bluuebunny/crossref_metadata_2025 huggingface dataset:
Co-receptor tropism prediction among 1045 Indian HIV-1 subtype C sequences: Therapeutic implications for India
Authors: Neogi Ujjwal , Prarthana Sreenivasa B , D'Souza George , DeCosta Ayesha , Kuttiatt Vijesh S , Ranga Udaykumar , Shet Anita
Published: July 2010

Background

Understanding co-receptor tropism of HIV-1 strains circulating in India will provide key analytical leverage for assessing the potential usefulness of newer antiretroviral drugs such as chemokine co-receptor antagonists among Indian HIV-infected populations. The objective of this study was to determine usingin silicomethods, HIV-1 tropism among a large number of Indian isolates both from primary clinical isolates as well as from database-derived sequences.

Results

R5-tropism was seen in 96.8% of a total of 1045 HIV-1 subtype C Indian sequences. Co-receptor prediction of 15 primary clinical isolates detected two X4-tropic strains using the C-PSSM matrix. R5-tropic HIV-1 subtype C V3 sequences were conserved to a greater extent than X4-tropic strains. X4-tropic strains were obtained from subjects who had a significantly longer time since HIV diagnosis (96.5 months) compared to R5-tropic strains (20.5 months).

Conclusions

High prevalence of R5 tropism and greater homogeneity of the V3 sequence among HIV-1 subtype C strains in India suggests the potential benefit of CCR5 antagonists as a therapeutic option in India.
Expressing gK gene of duck enteritis virus guided by bioinformatics and its applied prospect in diagnosis
Authors: Zhang Shunchuan , Ma Guangpeng , Xiang Jun , Cheng Anchun , Wang Mingshu , Zhu Dekang , Jia Renyong , Luo Qihui , Chen Zhengli , Chen Xiaoyue
Published: July 2010

Background

Duck viral enteritis, which is caused by duck enteritis virus (DEV), causes significant economic losses in domestic and wild waterfowls because of the high mortality and low egg production rates. With the purpose of eliminating this disease and decreasing economic loss in the commercial duck industry, researching on glycoprotein K (gK) of DEV may be a new kind of method for preventing and curing this disease. Because glycoproteins project from the virus envelope as spikes and are directly involved in the host immune system and elicitation of the host immune responses, and also play an important role in mediating infection of target cells, the entry into cell for free virus and the maturation or egress of virus. The gK is one of the major envelope glycoproteins of DEV. However, little information correlated with gK is known, such as antigenic and functional characterization.

Results

Bioinformatic predictions revealed that the expression of the full-length gK gene (fgK) in a prokaryotic system is difficult because of the presence of suboptimal exon and transmembrane domains at the C-terminal. In this study, we found that the fgK gene might not be expressed in a prokaryotic system in accordance with the bioinformatic predictions. Further, we successfully used bioinformatics tools to guide the prokaryotic expression of the gK gene by designing a novel truncated gK gene (tgK). These findings indicated that bioinformatics provides theoretical data for target gene expression and saves time for our research. The recombinant tgK protein (tgK) was expressed and purified by immobilized metal affinity chromatography (IMAC). Western blotting and indirect enzyme-linked immunosorbent assay (ELISA) showed that the tgK possessed antigenic characteristics similar to native DEV-gK.

Conclusions

In this work, the DEV-tgK was expressed successfully in prokaryotic system for the first time, which will provide usefull information for prokaryotic expression of alphaherpesvirus gK homologs, and the recombinant truncated gK possessed antigenic characteristics similar to native DEV gK. Because of the good reactionogenicity, specificity and sensitivity, the purified tgK could be useful for developing a sensitive serum diagnostic kit to monitor DEV outbreaks.
Knockdown resistance in Anopheles vagus, An. sinensis, An. paraliae and An. peditaeniatus populations of the Mekong region
Authors: Verhaeghen Katrijn , Van Bortel Wim , Trung Ho Dinh , Sochantha Tho , Keokenchanh Kalouna , Coosemans Marc
Published: July 2010

Background

In the Mekong region (Vietnam, Cambodia and Laos), a large investigation was conducted to assess the susceptibility of Anopheles species against DDT and pyrethroids. In this study, the resistance status of the potential malaria vectors An. vagus, An. sinensis, An. paraliae and An. peditaeniatus was assessed.

Methods

Bioassays were performed on field collected unfed female mosquitoes using the standard WHO susceptibility tests. In addition, the DIIS6 region of the para-type sodium channel gene was amplified and sequenced and four allele-specific PCR assays were developed to assess the kdr frequencies.

Results

In Southern Vietnam all species were DDT and pyrethroid resistant, which might suggest the presence of a kdr resistance mechanism. Sequence-analysis of the DIIS6 region of the para-type sodium channel gene revealed the presence of a L1014S kdr mutation in An. vagus, An. sinensis and An. paraliae. In An. peditaeniatus, a low frequency L1014S kdr mutation was found in combination with a high frequency L1014F kdr mutation. For pyrethroids and DDT, no genotypic differentiation was found between survivors and non-survivors for any of these species. In the two widespread species, An. vagus and An. sinensis, kdr was found only in southern Vietnam and in Cambodia near the Vietnamese border.

