Chronic tobacco smoking and neuropsychological impairments:A systematic review and meta-analysis

The link between neuropsychological impairments and chronic tobacco smoking is not clear and in the current literature there is a lack of robust analyses investigating this association. A systematic review of the literature was conducted in order to identify relevant longitudinal and cross-sectional studies conducted from 1946 to 2017. A meta-analysis was performed from 24 studies testing the performance of chronic tobacco smokers compared with non-smokers on neuropsychological tests related to eight different neuropsychological domains. The results revealed a cross-sectional association between neuropsychological impairments and chronic tobacco smoking in cognitive impulsivity, non-planning impulsivity, attention, intelligence, short term memory, long term memory, and cognitive flexibility, with the largest effect size being related to cognitive impulsivity (SDM = 0.881, p <0.005), and the smallest effect size being related to intelligence (SDM = 0.164, p < 0.05) according to Cohen’s benchmark criteria. No association was found between chronic smoking and motor impulsivity (SDM = 0.105, p = 0.248). Future research is needed to investigate further this association by focusing on better methodologies and alternative methods for nicotine administration.PostprintPeer reviewe

Multifaceted impairments in impulsivity and brain structural abnormalities in opioid dependence and abstinence

This study was part funded by an unrestricted educational grant provided by Schering-Plough, a grant by an anonymous trust and the Scottish Mental Health Research Network.Background: Chronic opioid exposure, as a treatment for a variety of disorders or as drug of misuse, is common worldwide, but behavioural and brain abnormalities remain under-investigated. Only a small percentage of patients who receive methadone maintenance treatment (MMT) for previous heroin misuse eventually achieve abstinence and studies on such patients are rare. Method: The Cambridge Neuropsychological Test Automated Battery and T1 weighted magnetic resonance imaging (MRI) were used to study a cohort of 122 male individuals: a clinically stable opioid-dependent patient group receiving MMT (n = 48), an abstinent previously MMT maintained group (ABS) (n = 24) and healthy controls (n = 50). Results: Stable MMT participants deliberated longer and placed higher bets earlier in the Cambridge Gambling Task (CGT) and showed impaired strategic planning compared with healthy controls. In contrast, ABS participants showed impairment in choosing the least likely outcome, delay aversion and risk adjustment on the CGT, and exhibited non-planning impulsivity compared with controls. MMT patients had widespread grey matter reductions in the orbitomedial prefrontal cortex, caudate, putamen and globus pallidus. In contrast, ABS participants showed midbrain–thalamic grey matter reductions. A higher methadone dose at the time of scanning was associated with a smaller globus pallidus in the MMT group. Conclusions: Our findings support an interpretation of heightened impulsivity in patients receiving MMT. Widespread structural brain abnormalities in the MMT group and reduced brain structural abnormality with abstinence suggest benefit of cessation of methadone intake. We suggest that a longitudinal study is required to determine whether abstinence improves abnormalities, or patients who achieve abstinence have reduced abnormalities before methadone cessation.Publisher PDFPeer reviewe

Statistical Mechanics of Semiflexible Bundles of Wormlike Polymer Chains

We demonstrate that a semiflexible bundle of wormlike chains exhibits a state-dependent bending stiffness that alters fundamentally its scaling behavior with respect to the standard wormlike chain. We explore the equilibrium conformational and mechanical behavior of wormlike bundles in isolation, in crosslinked networks, and in solution.Comment: 4 pages, 3 figures, final version as publishe

Structure and mechanics of supporting cells in the guinea pig organ of Corti.

The mechanical properties of the mammalian organ of Corti determine its sensitivity to sound frequency and intensity, and the structure of supporting cells changes progressively with frequency along the cochlea. From the apex (low frequency) to the base (high frequency) of the guinea pig cochlea inner pillar cells decrease in length incrementally from 75-55 µm whilst the number of axial microtubules increases from 1,300-2,100. The respective values for outer pillar cells are 120-65 µm and 1,500-3,000. This correlates with a progressive decrease in the length of the outer hair cells from >100 µm to 20 µm. Deiters'cell bodies vary from 60-50 µm long with relatively little change in microtubule number. Their phalangeal processes reflect the lengths of outer hair cells but their microtubule numbers do not change systematically. Correlations between cell length, microtubule number and cochlear location are poor below 1 kHz. Cell stiffness was estimated from direct mechanical measurements made previously from isolated inner and outer pillar cells. We estimate that between 200 Hz and 20 kHz axial stiffness, bending stiffness and buckling limits increase, respectively,~3, 6 and 4 fold for outer pillar cells, ~2, 3 and 2.5 fold for inner pillar cells and ~7, 20 and 24 fold for the phalangeal processes of Deiters'cells. There was little change in the Deiters'cell bodies for any parameter. Compensating for effective cell length the pillar cells are likely to be considerably stiffer than Deiters'cells with buckling limits 10-40 times greater. These data show a clear relationship between cell mechanics and frequency. However, measurements from single cells alone are insufficient and they must be combined with more accurate details of how the multicellular architecture influences the mechanical properties of the whole organ

t(15;21) translocations leading to the concurrent downregulation of RUNX1 and its transcription factor partner genes SIN3A and TCF12 in myeloid disorders.

