bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential anti‐cancer effect of curcumin in human lung squamous cell carcinoma
Authors: Zhao Wei , Wang Yan , Wang Ying , Gao Nan , Han Zhifeng , Yu Haixiang
Published: January 2015

Background

To explore the molecular mechanisms of the anti‐cancer effect of curcumin in human lung squamous cell carcinoma (LSQCC) SK‐MES‐1 cells.

Methods

Cell viability was determined using MTT assay. Ribonucleic acid sequencing was performed to measure expression levels of transcripts in LSQCC cells treated with 15 μmol/L curcumin (treatment groups) or an equal amount of dimethylsulfoxide (control). Cuffdiff software was used to identify differentially expressed genes (DEGs) in treatment groups, followed by enrichment analysis of DEGs using the Database for Annotation, Visualization and Integration Discovery. The protein‐protein interaction (PPI) networks for up and downregulated DEGs were constructed by Cytoscape software using Search Tool for the Retrieval of Interacting Genes data to identify hub nodes.

Results

Curcumin significantly reduced cell viability in LSQCC cells. In total, 380 DEGs including 154 upregulated and 126 downregulated genes were found in the treatment groups. The upregulated genes were enriched in base excision repair (BER, such as PCNA, POLL, and MUTYH) and Janus kinase‐signal transducer and activator of transcription (JAT‐STAT) signaling pathways (such as AKT1 and STAT5A), while the downregulated genes were enriched in nine pathways, including the vascular endothelial growth factor (VEGF) signaling pathway (such as PTK2, VEGFA, MAPK1, and MAPK14) and mitogen‐activated protein kinase (MAPK) signaling pathway (ARRB2, MAPK1, MAPK14, and NFKB1). PCNA and AKT1 were the hub nodes in the PPI network of upregulated genes while MAPK1, MAPK14, VEGFA, and NFKB1 were the hub nodes in the PPI network of downregulated genes.

Conclusions

Curcumin might exert anti‐cancer effects on LSQCC via regulating BER, JAT‐STAT, VEGF, and MAPK signaling pathways.
Survival predictors after resection of lung metastases of head or neck cancers
Authors: Yotsukura Masaya , Kinoshita Tomonari , Kohno Mitsutomo , Asakura Keisuke , Kamiyama Ikuo , Emoto Katsura , Hayashi Yuichiro , Ohtsuka Takashi
Published: January 2015

Background

Pulmonary metastasectomies are performed for a variety of cancers, though few reports have examined their merit for head and neck cancers. This study examined the relationship between clinical and pathological characteristics and survival after resection of lung metastases of these cancers.

Methods

Between 1986 and 2013, 34 patients presenting with pulmonary metastases of primary head or neck cancers underwent surgical resections at our institution. We retrospectively analyzed their clinical and pathological characteristics and the patients' survival after metastasectomy in search of adverse prognostic factors.

Results

The primary sites of cancer were: the tongue in eight patients, the pharynx and salivary glands each in seven, the larynx in five, and miscellaneous sites in seven patients. Squamous cell carcinoma (SCC) was present in 19, adenoid cystic carcinomas in 10, and other diagnoses in five patients. The median disease‐free interval (DFI) between the initial surgery and the metastasectomies was 40 months. The overall five‐year survival rate was 57.9%, and median survival time was 77 months. By single variable analysis, a DFI of ≤26 months, age ≥60 years, and histology of SCC were predictors; by multiple variable analysis, a short DFI (P = 0.018) and older age (P = 0.046) remained independent predictors of poor clinical outcomes.

Conclusions

Young age and a long DFI are factors in favor of pulmonary metastasectomy after surgical treatment of primary head or neck cancers.
Nicotine Enhances the Locomotor Stimulating but Not the Conditioned Rewarding Effect of Ethanol in DBA/2J Mice
Authors: Gubner Noah R. , Cunningham Christopher L. , Phillips Tamara J.
Published: January 2015

Background

One hypothesis to explain the high rate of nicotine and alcohol (ethanol [EtOH]) co‐abuse is that these drugs have enhanced rewarding effects when taken together. The goal of this work was to use the conditioned place preference (CPP) procedure to determine whether nicotine would enhance the development of EtOH‐induced CPP.

Methods

The conditioned rewarding effects of nicotine (1 or 2 mg/kg of nicotine tartrate), EtOH (1 g/kg), and nicotine plus EtOH in combination were assessed using a well‐established CPP procedure chosen specifically for examining alterations in the development of EtOH‐induced CPP by nicotine. In addition, the reference dose procedure was used to directly compare the conditioned rewarding effect of EtOH versus nicotine plus EtOH. DBA/2J mice were used because they are an inbred strain that has repeatedly been shown to develop CPP to EtOH.

Results

Neither dose of nicotine alone produced CPP, whereas EtOH did, using the standard EtOH CPP procedure. The magnitude of EtOH‐induced CPP was not affected by co‐administration of 1 mg/kg nicotine, but 2 mg/kg nicotine interfered with the development of EtOH‐induced CPP. Using the reference dose procedure, there was no significant preference or aversion for either nicotine + EtOH dose combination versus EtOH alone. However, combined nicotine and EtOH had a larger effect on locomotor activity, during the conditioning trials, compared to their additive effect when given alone, consistent with previous data.