Conclusions

Different levels of resistance were measured in Laos, Cambodia and Vietnam. The kdr mutation in different Anopheles species seems to occur in the same geographical area. These species breed in open agricultural lands where malaria endemicity is low or absent and vector control programs less intensive. It is therefore likely that the selection pressure occurred on the larval stages by insecticides used for agricultural purposes.
TNFRSF1B A1466G genotype is predictive of clinical efficacy after treatment with a definitive 5-fluorouracil/cisplatin-based chemoradiotherapy in Japanese patients with esophageal squamous cell carcinoma
Authors: Kuwahara Akiko , Yamamori Motohiro , Fujita Megumi , Okuno Tatsuya , Tamura Takao , Kadoyama Kaori , Okamura Noboru , Nakamura Tsutomu , Sakaeda Toshiyuki
Published: July 2010

Background

Currently definitive 5-fluorouracil (5-FU)/cisplatin (CDDP) -based chemotherapy is recognized as one of the most promising treatments for esophageal cancer. A series of studies performed found genetic polymorphisms and the plasma concentration of 5-FU to be predictive of acute severe toxicities and clinical response. Genetic polymorphisms of tumor necrosis factor (TNF) -α and its surface receptors, TNFRSF1A and TNFRSF1B have been examined in terms of susceptibility to various cancers. In this study, genetic polymorphisms of TNFRSF1B gene were evaluated Japanese esophageal squamous cell carcinoma (ESCC) patients treated with the definitive 5-FU/CDDP-based chemoradiotherapy and their predictive values of prognosis or severe acute toxicities were assessed.

Methods

Forty-six patients with ESCC were treated with the definitive 5-FU/CDDP-based chemoradiotherapy, one course of which consisted of the continuous infusion of 5-FU for days 1-5 and 8-12, the infusion of CDDP on days 1 and 8, and the radiation at 2 Gy/day on days 1-5, 8-12, and 15-19, with a second course repeated after 2-week interval. Genetic polymorphisms of a TNF-α receptor TNFRSF1B gene were determined by a TaqMan® MGB probe-based polymerase chain reaction.

Results

The genotype of TNFSR1B A1466G, but not M196R/T587G or C1493T, was found to be predictive of clinical response, i.e., a complete response or not (p = 0.040). Clinical response was predicted by tumor size (p = 0,002), lymph node metastasis (p = 0.007), distant metastasis (p = 0.001) and disease stage (p < 0.001), but TNFRSF1B A1466G genotype was independent of these factors.

Conclusions

Genetic polymorphism of TNFRSF1B A1466G was found to be predictive response in Japanese ESCC patients with a definitive 5-FU/CDDP-based chemoradiotherapy. Further clinical investigation with a large number of patients or experiments in vitro should be performed to assess the predictive value of TNFRSF1B A1466G genotype after chemoradiotherapy.
Serum and follicular anti-Mullerian hormone levels in women with polycystic ovary syndrome (PCOS) under metformin
Authors: Falbo Angela , Rocca Morena , Russo Tiziana , D'Ettore Antonietta , Tolino Achille , Zullo Fulvio , Orio Francesco , Palomba Stefano
Published: July 2010

Background

No data regarding metformin effects on follicular fluid anti-Müllerian hormone (AMH) levels were to date available in literature. The aim of the present study was to evaluate in patients with polycystic ovary syndrome (PCOS) whether metformin administration affects serum and follicular AMH levels, and whether this is related to ovarian response to the treatment.

Methods

Twenty young patients with PCOS who had received metformin were enrolled. Ten patients were anovulatory (Met-anov group), whereas the other 10 were ovulatory (Met-ov group) but had failed to conceive. Further untreated PCOS (PCOS controls, n. 10) and healthy controls (non-PCOS controls, n. 10) who were scheduled for laparoscopic surgery were enrolled. In each subjects, clinical and biochemical evaluations were performed. AMH concentrations in blood and antral follicular fluid were assayed.

Results

In both Met-anov and Met-ov groups, and without difference between them, serum androgens and AMH, and indices of insulin resistance were significantly (p < 0.05) improved after treatment. On the other hand, significant differences (p < 0.05) between the two groups were detected with respect to the same biochemical parameters in antral follicular fluid. In the Met-anov group, no significant correlation was observed between AMH concentrations in the follicular fluid and variation in serum androgens, AMH and insulin resistance indexes; whereas in Met-ov group significant correlations were detected between AMH levels in the follicular fluid and variation in serum androgens, AMH and insulin resistance indexes.

Conclusions

Metformin administration in patients with PCOS exerts a differential action on the ovarian AMH levels on the basis of ovulatory response. Changes in AMH levels in antral follicular fluid during metformin treatment could be involved in the local mechanisms mediating the ovulatory restoration.
Two pore domain potassium channels in cerebral ischemia: a focus on K2P9.1 (TASK3, KCNK9)
Authors: Ehling Petra , Bittner Stefan , Bobak Nicole , Schwarz Tobias , Wiendl Heinz , Budde Thomas , Kleinschnitz Christoph , Meuth Sven G
Published: July 2010

Background

Recently, members of the two-pore domain potassium channel family (K2Pchannels) could be shown to be involved in mechanisms contributing to neuronal damage after cerebral ischemia. K2P3.1-/-animals showed larger infarct volumes and a worse functional outcome following experimentally induced ischemic stroke. Here, we question the role of the closely related K2Pchannel K2P9.1.

Methods

We combine electrophysiological recordings in brain-slice preparations of wildtype and K2P9.1-/-mice with an in vivo model of cerebral ischemia (transient middle cerebral artery occlusion (tMCAO)) to depict a functional impact of K2P9.1 in stroke formation.

