entire yeast genome.

A biochemical evaluation of the restraints to posterior shoulder dislocation.

The biomechanics of posterior dislocation of the shoulder was evaluated using nine cadaver shoulders. Each was arthroscoped, roentgenograms were obtained, and then each was dislocated in a testing device. Force displacement data was obtained during testing, and posttesting roentgenograms, arthroscopic evaluation, and subsequent open dissections were performed to evaluate the pathology created. Although instability was created in all cases with displacement of the humerus to the diameter of the humeral head, force displacement of the humerus to the diameter of the humeral head, force displacement curves did not show an inflection point, implying a continuum between subluxation and dislocation. All shoulders had posterior Bankart lesions or posterior capsular lesions, or both. Anterior pathology was not seen. Posterior instability is most likely a continuum between subluxation dislocation with progressive injury to the posterior capsule and attachments such as the labrum as the principal restraint to posterior displacement.

Ectopic thyroid in the right carotid triangle.

A neck mass in the right carotid triangle of a 28-year-old woman was found to be the only thyroid tissue she possessed. Resection of the mass led to clinical and biochemical hypothyroidism. A possible explanation for the unlikely occurrence of lateral aberrant thyroid tissue and absence of a thyroid gland in the usual location is offered. It is suggested that patients with midline or low lateral neck masses undergo isotopic scanning of the thyroid gland before any iodinated contrast materials are administered or surgery performed.

Comminuted intraarticular fractures of the distal radius.

The comminuted intraarticular fracture of the distal radius requires early, accurate reduction of the articular surfaces and sustained restoration of anatomic position. The most commonly employed methods are pins and plaster, external fixation, percutaneous pinning, and open reduction and internal fixation. There are pitfalls, advantages, and disadvantages inherent in each method. Careful preoperative analysis of individual patients and fractures determines the therapeutic options.

An unusual rotational fracture-dislocation of the thoracic spine without neurologic sequelae internally fixed with a combined anterior and posterior approach.

A rare complete lateral dislocation of the thoracic spine with preservation of neurologic function is reported. Anatomic reduction was obtained using an anterior approach and Harrington distraction rods for reduction followed by a broad plate and subsequent posterior segmental fixation and fusion. Long-term followup showed an excellent result.

Severely comminuted distal radial fracture as an unsolved problem: complications associated with external fixation and pins and plaster techniques.

Seventy-six patients with severely comminuted distal radial fractures were treated at two institutions, of which the overwhelming majority were Frykman class VIII. Fifteen fractures were open. Thirty patients were seen at the University Hospital; 17 had pins and plaster and 13 had external fixation. Forty-six patients were seen at Kaiser Hospital; all had pins and plaster treatment. The complication rate for those with pins and plaster at the University Hospital was 53%; the complication for external fixation rate was 62%. The affiliated-hospital complication rate was 52%. All patients with ipsilateral forearm shaft and carpal fractures developed a nonunion of the carpal fracture. Few patients maintained anatomic reduction, and many had significant intra-articular malalignment. External fixation with threaded half pins did not obviate pin problems in our series. These methods may help manage severely comminuted distal radial fractures, but complications should be anticipated and alternative treatment considered, especially when ipsilateral carpal or forearm shaft fractures are present.

Clinical restoration of voice function after loss of the vagus nerve.

One hundred eleven patients with unilateral vocal cord paralysis underwent Teflon injection for the rehabilitation of laryngeal function. The most common etiology was vocal cord paralysis after surgical treatment of thoracic abdominal aortic aneurysms, which accounted for 36.9% of patients. Of the 111 patients, 85% had improved voice function after Teflon injection. Two patients developed airway obstruction secondary to edema and required temporary tracheostomy. Twenty-four patients with paralysis after aneurysm surgery were injected acutely with no morbidity and immediate restoration of voice function. We now advocate Teflon injection in patients with vocal cord paralysis after thoracic aneurysm surgery in the immediate convalescent period to restore voice function and lessen pulmonary complications.

Adhesives in orthopaedic surgery. A review of the literature and in vitro bonding strengths of bone-bonding agents.

Adhesives may offer a number of advantages over conventional metal osteosynthesis in the treatment of fractures: ease and speed of fixation are improved, they have the anatomy to anatomically coapt small fragments, and hardware removal is not necessary. A review of the literature was performed to evaluate experiments with collagen and other biologic adhesives, epoxy resins, polyurethane foam, cyanoacrylates, zinc polycarboxylate, polymethylmethacrylates, and fibrin adhesives pertaining to osteosynthesis. Cyanoacrylates, polymethylmethacrylates, and fibrin adhesives are currently being investigated. These agents are tested to evaluate their bone-bonding strength. Cyanoacrylates of biologically tolerated chain length did not develop useful bonding in cancellous bone; they bond well to cortical bone only with meticulous surface preparation. Fibrin adhesives developed only minimally useful bonding. Polymethylmethacrylate developed surgically useful bonding in osteosynthesis where conventional fixation is impossible.

A comparison of the mechanical properties of Simplex, Zimmer, and Zimmer low viscosity bone cements.

Many different methods have been used to compare polymethylmethacrylate bone cements. In this paper the three currently available cements were compared in regard to dough and set times, heat of polymerization, compressive, tensile, 3 and 4 point bending strengths, fracture toughness, flexural modulus, void density distribution, and viscosity. Methods used were ASTM designated for bone cement or plastics in general whenever possible. Significant differences in set and dough times and heat of polymerization were noted. All cements were equal in compressive, tensile, and fracture toughness testing; Zimmer Regular Cement was significantly weaker (p less than 0.001) in flexural testing and had a significantly (p less than 0.001) decreased modulus of elasticity when compared to LVC and Simplex Cements. Void density distributions were not significantly different. Viscosity was shown to vary between these cements as well. This data was analysed both to determine differences between various brands of cement and to assess the relevance to clinical use and failure modes in vivo of these different means of testing.

Histone modifications in the yeast S. Cerevisiae.

The content of the acetylated histone species associated with the highly transcriptionally active chromatin of yeast was examined. We found yeast chromatin to contain very high levels of the acetylated species for histones H3, H4 and possibly the H2B variants, H2B-1 and H2B-2. Sixty-three percent of the histone H4 species was represented by the di-, tri- and tetra-acetylated forms. These results make yeast chromatin among the most highly acetylated of any chromatins reported thus far. In addition, the results are consistent with the idea that hyperacetylation of histones allows chromatin to be transcribed at an increased rate.