Conclusions

These data do not support the hypothesis that nicotine enhances the conditioned rewarding effect of EtOH. This finding differs from the combined locomotor stimulant effects of nicotine and EtOH that were observed in this study and in our previously published work, and suggests that combined stimulant effects of nicotine and EtOH do not predict enhanced reward.
The Use of Alcohol Use Disorders Identification Test (AUDIT) in Detecting Alcohol Use Disorder and Risk Drinking in the General Population: Validation of AUDIT Using Schedules for Clinical Assessment in Neuropsychiatry
Authors: Lundin Andreas , Hallgren Mats , Balliu Natalja , Forsell Yvonne
Published: January 2015

Background

The Alcohol Use Disorders Identification Test (AUDIT) and AUDIT‐Consumption (AUDIT‐C) are commonly used in population surveys but there are few validations studies in the general population. Validity should be estimated in samples close to the targeted population and setting. This study aims to validate AUDIT and AUDIT‐C in a general population sample (PART) in Stockholm, Sweden.

Methods

We used a general population subsample age 20 to 64 that answered a postal questionnaire including AUDIT who later participated in a psychiatric interview (n = 1,093). Interviews using Schedules for Clinical Assessment in Neuropsychiatry was used as criterion standard. Diagnoses were set according to the fourth version of the Diagnostic and Statistical Manual of Mental Disorders (DSM‐IV). Agreement between the diagnostic test and criterion standard was measured with area under the receiver operator characteristics curve (AUC).

Results

A total of 1,086 (450 men and 636 women) of the interview participants completed AUDIT. There were 96 individuals with DSM‐IV‐alcohol dependence, 36 DSM‐IV‐Alcohol Abuse, and 153 Risk drinkers. AUCs were for DSM‐IV‐alcohol use disorder 0.90 (AUDIT‐C 0.85); DSM‐IV‐dependence 0.94 (AUDIT‐C 0.89); risk drinking 0.80 (AUDIT‐C 0.80); and any criterion 0.87 (AUDIT‐C 0.84).

Conclusions

In this general population sample, AUDIT and AUDIT‐C performed outstanding or excellent in identifying dependency, risk drinking, alcohol use disorder, any disorder, or risk drinking.
Worsening of Health and a Cessation or Reduction in Alcohol Consumption to Special Occasion Drinking Across Three Decades of the Life Course
Authors: Ng Fat Linda , Cable Noriko , Shelton Nicola
Published: January 2015

Background

Ex‐drinkers suffer from worse health than drinkers; however, whether a worsening of health is associated with a change in drinking status from early adulthood has not been previously investigated. We assess whether a worsening of health is associated with a cessation in consumption or reduction to special occasion drinking from early adulthood to middle age.

Methods

Multinomial logistic regression assessing whether a change in self‐reported limiting longstanding illness (LLI) was associated with ceasing alcohol consumption, or a reduction to special occasion drinking compared with being a persistent drinker from age 23 in separate models at ages 33, 42, and 50. All models adjusted for sex, poor psychosocial health, education, marital status, and children in the household. Sample included participants from Great Britain followed longitudinally in the National Child Development Study from ages 23 to 33 (N = 5,529), 42 (N = 4,787), and 50 (N = 4,476).

Results

Developing an LLI from the previous wave was associated with ceasing alcohol consumption at ages 33 (odds ratio [ORs] = 2.71, 95% confidence interval [CI] = 1.16–4.93), 42 (OR = 2.44, 95%CI = 1.24–4.81), and 50 (OR = 3.33, 95%CI = 1.56–7.12) and a reduction to special occasion drinking at ages 42 (OR = 2.04, 95%CI = 1.40–2.99) and 50 (OR = 2.04, 95%CI = 1.18–3.53). Having a persistent LLI across 2 waves increased the odds of ceasing consumption at ages 42 (OR = 3.22, 95%CI = 1.06–9.77) and 50 (OR = 4.03, 95%CI = 1.72–9.44) and reducing consumption to special occasion drinking at ages 33 (OR = 3.27, 95%CI = 1.34–8.01) and 42 (OR = 2.25, 95%CI = 1.23–4.50). Persistent drinkers at older ages had the best overall health suffering less from previous poor health compared with those who reduced or ceased consumption at an earlier time point.

Conclusions

Developing an LLI was associated with a cessation in alcohol consumption and a reduction in consumption to special occasion drinking from early adulthood. Persistent drinkers who drank at least till 50 were the healthiest overall. Health selection is likely to influence nondrinking across the life course.
Alcohol Intoxication Following Muscle Contraction in Mice Decreases Muscle Protein Synthesis But Not mTOR Signal Transduction
Authors: Steiner Jennifer L. , Lang Charles H.
Published: January 2015

Background

Alcohol (ethanol [EtOH]) intoxication antagonizes stimulation of muscle protein synthesis and mammalian target of rapamycin (mTOR) signaling. However, whether the anabolic response can be reversed when alcohol is consumed after the stimulus is unknown.

Methods

A single bout of electrically stimulated muscle contractions (10 sets of 6 contractions) was induced in fasted male C57BL/6 mice 2 hours prior to alcohol intoxication. EtOH was injected intraperitoneally (3 g/kg), and the gastrocnemius/plantaris muscle complex was collected 2 hours later from the stimulated and contralateral unstimulated control leg.

Results

Muscle contraction increased protein synthesis 28% in control mice, while EtOH abolished this stimulation‐induced increase. Further, EtOH suppressed the rate of synthesis ~75% compared to control muscle irrespective of stimulation. This decrease was associated with impaired protein elongation as EtOH increased the phosphorylation of eEF2 Thr56. In contrast, stimulation‐induced increases in mTOR protein complex‐1 (mTORC1) (S6K1 Thr421/Ser424, S6K1 Thr389, rpS6 Ser240/244, and 4E‐BP1 Thr37/46) and mitogen‐activated protein kinase (MAPK) (JNK Thr183/Tyr185, p38 Thr180/Tyr182, and rpS6S235/236) signaling were not reversed by acute EtOH.

