Temporal lobe abnormalities in semantic processing by criminal psychopaths as revealed by functional magnetic resonance imaging

We tested the hypothesis that psychopathy is associated with abnormalities in semantic processing of linguistic information. Functional magnetic resonance imaging (fMRI) was used to elucidate and characterize the neural architecture underlying lexico-semantic processes in criminal psychopathic individuals and in a group of matched control participants. Participants performed a lexical decision task in which blocks of linguistic stimuli alternated with a resting baseline condition. In each lexical decision block, the stimuli were either concrete words and pseudowords or abstract words and pseudowords. Consistent with our hypothesis, psychopathic individuals, relative to controls, showed poorer behavioral performance for processing abstract words. Analysis of the fMRI data for both groups indicated that processing of word stimuli, compared with the resting baseline condition, was associated with neural activation in bilateral fusiform gyrus, anterior cingulate, left middle temporal gyrus, right posterior superior temporal gyrus, and left and right inferior frontal gyrus. Analyses confirmed our prediction that psychopathic individuals would fail to show the appropriate neural differentiation between abstract and concrete stimuli in the right anterior temporal gyrus and surrounding cortex. The results are consistent with other studies of semantic processing in psychopathy and support the theory that psychopathy is associated with right hemisphere abnormalities for processing conceptually abstract material.     

Laryngoscopies in the obese: predicting problems and optimizing visualization

OBJECTIVES: This pilot study was designed to 1) identify predictors of difficult laryngeal exposure in obese patients, 2) develop strategies for efficient intubation and intraoperative visualization of the glottis, and 3) devise perioperative protocols for difficult laryngoscopies. METHODS: We undertook a retrospective study over a 1-year period of 14 consecutive patients with a body mass index of more than 30 kg/M2 who underwent elective direct laryngoscopy under general anesthesia. Measurements of height, weight, neck circumference, Mallampati score, and Cormack-Lehane classification of the airway were recorded. Problems encountered during anesthesia induction and emergence were also noted. The laryngologist recorded on a visual analog scale the degree of difficulty encountered in obtaining a binocular stereoscopic view and magnification, illumination, and suspension. RESULTS: Anatomic challenges during difficult laryngoscopy included decreased neck extension, redundant folds of tissue in the oropharynx and hypopharynx, and upper airway collapsibility. Overall, there was an association between the incidence of difficult laryngeal exposure and the Cormack-Lehane score (r = .57; p = .03), but the Mallampati score was of limited utility to the laryngologist. Neck size in female patients correlated with the Cormack-Lehane score (p = .02). Neither weight nor body mass index were predictive of a difficult laryngeal exposure. Straight blade laryngoscopes with a distal flange allowed greater depth of insertion and provided the best visualization of the glottis. CONCLUSIONS: An appropriate clinical examination may help predict a difficult airway. However, further studies are warranted to fully characterize the anatomic predictors of a difficult laryngeal exposure.     

Antilymphoid antibody preconditioning and tacrolimus monotherapy for pediatric kidney transplantation

OBJECTIVE: Heavy post-transplant immunosuppression may contribute to long-term immunosuppression dependence by subverting tolerogenic mechanisms; thus, we sought to determine if this undesirable consequence could be mitigated by pretransplant lymphoid depletion and minimalistic post-transplant monotherapy. STUDY DESIGN: Lymphoid depletion in 17 unselected pediatric recipients of live (n = 14) or deceased donor kidneys (n = 3) was accomplished with antithymocyte globulin (ATG) (n = 8) or alemtuzumab (n = 9). Tacrolimus was begun post-transplantation with subsequent lengthening of intervals between doses (spaced weaning). Maintenance immunosuppression, morbidity, graft function, and patient/graft survival were collated. RESULTS: Steroids were added temporarily to treat rejection in two patients (both ATG subgroup) or to treat hemolytic anemia in two others. After 16 to 31 months (mean 22), patient and graft survival was 100% and 94%, respectively. The only graft loss was in a nonweaned noncompliant recipient. In the other 16, serum creatinine was 0.85 +/- 0.35 mg/dL and creatinine clearance was 90.8 +/- 22.1 mL/1.73 m2. All 16 patients are on monotherapy (15 tacrolimus, one sirolimus), and 14 receive every other day or 3 times per week doses. There were no wound or other infections. Two patients developed insulin-dependent diabetes. CONCLUSION: The strategy of lymphoid depletion and minimum post-transplant immunosuppression appears safe and effective for pediatric kidney recipients.     

