Suppressing the encoding of new information in memory: a behavioral study derived from principles of hippocampal function.

Cognitive processes do not occur in isolation. Interactions between cognitive processes can be observed as a cost in performance following a switch between tasks, a cost that is greatest when the cognitive requirements of the sequential tasks compete. Interestingly, the long-term mnemonic goals associated with specific cognitive tasks can also directly compete. For example, encoding the sequential order in which stimuli are presented in the commonly-utilised 2-Back working memory (WM) tasks is counter-productive to task performance, as this task requires the continual updating of the contents of one's current mental set. Performance of this task consistently results in reduced activity within the medial temporal lobe (MTL), and this response is believed to reflect the inhibitory mnemonic component of the task. Conversely, there are numerous cognitive paradigms in which participants are explicitly instructed to encode incoming information and performance of these tasks reliably increases MTL activity. Here, we explore the behavioural cost of sequentially performing two tasks with conflicting long-term mnemonic goals and contrasting neural profiles within the MTL. We hypothesised that performing the 2-Back WM prior to a hippocampal-dependent memory task would impair performance on the latter task. We found that participants who performed the 2-Back WM task, prior to the encoding of novel verbal/face-name stimuli, recollected significantly fewer of these stimuli, compared to those who had performed a 0-Back control task. Memory processes believed to be independent of the MTL were unaffected. Our results suggest that the inhibition of MTL-dependent mnemonic function persists beyond the cessation of the 2-Back WM task and can alter performance on entirely separate and subsequently performed memory tasks. Furthermore, they indicate that performance of such tasks may induce a temporarily-sustained, virtual lesion of the hippocampus, which could be used as a probe to explore cognitive processes in the absence of hippocampal involvement

A double shunt technique for the prevention of ischaemia of a congenital, solitary, pelvic kidney during abdominal aortic aneurysm repair: a case report

<p>Abstract</p> <p>Introduction</p> <p>Congenital solitary pelvic kidney is a rare condition, and its association with an abdominal aortic aneurysm is even more unusual. To the best of our knowledge, only two such cases have been reported in the literature to date.</p> <p>Case presentation</p> <p>We report the case of a 59-year-old Caucasian man with a congenital solitary pelvic kidney, who was found to have an abdominal aortic aneurysm 83 mm in diameter. Abdominal computed tomography angiography clearly identified two renal arteries, one originating from the aortic bifurcation. and the other from the proximal portion of the right common iliac artery. At surgery, renal ischaemia was prevented by introduction of an axillofemoral shunt (consisting of two femoral cannulas and a vent tube of extracorporeal circulation) from the right axillary to the right femoral artery, and a second Argyle shunt from the right common iliac artery to the origin of the left renal artery. A 20 mm Dacron tube graft was then implanted. Our patient's postoperative renal function was normal.</p> <p>Conclusion</p> <p>The renal preservation double shunt technique used in this case seems to be effective during abdominal aortic aneurysm repair.</p

Pancreatic cancer in type 1 and young-onset diabetes: systematic review and meta-analysis

We conducted a systematic review of the risk of pancreatic cancer in people with type I and young-onset diabetes. In three cohort and six case–control studies, the relative risk for pancreatic cancer in people with (vs without) diabetes was 2.00 (95% confidence interval 1.37–3.01) based on 39 cases with diabetes

High BMI is significantly associated with positive progesterone receptor status and clinico-pathological markers for non-aggressive disease in endometrial cancer

