Diabetes and dental caries in US adults: an analysis of data from the National Health and Nutrition Examination Survey, 2011-2018.

OBJECTIVES: To determine the relationship between diabetes and dental caries among US adults participating in the 2011-2018 National Health and Nutrition Examination Survey (NHANES). BASIC RESEARCH DESIGN: The NHANES was a cross-sectional study including clinical assessments, laboratory analysis, and interviews. The sample included 16,635 participants aged 20 years and older that represent 187,596,215 individuals in the US in a probability weighted sample. Outcome variables included overall total caries score (or number of decayed, missing, filled permanent teeth - DMFT index) and the presence of caries. Bivariate analysis, Poisson regression for total caries score, logistic regression for the presence of caries were used for analysis. RESULTS: Controlling for covariates, multiple Poisson regression revealed that total DMFT scores were associated with diabetes status (adjusted relative risk ratio (RR)controlled diabetes = 1.13, RRuncontrolled diabetes = 1.18; p⟨0.001), no college education, female sex, white race, elderly (≥ 65 years), cigarette smoking, obesity, yearly dental visits, seeing a dentist only for treatment. Similarly, multiple logistic regression shows that the odds of adults with diabetes having dental caries were higher than among those without diabetes (adjusted risk ratio (OR)controlled diabetes = 1.84, ORuncontrolled diabetes = 1.87; p⟨0.05). CONCLUSIONS: Diabetes was associated with a higher caries score and a greater risk for dental caries among US adults.

Regulatory role of phosphoproteins in the development of bovine small intestine during early life.

The small intestine is the primary site of nutrient digestion and absorption, which plays a key role in the survival of neonatal calves. A comprehensive assessment of the phosphoproteomic changes in the small intestine of neonatal calves is unavailable; therefore, we used phosphopeptide enrichment coupled with liquid chromatography-tandem mass spectrometry to investigate the changes in the phosphoproteome profile in the bovine small intestine during the first 36 h of life. Twelve neonatal male calves were assigned to one of the following groups: (1) calves not fed colostrum and slaughtered approximately 2 h postpartum (n = 3), (2) calves fed colostrum at 1 to 2 h and slaughtered 8 h postpartum (n = 3), (3) calves fed 2 colostrum meals (at 1-2 and 10-12 h) and slaughtered 24 h postpartum (n = 3), (4) calves fed 3 colostrum meals (at 1-2, 10-12, and 22-24 h) and slaughtered 36 h postpartum (n = 3). Mid-duodenal, jejunal, and ileal samples of the calves were collected after slaughter. We identified 1,678 phosphoproteins with approximately 3,080 phosphosites, which were mainly Ser (89.9%), Thr (9.8%), and Tyr (0.3%) residues; they belonged to the prodirected (52.9%), basic (20.4%), acidic (16.6%), and Tyr-directed (1.7%) motif categories. The regional differentially expressed phosphoproteins included zonula occludens 2, sorting nexin 12, and protein kinase C, which are mainly associated with developmental processes, intracellular transport, vesicle-mediated transport, and immune system process. They are enriched in the endocytosis, tight junction, insulin signaling, and focal adhesion pathways. The temporal differentially expressed phosphoproteins included occludin, epsin 1, and bridging integrator 1, which were mainly associated with macromolecule metabolic process, cell adhesion, and growth. They were enriched in the spliceosomes, adherens junctions, and tight junctions. The observed changes in the phosphoproteins in the tissues of small intestine suggest the protein phosphorylation plays an important role in nutrient transport and immune response of calves during early life, which needs to be confirmed in a larger study.

Quantitative comparative phosphoproteomic analysis of the effects of colostrum and milk feeding on liver tissue of neonatal calves.

