bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining Social Support Among Adult Children of Incarcerated Parents
Authors: Luther Kate
Published: October 2015

Parental incarceration is related to many challenges and risks, yet we know little about resilience among this population. This study examined how social support contributed to the resilience of a sample of adult children of incarcerated parents. In‐depth qualitative interviews were conducted with 32 college students who had experienced parental incarceration during their childhoods. Social support from caring adults, including caregivers, incarcerated parents, grandparents, older siblings, teachers, and coaches helped facilitate success in light of parental criminality and incarceration. In particular, these adults promoted resilience in 3 ways: (a) providing access to conventional activities, (b) supporting a vision of a better life, and (c) encouraging turning points. Implications for those who work with children of incarcerated parents are discussed.
Structures of a diverse set of colchicine binding site inhibitors in complex with tubulin provide a rationale for drug discovery
Authors: Wang Yuxi , Zhang Hang , Gigant Benoît , Yu Yamei , Wu Yangping , Chen Xiangzheng , Lai Qinhuai , Yang Zhaoya , Chen Qiang , Yang Jinliang
Published: October 2015

Microtubules are dynamic assemblies of αβ‐tubulin heterodimers and have been recognized as highly attractive targets for cancer chemotherapy. A broad range of agents bind to tubulin and interfere with microtubule assembly. Despite having a long history of characterization, colchicine binding site inhibitors (CBSIs) have not yet reached the commercial phase as anti‐cancer drugs to date. We determined the structures of tubulin complexed with a set of structurally diverse CBSIs (lexibulin, nocodazole, plinabulin and tivantinib), among which nocodazole and tivantinib are both binary‐function inhibitors targeting cancer‐related kinases and microtubules simultaneously. High resolution structures revealed the detailed interactions between these ligands and tubulin. Our results showed that the binding modes of the CBSIs were different from previous docking models, highlighting the importance of crystal structure information in structure‐based drug design. A real structure‐based pharmacophore was proposed to rationalize key common interactions of the CBSIs at the colchicine domain. Our studies provide a solid structural basis for developing new anti‐cancer agents for the colchicine binding site.

Database

The atomic coordinates and structure factors for tubulin complexed with lexibulin, nocodazole, plinabulin and tivantinib have been deposited in the Protein Data Bank under accession codes 5CA0, 5CA1, 5C8Y and 5CB4, respectively.
Boards, Executive Excess Compensation, and Shared Power: Evidence from Nonprofit Firms
Authors: Garner Jacqueline L. , Harrison Teresa D.
Published: October 2015

We investigate how executives, the board, and excess compensation jointly affect the performance of nonprofits. Since the common measure of nonprofit performance often includes salaries, we also use expenses that directly benefit the targeted population. Our results suggest that above average compensation for executives is associated with poor firm performance. However, the negative relation of CEO pay to performance occurs for firms with only one executive, the CEO. We conclude that a powerful CEO with autonomy can harm firm performance, but other executives can mitigate these agency problems. The board also appears to monitor direct community benefits more than indirect benefits.
Bond Market Response to the Collapse of Prominent Investment Banks
Authors: Li Si , Madura Jeff , Richie Nivine
Published: October 2015

We find that the Bear Stearns rescue in March 2008 elicited a neutral or moderately favorable impact on bond prices. Conversely, we find that the Lehman Brothers failure (combined with news about Merrill Lynch and American International Group) in September 2008 elicited a pronounced negative impact. Bond prices of financial firms suffered more than bonds of nonfinancial firms following the Lehman failure. Our multivariate analysis shows that bonds issued by financial institutions that were previously presumed to be protected (based on bond rating and firm size) suffered more pronounced losses in response to the Lehman failure.
Liquidity Risk of Private Assets: Evidence from Real Estate Markets
Authors: Cheng Ping , Lin Zhenguo , Liu Yingchun
Published: October 2015

Investment in thinly traded private assets involves liquidity risk. Existing literature provides limited guidance as it mainly focuses on publicly traded security assets such as stocks and bonds. This paper develops an analytical tool for quantifying liquidity risk of private assets. Using commercial real estate as a model asset and under reasonable assumptions, we find that the magnitude of liquidity risk is too large to be ignored, especially in down markets when liquidity risk is a great concern.
Downstream Value of Upstream Finance
Authors: Hill Matthew D. , Kelly G. Wayne , Lockhart G. Brandon
Published: October 2015

We examine market value implications of managing liquidity via supplier financing. Results suggest a direct link between shareholder wealth and use of trade credit, and the relation exhibits significant cross‐sectional variation. In particular, the market value of trade credit varies with the liquidity of goods sold and competition in product markets. Evidence also indicates the value‐supplier financing association strengthens with financial constraint, which supports the financing motive for trade credit. Further findings are consistent with the transaction cost motive. Overall, we conclude that shareholders value the strategic benefits associated with supplier financing and that downstream firms’ characteristics influence this value.
The Development of L2 Japanese Self‐Introductions in an Asynchronous Computer‐Mediated Language Exchange
Authors: Hirotani Maki , Lyddon Paul A.
Published: October 2015

