bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of the teosinte transcriptome reveals adaptive sequence divergence during maize domestication
Authors: Huang Jun , Gao Youjun , Jia Haitao , Zhang Zuxin
Published: March 2016

Annual teosinte, the ancestor of cultivated maize (Zea mays ssp. mays), is a valuable germplasm for enhancing the genetic diversity and adaptability of maize to various environment stimuli. However, comprehensive transcriptomic and genomic resources are unavailable in public databases, which significantly impede the identification and utilization of favourable genes or alleles in teosinte. In this study, we globally sequenced the transcriptomes of six teosinte accessions by Illumina paired‐end sequencing. A high‐quality teosinte transcriptome was de novo assembled with an average length of 770 bp and 63.99% of annotated unigenes. We found approximately 75% of the genes were highly conserved between maize and teosinte. Moreover, we also found 1516 unigenes were specifically expressed in teosinte, of which 84 unigenes were supported by gene models of four plant species, and 571 unigenes were located in the intergenic regions of maize genome, showing evidence‐based expressed presence/absence variations (ePAVs). Furthermore, we also identified 99 unigenes with strong selection signals and 57 unigenes with >1 Ka/Ks ratios, suggesting that these genes might be under strong selection during maize domestication and improvement. Additionally, 11 286 teosinte unigene‐derived primer pairs were developed for amplifying simple sequence repeat (SSR) loci. This study provides a comprehensive transcriptome of teosinte, a subset of genes that are highly conserved or diverged during maize domestication and improvement, and a massive set of available SSR primer pairs. These results facilitate the investigation of the comparative genomics and molecular domestication of teosinte and the utilization of teosinte germplasm for maize improvement.
Domains of quality of life affecting elderly patients with hand osteoarthritis: a qualitative study in the Asian perspective
Authors: Thumboo Julian , Wu Li , Leung Ying Ying
Published: March 2016

Objectives

Hand osteoarthritis (HOA) is common but little is known about how HOA has impact on disability and quality of life (QoL).We aim to identify important domains of concern among participants suffering from symptomatic HOA in Singapore, representing an Asian socio‐cultural context.

Methods

A qualitative study using a focus group technique was performed. We ran focus groups stratified by gender, ethnicity and language. Two independent, trained analysts identified relevant categories and assigned codes to text segments through open coding, with discrepancies resolved through consensus. The final lists of domains and subthemes descriptive of QoL were then compared to the following commonly used HOA specific instruments: Functional Index for Hand Osteoarthritis (FIHOA), Score for Assessment and quantification of Chronic Rheumatic Affections of the Hand (SACRAH), Australian/Canadian Hand Osteoarthritis Index (AUSCAN); and Health Assessment Questionnaire (HAQ).

Results

Twenty‐six patients (23 women, three men; 24 Chinese and two Malay; mean ± SD age 62.9 ± 7.5 years) with symptomatic HOA according to the American College of Rheumatology Classification Criteria participated in seven focus groups. Two and five focus groups were conducted in Chinese and English, respectively. The qualitative analysis revealed pain, stiffness and functional disability as the main domains. However, psychological consequences, aesthetic concerns, participation in leisure activities, participation in family roles were important concepts from the focus groups which were not covered by existing instruments. Impact on work productivity by HOA and the unmet health care need is revealed.

Conclusion

The domains of concepts important to people with HOA in an Asian socio‐cultural context are not fully represented in the most commonly used instruments. Further studies on the selection of main domains relevant to HOA patients are necessary.
Private Financing of Health Care in Times of Economic Crisis: a Review of the Evidence
Authors: Wouters Olivier J. , McKee Martin
Published: March 2016

Many high‐income countries have cut public health care spending since the global economic downturn in 2008. In some cases these cuts have been accompanied by calls to expand private financing to improve the efficiency of health systems. In low and middle‐income countries seeking to increase access to health care, it is sometimes suggested that private financing is more effective than public financing because of weak state institutions and bureaucratic shortcomings.

In this paper, we review the theoretical and empirical evidence on private financing in terms of cost, efficiency, equity and financial protection. We consider private health insurance, medical savings accounts and user charges in high, middle and low‐income countries.

The theoretical and empirical evidence reveals major market failures in the health sector. It is unlikely that private financing generates better results than public financing. Still, as private financing options are heterogeneous, it is possible that a particular form might play a beneficial role in a specific setting. Given the current state of knowledge, however, any calls to increase private financing must be accompanied by robust evidence, such as real world pilot studies.
Nursing Taxonomies in Spain: Research Themes Presented at the AENTDE Conferences Over a 16‐Year Period
Authors: Guirao‐Goris Silamani J. Adolf , Lluch‐Canut Maria Teresa , Martín‐Iglesias Susana , Quero‐Rufián Aurora , Roldán Merino Juan Francisco
Published: March 2016

OBJECTIVE

To identify the types of studies of nursing taxonomies and priority research themes presented at AENTDE conferences between 1996 and 2012.

METHOD

Four hundred oral communications and posters and 27 lectures presented at the AENTDE meetings were reviewed by means of a descriptive analysis of the types of studies conducted and a content analysis of priority research themes.

RESULTS

The most commonly presented studies were descriptions of the implementation of nursing taxonomies, which accounted for 27.4% of the total over the 16‐year period. However, their prevalence fell from 31.8% in 1996 to 9.1% in 2012. Basic research studies accounted for 17.4% of studies overall but were the most frequent in 2012, when their proportion had risen to 37.5%.