Conclusions

These data suggest that EtOH‐induced decreases in protein synthesis in fasted mice may be independent of mTORC1 and MAPK signaling following muscle contraction and instead due to the antagonistic actions of EtOH on mRNA translation elongation. Therefore, EtOH suppresses the contraction‐induced increase in protein synthesis, and over time has the potential to prevent skeletal muscle hypertrophy induced by repeated muscle contraction.
Mediation of Cognitive Bias Modification for Alcohol Addiction via Stimulus‐Specific Alcohol Avoidance Association
Authors: Gladwin Thomas E. , Rinck Mike , Eberl Carolin , Becker Eni S. , Lindenmeyer Johannes , Wiers Reinout W.
Published: January 2015

Background

Cognitive bias modification (CBM) studies have provided evidence that cognitive biases play a causal role in alcohol use disorders. In this study, data from a CBM experiment in alcoholic patients were re‐analyzed. In the original study, no mediation by associations measured with an Implicit Association Test (IAT) was found. In this study, we explored the possibility that relevant alcohol‐related automatic processes may be cue‐specific.

Methods

Data from a previous clinical study in a sample of 214 alcohol‐addicted patients were re‐analyzed. Patients were assigned to a CBM intervention or control condition, performed an alcohol–approach IAT, and were followed up for relapse data a year after training. In this study, bias scores measured via the IAT were calculated and analyzed separately for different stimulus categories: Alcohol, Soft drink, Approach, and Avoid.

Results

Training reversed the alcohol–approach bias for all categories. This reversal of bias also predicted reduced relapse, but involved a complex stimulus category‐dependent pattern in which an avoidance bias for Alcohol stimuli was most predictive of reduced relapse.

Conclusions

The results contribute to evidence that CBM indeed affects relapse probability via changes in automatic processes, although future study is needed to determine the precise nature of mediating processes. Automatic processes underlying alcohol‐related associations may be stimulus‐specific, which may be important for the methods of future studies involving implicit measures.
Ethanol Intake Under Social Circumstances or Alone inSprague–Dawley Rats: Impact of Age, Sex, Social Activity, and Social Anxiety‐Like Behavior
Authors: Varlinskaya Elena I. , Truxell Eric M. , Spear Linda P.
Published: January 2015

Background

In human adolescents, heavy drinking is often predicted by high sociability in males and high social anxiety in females. This study assessed the impact of baseline levels of social activity and social anxiety‐like behavior in group‐housed adolescent and adult male and femaleSprague–Dawley rats on ethanol (EtOH) intake when drinking alone or in a social group.

Methods

Social activity and anxiety‐like behavior initially were assessed in a modified social interaction test, followed by 6 drinking sessions that occurred every other day in animals given ad libitum food and water. Sessions consisted of 30‐minute access to 10%EtOHin a “supersac” (3% sucrose + 0.1% saccharin) solution given alone as well as in groups of 5 same‐sex littermates, with order of the alternating session types counterbalanced across animals.

Results

Adolescent males and adults of both sexes overall consumed moreEtOHunder social than alone circumstances, whereas adolescent females ingested moreEtOHwhen alone. Highly socially active adolescent males demonstrated elevated levels ofEtOHintake relative to their low and medium socially active counterparts when drinking in groups, but not when tested alone. Adolescent females with high levels of social anxiety‐like behavior demonstrated the highestEtOHintake under social, but not alone circumstances. Among adults, baseline levels of social anxiety‐like behavior did not contribute to individual differences inEtOHintake in either sex.

Conclusions

The results clearly demonstrate that in adolescent rats, but not their adult counterparts, responsiveness to a social peer predictsEtOHintake in a social setting—circumstances under which drinking typically occurs in human adolescents. High levels of social activity in males and high levels of social anxiety‐like behavior in females were associated with elevated social drinking, suggesting that males ingestEtOHfor its socially enhancing properties, whereas females ingestEtOHfor its socially anxiolytic effects.
Social Network Moderators of Naltrexone and Behavioral Treatment Effects on Heavy Drinking in the COMBINE Study
Authors: Worley Matthew J. , Witkiewitz Katie , Brown Sandra A. , Kivlahan Daniel R. , Longabaugh Richard
Published: January 2015

Background

Oral naltrexone is an efficacious medication for treatment of alcohol dependence, but small effect sizes and variability in outcomes suggest the presence of person‐level moderators of naltrexone response. Identification of contextual or psychosocial moderators may assist in guiding clinical recommendations. Given the established importance of social networks in drinking outcomes, as well as the potential effects of naltrexone in reducing cue reactivity which may be especially important among those with more heavy drinkers and more alcohol cues in their networks, we examined pretreatment social network variables as potential moderators of naltrexone treatment effects in the COMBINE study.

Methods

The sample included all COMBINE study participants in medication conditions with full data on the Important People Inventory (IPI) and covariates at intake (N = 1,197). The intake IPI assessed whether participants had any frequent drinkers in their network and the average frequency of contact with these drinkers. The effects of treatment condition, pretreatment network variables, and their interactions on percent heavy drinking days were tested in hierarchical linear models, controlling for demographics and baseline clinical covariates.