Computer‐mediated communication is an increasingly popular means of conducting classroom language exchanges, but those requiring asynchronous modes must generally forgo oral options in favor of text. This study explores the potential of asynchronous video, focusing on 15 university learners of Japanese in the United States in an interclass project with 26 English‐learning peers in Japan. Both groups performed online video self‐introductions in their second language (L2) before modeling the same task in their first language, completing a language awareness–raising activity on target language models of their choice, and performing a second self‐introduction in L2. The second L2 performances showed more elaborate discourse but no improvement in syntactic complexity. Implications are discussed for maximizing the pedagogical benefits of similar asynchronous online exchanges.
Students' Immersion Experiences in Study Abroad
Authors: Goldoni Federica
Published: October 2015

Data show that a larger number of students than ever are participating in learning experiences abroad. However, such programs are not always as immersive and intensive as participants, faculty, program directors, and administrators would wish. This study examines the ways in which students created sustained opportunities to interact with members of the host community as well as episodes of cultural clash, miscommunication, and misunderstanding experienced at the intersection of two cultures that led to diminishing willingness to interact with members of the host community. The article concludes with recommendations for pre‐departure experiences that are designed to help students become more aware of their sociocultural identities, cultural values, learning goals, and program expectations as well as to invest in their own learning and prepare to engage in sustained and meaningful ways with members of the host culture.
Development and function of the midbrain dopamine system: what we know and what we need to
Authors: Bissonette G. B. , Roesch M. R.
Published: October 2015

The past two decades have seen an explosion in our understanding of the origin and development of the midbrain dopamine system. Much of this work has been focused on the aspects of dopamine neuron development related to the onset of movement disorders such as Parkinson's disease, with the intent of hopefully delaying, preventing or fixing symptoms. While midbrain dopamine degeneration is a major focus for treatment and research, many other human disorders are impacted by abnormal dopamine, including drug addiction, autism and schizophrenia. Understanding dopamine neuron ontogeny and how dopamine connections and circuitry develops may provide us with key insights into potentially important avenues of research for other dopamine‐related disorders. This review will provide a brief overview of the major molecular and genetic players throughout the development of midbrain dopamine neurons and what we know about the behavioral‐ and disease‐related implications associated with perturbations to midbrain dopamine neuron development. We intend to combine the knowledge of two broad fields of neuroscience, both developmental and behavioral, with the intent on fostering greater discussion between branches of neuroscience in the service of addressing complex cognitive questions from a developmental perspective and identifying important gaps in our knowledge for future study.
Violent and criminal manifestations in dementia patients
Authors: Cipriani Gabriele , Lucetti Claudio , Danti Sabrina , Carlesi Cecilia , Nuti Angelo
Published: October 2015

Although the older adults have been studied as victims of violence, geriatric patients can display violent behavior. The purpose of the present review was to explore the phenomenon of criminal violations and violent acts in people with dementia. The authors usedPubMed to search theMEDLINEdatabase and other sources for original research and review articles on criminal and violent manifestation in demented patients combining the terms “criminal manifestation,” “violence, aggressive behavior,” “homicide,” “suicide” and “homicide–suicide” together with “dementia”. Possible biomarkers of violence are considered. The present review highlights the risk factors for violence in patients suffering from dementia, and reviews the literature about criminal violations and homicidal/suicidal behavior in this patient group.Geriatr Gerontol Int 2016; 16: 541–549.
Effect of early rehabilitation on activities of daily living in patients with aspiration pneumonia
Authors: Yagi Maiko , Yasunaga Hideo , Matsui Hiroki , Fushimi Kiyohide , Fujimoto Masashi , Koyama Teruyuki , Fujitani Junko
Published: October 2015

Aim

To assess the effect of early rehabilitation on improving activities of daily living (ADL) in elderly patients with aspiration pneumonia.

Methods

Using the Japanese Diagnosis Procedure Combination inpatient database, we retrospectively analyzed consecutive patients with aspiration pneumonia at admission who received early rehabilitation (n = 48 201) or did not receive any rehabilitation (n = 64 357) from July 2010 to March 2013. Early rehabilitation was defined as any type of physical rehabilitation initiated within 7 days after admission. The proportions of improved ADL scores from admission to discharge were compared between the early rehabilitation group and the non‐rehabilitation group using a multivariable logistic regression analysis and instrumental variable analysis.

Results

The proportion of improved ADL scores was higher in the early rehabilitation group than in the non‐rehabilitation group (25.4% vs 33.9%; P < 0.001). The multivariable logistic regression analysis showed that the early rehabilitation group exhibited significant improvement in ADL (odds ratio 1.57; 95% confidence interval 1.50–1.64; P < 0.001). The instrumental variable analysis showed that early rehabilitation was associated with increased proportion of improved ADL (risk difference 8.2%; 95% confidence interval 6.9–9.5%; P < 0.001).

Conclusions

The present results suggest that early rehabilitation might improve ADL during hospitalization in patients with aspiration pneumonia. Geriatr Gerontol Int 2016; 16: 1181–1187.
Relationship among health‐related quality of life, depression and awareness of home care services in elderly patients
Authors: Polat Ülkü , Bayrak Kahraman Burcu , Kaynak İlknur , Görgülü Ümit
Published: October 2015

Aims

The present descriptive study was carried out to determine the relationship between health‐related quality of life, depression and awareness of home care services among elderly patients.