CONCLUSION

The prevalence of basic research studies increased notably over the 16‐year period. Content validity studies rose in number, while face validity studies fell. Studies of the practical implementation of taxonomies also declined.

OBJETIVO

Identificar los tipos de estudios de taxonomías enfermeras y los temas de investigación prioritarios presentados en las convenciones de AENTDE desde 1996 a 2012.

MÉTODO

Se revisaron 400 comunicaciones y 27 ponencias presentadas a 9 simposiums de AENTDE realizando un análisis del tipo de estudio y un análisis de contenido de los temas.

RESULTADOS

Los estudios más frecuentes son las experiencias de implantación de las taxonomías enfermeras con un porcentaje medio de un 27.4% que partiendo de un 31.8% en 1996 disminuyó a un 9,1% en 2012. La investigación básica tienen un porcentaje medio del 17.4% obteniéndose el mayor porcentaje en 2012 con un 37,5%.

CONCLUSIÓN

La prevalencia de los estudios de investigación básica se incrementó notablemente durante el período de 16 años. Los estudios de validez de contenido aumentaron en número, mientras que los estudios de validez aparente cayeron. Los estudios sobre la aplicación práctica de las taxonomías también disminuyeron.
Cyclone‐based spore trapping, quantitative real‐time polymerase chain reaction and high resolution melting analysis for monitoring airborne inoculum of Magnaporthe oryzae
Authors: Huang C.‐M. , Liao D.‐J. , Wu H.‐S. , Shen W.‐C. , Chung C.‐L.
Published: March 2016

Rice blast, caused by Magnaporthe oryzae, is one of the most devastating diseases in rice worldwide. We aimed to develop an integrated approach for convenient collection, quantification and characterisation of M. oryzae spores (airborne inoculum) in the field. We developed an easy‐to‐use cyclone‐based spore trap (the AirSampler) and a standard procedure for handling a small amount of airborne spores. Using a specific primer pair or a probe designed for the single‐copy gene mif23, SYBR Green and TaqMan assays could quantify 10 and 4 copy numbers, respectively, of M. oryzae DNA. During 2012 and 2013, the AirSampler and SYBR Green quantitative real‐time polymerase chain reaction were used to monitor temporal dynamics of M. oryzae spores in nursery fields of rice showing symptoms of blast disease. During four cropping seasons, the new techniques could detect M. oryzae spores before the appearance of rice blast symptoms. The amount of spores was low in the early season, then increased, with high fluctuations during the mid‐season and decreased to low levels at the heading stage in the late season. To improve the handling and storage of spore samples, we tested the effect of different treatments on the preservation of spore DNA. DNA loss was reduced with samples protected from ultraviolet B radiation, suspended in CTAB buffer, kept at room temperature or 4°C and used for DNA extraction in 2 weeks. Finally, we demonstrated that the high resolution melting analysis could be used for rapid determination of A, D, A + D and C alleles of the avirulence gene pex31 (Avr‐Pik/kp/km) in M. oryzae.
Adverse event assessment and reporting in trials of newer treatments for post‐operative pain
Authors: Hoffer D. , Smith S. M. , Parlow J. , Allard R. , Gilron I.
Published: March 2016

Background

Assessment and reporting of adverse events (AEs) in studies of perioperative interventions is critical given the potential for unintended and preventable iatrogenic morbidity and mortality. This focused review evaluated the quality of AE assessment and reporting in acute post‐operative pain treatment trials. Since older analgesics (e.g., opioids, NSAIDs) already have a well‐characterized safety profile, we concentrated on trials of pregabalin and gabapentin as a representative sample of studies where the perioperative safety profile was relatively unknown.

Methods

We reviewed primary reports of trials of pregabalin and gabapentin for treatment of acute post‐operative pain for: (1) adherence to the 10 recommendations from the ‘CONSORT Extension for Harms,’ (2) AE assessment method, (3) timing of AE assessment and reporting, and (4) assessment and reporting of AE severity.

Results

We identified 31 trials of pregabalin and 59 of gabapentin. The median number of CONSORT harms recommendations that were satisfied was 7 of 10. The most common (41%) method of AE assessment was direct questioning about specific AEs by investigators. However, AE assessment method was not described in 18% of trials. AE assessments were reported for specified perioperative time points in only 24% of trials. Of greatest concern, no AE data were reported whatsoever in 8 of the included publications.

Conclusions

Considerable widespread improvements are needed in AE reporting for post‐operative pain treatment trials. In addition to heightened awareness among clinical investigators, mandatory journal editorial policies may further facilitate improvements in safety assessment and reporting.
The Behavioral Economics and Neuroeconomics of Alcohol Use Disorders
Authors: MacKillop James
Published: March 2016

Background

Behavioral economics and neuroeconomics bring together perspectives and methods from psychology, economics, and cognitive neuroscience to understand decision making and choice behavior. Extending an operant behavioral theoretical framework, these perspectives have increasingly been applied to understand the alcohol use disorders (AUDs), and this review surveys the theory, methods, and findings from this approach. The focus is on 3 key behavioral economic concepts: delay discounting (i.e., preferences for smaller immediate rewards relative to larger delayed rewards), alcohol demand (i.e., alcohol's reinforcing value), and proportionate alcohol‐related reinforcement (i.e., relative amount of psychosocial reinforcement associated with alcohol use).