Selective Increases of Extracellular Brain Concentrations of Aromatic and Branched-Chain Amino Acids in Relation to Deterioration of Neurological Status in Acute (Ischemic) Liver Failure

Previous reports based on studies in brain tissue from humans and experimental animals suggest that aromatic amino acids (AAAs) and branched-chain amino acids (BCAA's) accumulate in brain in acute liver failure. In order to assess these changes in relation to the severity of neurological impairment and to the degree of hyperammonemia AAAs and BCAAs were measuredin vivo by cerebral microdialysis in frontal cortex of rats at various stages during the development of hepatic encephalopathy due to acute liver failure resulting from portacaval anastomosis followed by hepatic artery ligation. Extracellular brain concentrations of AAAs and of valine and leucine were elevated 2 to 4-fold following hepatic devascularization and these increases were significantly correlated to arterial ammonia concentration (r=0.71–0.84, p<0.05). Extracellular concentrations of tyrosine paralleled the deterioration of neurological status in acute liver failure rats. In view of their role as precursors of monoamine neurotransmitters, ammonia-induced alterations of intracellular/extracellular brain concentration ratios for AAAs could account for altered neuronal excitability and contribute to the encephalopathy characteristic of acute liver failure.     

Methylene blue dye injection for identification of occult gastrointestinal bleeding

The exact site of small bowel bleeding is difficult to detect intraoperatively. We present a simple method of on-table identification of the site of the bleed. A 55-year-old lady presented with recurrent episodes of melena and drop in hemoglobin. Digital subtraction angiography (DSA) revealed angiodysplasia of a vessel supplying the proximal jejunum. A microcatheter was placed at this site in the DSA suite, just prior to laparotomy. Two cubic centimeters of methylene blue dye was injected into the microcatheter on-table which demarcated the 6 in. of involved jejunum which was then resected. Patient is currently doing well over a 6-month follow up with no further episodes of melena. In conclusion, preoperative DSA and selective catheterization of the affected vessel allow for on-table localization of the exact site of bleed. This simple method avoids more invasive techniques of detection and enables limited segmental resection of the affected bowel.     

Zastosowanie cytometrii przepływowej oraz analizy proteomicznej w ocenie erytrocytarnych białek błonowych podczas przechowywania koncentratów krwinek czerwonych

For over 100 years the erythrocyte cell membrane attracted interest of transfusiologists mainly due to the antigens localized on their surface and associated risks of patient alloimmunisation and therefore the need of serological selection of donor's and recipient's blood. Presently it is known that RBC antigens and other membrane proteins play important transport and protective functions, and are involved in adhesion, maintenance of cell shape and in the process of aging and phagocytosis. Since the available results of retrospective clinical observations suggest an adverse effect of transfusion on selected groups of patients, it is important to undertake studies on the changes taking place within the cell membrane of erythrocytes stored in blood banks. Flow cytometric analysis of stored leucodepleted or non-leucodepleted erythrocyte concentrates, revealed significant changes in the level of expression of many RBC surface molecules: CD44, CD47, CD55, CD58, CD59, CD235a (GPA). In parallel, a significant development of proteomic analysis of stored RBCs is observed. Stored RBCs offer less variability of biological material, caused by drugs, illnesses, etc. when compared with clinical proteomics studies; however, the complexity of the methodology and the lack of uniform and comparable procedures may cause misinterpretation and even create artifacts. Still, modern research methods offer hope for the elaboration of aging biomarkers of stored RBCs as well as for raising the level of transfusion medicine quality.     