Methods

Patients aged 65 years or older staying at the surgery and internal medicine clinics were included in the study. The “Patient Introduction Form,” “Short Form‐36 Quality of Life Questionnaire” and “Geriatric Depression Scale” were utilized in the collection of data.

Results

In the present study, it was determined that only approximately half of elderly patients (54.9%) knew the concept of home care, most of them had not previously received home care and requested home care related to medical care. The mean scores were lower in some areas of the quality of life questionnaire in some factors that could influence home care awareness. These factors were determined as: female sex, history of falling, chronic illness, functionally, moderately or severely dependent, no previous receipt of home care and wishing to receive home care.

Conclusions

The home care requirement of elderly patients can be influenced by many physiological, psychological and social factors that can affect their quality of life. Thus, it is of utmost importance that medical professionals evaluate the quality of life of elderly individuals and its influencing factors. Geriatr Gerontol Int 2016; 16: 1211–1219.
Disruption of MeCP2 attenuates circadian rhythm in CRISPR/Cas9‐based Rett syndrome model mouse
Authors: Tsuchiya Yoshiki , Minami Yoichi , Umemura Yasuhiro , Watanabe Hitomi , Ono Daisuke , Nakamura Wataru , Takahashi Tomoyuki , Honma Sato , Kondoh Gen , Matsuishi Toyojiro , Yagita Kazuhiro
Published: October 2015

Methyl‐CpG‐binding protein 2 (Mecp2) is an X‐linked gene encoding a methylated DNA‐binding nuclear protein which regulates transcriptional activity. The mutation of MECP2 in humans is associated with Rett syndrome (RTT), a neurodevelopmental disorder. Patients with RTT frequently show abnormal sleep patterns and sleep‐associated problems, in addition to autistic symptoms, raising the possibility of circadian clock dysfunction in RTT. In this study, we investigated circadian clock function in Mecp2‐deficient mice. We successfully generated both male and female Mecp2‐deficient mice on the wild‐type C57BL/6 background and PER2Luciferase (PER2Luc) knock‐in background using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system. Generated Mecp2‐deficient mice recapitulated reduced activity in mouse models of RTT, and their activity rhythms were diminished in constant dark conditions. Furthermore, real‐time bioluminescence imaging showed that the amplitude of PER2Luc‐driven circadian oscillation was significantly attenuated in Mecp2‐deficient SCN neurons. On the other hand, in vitro circadian rhythm development assay using Mecp2‐deficient mouse embryonic stem cells (ESCs) did not show amplitude changes of PER2Luc bioluminescence rhythms. Together, these results show that Mecp2 deficiency abrogates the circadian pacemaking ability of the SCN, which may be a therapeutic target to treat the sleep problems of patients with RTT.
The Precambrian–Cambrian nonconformity at the Ercall Quarries, The Wrekin, Shropshire, UK
Authors: Pringle Jamie K. , Stimpson Ian G.
Published: October 2015

The Precambrian–Cambrian boundary is iconic, marking the first appearance of shelly fauna in the fossil record, and opening the Phanerozoic Eon. In England and Wales, the transition from predominantly Precambrian igneous rocks to Cambrian sedimentary strata is generally unconformable. An exceptional exposure of this transition can be observed in the Ercall Quarries in Shropshire, a classic locality in all senses of the word.
Evaluation of Methane Sources in Groundwater in Northeastern Pennsylvania
Authors: Molofsky Lisa J. , Connor John A. , Wylie Albert S. , Wagner Tom , Farhat Shahla K.
Published: October 2015

Testing of 1701 water wells in northeastern Pennsylvania shows that methane is ubiquitous in groundwater, with higher concentrations observed in valleys vs. upland areas and in association with calcium‐sodium‐bicarbonate, sodium‐bicarbonate, and sodium‐chloride rich waters—indicating that, on a regional scale, methane concentrations are best correlated to topographic and hydrogeologic features, rather than shale‐gas extraction. In addition, our assessment of isotopic and molecular analyses of hydrocarbon gases in the Dimock Township suggest that gases present in local water wells are most consistent with Middle and Upper Devonian gases sampled in the annular spaces of local gas wells, as opposed to Marcellus Production gas. Combined, these findings suggest that the methane concentrations in Susquehanna County water wells can be explained without the migration of Marcellus shale gas through fractures, an observation that has important implications for understanding the nature of risks associated with shale‐gas extraction.
Diagnosis and Clinical Features of Trigemino‐Autonomic Headaches
Authors: May Arne
Published: October 2015

