Update on the management of constipation in the elderly: new treatment options

Constipation disproportionately affects older adults, with a prevalences of 50% in community-dwelling elderly and 74% in nursing-home residents. Loss of mobility, medications, underlying diseases, impaired anorectal sensation, and ignoring calls to defecate are as important as dyssynergic defecation or irritable bowel syndrome in causing constipation. Detailed medical history on medications and co-morbid problems, and meticulous digital rectal examination may help identify causes of constipation. Likewise, blood tests and colonoscopy may identify organic causes such as colon cancer. Physiological tests such as colonic transit study with radio-opaque markers or wireless motility capsule, anorectal manometry, and balloon expulsion tests can identify disorders of colonic and anorectal function. However, in the elderly, there is usually more than one mechanism, requiring an individualized but multifactorial treatment approach. The management of constipation continues to evolve. Although osmotic laxatives such as polyethylene glycol remain mainstay, several new agents that target different mechanisms appear promising such as chloride-channel activator (lubiprostone), guanylate cyclase agonist (linaclotide), 5HT4 agonist (prucalopride), and peripherally acting μ-opioid receptor antagonists (alvimopan and methylnaltrexone) for opioid-induced constipation. Biofeedback therapy is efficacious for treating dyssynergic defecation and fecal impaction with soiling. However, data on efficacy and safety of drugs in elderly are limited and urgently needed

Unusual Occurrence of Peripheral Ossifying Fibroma in an Elderly Male

The present case is a scenario of occurrence of relatively common peripheral ossifying fibroma in an uncommon site of occurrence. It was noted in the maxillary posterior region incontrast to its usual occurrence in anterior maxillary region. The lesion was observed in elderly male subject aged 64 years, contradictory to its usual predilection for young females in thesecond or third decade of life. As this case contradicts the common norms of predilection of the lesion with regard to age, gender and site, it emphasizes the need for looking beyond theconventional norms for proper diagnosis and prompt treatment.&nbsp

Navigating Copper-Atom-Pair Structural Effect inside a Porous Organic Polymer Cavity for Selective Hydrogenation of Biomass-Derived 5-Hydroxymethylfurfural

In recent times, selective hydrogenation of biomass-derived 5-hydroxymethylfurfural (5-HMF) to produce the novel difuranic polyol scaffold 2,5-dihydroxymethylfuran (DHMF) has attracted the interest of the many researchers due to its peculiar symmetrical structure and its widespread application as a monomer for the preparation of cross-linked polyesters and polyurethane. Copper-based catalysts have been explored for selective catalytic hydrogenation; however, hurdles are still associated with the strongly reducing H2 atmosphere and oxidizing C–O bond that make the Cu0 and Cux+ surface active species unstable, limiting the rational design of highly efficient integrated catalyst systems. To address this, herein, we built catalytic systems for 5-HMF hydrogenation with stable and balanced Cu0 and Cux+ active surface species inside the nanocage of a catechol-based porous organic polymer (POP) endowed with large surface areas, impressive stabilities, and spatial restriction inhibiting nanoparticle aggregation. Batch reactor screening identified that a superior catalytic performance (DHMF selectivity of 98%) has been achieved with our newly designed Cu@C-POP at 150 °C temperature and 20 bar H2 pressure, which was also higher than that of other reported copper catalysts. Comprehensive characterization understanding with H2-TPR and X-ray photoelectron spectroscopy (XPS) study revealed that substantially boosted activity is induced by the presence of the bulk CuOx phase and atomically dispersed Cu species incorporating isolated Cu ions, which are further confirmed through the positive binding energy shift of Cu 2p3/2 XPS spectra (∼0.4 eV). The Cu environment in our catalytic systems comprises a predominantly square planar geometry (probably Jahn–Teller distorted OH), which we gleaned from the extended X-ray absorption for fine structure (EXAFS) analysis featuring two adjacent copper atoms with the valence state in between of 0 and +2, as validated by XANES absorption edge positions. EXAFS studies further revealed a lowering of the Cu coordination number for the most active Cu@C-POP-B catalyst, suggesting the presence of metal vacancies. Density functional theory calculations showed that the presence of Cu metal vacancies stabilized the reaction intermediates formed during 5-HMF hydrogenation and decreased the hydrogenation barriers, resulting in an enhanced catalytic activity of the Cu@C-POP-B catalyst

Stability Analysis of Frame Slotted Aloha Protocol

Frame Slotted Aloha (FSA) protocol has been widely applied in Radio Frequency Identification (RFID) systems as the de facto standard in tag identification. However, very limited work has been done on the stability of FSA despite its fundamental importance both on the theoretical characterisation of FSA performance and its effective operation in practical systems. In order to bridge this gap, we devote this paper to investigating the stability properties of FSA by focusing on two physical layer models of practical importance, the models with single packet reception and multipacket reception capabilities. Technically, we model the FSA system backlog as a Markov chain with its states being backlog size at the beginning of each frame. The objective is to analyze the ergodicity of the Markov chain and demonstrate its properties in different regions, particularly the instability region. By employing drift analysis, we obtain the closed-form conditions for the stability of FSA and show that the stability region is maximised when the frame length equals the backlog size in the single packet reception model and when the ratio of the backlog size to frame length equals in order of magnitude the maximum multipacket reception capacity in the multipacket reception model. Furthermore, to characterise system behavior in the instability region, we mathematically demonstrate the existence of transience of the backlog Markov chain.Comment: 14 pages, submitted to IEEE Transaction on Information Theor

Chronic renal insufficiency among Asian Indians with type 2 diabetes: I. Role of RAAS gene polymorphisms