Background: Endometrial cancer incidence is increasing in industrialised countries. High body mass index (BMI, kg m−2) is associated with higher risk for disease. We wanted to investigate if BMI is related to clinico-pathological characteristics, hormone receptor status in primary tumour, and disease outcome in endometrial cancer. Patients and methods: In total, 1129 women primarily treated for endometrial carcinoma at Haukeland University Hospital during 1981–2009 were studied. Body mass index was available for 949 patients and related to comprehensive clinical and histopathological data, hormone receptor status in tumour, treatment, and follow-up. Results: High BMI was significantly associated with low International Federation of Gynaecology and Obstetrics (FIGO) stage, endometrioid histology, low/intermediate grade, and high level of progesterone receptor (PR) mRNA by qPCR (n=150; P=0.02) and protein expression by immunohistochemistry (n=433; P=0.003). In contrast, oestrogen receptor (ERα) status was not associated with BMI. Overweight/obese women had significantly better disease-specific survival (DSS) than normal/underweight women in univariate analysis (P=0.035). In multivariate analysis of DSS adjusting for age, FIGO stage, histological subtype, and grade, BMI showed no independent prognostic impact. Conclusion: High BMI was significantly associated with markers of non-aggressive disease and positive PR status in a large population-based study of endometrial carcinoma. Women with high BMI had significantly better prognosis in univariate analysis of DSS, an effect that disappeared in multivariate analysis adjusting for established prognostic markers. The role of PR in endometrial carcinogenesis needs to be further studied

Cancer incidence and mortality in patients with insulin-treated diabetes: a UK cohort study

Raised risks of several cancers have been found in patients with type II diabetes, but there are few data on cancer risk in type I diabetes. We conducted a cohort study of 28 900 UK patients with insulin-treated diabetes followed for 520 517 person-years, and compared their cancer incidence and mortality with national expectations. To analyse by diabetes type, we examined risks separately in 23 834 patients diagnosed with diabetes under the age of 30 years, who will almost all have had type I diabetes, and 5066 patients diagnosed at ages 30–49 years, who probably mainly had type II. Relative risks of cancer overall were close to unity, but ovarian cancer risk was highly significantly raised in patients with diabetes diagnosed under age 30 years (standardised incidence ratio (SIR)=2.14; 95% confidence interval (CI) 1.22–3.48; standardised mortality ratio (SMR)=2.90; 95% CI 1.45–5.19), with greatest risks for those with diabetes diagnosed at ages 10–19 years. Risks of cancer at other major sites were not substantially raised for type I patients. The excesses of obesity- and alcohol-related cancers in type II diabetes may be due to confounding rather than diabetes per se

A Unified Model of the GABA(A) Receptor Comprising Agonist and Benzodiazepine Binding Sites

We present a full-length α(1)β(2)γ(2) GABA receptor model optimized for agonists and benzodiazepine (BZD) allosteric modulators. We propose binding hypotheses for the agonists GABA, muscimol and THIP and for the allosteric modulator diazepam (DZP). The receptor model is primarily based on the glutamate-gated chloride channel (GluCl) from C. elegans and includes additional structural information from the prokaryotic ligand-gated ion channel ELIC in a few regions. Available mutational data of the binding sites are well explained by the model and the proposed ligand binding poses. We suggest a GABA binding mode similar to the binding mode of glutamate in the GluCl X-ray structure. Key interactions are predicted with residues α(1)R66, β(2)T202, α(1)T129, β(2)E155, β(2)Y205 and the backbone of β(2)S156. Muscimol is predicted to bind similarly, however, with minor differences rationalized with quantum mechanical energy calculations. Muscimol key interactions are predicted to be α(1)R66, β(2)T202, α(1)T129, β(2)E155, β(2)Y205 and β(2)F200. Furthermore, we argue that a water molecule could mediate further interactions between muscimol and the backbone of β(2)S156 and β(2)Y157. DZP is predicted to bind with interactions comparable to those of the agonists in the orthosteric site. The carbonyl group of DZP is predicted to interact with two threonines α(1)T206 and γ(2)T142, similar to the acidic moiety of GABA. The chlorine atom of DZP is placed near the important α(1)H101 and the N-methyl group near α(1)Y159, α(1)T206, and α(1)Y209. We present a binding mode of DZP in which the pending phenyl moiety of DZP is buried in the binding pocket and thus shielded from solvent exposure. Our full length GABA(A) receptor is made available as Model S1

Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk

The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project–imputed genotype data in up to ~370,000 women, we identify 389 independent signals (P < 5 × 10$^{−8}$) for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain ~7.4% of the population variance in age at menarche, corresponding to ~25% of the estimated heritability. We implicate ~250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, independent of body mass index (BMI), between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men. In aggregate, our findings highlight the complexity of the genetic regulation of puberty timing and support causal links with cancer susceptibility