Although severe short‐lasting headaches are rare, they can be considered disabling conditions with a major impact on the quality of life of patients. These headaches can divided broadly in to those associated with autonomic symptoms, so called trigeminal autonomic cephalgias (TACs), and those with few or no autonomic symptoms. The TACs include cluster headache, paroxysmal hemicranias, hemicrania continua, and short‐lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms as well as short‐lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing syndrome. In all of these syndromes, half‐sided head pain and ipsilateral cranial autonomic symptoms such as lacrimation or rhinorrhea are prominent. The paroxysmal hemicranias have, unlike cluster headaches, a very robust response to indomethacin, leading to a notion of indomethacin‐sensitive headaches. The diagnosis of TACs is exclusively a clinical task. Because of the fact that cluster headache is strictly half‐sided, typically involves the region around the eye and temple and often starts in the upper jaw, most patients first consult a dentist or ophthalmologist. No single instrumental examination has yet been able to define, or ensure, the correct diagnosis, or differentiate idiopathic headache syndromes. It is crucial that a trained neurologist sees these patients early so that management can be optimized and unnecessary procedures can be avoided. Although TACS are, in comparison to migraine, quite rare, they are nevertheless clinically very important for the neurologist to consider as they are easy to diagnose and the treatment is very effective in most patients.
Intraductal tubulopapillary neoplasm of the bile duct: A case report and review of the published work
Authors: Nakagawa Takashi , Arisaka Yoshifumi , Ajiki Tetsuo , Fujikura Kohei , Masuda Atsuhiro , Takenaka Mamoru , Shiomi Hideyuki , Okabe Yoshihiro , Fukumoto Takumi , Ku Yonson , Azuma Takeshi , Zen Yoh
Published: October 2015

Recent studies have suggested that a peculiar tumor mimicking intraductal tubulopapillary neoplasms (ITPN) of the pancreas can develop in the bile duct. Here, we present a similar case and review the published work on the newly proposed biliary neoplasm. A 68‐year‐old woman was referred to us for further evaluation of a liver mass. On imaging, the tumor was 40 mm in size and intraductal in location, and was enhanced slightly on the contrast‐enhanced computed tomography. No mucin overproduction was found. She underwent right hepatectomy for suspected intraductal papillary neoplasm of the bile duct. The tumor histologically consisted of the biliary‐type epithelium arranged in a tubular architecture within the dilated bile duct. Tumor cells had features of high‐grade dysplasia but no stroma invasion. No expressions of MUC2 and MUC5AC were noted. On molecular studies, KRAS and GNAS appeared to be wild‐type genotypes. These features were in keeping with ITPN. In the published work review, “biliary ITPN” described in four manuscripts were characterized by predominantly intrahepatic/hilar in location, histological tubular architecture, negative expressions of MUC2 and MUC5AC, and uncommon alterations of KRAS, GNAS and BRAF. Although invasive malignancy was present in 71%, the outcome was favorable with the 5‐year survival expected to be approximately 90%. Biliary ITPN are supposedly uncommon, but a greater awareness of this condition may give more chance to diagnose the underrecognized neoplasm.
Subject or Signifier?: Food and the History of Early North America
Authors: LaCombe Michael A.
Published: October 2015

When food appears in the scholarly literature on early America, it is most often as part of a discussion of other subjects. Social historians and ethnohistorians have interpreted particular foods as a defining feature of African and Native American cultures, measuring their endurance and/or assimilation with European society by reference to those foods. Social historians of gender have found the roots of larger social relationships in the daily labor necessary to produce food. Other historians have seen in staple crops or characteristic recipes a means to trace either the regional variations in British America or the convergence of those cultures into an American national identity. A final group has focused on commodities, especially tea and sugar, as the driving force behind the development of 18th‐century consumer culture and norms of gentility. Food is a common thread in each of these fields of study but not, as yet, a field of its own.

More recent studies of food in early America suggest that a new phase in the scholarship is emerging, with distinct advances over these earlier approaches. Where earlier accounts interpreted food as deriving its meaning from a single discourse or stable set of symbols (gender, status, race, ethnicity, or gentility, for example), food in this newer literature is multifaceted and polyvalent. At any given place, time, and occasion, food can be a subject in its own right, a signifier with multiple connotations, or both: food is at once a biological necessity, the focus of daily life and household labor, a marker of identity, and a measure of social inequality. Given this complexity, newer literature has called into question historians' understanding of how cultures and identities are transmitted from place to place or generation to generation and has articulated a more nuanced understanding of cultural exchange and encounter. These are arguably food's greatest potential contributions to the historiography of early America and vice versa.
Museums, History and Migration in Australia
Authors: Henrich Eureka
Published: October 2015

It is easy to take the presence of migration histories in Australian museums for granted. After all, most Australians are descended from immigrants, Australia's cultural diversity is celebrated as a national strength, and museums must represent and explain that diversity in order to tell stories of the nation's past. However, it is only in the last 30 years that experiences of migration have become the subject of collections, exhibitions and even entire museums in Australia. In light of recent research and scholarly work, this article surveys how migration history is portrayed in Australian museums. It reveals that creators of migration exhibitions have constantly negotiated a tension between an inclusive and affirming ‘nation of immigrants’ story and the more difficult histories of conflict, difference and exclusion that characterise Australia's history of migration. Curatorial approaches to this tension have been shaped by changing political climates, public attitudes to migrants and multiculturalism, and community demands for representation in cultural institutions. International museological events, such as the opening of Ellis Island Immigration Museum in New York in 1990, have also been influential. When located within these institutional, social and political contexts, exhibitions of migration history in Australia can be understood through three broad and overlapping phases. The earliest exhibitions, beginning in the mid‐1980s, aimed to integrate minority migrant experiences into a pluralistic national story in order to overturn previous mono‐cultural narratives of national becoming. A second phase of exhibitions, from the mid‐1990s overtly democratised this ‘new’ migration narrative in an attempt to appeal to Anglo‐Celtic Australians who did not identify with multiculturalism. While elements of both approaches remain, in last decade Australian museums have begun to look beyond migrations to the nation and towards an exploration of transnational networks, personal belonging and dislocation, and the idea of home.
Animals and Imperialism: Recent Historiographical Trends
Authors: Skabelund Aaron
Published: October 2015

