Automatic processing of facial emotion in schizophrenia with and without affective negative symptoms

Introduction. It is assumed that people spontaneously evaluate any incoming stimulus as pleasant or unpleasant. The evaluative response appears to structure perception and to have direct links to emotional states.Methods. To investigate the automatic processing of face valence a sequential priming task based on emotional face stimuli was administered to schizophrenia patients with a flat affect expression, schizophrenia patients suffering from anhedonia, schizophrenia patients not suffering from anhedonia or flat affect, and healthy controls. The Scale for the Assessment of Negative Symptoms (Andreasen, 1989) was applied to evaluate affective symptoms and categorise patients into groups.Results. Schizophrenia patients without affective negative symptoms exhibited reversed priming effects similar to that of healthy subjects. In contrast, flat affect patients and anhedonic patients showed only a prime effect due to negative facial valence. In the flat affect patient group, negative prime faces facilitated the evaluation of target faces, whereas in the anhedonic patient group negative prime faces tended to inhibit the evaluation of subsequent target faces.Conclusions. The present findings support the idea that chronic schizophrenia patients extract automatically the valence of emotional facial expression but they also suggest processing differences between schizophrenia patients as a function of affective symptoms.     

Functionalized PLGA-doped zirconium oxide ceramics for bone tissue regeneration

Bone tissue engineering is an alternative approach to bone grafts. In our study we aim to develop a composite scaffold for bone regeneration made of doped zirconium oxide (ZrO₂) conjugated with poly(lactic-co-glycolic acid) (PLGA) particles for the delivery of growth factors. In this composite, the PLGA microspheres are designed to release a crucial growth factor for bone formation, bone morphogenetic protein-2 (BMP2). We found that by changing the polymer’s molecular weight and composition, we could control microsphere loading, release and size. The BMP2 released from PLGA microspheres retained its biological activity and increased osteoblastic marker expression in human mesenchymal stem cells (hMSCs). Uncapped PLGA microspheres were conjugated to ZrO₂ scaffolds using carbodiimide chemistry, and the composite scaffold was shown to support hMSCs growth. We also demonstrated that human umbilical vein endothelial cells (HUVECs) can be co-cultured with hMSCs on the ZrO₂ scaffold for future vascularization of the scaffold. The ZrO₂ composite scaffold could serve as a bone substitute for bone grafting applications with the added ability of releasing different growth factors needed for bone regeneration.     

Patients’ Reported Reasons for Non-Use of an Internet-Based Patient-Provider Communication Service: Qualitative Interview Study

Background

The adoption of Internet-based patient–provider communication services (IPPC) in health care has been slow. Patients want electronic communication, and the quality of health care can be improved by offering such IPPCs. However, the rate of enrollment in such services remains low, and the reasons for this are unclear. Knowledge about the barriers to use is valuable during implementation of IPPCs in the health care services, and it can help timing, targeting, and tailoring IPPCs to different groups of patients.

Objective

The goal of our study was to investigate patients’ views of an IPPC that they could use from home to pose questions to nurses and physicians at their treatment facility, and their reported reasons for non-use of the service.

Methods

This qualitative study was based on individual interviews with 22 patients who signed up for, but did not use, the IPPC.

Results

Patients appreciated the availability and the possibility of using the IPPC as needed, even if they did not use it. Their reported reasons for not using the IPPC fell into three main categories: (1) they felt that they did not need the IPPC and had sufficient access to information elsewhere, (2) they preferred other types of communication such as telephone or face-to-face contact, or (3) they were hindered by IPPC attributes such as login problems.

Conclusions

Patients were satisfied with having the opportunity to send messages to health care providers through an IPPC, even if they did not use the service. IPPCs should be offered to the patients at an appropriate time in the illness trajectory, both when they need the service and when they are receptive to information about the service. A live demonstration of the IPPC at the point of enrollment might have increased its use.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00971139","term_id":"NCT00971139"}}NCT00971139; http://clinicaltrial.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT00971139","term_id":"NCT00971139"}}NCT00971139 (Archived by WebCite at http://www.webcitation.org/6KlOiYJrW).     

In Vivo Imaging of Local Inflammation: Monitoring LPS-Induced CD80/CD86 Upregulation by PET

Purpose

The co-stimulatory molecules CD80 and CD86 are upregulated on activated antigen-presenting cells (APC). We investigated whether local APC activation, induced by subcutaneous (s.c.) inoculation of lipopolysaccharides (LPS), can be imaged by positron emission tomography (PET) with CD80/CD86-targeting ⁶⁴Cu-labelled abatacept.