Results

In treatment conditions involving medical management and combined behavioral intervention (CBI), the effects of active naltrexone on heavy drinking were significantly greater for individuals with frequent drinkers in their network (z = −2.66, p < 0.01) and greater frequency of contact with those drinkers (z = −3.19, p < 0.01). These network variables did not moderate the effects of active naltrexone without CBI.

Conclusions

When delivered in conjunction with behavioral interventions, naltrexone can be more potent for alcohol‐dependent adults who have greater contact with frequent drinkers prior to treatment, which may indicate patterns of environmental exposure to alcohol. Contextual, social risk factors are a potential avenue to guide personalized treatment of alcohol dependence.
Apoptotic Cell Death and Temporal Expression of Apoptotic Proteins Bcl‐2 and Bax in the Hippocampus, Following Binge Ethanol in the Neonatal Rat Model
Authors: Smith Caine C. , Guévremont Diane , Williams Joanna M. , Napper Ruth M. A.
Published: January 2015

Background

Binge‐like ethanol (EtOH) exposure during the early rat neonatal period results in acute cell loss in specific brain regions, but such acute cell death has not been well established in the hippocampus. Binge alcohol exposure can also result in protein expression changes in the cerebellum that could alter cell fate, but this has not been reported for the hippocampal subregions. This study investigates acute apoptotic cell death in hippocampal regions CA1, CA3, and dentate gyrus (DG) following a binge EtOH exposure on postnatal day (PN) 6, PN8, or PN6 + 8 and the alteration in pro‐ and anti‐apoptotic proteins following a single EtOH binge on PN6.

Methods

Apoptotic cell death was quantified 12 hours after EtOH binge exposure using the optical fractionator method. Western blot analysis determined expression of pro‐apoptotic Bax and anti‐apoptotic Bcl‐2, 12, 24, and 48 hours after binge EtOH exposure on PN6. The Bcl‐2:Bax ratio was used as a measure of vulnerability to apoptosis.

Results

Acute apoptosis increased significantly 12 hours following PN6 or 8 EtOH exposure in CA1, CA3, and DG, but the magnitude of apoptotic cell death was significantly greater in CA1 than in CA3 and DG, which did not differ. Significant cell death was not detected when a PN8 EtOH exposure was preceded by exposure on PN6. Binge EtOH exposure on PN6 resulted in a significant increase in expression of Bcl‐2 and the Bcl‐2:Bax ratio in the CA1/DG region at 24 hours after EtOH exposure on PN6. The Bcl‐2:Bax ratio in the CA3 region was not altered.

Conclusions

This study shows that repeated binge exposure does not have a cumulative effect on the magnitude of acute apoptotic cell death. This finding may be explained in part by changes in the Bcl‐2:Bax ratio after a single binge EtOH exposure.
β‐Endorphin Neuronal Transplantation Into the Hypothalamus Alters Anxiety‐Like Behaviors in Prenatal Alcohol‐Exposed Rats and Alcohol‐Non‐Preferring and Alcohol‐Preferring Rats
Authors: Logan Ryan W. , Wynne Olivia , Maglakelidze George , Zhang Changqing , O'Connell Stephanie , Boyadjieva Nadka I. , Sarkar Dipak K.
Published: January 2015

Background

Alcohol exposure has adverse effects on stress physiology and behavioral reactivity. This is suggested to be due, in part, to the effect of alcohol on β‐endorphin (β‐EP)‐producing neurons in the hypothalamus. In response to stress, β‐EP normally provides negative feedback to the hypothalamic–pituitary–adrenal axis and interacts with other neurotransmitter systems in the amygdala to regulate behavior. We examined whether β‐EP neuronal function in the hypothalamus reduces the corticosterone response to acute stress, attenuates anxiety‐like behaviors, and modulates alcohol drinking in rats.

Methods

To determine whether β‐EP neuronal transplants modulate the stress response, anxiety behavior, and alcohol drinking, we implanted differentiated β‐EP neurons into the paraventricular nucleus (PVN) of the hypothalamus of normal, prenatal alcohol‐exposed, and alcohol‐preferring (P) and alcohol‐non‐preferring (NP) rats. We then assessed corticosterone levels in response to acute restraint stress and other markers of stress response in the brain and anxiety‐like behaviors in the elevated plus maze and open‐field assays.

Results

We showed that β‐EP neuronal transplants into the PVN reduced the peripheral corticosterone response to acute stress and attenuated anxiety‐like behaviors. Similar transplants completely reduced the hypercorticosterone response and elevated anxiety behaviors in prenatal alcohol‐exposed adult rats. Moreover, we showed that β‐EP reduced anxiety behavior in P rats with minimal effects on alcohol drinking during and following restraint stress.

Conclusions

These data further establish a role of β‐EP neurons in the hypothalamus for regulating physiological stress response and anxiety behavior and resemble a potential novel therapy for treating stress‐related psychiatric disorders in prenatal alcohol‐exposed children and those genetically predisposed to increased alcohol consumption.
The cerebellum on cocaine: plasticity and metaplasticity
Authors: Vazquez‐Sanroman Dolores , Leto Ketty , Cerezo‐Garcia Miguel , Carbo‐Gas María , Sanchis‐Segura Carla , Carulli Daniela , Rossi Ferdinando , Miquel Marta
Published: January 2015