Results

Patch-clamp recordings reveal that currents mediated through K2P9.1 can be obtained in slice preparations of the dorsal lateral geniculate nucleus (dLGN) as a model of central nervous relay neurons. Current characteristics are indicative of K2P9.1 as they display an increase upon removal of extracellular divalent cations, an outward rectification and a reversal potential close to the potassium equilibrium potential. Lowering extracellular pH values from 7.35 to 6.0 showed comparable current reductions in neurons from wildtype and K2P9.1-/-mice (68.31 ± 9.80% and 69.92 ± 11.65%, respectively). These results could be translated in an in vivo model of cerebral ischemia where infarct volumes and functional outcomes showed a none significant tendency towards smaller infarct volumes in K2P9.1-/-animals compared to wildtype mice 24 hours after 60 min of tMCAO induction (60.50 ± 17.31 mm3and 47.10 ± 19.26 mm3, respectively).

Conclusions

Together with findings from earlier studies on K2P2.1-/-and K2P3.1-/-mice, the results of the present study on K2P9.1-/-mice indicate a differential contribution of K2Pchannel subtypes to the diverse and complex in vivo effects in rodent models of cerebral ischemia.
The delivery of evidence-based preventive care for older Americans with arthritis
Authors: Curtis Jeffrey R , Arora Tarun , Narongroeknawin Pongthorn , Taylor Allison , Bingham Clifton O , Cush Jack , Saag Kenneth G , Safford Monika , Delzell Elizabeth
Published: July 2010

Introduction

Previous research suggests patients with rheumatoid arthritis (RA) may receive suboptimal care with respect to preventive tests and services. We evaluated the proportion of older Americans with RA, psoriatic arthritis (PsA), and osteoarthritis (OA) receiving these services and the specialty of the providers delivering this care.

Methods

Using data from 1999 to 2006 from the Medicare Chronic Conditions Warehouse, we identified persons age >/= 65 in the national 5% sample. Over the required five-year observation period, we identified tests and services recommended for older adults and the associated healthcare provider. Services of interest included dual energy x-ray absorptiometry (DXA), influenza and pneumococcal vaccination, hyperlipidemia lab testing, mammography and colonoscopy.

Results

After accounting for the sampling fraction, we identified 141,140 RA, 6,300 PsA, and 770,520 OA patients eligible for analysis. Over five years, a majority of RA, PsA, and OA patients were tested for hyperlipidemia (84%, 89% and 87% respectively) and received DXA (69%, 75%, and 52%). Only approximately one-third of arthritis patients received pneumococcal vaccination; 19% to 22% received influenza vaccination each year. Approximately 20% to 35% of arthritis patients never underwent mammography and colonoscopy over five years. Concomitant care from both a rheumatologist and a primary care physician was significantly associated with a greater likelihood of receiving almost all preventive tests and services.

Conclusions

Among older Americans on Medicare, the absolute proportion of persons with arthritis receiving various recommended preventive services and screening tests was substantially less than 100%. Improved co-management between primary care and arthritis physicians may in part improve the delivery of preventive care for arthritis patients, but novel systematic interventions in this area are needed.
RNA polymerase mapping during stress responses reveals widespread nonproductive transcription in yeast
Authors: Kim Tae Soo , Liu Chih Long , Yassour Moran , Holik John , Friedman Nir , Buratowski Stephen , Rando Oliver J
Published: July 2010

Background

The use of genome-wide RNA abundance profiling by microarrays and deep sequencing has spurred a revolution in our understanding of transcriptional control. However, changes in mRNA abundance reflect the combined effect of changes in RNA production, processing, and degradation, and thus, mRNA levels provide an occluded view of transcriptional regulation.

Results

To partially disentangle these issues, we carry out genome-wide RNA polymerase II (PolII) localization profiling in budding yeast in two different stress response time courses. While mRNA changes largely reflect changes in transcription, there remains a great deal of variation in mRNA levels that is not accounted for by changes in PolII abundance. We find that genes exhibiting 'excess' mRNA produced per PolII are enriched for those with overlapping cryptic transcripts, indicating a pervasive role for nonproductive or regulatory transcription in control of gene expression. Finally, we characterize changes in PolII localization when PolII is genetically inactivated using the rpb1-1 temperature-sensitive mutation. We find that PolII is lost from chromatin after roughly an hour at the restrictive temperature, and that there is a great deal of variability in the rate of PolII loss at different loci.

Conclusions

Together, these results provide a global perspective on the relationship between PolII and mRNA production in budding yeast.
Manipulating signal delivery – plasma-membrane ERK activation in aPKC-dependent migration
Authors: Boeckeler Katrina , Rosse Carine , Howell Michael , Parker Peter J.
Published: July 2010

Members of the PKC superfamily have been implicated in various migratory models and in particular in spatially restricted processes. However, defining the precise local events that underlie the PKC-dependent processes is constrained by the unspecific nature of interventions. Here we address this problem in relation to atypical PKC (aPKC) action, which in conjunction with the exocyst complex controls the polarised delivery of promigratory signals. A drug-dependent recruitment approach was employed to manipulate the local recruitment of signals to the leading edge of migrating cells, under conditions where the aPKC-exocyst control is globally abrogated. We found that activation of ERK but not JNK at focal adhesions recovers the majority of the migratory loss attributed to ERK action, demonstrating a necessary role for active plasma membrane ERK in the downstream signalling of aPKC-dependent migration. The data further show that restored focal adhesion dynamics are a contributing mechanism through which localized ERK activity influences this aPKC-exocyst-dependent migration.
Muscle wasted: a novel component of theDrosophilahistone locus body required for muscle integrity
Authors: Bulchand Sarada , Menon Sree Devi , George Simi Elizabeth , Chia William
Published: July 2010