Posttranslational modifications, mostly phosphorylation, are critical for protein structure and function. However, the association between liver phosphoproteins in neonatal calves and colostrum intake is not well understood. In this study, we examined the liver phosphoproteome profile in neonatal calves after receiving colostrum or milk. Liver tissue samples were collected from control calves (CON, n = 3) 2 h after birth and from calves that received colostrum (CG, n = 3) or milk (MG, n = 3) 24 h after birth. Hepatic phosphoprotein expression profiles were analyzed using quantitative proteomics based on the liquid chromatography-tandem mass spectrometry method. In total, 1,587 phosphorylated sites were identified in 1,011 liver proteins. The most abundant phosphorylation site AA was serine (87.5%), followed by threonine (11.9%) and tyrosine (0.5%). Among the 1,011 phosphoproteins, 219, 453, and 26 displayed differential expression in the CG versus MG, CG versus CON, and MG versus CON comparisons, respectively. Differentially expressed phosphoproteins in the CG-MG comparison included 3-phosphoinositide-dependent protein kinase 1, glucose transporter member 4, protein kinase N2, and vinculin, which were mainly involved in the glycogen metabolic process, transport, growth and development, and cell adhesion process, according to Gene Ontology analysis. Pathway analysis indicated their enrichment in the insulin signaling pathway, spliceosome, and adherens junction. The CG-CON comparison identified differentially expressed phosphoproteins and their target genes that were largely involved in the cellular process, macromolecule metabolic process, developmental process, and transport. Pathway analysis indicated their association with endocytosis, mechanistic target of rapamycin, AMP-activated protein kinase, and insulin signaling pathways. These data demonstrate that changes in the phosphoproteins of liver tissues may play an important role in energy metabolism and immune response in the calves that received colostrum. These results provide novel insights into the crucial roles of protein phosphorylation during the early life of newborn calves.

Changes in expression of antimicrobial peptides and Fc receptors in the small intestines of neonatal calves during the passive immunity period.

The contribution of colostrum to passive immunity transfer and intestinal protection is well known; however, the effects of colostrum intake on the expression of antimicrobial peptides (AP) and Fc receptors in the intestine of neonatal calves are unclear. Our aim was to investigate changes in the expression of AP and Fc receptor in the small intestine of calves in the first 36 h postpartum. Twenty-four Holstein bull calves were used in this study, of which 18 calves were administered 3.2 L of pooled colostrum for each calf per meal via an esophageal tube. Calves were slaughtered at 8 h (1 meal at 1-2 h), 24 h (2 meals at 1-2 h and 10-12 h), and 36 h (3 meals at 1-2 h, 10-12 h, and 22-24 h) postpartum. The remaining 6 calves without any milk administration were slaughtered at 2 h postpartum. Samples of blood and jejunum digesta were collected to determine immunoglobulin concentration using ELISA. Samples of the duodenum, jejunum, and ileum tissues after slaughter were collected to determine AP and Fc receptor expression using quantitative real-time PCR. In calves administered colostrum, IgG concentration in jejunum digesta rapidly decreased in an age-dependent manner (33.41, 9.47, and 0.34 mg/mL at 8, 24, and 36 h, respectively), whereas serum IgG concentration increased significantly, from 0.25 µg/mL at 2 h to 21.72 mg/mL at 24 h. Cathelicidin-4, ß-defensin (DEFB)-7, and enteric ß-defensin expression was upregulated at 8 h postpartum in the duodenum and jejunum compared with that at 2 h, but progressive recovery was detected from 24 h onward. Higher expression of cathelicidin-4, regenerating family member 3γ, lysozyme (LYZ), LYZ1, and LYZ2 and lower expression of DEFB, DEFB1, DEFB7, DEFB10, and enteric ß-defensin were observed in the duodenum and jejunum compared with the ileum. Differences in AP expression between intestinal regions suggested that the innate immune defense mechanism varied significantly among the duodenum, jejunum, and ileum. No difference in the expression of Fc fragment of the IgG receptor was observed either among ages or small intestinal regions. The Fcγ receptor (FcγR)Ia and FcγRIIb expression was the highest at 8 h compared with that at 2, 24, and 36 h, and expression of FcγRIa, FcγRIIb, and FcγRIIIa was higher in the duodenum and jejunum than in the ileum. These results indicated that AP and Fcγ receptors might play important roles in intestinal defense during the passive immunity period.

Label-free quantitative proteomics analysis reveals the fate of colostrum proteins in the intestine of neonatal calves.