Findings

Delay discounting has been linked to AUDs in both cross‐sectional and longitudinal studies and has been investigated cross‐sectionally using neuroimaging. Alcohol demand and proportionate alcohol‐related reinforcement have both been robustly associated with drinking and alcohol misuse cross‐sectionally, but not over time. Both have also been found to predict treatment response to brief interventions. Alcohol demand has also been used to enhance the measurement of acute motivation for alcohol in laboratory studies. Interventions that focus on reducing the value of alcohol by increasing alternative reinforcement and response cost have been found to be efficacious, albeit in relatively small numbers of randomized controlled trials (RCTs). Mediators and moderators of response to these interventions have not been extensively investigated.

Future directions

The application of behavioral economics and neuroeconomics to AUDs has given rise to an extensive body of empirical work, although significant gaps in knowledge remain. In particular, there is a need for more longitudinal investigations to clarify the etiological roles of these behavioral economic processes, especially alcohol demand and proportionate alcohol reinforcement. Additional RCTs are needed to extend and generalize the findings for reinforcement‐based interventions and to investigate mediators and moderators of treatment success for optimization. Applying neuroeconomics to AUDs remains at an early stage and has been primarily descriptive to date, but has high potential for important translational insights into the future. The same is true for using these behavioral economic indicators to understand genetic influences on AUDs.
More inclusive bipolar mixed depression definitions by requiring fewer non‐overlapping mood elevation symptoms
Authors: Kim W. , Kim H. , Citrome L. , Akiskal H. S. , Goffin K. C. , Miller S. , Holtzman J. N. , Hooshmand F. , Wang P. W. , Hill S. J. , Ketter T. A.
Published: March 2016

Objective

Assess strengths and limitations of mixed bipolar depression definitions made more inclusive than that of the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM‐5) by requiring fewer than three ‘non‐overlapping’ mood elevation symptoms (NOMES).

Method

Among bipolar disorder (BD) out‐patients assessed with Systematic Treatment Enhancement Program for BD (STEP‐BD) Affective Disorders Evaluation, we assessed prevalence, demographics, and clinical correlates of mixed vs. pure depression, using less inclusive (≥3 NOMES, DSM‐5), more inclusive (≥2 NOMES), and most inclusive (≥1 NOMES) definitions.

Results

Among 153 depressed BD, compared to less inclusive DSM‐5 threshold, our more and most inclusive thresholds, yielded approximately two‐ and five‐fold higher mixed depression rates (7.2%, 15.0%, and 34.6% respectively), and important statistically significant clinical correlates for mixed compared to pure depression (e.g. more lifetime anxiety disorder comorbidity, more current irritability), which were not significant using the DSM‐5 threshold.

Conclusion

Further studies assessing strengths and limitations of more inclusive mixed depression definitions are warranted, including assessing the extent to which enhanced statistical power vs. other factors contributes to more vs. less inclusive mixed bipolar depression thresholds having more statistically significant clinical correlates, and whether ‘overlapping’ mood elevation symptoms should be counted.
Chronic mitragynine (kratom) enhances punishment resistance in natural reward seeking and impairs place learning in mice
Authors: Ismail Nurul Iman W. , Jayabalan Nanthini , Mansor Sharif Mahsufi , Müller Christian P. , Muzaimi Mustapha
Published: March 2016

Kratom (Mitragyna speciosa) is a widely abused herbal drug preparation in Southeast Asia. It is often consumed as a substitute for heroin, but imposing itself unknown harms and addictive burdens. Mitragynine is the major psychostimulant constituent of kratom that has recently been reported to induce morphine‐like behavioural and cognitive effects in rodents. The effects of chronic consumption on non‐drug related behaviours are still unclear. In the present study, we investigated the effects of chronic mitragynine treatment on spontaneous activity, reward‐related behaviour and cognition in mice in an IntelliCage® system, and compared them with those of morphine and Δ‐9‐tetrahydrocannabinol (THC). We found that chronic mitragynine treatment significantly potentiated horizontal exploratory activity. It enhanced spontaneous sucrose preference and also its persistence when the preference had aversive consequences. Furthermore, mitragynine impaired place learning and its reversal. Thereby, mitragynine effects closely resembled that of morphine and THC sensitisation. These findings suggest that chronic mitragynine exposure enhances spontaneous locomotor activity and the preference for natural rewards, but impairs learning and memory. These findings confirm pleiotropic effects of mitragynine (kratom) on human lifestyle, but may also support the recognition of the drug's harm potential.
Does cigarette reduction while using nicotine replacement therapy prior to a quit attempt predict abstinence following quit date?
Authors: Lindson‐Hawley Nicola , Shinkins Bethany , West Robert , Michie Susan , Aveyard Paul
Published: March 2016

Background and Aims

Previous studies have reported that people who use a smoking cessation medication while smoking and reduce cigarette consumption spontaneously are three times more likely to stop smoking after a quit date. The aim was to replicate this and assess whether it arises because of willed effortful reduction rather than unwilled reduced drive to smoke caused by medication.

Design

Secondary analysis of a trial where participants were randomised to smoke as normal or reduce by 75% over 2 weeks prior to quit date, using nicotine replacement therapy (NRT) in both arms.