Skeletal muscles arise by cellular differentiation and regulated gene expression. Terminal differentiation programmes such as muscle growth, extension and attachment to the epidermis, lead to maturation of the muscles. These events require changes in chromatin organization as genes are differentially regulated. Here, we identify and characterise muscle wasted (mute), a novel component of the Drosophila histone locus body (HLB). We demonstrate that a mutation in mute leads to severe loss of muscle mass and an increase in levels of normal histone transcripts. Importantly, Drosophila Myocyte enhancer factor 2 (Mef2), a central myogenic differentiation factor, and how, an RNA binding protein required for muscle and tendon cell differentiation, are downregulated. Mef2 targets are, in turn, misregulated. Notably, the degenerating muscles in mute mutants show aberrant localisation of heterochromatin protein 1 (HP1). We further show a genetic interaction between mute and the Stem-loop binding protein (Slbp) and a loss of muscle striations in Lsm11 mutants. These data demonstrate a novel role of HLB components and histone processing factors in the maintenance of muscle integrity. We speculate that mute regulates terminal muscle differentiation possibly through heterochromatic reorganisation.
Facilitated transport and diffusion take distinct spatial routes through the nuclear pore complex
Authors: Fiserova Jindriska , Richards Shane A. , Wente Susan R. , Goldberg Martin W.
Published: July 2010

Transport across the nuclear envelope is regulated by nuclear pore complexes (NPCs). Much is understood about the factors that shuttle and control the movement of cargos through the NPC, but less has been resolved about the translocation process itself. Various models predict how cargos move through the channel; however, direct observation of the process is missing. Therefore, we have developed methods to accurately determine cargo positions within the NPC. Cargos were instantly trapped in transit by high-pressure freezing, optimally preserved by low-temperature fixation and then localized by immunoelectron microscopy. A statistical modelling approach was used to identify cargo distribution. We found import cargos localized surprisingly close to the edge of the channel, whereas mRNA export factors were at the very centre of the NPC. On the other hand, diffusion of GFP was randomly distributed. Thus, we suggest that spatially distinguished pathways exist within the NPC. Deletion of specific FG domains of particular NPC proteins resulted in collapse of the peripheral localization and transport defects specific to a certain karyopherin pathway. This further confirms that constraints on the route of travel are biochemical rather than structural and that the peripheral route of travel is essential for facilitated import.
Screening for Cervical Cancer with the Human Papillomavirus Test in an Area of Central Italy with No Previous Active Cytological Screening Programme
Authors: Confortini Massimo , Rossi Paolo Giorgi , Barbarino Paolo , Passarelli Anna Maria , Orzella Letizia , Tufi Maria Concetta
Published: July 2010

Objective

We report performance indicators and costs of the first round of a cervical cancer screening programme based on the human papillomavirus (HPV)-DNA test.

Methods

We implemented a demonstration study using HPV as the primary test in Guidonia, Italy (90,000 inhabitants). All women aged 25-64 were invited to undergo a Hybrid Capture II high-risk HPV test. Two cervical samplings, smear and liquid, were taken. The smear was dyed and interpreted only for HPV-positive (HPV+) women. Women with a non-negative Pap smear were referred for colposcopy, women HPV+/cytology negative were referred to one-year follow-up with HPV. A cost-analysis indicated the price at which the HPV-based and cytological screening would cost the same per screened woman and per lesion found.

Results

Of 24,000 women invited, 7639 accepted and 427 (5.6%) were HPV+; 141 (34%) of these had a non-negative Pap test, and 20 cervical intraepithelial neoplasia (CIN) 2 or higher were found (positive predictive value 15%). Compliance to one-year follow-up was 58% (166/286); 90 (54%) were HPV-positive and five additional lesions were found (positive predictive value 9%; overall detection rate 3.4/1000). The cost analysis showed that at a price of 8.3 euros per HPV DNA test, the strategy using HPV as primary test followed by cytological triage would cost the same per screened woman, while at a price of 12.7 euros it would have the same cost per CIN2+ found.

Conclusion

The workload for management of positive women was similar to cytological screening. Low compliance to one-year follow-up was the main barrier to effectiveness. The price of HPV test should be about 9 euros to maintain the same screening budget, and can go as high as 13 euros per lesion found.
Risk Factors for Colonic Perforation after Screening Computed Tomographic Colonography: A Multicentre Analysis and Review of the Literature
Authors: Atalla Mohamed Anwar , Rozen Warren M , Niewiadomski Olga Dorota , Croxford Matthew A , Cheung Wa , Ho Yik-Hong
Published: July 2010

Background

Computed tomographic (CT) colonography (or ‘virtual’ colonoscopy) has become an increasingly popular tool for colorectal cancer screening. Colonic perforation, an uncommon complication, is a risk that has not been widely reported.

Methods

A systematic review of the literature was undertaken to identify all reported risk factors for colonic perforation following CT colonography. In addition, a retrospective multicentre study was undertaken, evaluating all CT colonographies in 10 major metropolitan tertiary referral centres. All colonic perforations were assessed for risk factors.