The contribution of intestinally absorbed colostral immunoglobulins to the transmission of passive immunity is widely reported in neonatal calves. However, changes in the colostral proteome in the gastrointestinal digesta remain unclear. Therefore, this study aimed to investigate changes in colostral proteome affected by gastrointestinal proteases in neonatal calves. Twenty-one neonatal Holstein calves were used in this study, including 18 colostrum-fed calves slaughtered at 8 (CI, n = 6), 24 (CII, n = 6), and 36 h (CIII, n = 6) postpartum and 3 milk-fed calves slaughtered 24 h postpartum (MI, n = 3). The ingested colostrum and milk samples were collected from the mid-jejunum segment, following the sacrifice. The undigested colostrum or milk along with their ingested colostrum or milk samples were investigated using a label-free proteomics approach. Hierarchical clustering and principal component analysis of the quantified proteins revealed that the ingested colostrum from the CII and CIII groups and the ingested mature milk from the MI group appeared to share similar patterns. Analysis of the intestinal digesta revealed a time-dependent decrease in caseins, lactoferrin, and osteopontin protein levels, and an increase in cationic trypsin, chymotrypsin, and carboxypeptidase. Several protease inhibitors, such as α-1-antiproteinase, α-2-antiplasmin, and early lactation protein, were identified in the colostrum and intestinal digesta. In addition, we detected identical levels in the intestinal digesta and colostrum for albumin, α-1-acid glycoprotein, and plasminogen. Pathway analysis indicated that proteins increased in the intestinal digesta belonged to the following categories: biosynthesis of antibiotics, carbon metabolism, and biosynthesis of amino acids. These results indicated that selected colostral proteins were digested by gastrointestinal proteases, contributing to their intestinal absorption in calves. These findings provide new insights into the fate of the colostral proteome in the gastrointestinal tract and may aid in the identification of factors contributing to health management in neonatal calves.

Alterations of the circular RNA profile in the jejunum of neonatal calves in response to colostrum and milk feeding.

Circular RNA (circRNA) have been suggested to contribute to regulating gene expression in various tissues and cells of eukaryotes. However, little is known regarding the expression pattern of circRNA and their potential function in the small intestine of neonatal calves that receive colostrum. In the current study, jejunum tissue samples were collected from control calves (2 h after birth; CT; n = 3) and neonatal calves that ingested colostrum (24 h after birth; CO; n = 3) or milk (24 h after birth; MK; n = 3) to compare the circRNA expression patterns using a high-throughput RNA sequencing approach. A total of 21,213, 17,861, and 21,737 circRNA were identified in the CT, CO, and MK groups, respectively. Only 13,254 of these circRNA were common to the 3 groups, suggesting high specificity of circRNA expression depending on nutrient type. In total, 243, 249, and 283 circRNA were differentially expressed in the CO versus CT, CO versus MK, and MK versus CT comparisons, respectively. Gene ontology analysis showed that the differentially expressed circRNA and their predicted or known target genes from the CO and MK groups were mainly involved in macromolecule metabolic process, response to stress, and vesicle-mediated transport. Moreover, pathway analysis showed that the Rap1 signaling pathway, focal adhesion, ubiquitin-mediated proteolysis, and extracellular matrix-receptor interaction were the most significantly enriched pathways. These data collectively indicate that circRNA are abundant and dynamically expressed when calves receive colostrum and act as microRNA sponges to regulate their target genes for jejunum function during the early development of newborn calves.

Changes in serum metabolites in response to ingested colostrum and milk in neonatal calves, measured by nuclear magnetic resonance-based metabolomics analysis.

Uptake of colostrum is of central importance for establishing a passive immunity transfer in neonatal calves. Studies of absorption and transmission of colostral immunoglobulins have been widely reported; however, changes in the serum in response to the absorption of colostral components in neonatal calves have not been completely characterized. Here, a nuclear magnetic resonance-based metabolomics approach was used to investigate the changes in metabolites in ingested colostrum, milk, and serum after neonatal calves were fed colostrum or milk. Twenty-seven neonatal male Holstein calves were assigned to 1 of the following groups: (1) calves not fed colostrum or milk and slaughtered approximately 2 h after birth (control group, n = 6), (2) calves fed colostrum at 1 to 2 h after birth and slaughtered 8 h after birth (n = 6), (3) calves fed 2 colostrum meals (at 1-2 and 10-12 h after birth) and slaughtered 24 h after birth (n = 6), (4) calves fed 3 colostrum meals (at 1-2, 10-12, and 22-24 h after birth) and slaughtered 36 h after birth (n = 6), or (5) calves fed 2 milk meals (1-2 and 10-12 h after birth) and slaughtered 24 h after birth (n = 3). Concentrations of valine, leucine, lactate, lysine, and isoleucine were higher and concentrations of lactose were lower in the groups fed colostrum and milk compared with groups not fed colostrum and milk, respectively. Metabolite changes between groups fed or not fed colostrum and milk were similar and may reflect the primary metabolic requirements of ingestion by the small intestine of neonatal calves. Concentrations of serum metabolites choline, valine, leucine, and glutamate were higher in the serum of calves that received colostrum compared with control calves. Furthermore, concentrations of serum phenylalanine, valine, and glutamate were significantly higher, whereas serum concentrations of citrate and very low density lipoproteins were lower in calves that received colostrum compared with calves fed milk. Our results indicate that concentrations of leucine, valine, and glutamate, which were higher in the calves that ingested colostrum, may transfer into the bloodstream, and that these metabolites are associated with health benefits in the neonatal calves that received colostrum. These findings provide novel information to help us understand the mechanism by which colostrum components are metabolized and absorbed in the small intestine and then transferred into bloodstream of neonatal calves.