Functional recovery after peripheral nerve injury via sustained growth factor delivery from mineral-coated microparticles

The gold standard for treating peripheral nerve injuries that have large nerve gaps where the nerves cannot be directly sutured back together because it creates tension on the nerve, is to incorporate an autologous nerve graft. However, even with the incorporation of a nerve graft, generally patients only regain a small portion of function in limbs affected by the injury. Although, there has been some promising results using growth factors to induce more axon growth through the nerve graft, many of these previous therapies are limited in their ability to release growth factors in a sustained manner and tailor them to a desired time frame. The ideal drug delivery platform would deliver growth factors at therapeutic levels for enough time to grow axons the entire length of the nerve graft. We hypothesized that mineral coated microparticles(MCMs) would bind, stabilize and release biologically active glial cell-derived neurotrophic factor(GDNF) and nerve growth factor(NGF) in a sustained manner. Therefore, the objective of this study was to test the ability of MCMs releasing growth factors at the distal end of a 10 mm sciatic nerve graft, to induce axon growth through the nerve graft and restore hind limb function. After sciatic nerve grafting in Lewis rats, the hind limb function was tested weekly by measuring the angle of the ankle at toe lift-off while walking down a track. Twelve weeks after grafting, the grafts were harvested and myelinated axons were analyzed proximal to the graft, in the center of the graft, and distal to the graft. Under physiological conditions in vitro, the MCMs delivered a burst release of NGF and GDNF for 3 days followed by a sustained release for at least 22 days. In vivo, MCMs releasing NGF and GDNF at the distal end of sciatic nerve grafts resulted in significantly more myelinated axons extending distal to the graft when compared to rats that received nerve grafts without growth factor treatment. The rats with nerve grafts incorporated with MCMs releasing NGF and GDNF also showed significant improvement in hind limb function starting at 7 weeks postoperatively and continuing through 12 weeks postoperatively when compared to rats that received nerve grafts without growth factor treatment. In conclusion, MCMs released biologically active NGF and GDNF in a sustained manner, which significantly enhanced axon growth resulting in a significant improvement of hind limb function in rats. The animal experiments were approved by University of Wisconsin-Madison Animal Care and Use Committee(ACUC, protocol# M5958) on January 3, 2018.     

Sexual dimorphism of spatial working memory profiles in schizophrenia

Introduction. The aim of the present study was to compare spatial working memory performance of females and males schizophrenia patients to verify whether the sexual dimorphism of spatial abilities present in the general population is found also in schizophrenia.

Methods. We analysed different types of errors committed by each gender on the spatial working memory test of the Cambridge Neuropsychological Test Automated Battery to determine potential differences between them.

Results. Despite the lack of difference in the number of errors between men and women, different profiles of errors were associated with the strategy used according to gender. The men's strategy was better compared to women. Specifically, for women strategy score correlated positively with searches in previously visited boxes, whereas for men it correlated with both previously visited boxes and never visited ones. However, men's strategy is more impaired by the number of revisits in boxes in which tokens have previously been found than female's one.

Conclusions. These results suggested impaired either central executive and/or visuospatial sketchpad of working memory in patients with schizophrenia. We demonstrated also that the worsening of strategy in men is principally due to central executive deficits compared to women with schizophrenia. The study of sex differences in cognitive performances could help in delineating partially different endophenotypes of schizophrenia in men and women.     

A novel WNT10A mutation causes non-syndromic hypodontia in an Egyptian family

Objective

Tooth agenesis is the most common dental anomaly, whose aetiology still remains to be fully elucidated. The aim of this study was to investigate the genetic cause of non-syndromic hypodontia with clinical variability in an Egyptian family.

Design

The entire coding regions including exon-intron boundaries of the MSX1, PAX9 and WNT10A genes were investigated by direct sequencing in all affected family members.

Results

Novel heterozygous mutation inherited in an autosomal dominant manner was identified in the WNT10A gene. This 21-bp deletion combined with 1-bp insertion, c.-14_7delinsC, eliminates the translation initiation codon leading to either no protein production or translation of alternative open reading frames. None of the control subjects (400 chromosomes) were carriers of this novel WNT10A mutation. No pathogenic mutations were found in the MSX1 and PAX9 genes.

Conclusions

The novel c.-14_7delinsC mutation might be the etiological variant of the WNT10A gene responsible for the permanent tooth agenesis in the Egyptian family. WNT10A is a major candidate gene for non-syndromic hypodontia.