Despite the fact that several data have supported the involvement of the cerebellum in the functional alterations observed after prolonged cocaine use, this brain structure has been traditionally ignored and excluded from the circuitry affected by addictive drugs. In the present study, we investigated the effects of a chronic cocaine treatment on molecular and structural plasticity in the cerebellum, including BDNF, D3 dopamine receptors, ΔFosB, the Glu2 AMPA receptor subunit, structural modifications in Purkinje neurons and, finally, the evaluation of perineuronal nets (PNNs) in the projection neurons of the medial nucleus, the output of the cerebellar vermis. In the current experimental conditions in which repeated cocaine treatment was followed by a 1‐week withdrawal period and a new cocaine challenge, our results showed that cocaine induced a large increase in cerebellar proBDNF levels and its expression in Purkinje neurons, with the mature BDNF expression remaining unchanged. Together with this, cocaine‐treated mice exhibited a substantial enhancement of D3 receptor levels. Both ΔFosB and AMPA receptor Glu2 subunit expressions were enhanced in cocaine‐treated animals. Significant pruning in Purkinje dendrite arborization and reduction in the size and density of Purkinje boutons contacting deep cerebellar projection neurons accompanied cocaine‐dependent increase in proBDNF. Cocaine‐associated effects point to the inhibitory Purkinje function impairment, as was evidenced by lower activity in these cells. Moreover, the probability of any remodelling in Purkinje synapses appears to be decreased due to an upregulation of extracellular matrix components in the PNNs surrounding the medial nuclear neurons.
The harmful dysfunction model of alcohol use disorder: revised criteria to improve the validity of diagnosis and prevalence estimates
Authors: Wakefield Jerome C. , Schmitz Mark F.
Published: January 2015

Aims

To formulate harmful dysfunction (HD) diagnostic criteria for alcohol use disorder (AUD) and test whether they increase validity relative to standard DSM criteria, as evidenced by lowered prevalence, increased validator levels including service use, severity and family history and enhanced specificity.

Design

DSM‐IV AUD, DSM‐IV dependence, DSM‐5 AUD and HD AUD definitions were compared on eight validity related tests using nationally representative community data.

Setting

United States.

Participants

National Epidemiologic Survey of Alcoholism and Related Conditions (NESARC) respondents, aged 18–54 years (wave 1, n = 29 673; wave 2, n = 24 244).

Measures

NESARC DSM‐IV and DSM‐5 criteria were taken from published studies. Whereas DSM‐5 diagnosis requires any two AUD symptoms, HD criteria were constructed from NESARC items to require symptoms of both impaired‐control dysfunction [withdrawal, drink to prevent/stop withdrawal, cannot stop/reduce drinking, or craving (wave 2 only)] and harm (sacrificed important activities, problems caring for home/family, job/school problems, health problems, psychological problems or problems with family/friends). Validators included service use, severity and family history, among others. Specificity was tested using a teen transient drinker criterion group.

Findings

Compared with DSM‐5 AUD (DSM‐IV results were similar), HD criteria yielded lower prevalence (95% confidence intervals): HD life‐time 6.7% (6.2, 7.2%), 1‐year 2.3% (2.0, 2.5%); and DSM‐5 life‐time 38.2% (36.5, 39.9%), 1‐year 12.4% (11.7, 13.1%). HD AUD was higher than DSM‐5 on pathology validators, including: life‐time alcohol‐related service use: HD 41.0% (38.1, 43.9%), DSM‐5 11.5% (10.7, 12.3%); severity (number of life‐time alcohol symptoms): HD 20.8 (20.4, 21.2), DSM‐5 10.6 (10.4, 10.8); and family history of alcohol problems: HD 50.1% (47.3, 52.9), DSM‐5 32.8% (31.6, 34.0). HD criteria eliminated 83% of a DSM‐5 teen transient drinker false‐positives criterion group.

Conclusions

Prevalence estimates of alcohol use disorder are lowered and diagnostic validity improved when using ‘harmful dysfunction’ diagnostic criteria compared with standard DSM criteria, partly by reducing misdiagnosis of teenage transient drinkers.
When Did the Swahili Become Maritime?
Authors: Fleisher Jeffrey , Lane Paul , LaViolette Adria , Horton Mark , Pollard Edward , Quintana Morales Eréndira , Vernet Thomas , Christie Annalisa , Wynne‐Jones Stephanie
Published: January 2015

In this article, we examine an assumption about the historic Swahili of the eastern African coast: that they were a maritime society from their beginnings in the first millennium C.E. Based on historical and archaeological data, we suggest that, despite their proximity to and use of the sea, the level of maritimity of Swahili society increased greatly over time and was only fully realized in the early second millennium C.E. Drawing on recent theorizing from other areas of the world about maritimity as well as research on the Swahili, we discuss three arenas that distinguish first‐ and second‐millennium coastal society in terms of their maritime orientation. These are variability and discontinuity in settlement location and permanence; evidence of increased engagement with the sea through fishing and sailing technology; and specialized architectural developments involving port facilities, mosques, and houses. The implications of this study are that we must move beyond coastal location in determining maritimity; consider how the sea and its products were part of social life; and assess whether the marine environment actively influences and is influenced by broader patterns of sociocultural organization, practice, and belief within Swahili and other societies. [maritime, fishing and sailing, long‐distance trade, Swahili, eastern Africa]
Fifty years of chasing lizards: new insights advance optimal escape theory
Authors: Samia Diogo S. M. , Blumstein Daniel T. , Stankowich Theodore , Cooper William E.
Published: January 2015