Results

A range of ‘patient’-related and ‘procedure’-related risk factors were identified in the literature. Among 3458 CT colonographies, there were two cases of colonic perforation contributing to an incidence of perforation of 0.06%. There was no statistical correlation between the incidence of perforation and institutional experience ( P = 0.66). Risk factors common to both cases and the literature included age, recent colonoscopy and manual colonic insufflation. Diverticular disease and recent colonic biopsy were also notable factors.

Conclusion

There is a small but real risk of perforation following CT colonography. Patient selection and preventative procedural measures may reduce this risk. The importance of the consent process is emphasized.
Flexible Sigmoidoscopy Screening for Colorectal Cancer: Uptake in a Population-based Pilot Programme
Authors: Robb Kathryn , Power Emily , Kralj-Hans Ines , Edwards Robert , Vance Maggie , Atkin Wendy , Wardle Jane
Published: July 2010

Objective

The aim of this study was is to examine uptake of population-based, flexible sigmoidoscopy (FS) screening delivered by nurses in a socioeconomically and ethnically diverse area of London, England.

Methods

All adults aged 58 and 59 years registered at 34 general practices in North London ( n = 2260) were mailed an invitation to attend FS screening at the local hospital.

Results

In total, 45% (1024/2260) accepted the invitation and attended, 5% (114/2260) accepted the invitation but failed to attend, 5% (111/2260) accepted the invitation but were unable to attend within the time-frame of the pilot study, 7% (165/2260) declined the offer, 27% (602/2260) did not respond, and 11% (244/2260) were ineligible or did not receive the invitation. Among those eligible to be screened, the uptake rate was 51% (1024/2016). Uptake did not differ by gender, but people living in the most affluent quintile of areas had a substantially higher uptake rate (63%) than those living in the most deprived quintile (38%).

Conclusion

Uptake of FS screening delivered as a population-based programme was over 50% among the eligible population in a socioeconomically and ethnically diverse area of London. Disparities in uptake should be addressed to avoid exacerbating health inequalities.
The Cost of Status Enhancement: Performance Effects of Individuals' Status Mobility in Task Groups
Authors: Bendersky Corinne , Shah Neha Parikh
Published: July 2010

Although we know that considerable benefits accrue to individuals with high social status, we do not know the performance effects of gaining or losing status in one's group over time. In two longitudinal studies, we measure the status positions of middle managers currently enrolled in a part-time MBA program at the beginning and end of their study group's life. In both samples, we compare the individual performance (course grades) of the students who gained or lost status to those who maintained high and low stable status positions in their groups. We find that higher status at the end of the group's life is associated with higher performance. We also find, however, that the performance of individuals who gain or lose status over time does not correspond to their final status positions. Instead, those who gain status—including those who eventually attain high status—perform worse than those who maintain high-status positions for the whole quarter. They perform no better than those in stable low-status positions throughout. Those who lose status over time actually perform as well as those who maintain high status. We interpret these results to suggest that people might trade off resources they could apply to individual performance for opportunities to enhance their status. After replicating this effect in our second sample, we identify overinvestment in increasing assertive communication and generosity as behavioral mechanisms through which individuals successfully gain status to the detriment of their own performance.
Expression of LMO2 Is Associated With t(14;18)/IGH-BCL2 Fusion but Not BCL6 Translocations in Diffuse Large B-Cell Lymphoma
Authors: Durnick David K. , Law Mark E. , Maurer Matthew J. , Natkunam Yasodha , Levy Ronald , Lossos Izidore S. , Kurtin Paul J. , McPhail Ellen D.
Published: July 2010

Diffuse large B-cell lymphoma (DLBCL) can be separated for prognostic purposes using gene expression profiling (GEP) into 2 subgroups: germinal center B-cell (GCB) and activated B-cell phenotypes. However, GEP is impractical for routine clinical use, and immunophenotyping is an imperfect surrogate. Therefore, we studied the relationship between expression of the purported germinal center marker LMO2 and the presence of IGH-BCL2 fusions, BCL6 translocations, and LMO2 translocations. In addition, we investigated the usefulness of LMO2 expression as a marker of GCB subtype in DLBCL. Immunohistochemical and fluorescence in situ hybridization studies were successfully performed on 101 cases of de novo DLBCL that had been incorporated into a tissue microarray. There was a statistically significant association between IGH-BCL2 fusion and LMO2 protein expression (P = .02) but not between BCL6 translocations and LMO2 expression. LMO2 translocations were not identified. Although uncommon, all cases that had both IGH-BCL2 fusion and BCL6 translocations expressed LMO2. The findings suggest LMO2 as a potential marker for the GCB phenotype.
Chairpersons of Pathology in the United States
Authors: Hedley-Whyte John , Milamed Debra R. , Hoaglin David C.
Published: July 2010

Pathology chairpersons continue their preeminence in US medical schools. The Hirsch (h) index of citation was analyzed for the chairpersons of 8 specialty departments in 41 US medical schools. The current h indices of department chairs (302 of 328 positions filled) were tabulated by specialty and medical school. The proportion of women was noted, as was whether the chairs had completed the first decade of this millennium continuously in post in the same medical school. Of the 8 specialties, pathology chairs at the 41 schools are the most likely to have been in the same post in 1999 and 2009, and the pathologists who remained are exclusively male. In the 41 medical schools studied, women chairs constituted only 3.7% of all heads of departments in 1999 and 7% in 2009. The paucity of female chairs 3 decades after women became at least one third of the medical student body is unfortunate.
Prospective, Multicenter Evaluation of the BD GeneOhm VanR Assay for Direct, Rapid Detection of Vancomycin-Resistant Enterococcus Species in Perianal and Rectal Specimens
Authors: Usacheva Elena A. , Ginocchio Christine C. , Morgan Margie , Maglanoc Geronimo , Mehta Maitry S. , Tremblay Sebastien , Karchmer Tobi B. , Peterson Lance R.
Published: July 2010

