Integration of nurse practitioners into a family health network

A randomized controlled study called Anticipatory and Preventative Team Care (APTCare) explored a new role for nurse practitioners (NPs) within a multidisciplinary team. The aim of the study was to evaluate whether integrating NPs and a pharmacist was an effective approach for the management of patients living with multiple chronic illnesses. Over an 18-month period, three part-time NPs and a pharmacist became part of a rural Family Health Network (FHN). They established relationships with study patients and collaborated to provide optimum care. Each NP had 40 patients, all of whom received care in the home. Study results showed that an initial home visit was invaluable for establishing a care plan, developing a relationship with the patient and assessing the home environment. Ongoing monitoring at home, however, was found to be an inefficient use of the NP role. By the end of the study, all clinicians agreed that the NP role had been successfully integrated into the multidisciplinary team.     

Plasma and Mucosal Fatty Acid Pattern in Colectomized Ulcerative Colitis Patients

Patients with inflammatory bowel disease (IBD)have increased plasma n3 polyunsaturated fatty acids(PUFAs), which in ulcerative colitis (UC) patientspersists six months after colectomy, suggesting aprimary abnormality in fatty acid (FA) metabolism inIBD. This finding needed to be confirmed in a largerseries of UC long-term colectomized patients. We aimedto assess the plasma FA pattern in UC colectomized patients with either Brooke's ileostomy (UC-BI)or ileal pouch anal anastomosis (UC-IPAA) and themucosal FA pattern in the ileal reservoir of the UC-IPAApatients. Plasma FAs were assessed in 63 UC colectomized patients (31 with BI and 32 with IPAA) and 30controls. In 26 UC-IPAA (8 with pouchitis and 18 withoutpouchitis) and in 13 healthy controls gut mucosal FAswere also investigated. FAs were detected by capillary column gas-liquid chromatography.Increased levels of saturated fatty acids (SFAs) anddecreased percentages of monounsaturated fatty acids(MUFAs) were observed in both groups of patients. There were no changes in plasma n3 and n6 PUFAs. Themucosal FA pattern of the ileal reservoir consisted ofincreased long-chain PUFAs, specially n6 PUFA, and adecrease of their essential precursors. High percentages of SFAs and low percentages of MUFAs were alsoseen. The plasma FA profile previously described in IBDis not observed long-term after colectomy in UC,suggesting that it is related with the presence of inflamed intestine. High concentrations of SFAsand decreased percentages of MUFAs might represent earlyevents in disturbed FA metabolism in IBD. The changes inFAs of the ileal reservoir, which closely resemble those found in human and experimentalIBD, probably represent a common pattern of intestinalinflammation.     

Establishment of erythropoiesis following bone marrow transplantation in a patient with congenital hypoplastic anemia (Diamond-Blackfan syndrome)

Marrow transplantation was attempted in a 13-yr-old boy with congenital hypoplastic anemia who had never responded to corticosteroid therapy. Prior to the transplant, he had received 238 transfusions, at least 12 of which were from his father. He was prepared for grafting with antilymphocyte globulin, procarbazine, and total body irradiation (1000 rads). The patient, whose red cells were Group B, then received marrow cells from his Group O, histocompatible, sister. Thereafter, reticulocytes, Group O erythrocytes, and female leukocytes appeared in the peripheral blood. Erythroid precursors were seen in the patient's marrow for the first time in his life, and all lacked fluorescent Y chromosomes. Dividing cells were all female. After initially progressing well, the patient developed interstitial pneumonia and died 55 days after the transplant. The successful erythroid graft suggested that this patient's failure to produce red blood cells was due to a defective stem cell rather than to a humoral defect, plasma inhibitor, or abnormal marrow microenvironment. It suggested further that sibling marrow may be engrafted in patients who have received multiple transfusions, even from a parent.     

Contractile Dysfunction of Left Ventricular Cardiomyocytes in Patients With Pulmonary Arterial Hypertension

Background

After lung transplantation, increased left ventricular (LV) filling can lead to LV failure, increasing the risk of post-operative complications and mortality. LV dysfunction in pulmonary arterial hypertension (PAH) is characterized by a reduced LV ejection fraction and impaired diastolic function.

Objectives

The pathophysiology of LV dysfunction in PAH is incompletely understood. This study sought to assess the contribution of atrophy and contractility of cardiomyocytes to LV dysfunction in PAH patients.