Setting

Thirty‐one UK primary care practices.

Participants

A total of 517 adult smokers seeking quitting support in the carbon monoxide (CO) analyses and 421 in the cigarettes/day analyses.

Measurements

Russell Standard abstinence was recorded 4 weeks after quit date. The randomized groups were combined and the association between reduction and abstinence examined. The second analysis assessed whether this association differed by whether smokers were, or were not, instructed to reduce.

Findings

In all participants, there was no evidence that reducing cigarettes/day or CO by at least half compared with not reducing predicted abstinence at 4 weeks [risk ratio (RR) = 0.88; 95% confidence interval (CI) = 0.68–1.14 and RR = 1.20; 95% CI = 1.00–1.44, respectively]. However, in smokers instructed to reduce, CO reduction was associated with 4‐week abstinence (RR = 1.52; 95% CI = 1.16–2.00), but not among people advised not to reduce (RR = 0.91; 95% CI = 0.67–1.24).

Conclusions

Smoking reduction prior to a target quit date while on a smoking cessation medication may only predict subsequent abstinence when smokers are consciously attempting to reduce.
Fracture resistance of endodontically treated mandibular first molars with conservative access cavity and different restorative techniques: An in vitro study
Authors: Al Amri Mohammad D. , Al‐Johany Sulieman , Sherfudhin Haneef , Al Shammari Badar , Al Mohefer Sami , Al Saloum Mohammed , Al Qarni Hatem
Published: March 2016

The aim was to investigate in vitro the fracture resistance (FR) of endodontically treated teeth (ETT) with conservative access cavity restored using various direct and indirect restorative materials and techniques. Seventy‐two mandibular first molars were equally divided into six groups. Teeth in Group 1 were untreated (controls). In Groups 2, 3, 4, 5 and 6, teeth were restored with amalgam, composite resin, ceramic inlay, ceramic onlay and zirconium crown, respectively. A fracture test was performed on all teeth using a static load. Compared with other groups, teeth in Groups 3 (P < 0.05) and 6 (P < 0.05) had the highest FR values with no significant difference in‐between them. Teeth in Group 4 had the lowest FR than other groups (P < 0.05). All restorative techniques tested led to a significant reduction in FR. It is necessary to consider type of fracture when evaluating fracture resistance of endodontically treated teeth. Crowned molars had the highest favourable fractures among the five treatment groups. Although the results of this in vitro study showed variations between tested techniques in ETT with a conservative access cavity, further long‐term controlled clinical trials are required to confirm these in vitro findings.
Dyslipidemia associated with heavy alcohol use
Authors: Capurso Noah A. , Petrakis Ismene
Published: March 2016

Background and Objectives

Alcohol has many effects on lipid metabolism and has been associated with elevated triglycerides. The purpose of this paper is to report a case of globally dysregulated lipids secondary to alcohol use and to describe the natural history of this phenomenon after drinking cessation.

Methods

We present a case of an otherwise healthy patient (N = 1) who was admitted to our facility for alcohol detoxification and found to have extreme lipid dysregulation. He was treated with benzodiazepines for alcohol withdrawal but no hypolipidemic agents were given.

Results

Lipid indices self‐corrected and were found to be normal following just several weeks of sobriety in the absence of treatment with any hypolipidemic agents.

Discussion

The literature regarding the effects of alcohol on lipid metabolism is briefly reviewed followed by a discussion of how these findings might apply to this patient in particular as well as implications for broader clinical practice.

Conclusion and Scientific Significance

Alcohol has the ability to dysregulate several lipid indices in addition to elevating triglycerides. The rapid resolution of dyslipidemia suggests that additional treatment may not be necessary for patients who are able to abstain from alcohol but that hypolipidemic agents may be indicated for those patients who continue to drink. Additionally, clinicians should consider checking lipid panels in patients who present with alcohol intoxication and are found to have other laboratory abnormalites or those who have risk factors for hyperlipidemia. (Am J Addict 2016;25:188–190)
Brief Report: A web‐based pilot study of childhood sexual abuse, recent stressful events, and alcohol use in women
Authors: Sartor Carolyn E. , O'Malley Stephanie S.
Published: March 2016

Background and Objectives

Childhood sexual abuse (CSA) is a well‐documented risk factor for problem drinking, but the possibility that recent stressful events exacerbate risk conferred by CSA has rarely been examined, and the few studies to do so have limited their investigations to negative events. The aim of the current study was to examine the associations between CSA, recent positive and negative stressful events, and women's alcohol consumption.

Methods

Eighty‐nine women (42.7% reporting CSA) completed weekly web‐based alcohol use surveys and a stressful event inventory assessing negative and positive events over a 12 week period.

Results

Independent of CSA history, experiencing negative events was associated with elevated likelihood of drinking to intoxication.

Discussion and Conclusions

Proximal distressing events are more closely linked than CSA history to short‐term drinking patterns.

Scientific Significance

Tracking stressful negative events may be informative for identifying precipitants of heavy drinking. (Am J Addict 2016;25:184–187)
An integrated model of depression, compulsion, and mindfulness among heroin abusers in Taiwan
Authors: Lee Kun‐Hua , Lin Huang‐Chi , Wang Peng‐Wei , Yen Cheng‐Fang
Published: March 2016

Background and Objectives

Prevailing literature explains how depression, compulsion, and mindfulness affect heroin use; however, there is no comprehensive framework that explains their overall relationships. We therefore proposed and examined a hypothetical depression‐compulsion‐heroin use and mindfulness (DCHm) model.