A single nucleotide polymorphism in the promoter region (rs10877887) of let-7 is associated with hepatocellular carcinoma in a Chinese population.

Hepatocellular carcinoma (HCC) is a complex polygenic disease whose development is dependent on many genetic factors. The let-7 family, an important and widely studied microRNA family, has been shown to play an important role in the initiation and progression of HCC. In this study, we examined the possible associations between single-nucleotide polymorphisms in the promoter region of the let-7 family (rs10877887) and the susceptibility and prognosis of HCC, using a case-control research model. Eighty-nine HCC patients and 95 healthy controls were genotypes by direct sequencing, and the correlation between rs10877887 genotypes and HCC susceptibility was evaluated using an unconditional logistic regression model. Populations with the CT + CC genotype were at a significantly higher risk of HCC compared to those with the TT genotype (CT + CC vs TT: odds ratio = 3.52, 95% confidence interval = 1.90-6.52; P < 0.05). Furthermore, we discovered that the genetic variant of rs10877887 might serve as a prognostic marker for survival in HCC patients, as the CT + CC genotype was associated with poor prognosis.

Root coverage by coronally advanced flap with connective tissue graft and/or enamel matrix derivative: a meta-analysis.

BACKGROUND AND OBJECTIVE: Previous systematic reviews have reported that the use of a coronally advanced flap (CAF) combined with a connective tissue graft (CTG) or enamel matrix derivative (EMD) is more likely to achieve complete root coverage (CRC) than other modalities. However, the details of periodontal parameters and comparisons among a variety of combinations of CAF with CTG and/or EMD are left to be investigated. This study aimed to analyze the differences in periodontal parameters between these treatment modalities. MATERIAL AND METHODS: A literature search was performed using the Cochrane library and MEDLINE (PubMed) for studies focused on the treatment of gingival recession (Miller Class I, II and III) with CAF alone or combined with CTG, EMD or both up to December 2011. Randomized controlled clinical trials with a follow-up duration ≥ 6 mo were included. The outcome analysis included changes in periodontal probing depth (PPD), clinical attachment level, recession depth (RED) and keratinized tissue width (KTW). RESULTS: Thirteen randomized controlled clinical trials, including 529 Miller Class I-III defects from 321 patients were included. For an increase in KTW, CAF + CTG significantly improved more than CAF alone. CAF + EMD also gained more KTW than CAF alone. EMD reduced PPD, however, a significant difference was not found. Furthermore, the effects on changes of RED and clinical attachment level were not identified in the study. CONCLUSION: When combined with CAF, CTG contributed more in the increase of KTW, while EMD seemed helpful for wound healing by its potential in PPD reduction. However, further research is needed to clarify the effects on changes in RED and clinical attachment level.

Experimental test and life estimation of the OLED at normal working stress based on the luminance degradation model.

In order to accurately acquire the life time information for the organic light emitting diode (OLED), an experiment based on the normal stress life test was carried out to gain the data for the luminance degradation tests. The luminance degradation model of OLED was established based on the Weibull function and the least square method. Combined with luminance degradation data, Weibull parameters were estimated, the qualitative and the quantitative relationship between the initial luminance and the OLED life was obtained, and the life estimation of the product was achieved. Numerical results show that the test scheme is feasible, the luminance degradation model proves to be reliable for the OLED life estimation, and the fitting accuracy is very high by comparison with the test data fluctuation. Moreover, the real life time of the OLED is measured, which can verify the validity of the assumptions used in accelerated life test methods and provide manufacturers and customers with significant guidelines.