Systematic reviews and meta‐analyses often examine data from diverse taxa to identify general patterns of effect sizes. Meta‐analyses that focus on identifying generalisations in a single taxon are also valuable because species in a taxon are more likely to share similar unique constraints. We conducted a comprehensive phylogenetic meta‐analysis of flight initiation distance in lizards. Flight initiation distance (FID) is a common metric used to quantify risk‐taking and has previously been shown to reflect adaptive decision‐making. The past decade has seen an explosion of studies focused on quantifying FID in lizards, and, because lizards occur in a wide range of habitats, are ecologically diverse, and are typically smaller and differ physiologically from the better studied mammals and birds, they are worthy of detailed examination. We found that variables that reflect the costs or benefits of flight (being engaged in social interactions, having food available) as well as certain predator effects (predator size and approach speed) had large effects on FID in the directions predicted by optimal escape theory. Variables that were associated with morphology (with the exception of crypsis) and physiology had relatively small effects, whereas habitat selection factors typically had moderate to large effect sizes. Lizards, like other taxa, are very sensitive to the costs of flight.
Methotrexate is effective for the treatment of neuromyelitis optica spectrum disorders in Asian patients
Authors: Ng Adeline S.L. , Tan Kevin
Published: January 2015

Background

Immunosuppression is effective in the secondary prevention of neuromyelitis optica spectrum disorder (NMOSD) relapse. However, some of the newer immunosuppressive agents are costly or unavailable in resource‐poor countries; older immunosuppressive agents might be just as effective. We aimed to evaluate the efficacy and tolerability of methotrexate in treating NMOSD in an Asian cohort.

Methods

We retrospectively reviewed all patients with NMOSD treated with methotrexate at the National Neuroscience Institute, Singapore, between 1992 and September 2012. We compared the annualized relapse rates and disability as measured by the Expanded Disability Status Scale before and after methotrexate treatment.

Results

Eight of 180 patients with central nervous system demyelinating diseases fulfilled the inclusion criteria. At median follow up of 53 months (range 42–70 months), the median post‐treatment annualized relapse rate was significantly lower than the pretreatment rate (0.00 [range 0.00–3.09] vs 0.97 [range 0.08–10.14] relapses). The median Expanded Disability Status Scale remained stable (pretreatment 6.5 [range 3.0–8.0] vs post‐treatment 6.0 [range 2.0–8.0], P = 0.238); 75% of our cohort remained relapse‐free on treatment. None of our patients were intolerant of methotrexate.

Conclusions

Methotrexate is well‐tolerated in our NMOSD patients, and appears to be effective in decreasing relapse rates and preventing disability progression. It is widely available and less costly than newer immunomodulatory agents. As such, it can be recommended as a therapeutic option for NMOSD in patients who fail first‐line therapy.
Prenatal findings of holoprosencephaly
Authors: Hayashi Yuko , Suzumori Nobuhiro , Sugiura Tokio , Sugiura‐Ogasawara Mayumi
Published: January 2015

Holoprosencephaly (HPE) is a rare brain abnormality characterized by an incomplete cleavage of the primitive prosencephalon of forebrain during early embryogenesis. To determine the clinical characteristics and outcome of fetuses with HPE, we retrospectively analyzed nine patients who were prenatally diagnosed as fetal HPE by ultrasounds. The mean diagnostic weeks were 20 weeks of gestation. Two cases died within one day after birth. The chromosomal examinations were performed in seven cases (trisomy 18: n = 2; trisomy 13: n = 2; 45,XX,der(18)t(18;21)(p10;p10)mat: n = 1; normal karyotype: n = 2). In our HPE cases, most cases had serious facial anomalies and poor prognosis. Our data suggested that the early prenatal diagnosis of HPE allowed time for parental counseling and delivery planning.
Effects of dynamic hyperinflation on exercise capacity and quality of life in stable COPD patients
Authors: Zhao Li , Peng Liyue , Wu Baomei , Bu Xiaoning , Wang Chen
Published: January 2015

Background and Aims

Dynamic hyperinflation (DH) is an important pathophysiological characteristic of chronic obstructive pulmonary disease (COPD). There is increasing evidence that DH has negative effects on exercise performance and quality of life. The objective of this study was to explore effects of DH on exercise capacity and quality of life in stable COPD patients.

Methods

Fifty‐eight COPD patients and 20 matched healthy individuals underwent pulmonary function test, 6‐min walk test and symptom‐limited cardiopulmonary exercise test (CPET). End‐expiratory lung volume/total lung capacity ratio (EELVmax/TLC) at peak exercise of CPET was evaluated, and EELVmax/TLC ≥ 75% was defined as ‘severe dynamic hyperinflation (SDH)’.

Results

Of the 58 patients studied, 29 (50.0%) presented with SDH (SDH+ group, EELVmax/TLC 79.60 ± 3.60%), having worse maximal exercise capacity reflected by lower peakload, maximal oxygen uptake (VO2max), maximal carbon dioxide output (VCO2max) and maximal minute ventilation (VEmax) than did those without SDH (SDH− group, EELVmax/TLC 67.44 ± 6.53%). The EELVmax/TLC ratio at peak exercise had no association with variables of pulmonary function and 6‐min walk distance (6MWD), but correlated inversely with peakload, VO2max, VCO2max and VEmax (r = −0.300~−0.351, P < 0.05). Although no significant differences were observed, patients with EELVmax/TLC ≥ 75% tended to have higher COPD assessment test score (15.07 ± 6.55 vs 13.28 ± 6.59, P = 0.303).