In the last decade or so, an increasing number of historians have written about the relationship between animals and imperialism. Their work builds on pioneering scholarship by environmental historian Alfred Crosby and cultural historians Harriet Ritvo and John MacKenzie, among others. Recent writing on animals and imperialism, influenced by wider trends in animal studies and history, has taken this topic in new directions. Namely, history writing on animals and imperialism has become more concerned with actual animals and their relationship with people, the metaphorical deployment of creatures, animal agency, and sources that give voice to animals. Work on animals and imperialism will likely benefit from becoming less Western‐centric and more transnational and transimperial.
“We are Brothers! Let us Separate!” Jews and Community Building in American Cities during the 19th Century
Authors: Brinkmann Tobias
Published: October 2015

The article examines the evolution of organized Jewish communities in the United States during the second half of the 19th century. After discussing why the historiography tends to focus on New York, the beginnings of the organized Jewish community in Chicago serves as a case study to highlight the challenges Jewish immigrants faced as they tried to build communities. Landsmanshaft, class, religion, voluntary membership, and the enormous size and diversity of urban Jewish populations after 1850 precluded the recreation of tight‐knit European‐style communities. By avoiding sources of conflict, notably religion, the traditional social tasks of the community emerged as the smallest common denominator bringing Jews of different backgrounds together on a single platform.
Micro‐CT evaluation of the efficacy of hard‐tissue removal from the root canal and isthmus area by positive and negative pressure irrigation systems
Authors: Versiani M. A. , Alves F. R. F. , Andrade‐Junior C. V. , Marceliano‐Alves M. F. , Provenzano J. C. , Rôças I. N. , Sousa‐Neto M. D. , Siqueira J. F.
Published: October 2015

Aim

To evaluate the removal of accumulated hard‐tissue debris (AHTD) from the root canal system of mandibular molars by positive and negative pressure irrigation systems, using micro‐CT imaging analysis.

Methodology

Mandibular molars with a single canal in the distal root and 2 canals connected by an isthmus in the mesial root were matched based on similar morphological dimensions using micro‐CT evaluation and assigned to 2 experimental groups (n = 20 mesial and 10 distal canals), according to the irrigation protocol: apical positive (conventional irrigation) or negative (EndoVac system) pressure. Changes in root canal volume and surface area as well as percentage of uninstrumented canal wall surface and accumulated hard‐tissue debris (AHTD) after canal preparation were compared statistically using the independent sample t‐test and Mann–Whitney U‐test, with the significance level set at 5%.

Results

Volume, surface area and percentage of static voxels in either mesial or distal root canal systems were not significantly different between groups before or after root canal preparation (P > 0.05). After preparation, AHTD was not observed in the distal canal of both groups. However, in the mesial root canal system, the conventional irrigation group was associated with a significantly higher median percentage of AHTD (11.48%; IQR: 5.9–22.6; range: 1.86–41.98) than the EndoVac group (3.40%; IQR: 1.5–7.3; range: 0.82–12.84) (P < 0.05).

Conclusions

Neither irrigation protocol succeeded in rendering the mesial canal system free of AHTD; however, apical negative pressure irrigation resulted in lower levels of AHTD than conventional irrigation.
Surgical management of damaged inferior alveolar nerve caused by endodontic overfilling of calcium hydroxide paste
Authors: Byun S.‐H. , Kim S.‐S. , Chung H.‐J. , Lim H.‐K. , Hei W.‐H. , Woo J.‐M. , Kim S.‐M. , Lee J.‐H.
Published: October 2015

Aim

To evaluate the neurosensory outcome of management of damaged inferior alveolar nerves caused by endodontic overfilling and to assess the efficacy of delayed surgical intervention.

Methodology

Nine patients who underwent surgical removal of extruded endodontic material were included. All patients were evaluated for neurosensory function using a set of standardized tests. The outcome of surgical intervention was evaluated through patient interview and quantitative statistical analysis.

Results

Surgical procedures included foreign body removal, microsurgical external/internal decompression, excision of neuroma followed by nerve repair, and excision of damaged nerve segment with interpositional nerve graft. Seven of the nine patients had significant improvement according to the follow‐up neurosensory assessment. Four patients reported significant improvement, three patients reported mild improvement and two patients reported no appreciable improvement in the Visual Analog Scale (VAS). Two patients who reported no appreciable improvement in VAS also did not achieve FSR. In these patients, calcium hydroxide was spread widely along the IAN and a surgical approach was obtained via sagittal spit osteotomy. The mean time to reach FSR was 222.7 (±41.8) days with a range of 106–397 days. In the early repair group who received surgery within 60 days, three out of five patients achieved FSR in a mean time of 198.0 (±76.2) days. The mean time to FSR in all four subjects who received surgical attention over 60 days after injury was 241.3 (±139.8) days with a range of 106–397 days. As all four cases in the late repair group with limited amount of nerve injury achieved FSR, only 3 of 5 early repair cases with wide‐spread injury achieved a similar outcome.