BACKGROUND: Renal failure in diabetes is mediated by multiple pathways. Experimental and clinical evidences suggest that renin-angiotensin-aldosterone system (RAAS) has a crucial role in diabetic kidney disease. A relationship between the RAAS genotypes and chronic renal insufficiency (CRI) among type 2 diabetes subjects has therefore been speculated. We investigated the contribution of selected RAAS gene polymorphisms to CRI among type 2 diabetic Asian Indian subjects. METHODS: Twelve single nucleotide polymorphisms (SNPs) from six genes namely-renin (REN), angiotensinogen (ATG), angiotensin converting enzyme I (ACE), angiotensin II type 1 receptor (AT1) and aldosterone synthase (CYP11B2) gene from the RAAS pathway and one from chymase pathway were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and tested for their association with diabetic CRI using a case-control approach. Successive cases presenting to study centres with type 2 diabetes of ≥2 years duration and moderate CRI diagnosed by serum creatinine ≥3 mg/dl after exclusion of non-diabetic causes of CRI (n = 196) were compared with diabetes subjects with no evidence of renal disease (n = 225). Logistic regression analysis was carried out to correlate various clinical parameters with genotypes, and to study pair wise interactions between SNPs of different genes. RESULTS: Of the 12 SNPs genotyped, Glu53Stop in AGT and A>T (-777) in AT1 genes, were monomorphic and not included for further analysis. We observed a highly significant association of Met235Thr SNP in angiotensinogen gene with CRI (O.R. 2.68, 95%CI: 2.01–3.57 for Thr allele, O.R. 2.94, 95%CI: 1.88–4.59 for Thr/Thr genotype and O.R. 2.68, 95%CI: 1.97–3.64 for ACC haplotype). A significant allelic and genotypic association of T>C (-344) SNP in aldosterone synthase gene (O.R. 1.57, 95%CI: 1.16–2.14 and O.R. 1.81, 95%CI: 1.21–2.71 respectively), and genotypic association of GA genotype of G>A (-1903) in chymase gene (O.R. 2.06, 95%CI: 1.34–3.17) were also observed. CONCLUSION: SNPs Met235Thr in angiotensinogen, T>C (-344) in aldosterone synthase, and G>A (-1903) in chymase genes are significantly associated with diabetic chronic renal insufficiency in Indian patients and warrant replication in larger sample sets. Use of such markers for prediction of susceptibility to diabetes specific renal disease in the ethnically Indian population appears promising

The Goldbeter-Koshland switch in the first-order region and its response to dynamic disorder

In their classical work (Proc. Natl. Acad. Sci. USA, 1981, 78:6840-6844), Goldbeter and Koshland mathematically analyzed a reversible covalent modification system which is highly sensitive to the concentration of effectors. Its signal-response curve appears sigmoidal, constituting a biochemical switch. However, the switch behavior only emerges in the "zero-order region", i.e. when the signal molecule concentration is much lower than that of the substrate it modifies. In this work we showed that the switching behavior can also occur under comparable concentrations of signals and substrates, provided that the signal molecules catalyze the modification reaction in cooperation. We also studied the effect of dynamic disorders on the proposed biochemical switch, in which the enzymatic reaction rates, instead of constant, appear as stochastic functions of time. We showed that the system is robust to dynamic disorder at bulk concentration. But if the dynamic disorder is quasi-static, large fluctuations of the switch response behavior may be observed at low concentrations. Such fluctuation is relevant to many biological functions. It can be reduced by either increasing the conformation interconversion rate of the protein, or correlating the enzymatic reaction rates in the network.Comment: 23 pages, 4 figures, accepted by PLOS ON

An investigation of the effects of lipid-lowering medications: genome-wide linkage analysis of lipids in the HyperGEN study

BACKGROUND: Use of anti-hyperlipidemic medications compromises genetic analysis because of altered lipid profiles. We propose an empirical method to adjust lipid levels for medication effects so that the adjusted lipid values substitute the unmedicated lipid values in the genetic analysis. RESULTS: Published clinical trials were reviewed for HMG-CoA reductase inhibitors and fibric acid derivatives as mono-drug therapy. HMG-CoA reductase inhibitors showed similar effects in African Americans (AA) and non-African Americans (non-AA) for lowering total cholesterol (TC, -50.7 mg/dl), LDL cholesterol (LDL-C, -48.1 mg/dl), and triglycerides (TG, -19.7 mg/dl). Their effect on increasing HDL cholesterol (HDL-C) in AA (+0.4 mg/dl) was lower than in Non-AA (+2.3 mg/dl). The effects of fibric acid derivatives were estimated as -46.1 mg/dl for TC, -40.1 mg/dl for LDL-C, and +5.9 mg/dl for HDL-C in non-AA. The corresponding effects in AA were less extreme (-20.1 mg/dl, -11.4 mg/dl, and +3.1 mg/dl). Similar effect for TG (59.0 mg/dl) was shown in AA and non-AA. The above estimated effects were applied to a multipoint variance components linkage analysis on the lipid levels in 2,403 Whites and 2,214 AA in the HyperGEN study. The familial effects did vary depending on whether the lipids were adjusted for medication use. For example, the heritabilities increased after medication adjustment for TC and LDL-C, but did not change significantly for HDL-C and TG. CONCLUSION: Ethnicity-specific medication adjustments using our empirical method can be employed in epidemiological and genetic analysis of lipids.National Heart, Lung, and Blood Institute (HL554471, HL54472, HL54473, HL54495, HL54496, HL54497, HL54509, HL54515