Procedures

Mice were inoculated s.c. with extracellular-matrix gel containing either LPS or vehicle (PBS). Immune cell populations were analysed by flow cytometry and marker expression by RT-qPCR. ⁶⁴Cu-NODAGA-abatacept distribution was analysed using PET/CT and ex vivo biodistribution.

Results

The number of CD80⁺ and CD86⁺ immune cells at the LPS inoculation site significantly increased a few days after inoculation. CD68 and CD86 expression were higher at the LPS than the PBS inoculation site, and CD80 was only increased at the LPS inoculation site. CTLA-4 was highest 10 days after LPS inoculation, when CD80/CD86 decreased again. A few days after inoculation, ⁶⁴Cu-NODAGA-abatacept distribution to the inoculation site was significantly higher for LPS than PBS (4.2-fold). Co-administration of unlabelled abatacept or human immunoglobulin reduced tracer uptake. The latter reduced the number of CD86⁺ immune cells at the LPS inoculation site.

Conclusions

CD80 and CD86 are upregulated in an LPS-induced local inflammation, indicating invasion of activated APCs. ⁶⁴Cu-NODAGA-abatacept PET allowed following APC activation over time.

     

Restoration of Glucose Counterregulation by Islet Transplantation in Long-standing Type 1 Diabetes

Patients with long-standing type 1 diabetes (T1D) may exhibit defective glucose counterregulation and impaired hypoglycemia symptom recognition that substantially increase their risk for experiencing severe hypoglycemia. The purpose of this study was to determine whether intrahepatic islet transplantation improves endogenous glucose production (EGP) in response to hypoglycemia in T1D patients experiencing severe hypoglycemia. We studied longitudinally subjects (n = 12) with ∼30 years, disease duration before and 6 months after intrahepatic islet transplantation using stepped hyperinsulinemic-hypoglycemic and paired hyperinsulinemic-euglycemic clamps with infusion of 6,6-²H₂-glucose and compared the results with those from a nondiabetic control group (n = 8). After islet transplantation, HbA_1c was normalized, and time spent while hypoglycemic (<70 mg/dL) was nearly abolished as indicated by continuous glucose monitoring. In response to insulin-induced hypoglycemia, C-peptide (absent before transplant) was appropriately suppressed, glucagon secretion was recovered, and epinephrine secretion was improved after transplantation. Corresponding to these hormonal changes, the EGP response to insulin-induced hypoglycemia, which was previously absent, was normalized after transplantation, with a similar effect seen for autonomic symptoms. Because the ability to increase EGP is ultimately required to circumvent the development of hypoglycemia, these results provide evidence that intrahepatic islet transplantation can restore glucose counterregulation in long-standing T1D and support its consideration as treatment for patients with hypoglycemia unawareness experiencing severe hypoglycemia.     

Pharmacokinetics of rituximab in a pediatric patient with therapy-resistant nephrotic syndrome

Background

Rituximab (RTX) has recently been introduced as a second-line therapy for nephrotic syndrome in children. Studies show that RTX given during the nephrotic state may be less effective than treatment during a non-nephrotic state, possibly due to loss of RTX in the urine.

Case-Diagnosis/Treatment

We describe a 10-year-old boy with steroid-resistant nephrotic syndrome (SRNS) treated with RTX during a phase of active non-selective proteinuria. The serum half-life of RTX in this patient was less than 1 day compared to 20 days in patients without protein losses. Urinary clearance was at least 25 %, compared to approximately 0 % in control patients. However, RTX loss in the urine, as well as in pleural effusion and ascites, only partly explains the rapid drop in the serum RTX concentration of this patient.

Conclusions

Serum half-life of RTX can be extremely short, partly due to excessive urinary losses in therapy-resistant nephrotic syndrome with non-selective proteinuria, as seen in our patient. These findings may help to explain the poor results of RTX treatment in patients with active proteinuria.