Conclusion

The results of this case series confirmed the notion that surgical management of the inferior alveolar nerve is effective in the treatment of nerve injuries caused by endodontic extrusion of calcium hydroxide paste. Delayed surgical repair of the inferior alveolar nerve can be indicated and helpful for the neurosensory recovery of damaged IAN, however, the surgical management was less effective in case of widespread nerve injuries.
16th IHIW: Immunogenetics of Aging
Authors: Naumova E. , Ivanova M. , Pawelec G. , Constantinescu I. , Bogunia‐Kubik K. , Lange A. , Oguz F. , Ozdilli K. , Franceschi C. , Caruso C. , Mishra M. , Middleton D.
Published: October 2015

Ageing is a process characterised by progressive loss of function in multiple different organ systems, such as the nervous, endocrine and immune systems. Current data showing that ageing processes may be associated with alterations in the immune system suggest that some of the genetic determinants of senescence might be polymorphic genes that regulate immune responses. The ‘Immunogenetics of Aging’ programme was a component introduced in the 14th International HLA and Immunogenetics Workshop (IHIWS) and developed further within the 15th and 16th. The aim of this component was to determine the contribution of immune genes to successful ageing and an increased capacity to reach the extreme limits of lifespan. Within the 16th IHIWS, new populations were included, and the number of samples analysed was increased. Analysis was focused on innate immunity genes (KIR and MBL2) and their correlation with CMV serostatus. Collaborative studies suggested that both activating and inhibitory KIR and functionally relevant MBL2 haplotypes are important factors for control of CMV infection in the elderly and therefore for chronic low‐grade inflammation. Results showed that these genes might be predictive biomarkers in ageing and longevity. Prevalence of MBL2 haplotypes determining absence of the protein (LYPB, LYQC and HYPD) was observed in elderly people with a higher CMV antibody titre. The high CMV titre was also associated with a decreased frequency of the activatory KIR2DS5 and A1B10 haplotypes in elderly. Due to the role of KIR and low or deficient MBL haplotypes in viral infections, these genetic markers could be considered as indicators of a need for CMV prophylaxis at younger age and therefore increased probability of longer lifespan.
Serine protease inhibitors and cytotoxic T lymphocytes
Authors: Ashton‐Rickardt Philip G.
Published: October 2015

Summary:  Serine proteases control a wide variety of physiological and pathological processes in multi‐cellular organisms, including blood clotting, cancer, cell death, osmoregulation, tissue remodeling, and immunity to infection. Cytotoxic T lymphocytes (CTLs) are required for adaptive cell‐mediated immunity to intracellular pathogens by killing infected cells and through the development of memory T cells. Serine proteases not only allow a CTL to kill but also impose homeostatic control on CTL number. Serine protease inhibitors (serpins) are the physiological regulators of serine proteases’ activity. In this review, I discuss the role of serpins in controlling the recognition of antigen, effector function, and homeostatic control of CTLs through the inhibition of physiological serine protease targets. An emerging view of serpins is that they are important promoters of cellular viability through their inhibition of executioner proteases. This view is discussed in the context of the T‐lymphocyte survival during effector responses and the development and persistence of long‐lived memory T cells. Given the important role serpins play in CTL immunity, I discuss the potential for developing new immunotherapeutic approaches based directly on serpins or knowledge gained from identifying their physiologically relevant protease targets.
Heterologous immunity between viruses
Authors: Welsh Raymond M. , Che Jenny W. , Brehm Michael A. , Selin Liisa K.
Published: October 2015

Summary:  Immune memory responses to previously encountered pathogens can sometimes alter the immune response to and the course of infection of an unrelated pathogen by a process known as heterologous immunity. This response can lead to enhanced or diminished protective immunity and altered immunopathology. Here, we discuss the nature of T‐cell cross‐reactivity and describe matrices of epitopes from different viruses eliciting cross‐reactive CD8+ T‐cell responses. We examine the parameters of heterologous immunity mediated by these cross‐reactive T cells during viral infections in mice and humans. We show that heterologous immunity can disrupt T‐cell memory pools, alter the complexity of the T‐cell repertoire, change patterns of T‐cell immunodominance, lead to the selection of viral epitope‐escape variants, alter the pathogenesis of viral infections, and, by virtue of the private specificity of T‐cell repertoires within individuals, contribute to dramatic variations in viral disease. We propose that heterologous immunity is an important factor in resistance to and variations of human viral infections and that issues of heterologous immunity should be considered in the design of vaccines.
Granzyme A activates another way to die
Authors: Lieberman Judy
Published: October 2015