Methods

LV function was assessed by cardiac magnetic resonance imaging. In addition, LV biopsies were obtained in 9 PAH patients and 10 donors. The cross-sectional area (CSA) and force-generating capacity of isolated single cardiomyocytes was investigated.

Results

Magnetic resonance imaging analysis revealed a significant reduction in LV ejection fraction in PAH patients, indicating a reduction in LV contractility. The CSA of LV cardiomyocytes of PAH patients was significantly reduced (∼30%), indicating LV cardiomyocyte atrophy. The maximal force-generating capacity, normalized to cardiomyocyte CSA, was significantly reduced (∼25%). Also, a reduction in the number of available myosin-based cross-bridges was found to cause the contractile weakness of cardiomyocytes. This finding was supported by protein analyses, which showed an ∼30% reduction in the myosin/actin ratio in cardiomyocytes from PAH patients. Finally, the phosphorylation level of sarcomeric proteins was reduced in PAH patients, which was accompanied by increased calcium sensitivity of force generation.

Conclusions

The contractile function and the CSA of LV cardiomyocytes is substantially reduced in PAH patients. We propose that these changes contribute to the reduced in vivo contractility of the LV in PAH patients.     

Structural Basis of the Avian Influenza NS1 Protein Interactions with the Cell Polarity Regulator Scribble

Scribble is a highly conserved regulator of cell polarity, a process that enables the generation of asymmetry at the cellular and tissue level in higher organisms. Scribble acts in concert with Disc-large (Dlg) and Lethal-2-giant larvae (Lgl) to form the Scribble polarity complex, and its functional dysregulation is associated with poor prognosis during viral infections. Viruses have been shown to interfere with Scribble by targeting Scribble PDZ domains to subvert the network of interactions that enable normal control of cell polarity via Scribble, as well as the localisation of the Scribble module within the cell. The influenza A virus NS1 protein was shown to bind to human Scribble (SCRIB) via its C-terminal PDZ binding motif (PBM). It was reported that the PBM sequence ESEV is a virulence determinant for influenza A virus H5N1 whilst other sequences, such as ESKV, KSEV and RSKV, demonstrated no affinity towards Scribble. We now show, using isothermal titration calorimetry (ITC), that ESKV and KSEV bind to SCRIB PDZ domains and that ESEV unexpectedly displayed an affinity towards all four PDZs and not just a selected few. We then define the structural basis for the interactions of SCRIB PDZ1 domain with ESEV and ESKV PBM motifs, as well as SCRIB PDZ3 with the ESKV PBM motif. These findings will serve as a platform for understanding the role of Scribble PDZ domains and their interactions with different NS1 PBMs and the mechanisms that mediate cell polarity within the context of the pathogenesis of influenza A virus.     

Increase in fecal primary bile acids and dysbiosis in patients with diarrhea-predominant irritable bowel syndrome

Background Irritable bowel syndrome (IBS) is a multifactorial disease for which a dysbiosis of the gut microbiota has been described. Bile acids (BA) could play a role as they are endogenous laxatives and are metabolized by gut microbiota. We compared fecal BA profiles and microbiota in healthy subjects (HS) and patients with diarrhea‐predominant IBS (IBS‐D), and we searched for an association with symptoms. Methods Clinical features and stool samples were collected in IBS‐D patients and HS. Fecal BA profiles were generated using HPLC coupled to tandem mass spectrometry. The fecal microbiota composition was assessed by q‐PCR targeting dominant bacterial groups and species implicated in BA transformation. Key Results Fourteen IBS‐D patients and 18 HS were included. The two groups were comparable in terms of age and sex. The percentage of fecal primary BA was significantly higher in IBS‐D patients than in HS, and it was significantly correlated with stool consistency and frequency. Fecal counts of all bacteria, lactobacillus, coccoides, leptum and Faecalibacterium prausnitzii were similar. There was a significant increase of Escherichia coli and a significant decrease of leptum and bifidobacterium in IBS‐D patients. Conclusions & Inferences We report an increase of primary BA in the feces of IBS‐D patients compared to HS, correlated with stool consistency and frequency. A dysbiosis of different bacterial groups was detected, some of them involved in BA transformation. As the gut microbiota is the exclusive pathway to transform primary into secondary BA, this suggests a functional consequence of dysbiosis, leading to lower BA transformation.