Conclusions

DH develops variably during exercise and has a greater impact on maximal exercise capacity than 6MWD, even in those with the same extent of pulmonary function impairment at rest.
The role of transbronchial cryobiopsy and surgical lung biopsy in the diagnostic algorithm of interstitial lung disease
Authors: Hagmeyer Lars , Theegarten Dirk , Wohlschläger Jeremias , Treml Marcel , Matthes Sandhya , Priegnitz Christina , Randerath Winfried J.
Published: January 2015

Background and Aims

It is not yet known if transbronchial cryobiopsy (TCB) is a reliable and safe diagnostic tool in the investigation of interstitial lung disease (ILD). To date, there have been no studies directly comparing the value of TCB with that of surgical lung biopsy (SLB). The study was initiated to determine whether the samples taken by TCB lead to a reliable diagnosis and whether SLB can be avoided in a relevant percentage of cases.

Methods

We analyzed 32 subjects with suspected ILD who underwent a TCB. Subjects' baseline characteristics, pathological findings after TCB and SLB, and complication rates were analyzed. The pathological inter‐rater agreement was quantified statistically.

Results

The overall inter‐rater agreement concerning TCB sample evaluation was good with a kappa value of 0.80. In 23/32 cases (72%), the findings from the TCB showed a strong congruence with all other clinical data, thereby enabling a definitive diagnosis. Eight of the remaining nine subjects gave their consent for an SLB, which led to a definitive histological diagnosis in six cases (75%). Following TCB, pneumothorax occurred in 6/32 subjects (19%) and endobronchial bleeding was moderate in 8/32 (25%) and was severe in 17/32 cases (53%).

Conclusion

This is the first study to correlate histological results and complications following TCB and SLB in ILD subjects, some of whom underwent both procedures. TCB is a suitable diagnostic tool in ILD, potentially completely dispensing with the need for an SLB in some cases. In all cases, an interdisciplinary case evaluation is necessary as a final step.
The sonographic features of malignant mediastinal lymph nodes and a proposal for an algorithmic approach for sampling during endobronchial ultrasound
Authors: Alici Ibrahim Onur , Yılmaz Demirci Nilgün , Yılmaz Aydın , Karakaya Jale , Özaydın Esra
Published: January 2015

Introduction

There are several papers on the sonographic features of mediastinal lymph nodes affected by several diseases, but none gives the importance and clinical utility of the features.

Objective

In order to find out which lymph node should be sampled in a particular nodal station during endobronchial ultrasound, we investigated the diagnostic performances of certain sonographic features and proposed an algorithmic approach.

Methods

We retrospectively analyzed 1051 lymph nodes and randomly assigned them into a preliminary experimental and a secondary study group. The diagnostic performances of the sonographic features (gray scale, echogeneity, shape, size, margin, presence of necrosis, presence of calcification and absence of central hilar structure) were calculated, and an algorithm for lymph node sampling was obtained with decision tree analysis in the experimental group. Later, a modified algorithm was applied to the patients in the study group to give the accuracy.

Results

The demographic characteristics of the patients were not statistically significant between the primary and the secondary groups. All of the features were discriminative between malignant and benign diseases. The modified algorithm sensitivity, specificity, and positive and negative predictive values and diagnostic accuracy for detecting metastatic lymph nodes were 100%, 51.2%, 50.6%, 100% and 67.5%, respectively.

Conclusions

In this retrospective analysis, the standardized sonographic classification system and the proposed algorithm performed well in choosing the node that should be sampled in a particular station during endobronchial ultrasound.
CCDC40 mutation as a cause of primary ciliary dyskinesia: a case report and review of literature
Authors: Sui Weiguo , Hou Xianliang , Che Wenti , Ou Minglin , Sun Guoping , Huang Shengxing , Liu Fuhua , Chen Peng , Wei Xiaolian , Dai Yong
Published: January 2015

Background and Aims

Primary ciliary dyskinesia (PCD) is a rare, genetically heterogeneous disorder. Genetic defects affecting motility of cilia and flagella cause chronic destructive airway disease, situs inversus and, frequently, male infertility in PCD. To date, although several genes have been implicated in PCD, the genetic bases of most cases of PCD remain elusive.

Methods

By applying a whole‐exome sequencing strategy, we reported a case of PCD carrying a novel mutant alleles in CCDC40 gene, and did literature review.

Results

A 36‐year‐old nonsmoking Chinese man suffered from chronic cough since childhood and an 8‐year history of primary infertility. Lung biopsy showed respiratory bronchiolitis. Chest images showed bronchiectasis and situs inversus. Semen analysis showed high sperm counts and poor sperm motility. Transmission electron microscopy (TEM) of cilia cross‐sections showed ultrastructural defects, including inner dynein arms (IDA) defect and axonemal disorganization. To identify gene mutations that cause PCD, we performed exome sequencing to analyze genome of this patient, and discovered a previously uncharacterized mutant alleles (NM_001243342.1:c.2609G>A; p. R870H) in CCDC40 gene. In addition, we summarize the PCD disease‐causing genes and CCDC40 mutant sites based on current literature.

Conclusions

We identified a novel mutant alleles in CCDC40 gene, which altered the protein sequence and resulted in the ultrastructural defects in the microtubule structure of cilia. Thereby, these defects lead to the patient with bronchiectasis, bronchiolitis and infertility.
Deep breathing exercises with positive expiratory pressure in patients with multiple sclerosis – a randomized controlled trial
Authors: Westerdahl Elisabeth , Wittrin Anna , Kånåhols Margareta , Gunnarsson Martin , Nilsagård Ylva
Published: January 2015

Introduction

Breathing exercises with positive expiratory pressure are often recommended to patients with advanced neurological deficits, but the potential benefit in multiple sclerosis (MS) patients with mild and moderate symptoms has not yet been investigated in randomized controlled trials.

