The psychological impact of heavy drinking among the elderly on their co-residents: the 10/66 group population based survey in the Dominican Republic

Background

There is very limited literature on alcohol use among the elderly and little is known about the impact it has on family and caregivers, especially in low and middle income countries.

Aim

To estimate the independent effect of heavy alcohol use among the elderly on the psychological health of their co-residents.

Methods

This is a secondary analysis using data from the comprehensive cross-sectional survey of the 10/66 dementia research group population-based research programme in the Dominican Republic. The characteristics of the elderly participants as well as the co-residents were described. The independent association of heavy drinking among the participants with psychological morbidity in their co-residents was estimated. Different models were generated to rule out potential mediating effects of disability and behavioural symptoms.

Results

Prevalence of heavy alcohol use in the elderly in Dominican Republic was 10.6%. There was a statistically significant independent effect of heavy alcohol use by the elderly on their co-residents mental health (PR = 1.47; 95% CI 1.07-2.01) which was not accounted by disability (Sobel-Goodman test, p = 0.15). Severity of psychological and behavioural symptoms partially (29.1% of the total effect) explained this association (Sobel-Goodman mediation test, p = 0.006).

Conclusions

Health services for the elderly in low and middle income countries will have to be configured around detection of alcohol problems among the elderly as well as offering appropriate support to their co-residents.     

Gold nanorod mediated plasmonic photothermal therapy: a tool to enhance macromolecular delivery

Plasmonic photothermal therapy (PPTT) with gold nanostructures has been used to generate significant heat within tumors to ablate vasculature. Here we report the use of gold nanorod (GNR) mediated PPTT to induce moderate hyperthermia as a tool to enhance the delivery of macromolecules. GNRs were injected intravenously in a mouse sarcoma (S-180) tumor model. After 24h Evans blue dye (EBD) was injected and the right tumor was radiated with a laser diode for 10 min. EBD content in the right and left tumors were extracted in formamide, measured spectrophotometrically and expressed as a thermal enhancement ratio (TER). Enhanced delivery of EBD was observed (up to 1.8-fold) when tumor temperatures reached 43°C or 46°C. No statistical difference was observed between tumors at these two temperatures, though significant hemorrhage was observed in tumors and surrounding areas receiving the higher thermal dose (46°C). These results indicate that tumor directed PPTT may be used to induce moderate hyperthermia and therefore selectively increase the delivery of macromolecules with therapeutic anticancer drugs.     

Modulation of cytochrome-P450 inhibition (CYP) in drug discovery: a medicinal chemistry perspective

Cytochrome P450 (CYP450) has widely been implicated for drug-drug interactions (DDI) in the pharmaceutical industry. Inhibition or induction of this enzyme family has led to withdrawal of multiple drugs from the market leading to major time and financial losses for the pharmaceutical industry. CYP450 plays a prevailing role in the biotransformation of a large number of structurally diverse drugs. Few isoenzymes of the CYP enzyme family (CYP3A4, 2D6 and 2C9 family) are mainly involved in metabolism of most of the drugs. To avoid such interactions and potentially minimize DDI, major pharmaceutical organizations prefer to incorporate CYP enzyme screening at an early stage of their discovery program. While this has been a prevalent practice in the pharmaceutical industry lately, there is very limited literature available reviewing the relationship between chemotypes and CYP isoforms. This review will collate literature pertaining to CYP-inhibition modulation through physicochemical parameters and chemical modification and thus bring to focus commonly used trends by medicinal chemists world-wide.     

Preoperative predictors of mortality in adult patients with perforation peritonitis

Introduction:

There is paucity of data from India regarding the etiology, prognostic indicators, morbidity, and mortality patterns of perforation peritonitis. The objective of our study was to evaluate the predictors of mortality, preoperatively, for risk stratification of the patients and institution of an early goal-directed therapy.

Materials and Methods:

Eighty-four consecutive patients presenting with perforation peritonitis, in the age group of 14–70 years scheduled for emergency laparotomy were studied prospectively. The parameters studied were age and sex of the patients, associated co-morbidities, duration of symptoms, delay in initiating surgical intervention, and preoperative biochemical parameters such as hemoglobin, random blood sugar, blood urea, serum creatinine, pH, base excess, and serum lactate levels. In-hospital mortality was taken as the outcome.

Results:

We encountered a mortality of 17.8% in our study. Multiple linear (enter) regression identified the age, duration of symptoms, preoperative blood sugar levels, blood urea, serum creatinine levels, Mannheim Peritonitis Index, and the delay in instituting surgical intervention as independent predictors of mortality. Hyperlactatemia, acidosis and base excess were not found to be associated with mortality.

Conclusion:

Routine biochemical investigations, delay in presentation, and surgical intervention are good predictors of mortality. Recognizing such patients early may help the anesthesiologists in risk stratification and in providing an early goal-directed therapy.     

Managing pressures ulcers in a resource constrained situation: a holistic approach

Managing pressure ulcers remain a challenge and call for a multidisciplinary team approach to care. Even more daunting is the management of such patients in remote locations and in resource constrained situations. The management of pressure sores in a patient with progressive muscular atrophy has been discussed using resources that were locally available, accessible, and affordable. Community participation was encouraged. A holistic approach to care was adopted.     