Summary:  Granzyme A (GzmA) is the most abundant serine protease in killer cell cytotoxic granules. GzmA activates a novel programed cell death pathway that begins in the mitochondrion, where cleavage of NDUFS3 in electron transport complex I disrupts mitochondrial metabolism and generates reactive oxygen species (ROS). ROS drives the endoplasmic reticulum‐associated SET complex into the nucleus, where it activates single‐stranded DNA damage. GzmA also targets other important nuclear proteins for degradation, including histones, the lamins that maintain the nuclear envelope, and several key DNA damage repair proteins (Ku70, PARP‐1). Cells that are resistant to the caspases or GzmB by overexpressing bcl‐2 family anti‐apoptotic proteins or caspase or GzmB protease inhibitors are sensitive to GzmA. By activating multiple cell death pathways, killer cells provide better protection against a variety of intracellular pathogens and tumors. GzmA also has proinflammatory activity; it activates pro‐interleukin‐1β and may also have other proinflammatory effects that remain to be elucidated.
The transcriptional control of the perforin locus
Authors: Pipkin Matthew E. , Rao Anjana , Lichtenheld Mathias G.
Published: October 2015

Summary:  Natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) use cytotoxic granules containing perforin and granzymes to lyse infected or malignant host cells, thereby providing immunity to intracellular microbes and tumors. Perforin is essential for cytotoxic granule‐mediated killing. Perforin expression is regulated transcriptionally and correlates tightly with the development of cells that can exhibit cytotoxic activity. Although a number of genes transcribed by T cells and NK cells have been studied, the cell‐specificity of perforin gene expression makes it an ideal model system in which to clarify the transcriptional mechanisms that guide the development and activation of cytotoxic lymphocytes. In this review, we discuss what is known about perforin expression and its regulation, then elaborate on recent studies that utilized chromosome transfer and bacterial artificial chromosome transgenics to define a comprehensive set of cis‐regulatory regions that control transcription of the human PRF1 gene in a near‐physiologic context. In addition, we compare the human and murine Prf1 loci and discuss how transcription factors known to be important for driving CTL differentiation might also directly regulate the cis‐acting domains that control Prf1. Our review emphasizes how studies of PRF1/Prf1 gene transcription can illuminate not only the mechanisms of cytotoxic lymphocyte differentiation but also some basic principles of transcriptional regulation.
Main mutations in the hepatitis B virus basic core promoter (A1762T/G1764A) before HBeAg loss are markers that identify patients who will require long‐term treatment
Authors: Tabernero D. , Sánchez M. J. , Homs M. , Rodríguez‐Frías F. , Jardí R. , Schaper M. , Esteban R. , Buti M.
Published: October 2015

Aliment Pharmacol Ther 2010; 32: 97–104

Background  Some patients continue to have detectable HBV‐DNA levels with liver disease progression after hepatitis B e antigen (HBeAg) loss. It is important to identify these patients, candidates for long‐term treatment.

Aims  To evaluate hepatitis B virus (HBV) genotype and the main mutations in the basic core promoter (BCP, A1762T/G1764A) and precore (G1896A) sequences as markers of persistent HBV‐DNA after HBeAg loss.

Methods  We analysed 60 serum samples from 20 Caucasian, HBeAg‐positive, chronic hepatitis B patients, who lost HBeAg and were followed‐up longitudinally. HBV genotype and precore and BCP mutations were determined before, at the time of, and after HBeAg loss.

Results  After HBeAg loss, eight (40%) patients continued to have undetectable HBV‐DNA and 12 (60%) had persistent HBV‐DNA (median level 4.7 log10 copies/mL). The presence of BCP mutations prior to therapy was the only variable associated with persistently detectable viraemia (P = 0.017). Four patients with genotype A and no mutations in the BCP region experienced hepatitis B surface antigen (HBsAg) loss after a mean period of 35 months from baseline.

Conclusions  Main BCP mutations in HBeAg‐positive patients are useful markers to identify patients who will not have sustained virological suppression after HBeAg loss and therapy discontinuation and could benefit from long‐term treatment.
Guidelines for the use of imaging in the management of myeloma
Authors: D'Sa Shirley , Abildgaard Niels , Tighe Jane , Shaw Penny , Hall‐Craggs Margaret
Published: October 2015

In 2001, reference to the use of imaging in the British Committee for Standards in Haematology guidelines for the diagnosis and management of myeloma was confined to the standard use of plain X‐rays in the diagnostic skeletal survey and emergency use of computed tomography (CT) and magnetic resonance (MR) imaging in the setting of cord compression. Since then, there has been a steady rise in interest in the use of various imaging techniques in the management of myeloma. The purpose of imaging in the management of myeloma includes the assessment of the extent and severity of the disease at presentation, the identification and characterisation of complications, and the assessment of response to therapy. Plain radiography, CT, and MR imaging are generally established examination techniques in myeloma whilst positron emission tomography (PET) and 99Technetium sestamibi (MIBI) imaging are promising newer scanning techniques under current evaluation. These stand‐alone imaging guidelines discuss recommendations for the use of each modality of imaging at diagnosis and in the follow up of patients with myeloma.
Current concepts of IgE regulation and impact of genetic determinants
Authors: Potaczek D. P. , Kabesch M.
Published: October 2015