The BD GeneOhm VanR assay (BD Diagnostics, San Diego, CA), a qualitative test for the rapid detection of vancomycin-resistant enterococci (VRE) from rectal and/or perianal swabs, combines integrated nucleic acid extraction and automated polymerase chain reaction for the detection of vanA and/or vanB gene sequences. We studied 1,027 perianal and rectal swab specimens from 3 geographically distinct US sites (prevalence rates, 13.1%–25.8%). Direct swab specimens were tested by the assay and compared with direct culture. The sensitivity, specificity, and positive and negative predictive values of the assay were 93.2%, 81.9%, 54.4%, and 98.1%, respectively. The specificity was limited largely due to false-positives in the vanB portion of the assay. Specificity with perianal swabs was significantly greater than with rectal swabs, 87.1% vs 74.7%, respectively (P < .0001). When used only to detect resistance conferred by vanA, the assay was 88.3% (158/179) sensitive and 95.8% (802/837) specific, with positive and negative predictive values of 81.9% and 97.4%, respectively. The assay is a simple, rapid, and acceptable method for screening for VRE in a variety of populations in which vanA is the predominant genotype. Samples positive for the vanB genotype should be confirmed by culture owing to the apparent high number of false-positive results.
Marrow Penicilliosis
Authors: Wong K. F.
Published: July 2010

Penicillium marneffei is a dimorphic fungus that causes one of the most common opportunistic infections in Asian patients with AIDS. The diagnosis is established by microbiologic culture, requiring at least several days. A presumptive diagnosis can be made by cytologic or histologic examination of biopsied or aspirated tissue. Bone marrow biopsy is often performed in the workup of patients with AIDS who have fever or hematologic abnormalities and can provide prompt diagnosis of opportunistic infection. We report the bone marrow findings in the largest series of patients with culture-proven P marneffei infection. In the bone marrow, the histiocytes can occur in large numbers and be easily recognized or may be extremely subtle. P marneffei infection is sometimes not accompanied by granuloma formation despite marked histiocytic proliferation. The histiocytes contain a few to many intracellular yeast-form cells that resemble cellular debris because of their small size and staining pattern. The characteristic septate forms and the absence of budding help distinguish the condition from histoplasmosis and toxoplasmosis. Routine performance of silver methenamine stain for fungi in marrow biopsy specimens of febrile patients with AIDS is recommended to detect a subtle infection.
Increasing Radiation From Sentinel Node Specimens in Pathology Over Time
Authors: Renshaw Andrew A. , Kish Richard , Gould Edwin W.
Published: July 2010

Previous studies have recommended no special precautions for radiation when handling sentinel node specimens in the pathology laboratory. We reviewed 7 years of data concerning radioactivity in 2,902 sentinel node and primary resection specimens received in our pathology laboratory. The percentage of specimens with greater than background radiation (≥0.2 mrem/h) rose from 6.3% to 34.8% from 2003 to 2009 (P < .001); specimens with more than 10 mrem/h rose from 0.0% to 9.3% (P < .001). Four specimens were measured at 100 mrem/h. While mastectomy followed by skin excisions for melanoma were the most common specimens to have radiation more than 2.0 mrem/h (32.2% and 27.3%, respectively), this level of radiation was found in all types of cases examined. The radiation dose administered to individual patients for specimens with more than 30 mrem/h was significantly higher than a sample of specimens with less than 0.2 mrem/h (n = 25 each; median, 1.3 and 1.0 mCi, respectively; P = .02). While the higher level of radiation we found correlates with increasing administered dose of radiation, other factors may also have a role. Routine measurement of radioactivity for all sentinel node specimens in the pathology laboratory is recommended.
Thoughts and Acts of Aggression/Violence Toward Others Reported in Association with Varenicline
Authors: Moore Thomas J , Glenmullen Joseph , Furberg Curt D
Published: July 2010

Background:

Thoughts and acts of aggression/violence toward others have been reported in postmarketing surveillance of varenicline, an aid to smoking cessation.

Objective:

To identify the common characteristics of these thoughts and acts of aggression/violence toward others and assess the likely relationship to varenicline treatment.

Methods:

We obtained 78 adverse event reports from the Food and Drug Administration MedWatch database containing medical terms describing possible acts or thoughts of aggression/violence; 4 additional cases were reported in clinical trials, and 3 others came from the published literature. We used psychiatric diagnostic criteria and an adverse event causality assessment tool to identify 26 case reports for study.

Results:

The selected cases described 10 events with assault, 9 cases of homicidal ideation, and 7 cases of other thoughts or acts of aggression/violence. The most frequent common characteristics were (1) inexplicable and unprovoked event, (2) the victim was anyone nearby, (3) no indication of a prior history of similar behavior in the patient, and (4) early onset of psychiatric adverse effects, often before stopping smoking. Where dechaltenge/rechalfenge information was available, psychiatric adverse effects resolved in 13/14 (93%) cases after discontinuation.