Objectives

To study the effects of 2 months of home‐based breathing exercises for patients with mild to moderate MS on respiratory muscle strength, lung function, and subjective breathing and health status outcomes.

Methods

Forty‐eight patients with MS according to the revised McDonald criteria were enrolled in a randomized controlled trial. Patients performing breathing exercises (n = 23) were compared with a control group (n = 25) performing no breathing exercises. The breathing exercises were performed with a positive expiratory pressure device (10–15 cmH2O) and consisted of 30 slow deep breaths performed twice a day for 2 months. Respiratory muscle strength (maximal inspiratory and expiratory pressure at the mouth), spirometry, oxygenation, thoracic excursion, subjective perceptions of breathing and self‐reported health status were evaluated before and after the intervention period.

Results

Following the intervention, there was a significant difference between the breathing group and the control group regarding the relative change in lung function, favoring the breathing group (vital capacity: P < 0.043; forced vital capacity: P < 0.025). There were no other significant differences between the groups.

Conclusion

Breathing exercises may be beneficial in patients with mild to moderate stages of MS. However, the clinical significance needs to be clarified, and it remains to be seen whether a sustainable effect in delaying the development of respiratory dysfunction in MS can be obtained.
Evaluation of our self‐designed nanometer silicon membrane sandwich cup system for diagnosing tuberculosis
Authors: Peng Jun , Liu Wen‐en , Li Hong‐Ling , Liu Qing‐Xia , Liang Xiang‐Hui , Hu Ke , Jian Zi‐Juan , Li Yan‐Bing , Peng Wan‐Chan
Published: January 2015

Background and Aims

A nanometer silicon membrane sandwich cup system was self‐designed. It could concentrate the bacilli via 0.45‐μm microporous filter membrane and semi‐automate the acid‐fast bacilli (AFB) by a bacteria‐staining machine. The aim of the study was to assess the clinical value of our self‐designed system for diagnosing tuberculosis (TB).

Methods

A total of 1993 sputum specimens obtained from patients with confirmed or suspected TB were subjected to direct or concentrated specimens smear at XiangYa Hospital, Central South University between May 2012 and February 2013. In addition, all the specimens were also inoculated into Lowenstein–Jensen (L‐J) media, and culture results were considered as the gold standard for calculating sensitivity and specificity.

Results

Compared with direct smear examination, an increased density of red stained bacilli was observed in the self‐designed nanometer silicon membrane sandwich cup analysis under the microscope. The positive rate of the self‐designed analysis was significantly higher than that of direct AFB smear [10.9% (217/1993) vs 6.2% (123/1993), P < 0.05]. The sensitivity of the self‐designed system increased (97.3% vs 55.2%, P < 0.05) without a loss of specificity (100% vs 100%) for identifying positive TB cases compared with the direct smear method.

Conclusion

The self‐designed nanometer silicon membrane sandwich cup and semi‐automatic bacteria‐staining machine could more efficiently and rapidly detect the AFB in respiratory specimens than direct microscopy. This is a novel and safe examination, and it may replace direct smear examination for the diagnosis of patients with TB.
Tonsillar metastasis of small cell lung carcinoma
Authors: Unsal Meftun , Kutlar Gokhan , Sullu Yurdanur , Yurtlu Sirin
Published: January 2015

Metastasis to palatine tonsils are rare, accounting from only 0.8% of all tonsillar tumors, so far only 100 cases reported in the English literature. Only a few cases have been reported for small cell and non‐small cell lung cancer as a primary site. With a diagnosis of small cell lung cancer, a 68‐year‐old male patient relapsed after six cycles of chemotherapy in tonsilla palatina and cervical lymph nodes. Patients died 26 months after being diagnosed with lung cancer and 2 months after detection of tonsil metastasis. We present the current case report because of the rarity of metastasis to tonsil in lung cancer.
Definition of the transcription factor TdIF1 consensus‐binding sequence through genomewide mapping of its binding sites
Authors: Koiwai Kotaro , Kubota Takashi , Watanabe Nobuhisa , Hori Katsutoshi , Koiwai Osamu , Masai Hisao
Published: January 2015

TdIF1 was originally identified as a protein that directly binds to terminal deoxynucleotidyltransferase, TdT. Through in vitro selection assays (SELEX), we recently showed that TdIF1 recognizes both AT‐tract and a specific DNA sequence motif, 5′‐TGCATG‐3′, and can up‐regulate the expression of RAB20 through the latter motif. However, whether TdIF1 binds to these sequences in the cells has not been clear and its other target genes remain to be identified. Here, we determined in vivo TdIF1‐binding sequences (TdIF1‐invivoBMs) on the human chromosomes through ChIP‐seq analyses. The result showed a 160‐base pair cassette containing ‘AT‐tract~palindrome (inverted repeat)~AT‐tract’ as a likely target sequence of TdIF1. Interestingly, the core sequence of the palindrome in the TdIF1‐invivoBMs shares significant similarity to the above 5′‐TGCATG‐3′ motif determined by SELEX in vitro. Furthermore, spacer sequences between AT‐tract and the palindrome contain many potential transcription factor binding sites. In luciferase assays, TdIF1 can up‐regulate transcription activity of the promoters containing the TdIF1‐invivoBM, and this effect is mainly through the palindrome. Clusters of this motif were found in the potential target genes. Gene ontology analysis and RT‐qPCR showed the enrichment of some candidate targets of TdIF1 among the genes involved in the regulation of ossification. Potential modes of transcription activation by TdIF1 are discussed.