Immunoglobulin E (IgE) mediated immune responses seem to be directed against parasites and neoplasms, but are best known for their involvement in allergies. The IgE network is tightly controlled at different levels as outlined in this review. Genetic determinants were suspected to influence IgE regulation and IgE levels considerably for many years. Linkage and candidate gene studies suggested a number of loci and genes to correlate with total serum IgE levels, and recently genome‐wide association studies (GWAS) provided the power to identify genetic determinants for total serum IgE levels: 1q23 (FCER1A), 5q31 (RAD50, IL13, IL4), 12q13 (STAT6), 6p21.3 (HLA‐DRB1) and 16p12 (IL4R, IL21R). In this review, we analyse the potential role of these GWAS hits in the IgE network and suggest mechanisms of how genes and genetic variants in these loci may influence IgE regulation.
Increased alpha‐B‐crystallin expression in mammary metaplastic carcinomas
Authors: Chan Siu‐Ki , Lui Philip C W , Tan Puay‐Hoon , Yamaguchi Rin , Moriya Takuya , Yu Alex M C , Shao Mu‐Min , Hliang Thazin , Wong Sio‐In , Tse Gary M
Published: October 2015

Chan S‐K, Lui P C W, Tan P‐H, Yamaguchi R, Moriya T, Yu A M C, Shao M‐M, Hliang T, Wong S‐I & Tse G M (2011) Histopathology59, 247–255

Increased alpha‐B‐crystallin expression in mammary metaplastic carcinomas

Aims:  Mammary metaplastic carcinoma is a rare breast carcinoma, and may present diagnostic difficulty. Alpha‐B‐crystallin has been recently reported to be expressed in basal‐like and metaplastic carcinomas.

Methods and results:  Thirty‐three metaplastic carcinomas, 44 conventional high‐grade carcinomas and 28 mesenchymal spindle cell neoplasms as controls were assessed for their expression of αB‐crystallin and conventional basal‐like phenotypic markers CK5/6, CK14, p63, c‐kit and epidermal growth factor receptor (EGFR) by immunohistochemistry. Alpha‐B‐crystallin staining was positive in 68% of the metaplastic carcinomas with cytoplasmic staining in all tumour cell components. CK5/6, CK14, p63, c‐kit and EGFR stained 43%, 68%, 45%, 21% and 25% of the metaplastic carcinomas, respectively. Combining these markers, 84% of the metaplastic carcinomas expressed either αB‐crystallin or CK14. In comparison, only 14% (six cases) of conventional high‐grade carcinoma and 7% (two cases) of mesenchymal spindle cell neoplasm expressed αB‐crystallin; all but one of these carcinomas were ER/PR/HER2 triple‐negative.

Conclusions:  Using αB‐crystallin for diagnosis of metaplastic carcinoma gives a 68% sensitivity, 88% specificity, 74% positive predictive value, 85% negative predictive value and 78% accuracy. The sensitivity is enhanced to 84% with combinations of αB‐crystallin/CK14. Alpha‐B‐crystallin may be used as an adjunct marker in the diagnosis of metaplastic carcinoma.
Epidermal growth factor receptor gene amplification and protein overexpression in basal‐like carcinoma of the breast
Authors: Shao Mu‐Min , Zhang Fan , Meng Gang , Wang Xing‐Xing , Xu Hua , Yu Xue‐Weng , Chen Liang‐Yan , Tse Gary M
Published: October 2015

Shao M‐M, Zhang F, Meng G, Wang X‐X, Xu H, Yu X‐W, Chen L‐Y & Tse G M  (2011) Histopathology59, 264–273

Epidermal growth factor receptor gene amplification and protein overexpression in basal‐like carcinoma of the breast

Aims:  Epidermal growth factor receptor (EGFR) is frequently expressed in basal‐like breast cancer (BLBC). The aim of this study was to evaluate their correlation as detected by immunohistochemistry (IHC) or fluorescence in‐situ hybridization (FISH).

Methods and results:  IHC for oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER) 2, cytokeratin (CK) 5/6 and EGFR, and FISH for EGFR amplification, were performed in 59 cases of BLBC. EGFR IHC results were scored semiquantitatively, and compared with its gene amplification status. ER, PR and HER2 were negative in all cases, whereas 35 and 55 cases were positive for CK5/6 and EGFR. For EGFR IHC, 20, 11, 11 and 17 cases showed a negative, a low, an intermediate or a high staining level, respectively, and seven cases showed gene amplification by FISH, with two, 19, 11 and 20 cases showing balanced monosony, disomy, trisomy, and polysomy respectively. Immunohistochemical expression in gene‐amplified tumours was significantly higher than in those without amplification, including balanced polysomy tumours. EGFR immunohistochemical expression also correlated with the EGFR/chromosome 7 ratio. High sensitivity (86%) and negative predictive value (98%) were achieved with high‐level immunohistochemical expression as a cut‐off to predict gene amplification.

Conclusions:  High‐level EGFR immunohistochemical expression correlated with and predicted EGFR amplification, and may be used as a screening method to exclude gene amplification.