Through a combined approach integrating RNA-Seq, SNP-array, FISH and PCR techniques, we identified two novel t(15;21) translocations leading to the inactivation of RUNX1 and its partners SIN3A and TCF12. One is a complex t(15;21)(q24;q22), with both breakpoints mapped at the nucleotide level, joining RUNX1 to SIN3A and UBL7-AS1 in a patient with myelodysplasia. The other is a recurrent t(15;21)(q21;q22), juxtaposing RUNX1 and TCF12, with an opposite transcriptional orientation, in three myeloid leukemia cases. Since our transcriptome analysis indicated a significant number of differentially expressed genes associated with both translocations, we speculate an important pathogenetic role for these alterations involving RUNX1

Postdischarge antibiotic use for prophylaxis following spinal fusion

OBJECTIVE: Despite recommendations to discontinue prophylactic antibiotics after incision closure or \u3c24 hours after surgery, prophylactic antibiotics are continued after discharge by some clinicians. The objective of this study was to determine the prevalence and factors associated with postdischarge prophylactic antibiotic use after spinal fusion. DESIGN: Multicenter retrospective cohort study. PATIENTS: This study included patients aged ≥18 years undergoing spinal fusion or refusion between July 2011 and June 2015 at 3 sites. Patients with an infection during the surgical admission were excluded. METHODS: Prophylactic antibiotics were identified at discharge. Factors associated with postdischarge prophylactic antibiotic use were identified using hierarchical generalized linear models. RESULTS: In total, 8,652 spinal fusion admissions were included. Antibiotics were prescribed at discharge in 289 admissions (3.3%). The most commonly prescribed antibiotics were trimethoprim/sulfamethoxazole (22.1%), cephalexin (18.8%), and ciprofloxacin (17.1%). Adjusted for study site, significant factors associated with prophylactic discharge antibiotics included American Society of Anesthesiologists (ASA) class ≥3 (odds ratio [OR], 1.31; 95% CI, 1.00-1.70), lymphoma (OR, 2.57; 95% CI, 1.11-5.98), solid tumor (OR, 3.63; 95% CI, 1.62-8.14), morbid obesity (OR, 1.64; 95% CI, 1.09-2.47), paralysis (OR, 2.38; 95% CI, 1.30-4.37), hematoma/seroma (OR, 2.93; 95% CI, 1.17-7.33), thoracic surgery (OR, 1.39; 95% CI, 1.01-1.93), longer length of stay, and intraoperative antibiotics. CONCLUSIONS: Postdischarge prophylactic antibiotics were uncommon after spinal fusion. Patient and perioperative factors were associated with continuation of prophylactic antibiotics after hospital discharge

Surgeon choice in the use of postdischarge antibiotics for prophylaxis following mastectomy with and without breast reconstruction

Multiple guidelines recommend discontinuation of prophylactic antibiotics \u3c24 hours after surgery. In a multicenter, retrospective cohort of 2,954 mastectomy patients ± immediate breast reconstruction, we found that utilization of prophylactic postdischarge antibiotics varied dramatically at the surgeon level among general surgeons and was virtually universal among plastic surgeons

Next-generation sequencing approach to hyperCKemia: A 2-year cohort study

ObjectiveNext-generation sequencing (NGS) was applied in molecularly undiagnosed asymptomatic or paucisymptomatic hyperCKemia to investigate whether this technique might allow detection of the genetic basis of the condition.MethodsSixty-six patients with undiagnosed asymptomatic or paucisymptomatic hyperCKemia, referred to tertiary neuromuscular centers over an approximately 2-year period, were analyzed using a customized, targeted sequencing panel able to investigate the coding exons and flanking intronic regions of 78 genes associated with limb-girdle muscular dystrophies, rhabdomyolysis, and metabolic and distal myopathies.ResultsA molecular diagnosis was reached in 33 cases, corresponding to a positive diagnostic yield of 50%. Variants of unknown significance were found in 17 patients (26%), whereas 16 cases (24%) remained molecularly undefined. The major features of the diagnosed cases were mild proximal muscle weakness (found in 27%) and myalgia (in 24%). Fourteen patients with a molecular diagnosis and mild myopathic features on muscle biopsy remained asymptomatic at a 24-month follow-up.ConclusionsThis study of patients with undiagnosed hyperCKemia, highlighting the advantages of NGS used as a first-tier diagnostic approach in genetically heterogeneous conditions, illustrates the ongoing evolution of molecular diagnosis in the field of clinical neurology. Isolated hyperCKemia can be the sole feature alerting to a progressive muscular disorder requiring careful surveillance