Methods

We recruited 234 male heroin users. Self‐reported levels of depression, mindfulness, compulsion to use, and severity of heroin use were measured. Structural equation modeling was used to examine the proposed DCHm model.

Results

Compulsion was a mediator between depression and heroin use. In addition, the DCHm model had satisfactory model fit indices. Depression indirectly affected heroin use through compulsion to use. The moderating effects of mindfulness in the two competing models were compared between the high‐ and low‐mindfulness groups. The DCHm model in the high‐mindfulness group had more favorable model fit indices than it did in the low‐mindfulness group.

Conclusions

Through learned emotional regulation strategies, addicted people with higher mindfulness were less likely to compulsively take drugs because of a depressive mood than were those with lower mindfulness. Furthermore, effective emotion‐regulation strategies should be developed and examined in future studies.

Scientific Significance

These results raise questions about the effect of compulsion on heroin use disorders. Mindfulness‐based approaches to emotional regulatory strategies should be developed based on these findings. Further experimentation and prospective studies are needed to more fully examine the moderating role of mindfulness on depression and compulsion. (Am J Addict 2016;25:227–232)
Langerhans cell histiocytosis mimicking lichen nitidus with bone involvement
Authors: Lozano Masdemont Belén , Gómez‐Recuero Muñoz Laura , Villanueva Álvarez‐Santullano Ana , Parra Blanco Verónica , Campos Domínguez Minia
Published: March 2016

We report the case of a 6‐month‐old Hispanic boy with a 4‐month history of widespread pruritic hypopigmented papules mimicking lichen nitidus. The final diagnosis was multisystem non‐risk‐organ Langerhans cell histiocytosis (LCH), with cutaneous and multiple bone involvement. With this patient and others previously reported in the literature, we suggest an early biopsy of the hypopigmented rash in children.
Mouth breathing, another risk factor for asthma: the Nagahama Study
Authors: Izuhara Y. , Matsumoto H. , Nagasaki T. , Kanemitsu Y. , Murase K. , Ito I. , Oguma T. , Muro S. , Asai K. , Tabara Y. , Takahashi K. , Bessho K. , Sekine A. , Kosugi S. , Yamada R. , Nakayama T. , Matsuda F. , Niimi A. , Chin K. , Mishima M. ,   the Nagahama Study Group
Published: March 2016

Background

Allergic rhinitis, a known risk factor for asthma onset, often accompanies mouth breathing. Mouth breathing may bypass the protective function of the nose and is anecdotally considered to increase asthma morbidity. However, there is no epidemiological evidence that mouth breathing is independently associated with asthma morbidity and sensitization to allergens. In this study, we aimed to clarify the association between mouth breathing and asthma morbidity and allergic/eosinophilic inflammation, while considering the effect of allergic rhinitis.

Methods

This community‐based cohort study, the Nagahama Study, contained a self‐reporting questionnaire on mouth breathing and medical history, blood tests, and pulmonary function testing. We enrolled 9804 general citizens of Nagahama City in the Shiga Prefecture, Japan.

Results

Mouth breathing was reported by 17% of the population and was independently associated with asthma morbidity. The odds ratio for asthma morbidity was 1.85 (95% CI, 1.27–2.62) and 2.20 (95% CI, 1.72–2.80) in subjects with mouth breathing alone and allergic rhinitis alone, which additively increased to 4.09 (95% CI, 3.01–5.52) when mouth breathing and allergic rhinitis coexisted. Mouth breathing in nonasthmatics was a risk for house dust mite sensitization, higher blood eosinophil counts, and lower pulmonary function after adjusting for allergic rhinitis.

Conclusion

Mouth breathing may increase asthma morbidity, potentially through increased sensitization to inhaled allergens, which highlights the risk of mouth‐bypass breathing in the ‘one airway, one disease’ concept. The risk of mouth breathing should be well recognized in subjects with allergic rhinitis and in the general population.
Androgen receptor‐related diseases: what do we know?
Authors: Shukla G. C. , Plaga A. R. , Shankar E. , Gupta S.
Published: March 2016

The androgen receptor (AR) and the androgen–AR signaling pathway play a significant role in male sexual differentiation and the development and function of male reproductive and non‐reproductive organs. Because of AR's widely varied and important roles, its abnormalities have been identified in various diseases such as androgen insensitivity syndrome, spinal bulbar muscular atrophy, benign prostatic hyperplasia, and prostate cancer. This review provides an overview of the function of androgens and androgen–AR mediated diseases. In addition, the diseases delineated above are discussed with respect to their association with mutations and other post‐transcriptional modifications in the AR. Finally, we present an introduction to the potential therapeutic application of most recent pharmaceuticals including miRNAs in prostate cancer that specifically target the transactivation function of the AR at post‐transcriptional stages.
Enterobius vermicularis and its role in paediatric appendicitis: protection or predisposition?
Authors: Lala Shareena , Upadhyay Vipul
Published: March 2016

Background

E

nterobius vermicularis is one of the most common parasitic infections of the gastrointestinal tract, and has been shown to infest up to 28% of children worldwide. The role of
E

. vermicularis in acute appendicitis has previously been questioned, with some studies identifying infection as a precursor for inflammation of the appendix, with others refuting such a link.