     

Different steroids co-regulate long-term expansion versus terminal differentiation in primary human erythroid progenitors

Outgrowth, long-term self-renewal, and terminal maturation of human erythroid progenitors derived from umbilical cord blood in serum-free medium can be modulated by steroid hormones. Homogeneous erythroid cultures, as characterized by flow cytometry and dependence on a specific mixture of physiologic proliferation factors, were obtained within 8 days from a starting population of mature and immature mononuclear cells. Due to previous results in mouse and chicken erythroblasts, the proliferation-promoting effect of glucocorticoids was not unexpected. Surprisingly, however, androgen had a positive effect on the sustained expansion of human female but not male erythroid progenitors. Under optimal conditions, sustained proliferation of erythroid progenitors resulted in a more than 10(9)-fold expansion within 60 days. Terminal erythroid maturation was significantly improved by adding human serum and thyroid hormone (3,5,3'-triiodothyronine [T3]) to the differentiation medium. This resulted in highly synchronous differentiation of the cells toward enucleated erythrocytes within 6 days, accompanied by massive size decrease and hemoglobin accumulation to levels comparable to those in peripheral blood erythrocytes. Thus, obviously, different ligand-activated nuclear hormone receptors massively influence the decision between self-renewal and terminal maturation in the human erythroid compartment.     

Discrimination and abuse in internal medicine residency

OBJECTIVE: To survey the extent to which internal medicine housestaff experience abuse and discrimination in their training. DESIGN: Through a literature review and resident focus groups, we developed a self-administered questionnaire. In this cross-sectional survey, respondents were asked to record the frequency with which they experienced and witnessed different types of abuse and discrimination during residency training, using a 7-point Likert scale. PARTICIPANTS: Internal medicine housestaff in Canada. MEASUREMENTS AND MAIN RESULTS: Of 543 residents in 13 programs participating (84% response rate), 35% were female. Psychological abuse, as reported by attending physicians (68%), patients (79%), and nurses or other health workers (77%), was widespread. Female residents experienced gender discrimination by attending physicians (70%), patients (88%), and nurses (71%); rates for males were 23%, 38%, and 35%, respectively. Females reported being sexually harassed more often than males, by attending physicians (35% vs 4%,p<.01), peers (30% vs 6%,p<.01), and patients (56% vs 18%,p<.01). Physical assault by patients was experienced by 40% of residents. Half of the residents surveyed reported racial discrimination and homophobic remarks in the workplace, perpetrated by all groups of health professionals. CONCLUSIONS: Psychological abuse, gender discrimination, sexual harassment, physical abuse, homophobia, and racial discrimination are prevalent problems during residency training. Housestaff, medical educators, allied health workers, and the public need to work together to address these problems in the training environment. Dr. Cook is a Career Scientist with the Ontario Ministry of Health. For a complete listing, see Appendix A. This study was supported by the Royal College of Physicians and Surgeons of Canada.     

Increased pulmonary prostacyclin synthesis in rats with chronic hypoxic pulmonary hypertension

OBJECTIVE: The regulation of pulmonary prostacyclin synthesis is not completely understood. We tested the hypothesis that prostacyclin production is predominantly stimulated by hemodynamic factors, such as increased shear-stress, and is thus increased in rats with chronic hypoxic pulmonary hypertension. METHODS: To this end, we determined pulmonary prostacyclin synthase (PGIS) gene expression, circulating levels of the stable prostacyclin metabolite 6-keto prostaglandin F(1alpha) (6-keto-PGF(1alpha)), pulmonary endothelin (ET)-1 gene expression, and ET-1 plasma levels in rats exposed to 4 weeks of hypoxia (10% O(2)) in the presence or absence of either the nitric oxide (NO) donor molsidomine (MD, 15 mg/kg/day) or the ET-A receptor antagonist LU135252 (LU, 50 mg/kg/day). RESULTS: Right ventricular systolic pressure (RVSP), the cross-sectional medial vascular wall area of pulmonary arteries, and ET-1 production increased significantly during hypoxia. PGIS mRNA levels increased 1.7-fold, and 6-keto-PGF(1alpha) plasma levels rose from 8.2+/-0.8 to 12.2+/-2.2 ng/ml during hypoxia (each P<0.05 vs. normoxic controls). MD and LU reduced RVSP and pulmonary vascular remodeling similarly (each P<0.05 vs. hypoxia), but only MD inhibited pulmonary ET-1 formation (P<0.05 vs. hypoxia). Nevertheless, both drugs attenuated the increase in PGIS gene expression and plasma 6-keto-PGF(1alpha) levels (each P<0.05 vs. hypoxia). CONCLUSION: Our data suggest that prostacyclin production in hypertensive rat lungs is predominantly increased by hemodynamic factors while hypoxia, NO and ET-1 per are less important stimuli, and that this increase may serve as a compensatory mechanism to partially negate the hypoxia-induced elevation in pulmonary vascular tone.