Study on constant-step stress accelerated life tests in white organic light-emitting diodes.

In order to obtain reliability information for a white organic light-emitting diode (OLED), two constant and one step stress tests were conducted with its working current increased. The Weibull function was applied to describe the OLED life distribution, and the maximum likelihood estimation (MLE) and its iterative flow chart were used to calculate shape and scale parameters. Furthermore, the accelerated life equation was determined using the least squares method, a Kolmogorov-Smirnov test was performed to assess if the white OLED life follows a Weibull distribution, and self-developed software was used to predict the average and the median lifetimes of the OLED. The numerical results indicate that white OLED life conforms to a Weibull distribution, and that the accelerated life equation completely satisfies the inverse power law. The estimated life of a white OLED may provide significant guidelines for its manufacturers and customers.

Urinary microRNAs miR-15b and miR-30a as novel noninvasive biomarkers for gentamicin-induced acute kidney injury.

MicroRNAs serve as potential biomarkers in various pathological models, and are stable and detectable in biofluids. We investigated the urinary microRNA expression profile in a gentamicin-induced acute kidney injury canine model using RNA sequencing. A total of 234 differentially expressed microRNAs were screened after 12 consecutive days of gentamicin administration (P < 0.05). Six candidate microRNAs (miR-15b, -15b-3p, -16, -30a, -30a-3p, and -30c-2-3p) were selected according to a set criterion, and validated by real-time quantitative PCR. The diagnostic values of these six candidate microRNAs were better than the traditional serum biomarkers (all P < 0.05). Further, using receiver operating characteristic curve analysis, we found that miR-15b and -15b-3p were superior to urinary kidney injury molecule-1 (both P < 0.05). Moreover, miR-15b and -30a levels in the urine samples significantly correlated with their respective levels in the kidney tissue samples (r=0.512 and 0.505, respectively, both P < 0.05). Our data concluded that miR-15b and -30a may be promising biomarkers for renal toxicity.

Chronic subdural hematoma management: clarifying the definitions of outcome measures to better understand treatment efficacy - a systematic review and meta-analysis.

OBJECTIVE: A long history of inconsistencies in the definitions of the outcome measures for chronic subdural hematomas (CSDHs) has contributed to the controversy over the optimal surgical strategy for CSDH treatment. Clarifying these definitions, reassess the available data, and systematically review the prior literature may provide better insight into the differences in treatment efficacy for CSDH. MATERIALS AND METHODS: The clinical course of CSDH was described with a series of strictly defined outcome measures. PubMed, Cochrane Library, and ScienceDirect databases were searched for comparative studies of two main surgical techniques for CSDH, including burr hole craniotomy (BHC) and twist drill craniotomy (TDC). Data were collected with uniform criteria and analyzed using a random-effects model to estimate the mortality, recurrence, operative failure, and cure rates of each treatment. RESULTS: Twelve comparative studies that examined 2,027 CSDH patients were included. The analysis results indicated that TDC and BHC treatments were similar in the mortality rates (RR, 1.25; 95% CI, 0.83-1.87; I2 = 0%; p = 0.28) and the recurrence rates (RR, 1.29; 95% CI, 0.87-1.92; I2 = 13%; p = 0.21) for CSDH patients. However, TDC had a significantly higher operative failure rate compared with BHC (RR, 0.35; 95% CI, 0.15-0.83; I2 = 0%; p = 0.02), whereas patients treated by a TDC approach tended to achieve higher cure rates compared with BHC (RR, 0.92; 95% CI, 0.86-0.99; I2 = 55%; p = 0.02). CONCLUSIONS: The clarification of the definitions related to CSDH outcome facilitates the interpretation of differences in treatment efficacy. The TDC approach manifested a significantly higher operative failure rate compared with the BHC approach; however, TDC showed a tendency in achieving a long-term neurologic cure.

Digital replantation. A ten-year retrospective study.