Methods

A retrospective review was conducted of all appendices received for histological analysis at our unit from January 2002 to December 2011 (10‐year period), removed in the course of acute appendicectomy in children aged 3 to 15 years. Appendices were categorized by degree of inflammation and infestation with
E

. vermicularis.

Results

Appendicectomy for clinical suspicion of acute appendicitis was performed in 2923 patients, 1694 (58%) male, median age 11.6 years.
E

. vermicularis was present in 4% of appendices; 25% of which showed concurrent acute inflammation.
E

. vermicularis infestation was more common in females (F : M 76% versus 24% of inflamed appendices and 66.7% versus 33.3% for non‐inflamed appendices). European individuals showed higher representation in the
E

. vermicularis group than the total study population (79% versus 53% respectively).

Conclusion

E

. vermicularis was found to be more common in females and those of European descent. Seventy‐seven percent of patients with
E

. vermicularis did not have concurrent acute inflammation of the appendix on histological examination. The question remains as to whether infestation is protective of inflammation or whether infestation causes appendiceal colic and subsequent appendicectomy of a non‐inflamed appendix, thereby protective of the morbidity of acute appendicitis.
Hereditary non‐polyposis colorectal cancer/Lynch syndrome in three dimensions
Authors: Kravochuck Sara E. , Church James M.
Published: March 2016

Background

Hereditary non‐polyposis colorectal cancer (HNPCC) is defined by family history, and Lynch syndrome (LS) is defined genetically. However, universal tumour testing is now increasingly used to screen for patients with defective mismatch repair. This mixing of the results of family history, tumour testing and germline testing produces multiple permutations and combinations that can foster confusion. We wanted to clarify hereditary colorectal cancer using the three dimensions of classification: family history, tumour testing and germline testing.

Methods

Family history (Amsterdam I or II criteria versus not Amsterdam criteria) was used to define patients and families with HNPCC. Tumour testing and germline testing were then performed to sub‐classify patients and families. The permutations of these classifications are applied to our registry.

Results

There were 234 HNPCC families: 129 had LS of which 55 were three‐dimensional Lynch (family history, tumour testing and germline testing), 66 were two‐dimensional Lynch and eight were one‐dimensional Lynch. A total of 10 families had tumour Lynch (tumours with microsatellite instability or loss of expression of a mismatch repair protein but an Amsterdam‐negative family and negative germline testing), five were Lynch like (Amsterdam‐positive family, tumours with microsatellite instability or loss of expression of a mismatch repair protein on immunohistochemistry but negative germline testing), 26 were familial colorectal cancer type X and 95 were HNPCC.

Conclusion

Hereditary colorectal cancer can be confusing. Sorting families in three dimensions can clarify the confusion and may direct further testing and, ultimately, surveillance.
Prevalence of anal incontinence during pregnancy and 1 year after delivery in a cohort of primiparous women and a control group of nulliparous women
Authors: Svare Jens A. , Hansen Bent B. , Lose Gunnar
Published: March 2016

Introduction

The aim of the study was to examine the prevalence of anal incontinence (AI) during pregnancy and 1 year after delivery in primiparous women and to compare it with the prevalences in nulliparous women.

Material and methods

A validated questionnaire regarding AI was filled in by 1018 primiparous women after delivery and by 1836 nulliparous women (baseline). A similar questionnaire was filled in 1 year later by both groups.

Results

At baseline the prevalence of flatus incontinence was significantly higher in the primiparous than the nulliparous women (35 vs. 25%), while incontinence for liquid stools was significantly less frequent (8 vs. 20%). Prevalences of incontinence for solid stools were similar. One year later the prevalence of AI was similar in the two groups (flatus incontinence 24 vs. 25%, incontinence for liquid stools 18 vs. 19% and incontinence for solid stools 4 vs. 3%). AI 1 year after the delivery was not related to the mode of delivery. Women with grade 3 or 4 perineal lesions had a significantly higher prevalence of flatus incontinence 1 year after the delivery compared with women without such lesions (48 vs. 23%, p = 0.00).

Conclusions

This prospective cohort study showed remarkably high prevalences of AI during pregnancy and 1 year after delivery in primiparous women and likewise in nulliparous women at baseline and 1 year later. These results may indicate that factors other than pregnancy and delivery are of importance for AI in young women.
Nodular fasciitis of the vulva: a challenging histopathologic diagnosis supported by the detection of USP6 gene rearrangement
Authors: Pichler Sekulic Simona , Sekulic Miroslav
Published: March 2016

Nodular fasciitis involving the vulva on physical examination can mimic a Bartholin gland lesion, and histologically can have overlapping features with more ominous mesenchymal pathologies. We describe a case in which a 52‐year‐old perimenopausal woman presents with a vulvar mass. After an initial biopsy and later excision, the myofibroblastic lesion was noted to have areas of differing cellularity, with compact nodule formations at the periphery. Immunohistochemical staining showed lesional cells to be positive for desmin, estrogen receptor, progesterone receptor, and smooth muscle actin, and negative for CD34, ALK‐1, myogenin, caldesmon, S100, and wide spectrum (Oscar) cytokeratin. Desmin is generally negative in this lesion type, but the positivity in this case was considered to be secondary to the origin of the myofibroblastic cells of the vulva. The morphologic pattern and immunophenotype favored a diagnosis of nodular fasciitis, however, the degree of hypercellularity and desmin positivity warranted further analysis. The diagnosis was supported with fluorescence in situ hybridization that demonstrated USP6 gene rearrangement. This highlights the necessity in certain challenging cases for ancillary molecular and/or cytogenetic analysis.
Presence of hepatitis C (HCV) infection in Baby Boomers with Medicare is independently associated with mortality and resource utilisation
Authors: Sayiner M. , Wymer M. , Golabi P. , Ford J. , Srishord I. , Younossi Z. M.
Published: March 2016