Conclusions:

The clear temporal relationship, lack of prior history of this behavior, and unusual nature of these events strengthens the accumulating scientific evidence that varenicline is associated with thoughts and acts of aggression/violence. We recommend that physicians and pharmacists ensure that all patients are informed of possible psychiatric symptoms of varenicline, including violent and aggressive thoughts. All patients should be advised to contact a heafth-care provider immediately if these symptoms occur and varenicline should be discontinued without delay.
Hospital-specific calculation of heparin-induced thrombocytopenia costs: a review/Kalkulation der Kosten für eine Heparin-induzierte Thrombozytopenie (HIT) in Krankenhaüsern
Authors: Wilke Thomas , Greinacher Andreas
Published: July 2010

Costs for heparin-induced thrombocytopenia (HIT) should be considered for any assessment of the cost-effectiveness of a certain strategy of thrombosis prophylaxis in a hospital. Five recent studies analyzed the cost of HIT as primary outcome. These studies reported widely differing estimates for the costs of a HIT case, which might be largely related to the different methodological approaches. The most plausible HIT cost estimates range between €9,000 and €15,000 per case for European hospitals and US$30,000–45,000 per case for hospitals in the United States. The approximate threefold cost difference between Europe and the US is to some extent caused by the very different costs for certain interventions and treatments, i.e., they are dependent on the economic environment of the hospitals analyzed. Based on the assumption that clinical management of acute HIT does not differ substantially between different medical systems, we recently developed the HIT cost calculator (http://www.wi.hs-wismar.de/~ipam/html_neu/hittool.html) based on detailed analysis of additional resources required owing to the presence of HIT in 128 patients with clinical HIT. This tool offers interested hospitals a very transparent method to calculate their own HIT-related costs.
BRAF in primary and recurrent papillary thyroid cancers: the relationship with 131I and 2-[18F]fluoro-2-deoxy-d-glucose uptake ability
Authors: Barollo Susi , Pennelli Gianmaria , Vianello Federica , Watutantrige Fernando Sara , Negro Isabella , Merante Boschin Isabella , Pelizzo Maria Rosa , Rugge Massimo , Mantero Franco , Nacamulli Davide , Girelli Maria Elisa , Busnardo Benedetto , Mian Caterina
Published: July 2010

Objective

BRAF V600E is a potential marker of poor prognosis in papillary thyroid cancers (PTC). In a previous report, we showed that recurrent PTC with no radioiodine (131I) uptake are frequently associated with BRAF mutations, a low expression of thyroid-related genes and a high expression of glucose type-1 transporter gene.

Aim

The aim of the present study was to assess BRAF status in a large series of recurrent PTC patients, considering paired primary and recurrent cancers. The BRAF genotype was correlated with the ability to concentrate 131I and/or 2-[18F]fluoro-2-deoxi-d-glucose (18F-FDG) in the recurrent cancers, serum markers of recurrence, and patient outcome.

Design and methods

We studied 50 PTC patients with recurrent cervical disease submitted to a re-intervention, followed up in median for 9 years. BRAF analysis was conducted by direct sequencing and mutant allele-specific PCR amplification. In 18 cases, molecular analysis was also assessed in the primary cancer. Out of 50 patients, 30 underwent 18F-FDG-positron emission tomography–computed tomography.

Results

BRAF V600E-positive recurrent patients were found 131I-negative in 94% of cases (P<0.001); 73% of the cancers carrying BRAF V600E were both 131I-negative and 18F-FDG positive. In paired primary and recurrent PTC, BRAF V600E was observed in 79% of the primary cancers and 84% of their recurrences. Three patients with 131I-negative and BRAF V600E-positive recurrent cancers deceased during follow-up.

Conclusions

BRAF mutations are more common in thyroid recurrences with no 131I uptake than in 131I-positive cases. They are correlated with the ability to concentrate 18F-FDG, and they can appear, albeit rarely, as a de novo event in the course of PTC recurrences.
A Drosophila Chromatin Factor Interacts With the Piwi-Interacting RNA Mechanism in Niche Cells to Regulate Germline Stem Cell Self-Renewal
Authors: Smulders-Srinivasan Tora K , Szakmary Akos , Lin Haifan
Published: July 2010

Stem cell research has been focused on niche signaling and epigenetic programming of stem cells. However, epigenetic programming of niche cells remains unexplored. We showed previously that Piwi plays a crucial role in Piwi-interacting RNA-mediated epigenetic regulation and functions in the niche cells to maintain germline stem cells (GSCs) in the Drosophila ovary. To investigate the epigenetic programming of niche cells by Piwi, we screened mutations in the Polycomb and trithorax group genes, and an enhancer of Polycomb and trithorax called corto, for their potential genetic interaction with piwi. corto encodes a chromatin protein. corto mutations restored GSC division in mutants of piwi and fs(1)Yb (Yb), a gene that regulates piwi expression in niche cells to maintain GSCs. Consistent with this, corto appears to be expressed in the niche cells and is not required in the germline. Furthermore, in corto-suppressed Yb mutants, the expression of hedgehog (hh) is restored in niche cells, which is likely responsible for corto suppression of the GSC and somatic stem cell defects of Yb mutants. These results reveal a novel epigenetic mechanism involving Corto and Piwi that defines the fate and signaling function of niche cells in maintaining GSCs.
Effect of Defective Collagen Synthesis on Epithelial Implant Interface: Lathyritic Model in Dogs. An Experimental Preliminary Study
Authors: Cengiz Murat Inanç , Kirtiloğlu Tuğrul , Acikgoz Gökhan , Trisi Paolo , Wang Hom-Lay
Published: July 2010