Eight hundred and two digits (592 complete amputation and 210 incomplete amputations) of 549 patients were replanted. The male to female ratio was 3:1 and the age range 1-63 years. 728 digits survived and 74 digits failed. The overall survival rate was 90.8%. Special varieties of complicated amputation were encountered in this series: (1) distal segment replantation, 139 digits, 131 digits (94%) survived; (2) digital replantation of children, 45 cases, 78 digits, average age 3.8 years, the youngest being 1 year old, 68 digits survived (88.7%); (3) rotational avulsion amputation of thumb, 26 digits, 23 digits (88.4%) survived; (4) bilateral digit amputation, 8 cases, 44 digits amputated, 38 digits replanted, including 9 digits of a ten-digit guillotined case. All the digits were salvaged. We conclude that thorough debridement, meticulous anastomosis of blood vessels and timely management of vascular crisis are keys to high survival rate, while judicious selection of indication, proper internal fixation of bone, anastomosis of as many blood vessels as possible, attentive repair of nerves and tendons, sound rehabilitation program are important measures in improving postoperative function.

[Toe-to-hand transfer in thumb and finger reconstruction in 6 cases without a dorsalis pedis].

Absence of dorsalis pedis artery in 6 feet of 6 patients was found in 160 feet of 148 cases operated upon for toe-to-hand transfer, rating 3.8%. In such a transfer, the first dorsal metatarsal artery, or the first plantar metatarsal artery, if the former was also absent, which was always larger than usual, was dissected out and cut off at its origin. Being the nutrient vessel for the transfer, it was anastomosed to the distal segment of the radial artery at or beyond the anatomic snuffbox. Otherwise, vein grafting was done to bridge the gap in between, or direct anastomosis of the common digital arteries of the toe with that of the thumb or finger (s) might be carried out. In case necessary for 2 or more toe-units, the first dorsal metatarsal and the first plantar metatarsal arteries were anastomosed to radial artery in a paralleled fashion to feed the transplants with one recipient artery. The operations were success in 5 patients and failed in 1. The technical detail and the benefits of this method are discussed.

[Thumb and finger reconstruction by anastomosing the digital arteries of the toe to finger transplant].

In a series of 295 cases of toe-to-finger reconstruction, 30 cases with 40 digits were reconstructed by arterial anastomosis between digital arteries of the toe transplant and the recipient thumb or fingertoe. Among them 5 thumbs were reconstructed by the distal segment of the big toe. 11 thumbs (10 cases), 15 fingers (8 cases) and 1 case with concomitant thumb and 3 fingers were reconstructed by toe transfer. Six cases of thumb pulp defect were also reconstructed by the big toe pulp transfer. The anastomosis of digital arteries instead of dorsalis pedis artery and radial artery and saphenous vein with cephali vein to re-establish circulation is an innovation and has the advantages of simplifying the operative procedure, minimizing operative trauma, reducing operation time, attenuating patients suffering, and obtaining good appearance and function after reconstruction. Besides the operation would not be hindered by anatomical variations of the artery and would reduce blood supply disturbance of the donor foot.

Heroin abuse accelerates biological aging: a novel insight from telomerase and brain imaging interaction.

Heroin abuse and natural aging exert common influences on immunological cell functioning. This observation led to a recent and untested idea that aging may be accelerated in abusers of heroin. We examined this claim by testing whether heroin use is associated with premature aging at both cellular and brain system levels. A group of abstinent heroin users (n=33) and matched healthy controls (n=30) were recruited and measured on various biological indicators of aging. These measures included peripheral blood telomerase activity, which reflects cellular aging, and both structural and functional measures of brain magnetic resonance imaging. We found that heroin users were characterized by significantly low telomerase activity (0.21 vs 1.78; 88% reduction; t(61)=6.96, P<0.001; 95% confidence interval=1.12-2.02), which interacted with heroin use to affect the structural integrity of gray and white matter of the prefrontal cortex (PFC; AlphaSim corrected P<0.05), a key brain region implicated in aging. Using the PFC location identified from the structural analyses as a 'seed' region, it was further revealed that telomerase activity interacted with heroin use to impact age-sensitive brain functional networks (AlphaSim corrected P<0.05), which correlated with behavioral performance on executive functioning, memory and attentional control (Pearson correlation, all P<0.05). To our knowledge, this study is the first to attempt a direct integration of peripheral molecular, brain system and behavioral measures in the context of substance abuse. The present finding that heroin abuse is associated with accelerated aging at both cellular and brain system levels is novel and forms a unique contribution to our knowledge in how the biological processes of drug abusers may be disrupted.