Genome‐wide high‐resolution analysis of DNA copy number alterations in NF1‐associated malignant peripheral nerve sheath tumors using 32K BAC array

Neurofibromatosis Type I (NF1) is an autosomal dominant disorder characterized by the development of both benign and malignant tumors. The lifetime risk for developing a malignant peripheral nerve sheath tumor (MPNST) in NF1 patients is ～10% with poor survival rates. To date, the molecular basis of MPNST development remains unclear. Here, we report the first genome‐wide and high‐resolution analysis of DNA copy number alterations in MPNST using the 32K bacterial artificial chromosome microarray on a series of 24 MPNSTs and three neurofibroma samples. In the benign neurofibromas, apart from loss of one copy of the NF1 gene and copy number polymorphisms, no other changes were found. The profiles of malignant samples, however, revealed specific loss of chromosomal regions including 1p35‐33, 1p21, 9p21.3, 10q25, 11q22‐23, 17q11, and 20p12.2 as well as gain of 1q25, 3p26, 3q13, 5p12, 5q11.2‐q14, 5q21‐23, 5q31‐33, 6p23‐p21, 6p12, 6q15, 6q23‐q24, 7p22, 7p14‐p13, 7q21, 7q36, 8q22‐q24, 14q22, and 17q21‐q25. Copy number gains were more frequent than deletions in the MPNST samples (62% vs. 38%). The genes resident within common regions of gain were NEDL1 (7p14), AP3B1 (5q14.1), and CUL1 (7q36.1) and these were identified in >63% MPNSTs. The most frequently deleted locus encompassed CDKN2A, CDKN2B, and MTAP genes on 9p21.3 (33% cases). These genes have previously been implicated in other cancer conditions and therefore, should be considered for their therapeutic, prognostic, and diagnostic relevance in NF1 tumorigenesis. © 2009 Wiley‐Liss, Inc.     

Involvement of adipokines in rimonabant‐mediated insulin sensitivity in ob/ob mice

Objectives It has been recently reported that blockade of type 1 cannabinoid (CB1) receptors by specific antagonists or genetic manipulation alleviates dyslipidaemia, hyperglycaemia and insulin resistance in animal models of obesity and type 2 diabetes. However, the precise role of adipokines in the insulin‐sensitising effects of the CB1 antagonist rimonabant is not clear. Methods ob/ob mice were treated with different doses of rimonabant and then subjected to an oral glucose tolerance test. The expression of different adipokines in white adipose tissue was analysed by quantitative real‐time PCR. Key findings Rimonabant (30 mg/kg) significantly inhibited body weight and fat pad weight gain (P < 0.05) and improved glucose tolerance. Gene expression analysis indicated that tumour necrosis factor‐α, visfatin and retinol binding protein‐4 were downregulated in the adipose tissue of ob/ob mice treated with rimonabant compared with controls, whereas adiponectin was significantly upregulated. Conclusions Rimonabant‐mediated alteration of adipokines in white adipose tissues may play a role in improving insulin sensitivity in obese animals.     

Effects of rapid and slow potassium repolarization currents and calcium dynamics on hysteresis in restitution of action potential duration

We used a mathematical model to investigate effects of repolarizing currents I_kr and I_ks, calcium (Ca) current I_CaL, and Ca dynamics in network sarcoplasmic reticulum and junctional sarcoplasmic reticulum (JSR) on hysteresis in restitution of action potential duration. Enhanced I_kr increased slope of restitution, hysteresis loop thickness, and delay between peaks of diastolic intervals and action potential duration. Increase in I_ks decreased loop thickness and peak delay. Decrease in I_CaL had effects similar to increasing I_kr, except slope of restitution decreased markedly. Uptake of Ca into the network sarcoplasmic reticulum had less effect on hysteresis than transfer of Ca into JSR. Faster transfer of Ca into JSR markedly decreased loop thickness and peak delay. Our results provide insight into mechanisms responsible for this newly identified property of restitution. Such information will be valuable in studies where modification of hysteresis is used to investigate its role in arrhythmogenesis.     

Antibodies to periodontal organisms are associated with decreased kidney function. The Dental Atherosclerosis Risk In Communities study

BACKGROUND/AIMS: Increasing evidence suggests that clinical signs of periodontal disease are independently associated with renal impairment. However, no studies have examined the possible linkage of kidney disease with serum antibody to oral pathogens. METHODS: The periodontal disease status was assessed in an older community-dwelling population (Dental Atherosclerosis Risk in Communities) to include: clinical measurements; oral biofilm microbial composition by DNA checkerboard, and serum antibody immunoglobulin-gamma (IgG) titers to specific bacteria by immunocheckerboard. Baseline characteristics were used to compute estimated glomerular filtration rate defining eGFR <60 ml/min/1.73 m(2) as impaired renal function in 103 of 5,032 subjects. Levels of serum IgG to specific oral bacteria were categorized by quartiles (comparing upper vs. lower three) as high titer and GFR <60 as the dependent variable in logistic regression models, adjusting for multiple comparisons (Hotelling T(2)) and traditional risk factors including age, race, smoking, diabetes, hypertension, body mass, waist-to-hip ratio, serum triglycerides, HDL, and LDL cholesterol. RESULTS: High levels of serum IgG to selected periodontal pathogens including Porphyromonas gingivalis, Treponema denticola and Aggregobacter actinomycetemcomitans were associated with an increased odds for GFR <60 ml/min/1.73 m(2), adjusted odds ratio ranging from 1.6 to 1.8 and p < 0.05. CONCLUSIONS: Elevated IgG to periodontal pathogens is significantly associated with impaired kidney function, independent of traditional risk factors. Prospective studies are necessary to confirm these findings.