Peri-implant mucosa is composed of 2 compartments: a marginal junctional epithelium and a zone of connective tissue attachment. Both structures consist mainly of collagen. Lathyrism is characterized by defective collagen synthesis due to inhibition of lysyl oxidase, an enzyme that is essential for interfibrillar collagen cross-linking. The lathyritic agent beta-aminoproprionitrile (β-APN) is considered a suitable agent to disrupt the connective tissue metabolism. Therefore, the purpose of this study was to assess the effect of defective connective tissue metabolism on epithelial implant interface by using β-APN created chronic lathyrism in the canine model. Two 1-year-old male dogs were included in this study. A β-APN dosage of 5 mg/0.4 mL/volume 100 g/body weight was given to the test dog for 10 months, until lathyritic symptoms developed. After this, the mandibular premolar teeth (p2, p3, p4) of both dogs were atraumatically extracted, and the investigators waited 3 months before implants were placed. In the test dog, 3 implants were placed in the left mandible, and 2 implants were placed in the right mandible. In the control dog, 2 implants were placed in the left mandibular premolar site. The dogs were sacrificed 10 months after healing. Peri-implant tissues obtained from the dogs were examined histomorphologically and histopathologically. Bone to implant contact (BIC) values and bone volumes (BV) were lower in the lathyritic group compared to the control group; however, no statistical significance was found. Significant histologic and histomorphometric changes were observed in peri-implant bone, connective tissue, and peri-implant mucosal width between test and control implants. Defective collagen metabolism such as lathyrism may negatively influence the interface between implant and surrounding soft tissue attachment.
Hydroxyapatite as a Carrier for Bone Morphogenetic Protein
Authors: Rohanizadeh Ramin , Chung Kimberly
Published: July 2010

Bone morphogenetic proteins (BMPs) can induce the formation of new bone in numerous orthopedic and dental applications in which loss of bone is the main issue. The combination of BMP with a biomaterial that can carry and deliver proteins has been demonstrated to maximize the therapeutic effects of BMPs. However, no ideal candidate with optimal characteristics as a carrier has emerged for clinical use of BMPs. Hydroxyapatite (HA) is a potential BMP carrier with its osteoconductive properties and desirable characteristics as a bone graft biomaterial. In this study, 3 different methods to load BMP into HA materials were characterized and compared based on the BMP uptake and release profile. BMP was loaded into HA in 3 ways: (1) incorporation of BMP during HA precipitation, (2) HA immersion in BMP solution, and (3) BMP incorporation during dicalcium phosphate dihydrate (DCPD) conversion to HA. The size of HA crystals decreased when BMP was loaded during HA precipitation and HA immersion in BMP solution; however, it did not change when BMP was loaded during DCPD-to-HA conversion. The highest BMP uptake was achieved using the immersion method followed by HA precipitation, and the lowest via DCPD conversion. It is interesting to note that BMP loading during HA precipitation resulted in sustained and prolonged BMP release compared with the 2 other BMP loading methods. In conclusion, BMP incorporation during HA precipitation revealed itself to be the best loading method.
Presence of Aspartate Aminotransferase in Peri-Implant Crevicular Fluid With and Without Mucositis
Authors: Sánchez-Pérez Arturo , Moya-Villaescusa María José , Caffesse Raúl Guillermo
Published: July 2010

The aim of this study was to assess the presence of aspartate aminotransferase (AST) in peri-implant crevicular fluid, with or without clinical signs of mucositis, to determine its predictive diagnostic value, sensitivity, and specificity. The AST levels were determined (at a threshold of 1200 µIU/mL) for 60 clinically successful implants in 25 patients with or without peri-implant mucositis. Samples were taken prior (AST1) to peri-implant probing with a manual constant-pressure probe (0.2 N) and 15 minutes after probing (AST2). Clinical assessments included radiographic determination of preexisting bone loss, probing, and the evaluation of mucositis, plaque, and bleeding upon probing. Analysis was performed at both the level of the implant and the patient as a unit. We detected a significant difference between AST1 and AST2 at both levels. A significant difference was observed at AST1 between implants that bled upon probing and those that did not. However, when we considered the patient as a unit, there were no significant differences. The plaque index was not significant at either level. AST1 had high specificity and positive predictive diagnostic value (80%) for bleeding upon probing. Probing induces a greater release of AST from inflamed tissues compared with healthy tissues in situ but not at the systemic level. At the implant level, the implant position could be responsible for this difference. Aspartate aminotransferase was a reliable predictor of patients with mucositis.
Consenso sobre diabetes gestacional e diabetes pré-gestacional
Authors: Schmidt Maria I. , Reichelt Angela J.
Published: July 2010

O Grupo de Trabalho em Diabetes e Gravidez, reunido durante o XI Congresso Brasileiro de Diabetes, em 1997, elaborou normas para o manejo do diabetes gestacional e pré-gestacional. O rastreamento do diabetes gestacional deve ser seletivo, isto é, dirigido a gestantes com fatores de risco. Para tanto, é sugerido o emprego da glicemia de jejum a partir da 20ª semana de gestação. Pontos de corte de 85mg/dl ou 90mg/dl são sugeridos para classificação de rastreamento positivo, que indica a necessidade de um teste oral de tolerância com 75g de glicose. Esse teste deve ser interpretado de acordo com os critérios sugeridos pela Organização Mundial da Saúde (glicemia de jejum ³126mg/dl ou glicemia de 2h ³140mg/dl). São apresentadas também estratégias de manejo metabólico e obstétrico do diabetes gestacional e do diabetes pré-gestacional.