AMP-activated Protein Kinase in the Control of Cardiac Metabolism and Remodeling

The AMP-activated protein kinase (AMPK) can be firstly considered as a cellular fuel gauge. AMPK rapidly senses energy deprivation and orchestrates a metabolic response to maintain an acceptable energy level required for cell survival under such adverse condition. Its protective role during myocardial ischemia has been deeply documented. More recently, it has been shown that the role of AMPK extends to several nonmetabolic effects related to other cardiac pathologies comprising diabetic cardiomyopathy, cardiac hypertrophy, and heart failure. Here, we briefly review the different roles played by AMPK in the control of cardiac metabolism and function under normal and pathological conditions. The potential cardioprotective actions of AMPK and the relative importance of its energetic and nonmetabolic effects in these mechanisms are deeply discussed.     

Early prediction of failure to lose weight after obesity surgery

BackgroundAfter Roux-en-Y gastric bypass (RYGB), failing to lose enough weight or regaining weight is a concern for both patients and healthcare professionals. Our objective was to report the criteria for an early prediction of the failure to lose enough weight in the setting of a private practice and an academic center of obesity surgery.Patients and MethodsA retrospective analysis of the 2-year weight loss profiles of patients after RYGB was performed using nonlinear mixed models. A total of 375 morbidly obese adult patients, with a body mass index of 49.3 ± 7.7 kg/m², were included. Weight loss success was determined 2 years after surgery using the percentage of excess weight loss criteria. The surgical treatment and the main outcome measurement was standardized RYGB and the percentage of excess weight loss time profiles.ResultsThe patients who failed, succeeded, or had intermediate results at 2 years after surgery had different percentage of excess weight loss profiles during this period. At 6 months, 71% of those who had lost <30% of their initial excess weight had not lost ≥50% at 24 months. In contrast, those who had lost >45% were unlikely to have lost <50% of their excess weight.ConclusionAn early (month 6) prediction of failure to lose significant weight after RYGB can be made, with the threshold at 30% of the initial excess weight loss. Patients who have lost <30% of their initial excess weight are unlikely to have lost ≥50% at 24 months.     

Impact of behavioral subsyndromes on cognitive decline in Alzheimer’s disease: data from the ICTUS study

Behavioral and psychological symptoms of dementia (BPSD) represent common manifestations among patients affected by Alzheimer’s disease (AD). Some reports have recently classified BPSD into specific clusters/subsyndromes exploring the internal structure of the Neuropsychiatric Inventory (NPI). We evaluated whether specific behavioral subsyndromes are associated with worsening cognitive function. Mild to moderate AD patients were recruited from the cohort of the Impact of Cholinergic Treatment USe (ICTUS) study. Neuropsychiatric symptoms were classified in three subsyndromes, identified at baseline, grouping different combinations of NPI items: (1) “psychotic” (“delusions” and/or “hallucinations”); (2) “affective” (“agitation” and/or “depression” and/or “anxiety” and/or “irritability”); and (3) “behavioral” (“euphoria” and/or “apathy” and/or “disinhibition” and/or “aberrant motor behavior”). Mixed model analyses were performed to measure six-monthly changes in the ADAS-Cog score over a follow-up of 2 years, according to these subsyndromes. All analyses were stratified according to AD severity as defined by the Clinical Dementia Rating (CDR). A total of 1,375 AD subjects were recruited. No NPI cluster was found to significantly (p < 0.05) affect the rate of cognitive decline across the 3 CDR classes. Our results suggest that the cognitive course of AD is not substantially influenced by the presence of specific neuropsychiatric phenotypes. Further studies are needed to extend the present findings and identify possible biological and clinical bases for behavioral subsyndromes.     

The association between killer‐cell immunoglobulin‐like receptor (KIR) and KIR ligand genotypes and the likelihood of BK virus replication after kidney transplantation

BK virus is a common opportunistic post‐transplantation viral infection. Although some risk factors have been studied in this context, the contribution of NK cells has not been assessed in detail. In a group of kidney transplant recipients, we studied the association between (i) the likelihood of BK virus replication during the two‐year period after kidney transplantation and (ii) the genotypes of the killer cell immunoglobulin‐like receptor (KIR) repertoire and their human leukocyte antigen (HLA) ligands. Other clinical factors (such as defective organ recovery and immunosuppressive treatment) were also assessed. BK virus replication was observed in 43 of the 103 recipients (41%). Patients with BK virus replication in the plasma were more likely to display defective organ recovery in the first seven days post‐transplantation. BK virus replication was not associated with Missing KIR ligands. However, BK virus replication was more frequent in patients with responsive NK cells (i.e. when a ligand for activating KIRs was not homozygous in the recipient and present in the donor). Our results suggest that defective organ recovery and the recipient's activating KIR repertoire may be related (depending on HLA ligands present in the couple recipient / donor) to the reactivation of BK virus replication after kidney transplantation.     

Comprehensive PKD1 and PKD2 Mutation Analysis in Prenatal Autosomal Dominant Polycystic Kidney Disease

Prenatal forms of autosomal dominant polycystic kidney disease (ADPKD) are rare but can be recurrent in some families, suggesting a common genetic modifying background. Few patients have been reported carrying, in addition to the familial mutation, variation(s) in polycystic kidney disease 1 (PKD1) or HNF1 homeobox B (HNF1B), inherited from the unaffected parent, or biallelic polycystic kidney and hepatic disease 1 (PKHD1) mutations. To assess the frequency of additional variations in PKD1, PKD2, HNF1B, and PKHD1 associated with the familial PKD mutation in early ADPKD, these four genes were screened in 42 patients with early ADPKD in 41 families. Two patients were associated with de novo PKD1 mutations. Forty patients occurred in 39 families with known ADPKD and were associated with PKD1 mutation in 36 families and with PKD2 mutation in two families (no mutation identified in one family). Additional PKD variation(s) (inherited from the unaffected parent when tested) were identified in 15 of 42 patients (37.2%), whereas these variations were observed in 25 of 174 (14.4%, P=0.001) patients with adult ADPKD. No HNF1B variations or PKHD1 biallelic mutations were identified. These results suggest that, at least in some patients, the severity of the cystic disease is inversely correlated with the level of polycystin 1 function.