Background

Hepatitis C virus is common among Baby Boomers (BB). As this cohort ages, they will increasingly become Medicare eligible.

Aim

To evaluate resource utilisation and mortality of BB‐Medicare recipients with HCV.

Methods

We used in‐patient and out‐patient Medicare databases (2005–2010). HCV was identified using ICD‐9 codes. Outcomes included resource utilisation [payment/case and in‐patient length of stay (LOS)] and short‐term mortality.

Results

Of 1 153 862 BB Medicare recipients (2005–2010), 3.2% (N = 37 365) had HCV. During this period, in‐patient Medicare‐BB (39 793–55 235) and their claims (78 924–106 232) increased. Furthermore, their overall mortality increased from 8.94% to 10.25% (P < 0.0001). In multivariate analysis, HCV [OR = 1.23 (1.16–1.29)], older age [OR = 1.98 (1.82–2.14)], male gender [OR = 1.25 (1.22–1.29)], ESRD [OR = 1.31 (1.26–1.36)], Charlson score [OR = 1.41 (1.40–1.42)] and LOS [OR = 1.02 (1.02–1.02)] predicted mortality. LOS decreased from 12.98 to 11.74 days (P < 0.0001), whereas total payments increased from $22 157 to $23 185 (P < .0001). During the study, the number of out‐patient Medicare BB patients (123 097–192 110) and claims (863 978–1 340 260) also increased. Furthermore, overall mortality increased from 3.15% to 3.31% (P = 0.0131). Again, HCV [OR = 1.23 (1.16–1.30)], older age [OR = 2.03 (1.89–2.17)], ESRD [OR = 3.40 (3.28–3.51)], disabled status [OR = 1.49 (1.40–1.58)] and Charlson score [OR = 1.39 (1.38–1.40)] predicted mortality. Annual total out‐patient payments increased from $3781 to $4001 (P < 0.0001). HCV [36.04% [34.28–37.82%)], 45–49 age [4.21% (3.14–5.28%)], ESRD [966.31% (954.86–977.88%)], disabled status [43.22% (41.67–44.80%)], Charlson score [46.78% (46.31–47.26%)] and study year [2.72% (2.58–2.85%)] independently predicted increases in payments.

Conclusions

In Baby Boomer Medicare recipients, diagnosis of HCV is independently associated with higher mortality and resource utilisation.
Violence in Context: Embracing an Ecological Approach to Violent Media Exposure
Authors: Glackin Erin , Gray Sarah A. O.
Published: March 2016

This commentary expands on Anderson, Bushman, Donnerstein, Hummer, and Warburton's agenda for minimizing the impacts of violent media exposure (VME) on youth aggression. We argue that, in order to effectively intervene in the development of aggression and other maladaptive traits, researchers and policy‐makers should take an ecological, developmental psychopathology approach to understanding children's exposure to VME within developmental, relational, environmental, and cultural contexts. Such a framework holds the most promise for identifying at‐risk groups, establishing targets of intervention, and testing mechanisms of change.
Validation of feasibility and quality of chicken breast meat cooked under various water‐cooking conditions
Authors: Chumngoen Wanwisa , Chen Hsin‐Yi , Tan Fa‐Jui
Published: March 2016

Under laboratory conditions, the qualities of boneless chicken breasts are commonly determined by placing them in a bag and cooking them in a water bath. The results are often applied as references for comparing the influences of cooking techniques. However, whether a sample cooked under this “laboratory” condition actually represents the meat cooked under the “real‐life” condition in which meat is frequently cooked directly in water without packaging remains unclear. Whether the two cooking conditions lead to comparable results in meat quality should be determined. This study evaluated the influence of cooking conditions, including “placed‐in‐bag and cooked in a water bath (BC)” and “cooked directly in hot water (WC)” conditions, on the quality of chicken meat. The results reveal that BC samples had a longer cooking time. Deboned‐and‐skinless BC samples had a higher cooking loss and lower protein solubility (P < 0.01). BC samples with bone and skin had a higher lightness in both skin and muscle. No significant differences were observed in attributes, including shear force, collagen solubility, microstructures, redness, yellowness and descriptive sensory characteristics between treatments. Based on the results, considering the quality attributes that might be influenced, is critical when conducting relevant research.
Therapeutic protein–drug interaction assessment for daclizumab high‐yield process in patients with multiple sclerosis using a cocktail approach
Authors: Tran Jonathan Q. , Othman Ahmed A. , Wolstencroft Paul , Elkins Jacob
Published: March 2016

Aims

To characterize the potential effect of daclizumab high‐yield process (DAC HYP), a monoclonal antibody that blocks the high‐affinity interleukin‐2 receptors for treatment of multiple sclerosis, on activity of cytochrome P450 (CYP) enzymes.

Methods

Twenty patients with multiple sclerosis received an oral cocktail of probe substrates of CYP1A2 (caffeine 200 mg), CYP2C9 (warfarin 10 mg/vitamin K 10 mg), CYP2C19 (omeprazole 40 mg), CYP2D6 (dextromethorphan 30 mg) and CYP3A (midazolam 5 mg) on two sequential occasions: 7 days before and 7 days after subcutaneous administration of DAC HYP 150 mg every 4 weeks for three doses. Serial pharmacokinetic blood samples up to 96 h post dose and 12‐h urine samples were collected on both occasions. Area under the curve (AUC) for caffeine, S‐warfarin, omeprazole and midazolam, and urine dextromethorphan to dextrorphan ratio were calculated. Statistical analyses were conducted on log‐transformed parameters using a linear mixed‐effects model.

Results

The 90% confidence intervals (CIs) for the geometric mean ratio (probe substrate with DAC HYP/probe substrate alone) for caffeine AUC from 0–12 h (0.93–1.15), S‐warfarin AUC from 0 to infinity (AUC[0–inf]) (0.95–1.06), omeprazole AUC(0–inf) (0.88–1.13) and midazolam AUC(0–inf) (0.89–1.15) were within the no‐effect boundary of 0.80–1.25. The geometric mean ratio for urine dextromethorphan to dextrorphan ratio was 1.01, with the 90% CI (0.76–1.34) extending slightly outside the no‐effect boundary, likely due to high variability with urine collections and CYP2D6 activity.

Conclusions

DAC HYP treatment in patients with multiple sclerosis had no effect on CYP 1A2, 2C9, 2C19, 2D6 and 3A activity.
Twenty‐five years of prescription opioid use in Australia: a whole‐of‐population analysis using pharmaceutical claims
Authors: Karanges Emily A. , Blanch Bianca , Buckley Nicholas A. , Pearson Sallie‐Anne
Published: March 2016

Aim

The aim of this paper is to investigate 25‐year trends in community use of prescribed opioid analgesics in Australia, and to map these trends against major changes to opioid registration and subsidy.

Methods

We obtained dispensing data from 1990 to 2014 from two sources: dispensing claims processed under Australia's national drug subsidy programme, the Pharmaceutical Benefits Scheme, including under co‐payment records from 2012; and estimates of non‐subsidized medicine use from a survey of Australian pharmacies (until 2011). Utilization was expressed in defined daily doses (DDD)/1000 population/day.

Results

Opioid dispensing increased almost four‐fold between 1990 and 2014, from 4.6 to 17.4 DDD/1000 pop/day. In 1990, weak, short‐acting or orally administered opioids accounted for over 90% of utilization. Use of long‐acting opioids increased over 17‐fold between 1990 and 2000, due primarily to the subsidy of long‐acting morphine and increased use of methadone for pain management. Between 2000 and 2011, oxycodone, fentanyl, buprenorphine, tramadol and hydromorphone use increased markedly. Use of strong opioids, long‐acting and transdermal preparations also increased, largely following the subsidy of various opioids for noncancer pain. In 2011, the most dispensed opioids were codeine (41.1% of total opioid use), oxycodone (19.7%) and tramadol (16.1%); long‐acting formulations comprised approximately half, and strong opioids 40%, of opioid dispensing.

Conclusions

Opioid utilization in Australia is increasing, although these figures remain below levels reported in the US and Canada. The increased use of opioids was largely driven by the subsidy of long‐acting formulations and opioids for the treatment of noncancer pain.
Characteristics and follow‐up of postmarketing studies of conditionally authorized medicines in the EU
Authors: Hoekman Jarno , Klamer Thea T. , Mantel‐Teeuwisse Aukje K. , Leufkens Hubert G. M. , De Bruin Marie L.
Published: March 2016

Aim

The aim of the present study was to provide an insight into the characteristics and follow‐up of postmarketing studies of medicines that were conditionally authorized in the European Union (EU).

Methods

We compiled a list of all postmarketing studies attached as specific obligations to the licence of medicines that were granted conditional marketing authorization from January 2006 to April 2014. Studies were characterized based on their objective, design, status upon marketing authorization (MA) and due data set by authorities. They were linked to online study registrations (Clinicaltrials.gov, ENCePP) to determine completion date. We described and associated characteristics of studies and medicines, and determined whether studies were completed on time.

Results

A total of 59 postmarketing studies were requested for 21 conditionally authorized medicines. Most studies had an interventional study design (73%), were ongoing upon MA (61%) and aimed to provide additional data on efficacy (45%). Interventional studies were more often ongoing and providing efficacy data, while observational and other studies were more often new and providing safety data. Frequent grounds for requesting postmarketing studies were ‘long‐term follow‐up’ and ‘increase data on subpopulations’. Of the 34 studies eligible for follow‐up analysis, 26 (76%) were completed and 17 (50%) completed on time. Actual completion time took a median (interquartile range) of 274 (−121 to 556) days longer than expected.

Conclusions

Our results indicated that most postmarketing studies attached to a conditional marketing authorization were eventually completed but that half were completed with a substantial delay. The observations suggest caution when broadening the use of postmarketing studies for resolving uncertainties about benefits and risks after MA.