bluuebunny/crossref_metadata_2025 huggingface dataset:
Mortality in type 2 diabetes mellitus: magnitude of the evidence from a systematic review and meta-analysis
Authors: Nwaneri Chukwuemeka , Cooper Helen , Bowen-Jones David
Published: July 2013

Background:

Type 2 diabetes is associated with an increase in age-related mortality. A systematic review and meta-analysis were performed to define the relative risks (RR) of all-cause or cause-specific mortality in type 2 diabetes and to determine gaps in current research.

Methods:

A comprehensive literature search was undertaken for studies (published 1990–2010) on mortality in type 2 diabetes. The study reports on the measure of mortality as defined by RR for all-cause and cause-specific mortality, heterogeneity, sensitivity analyses and biases.

Results:

In total 35 studies (220,689 patients; mean follow-up of 10.7 years) were eligible for inclusion: 33 studies reported increased mortality risks; 24 had full data on 95% confidence intervals (CIs), one study reported no excess mortality in men diagnosed after 65 years whereas three reported increased mortality in similar age groups in both sexes. Meta-analysis showed RR = 1.85 (95% CI 1.79–1.92) for all-cause mortality [men RR=1.57 (95% CI 1.46–1.68); women RR=2.0 (95% CI 1.89–2.12)], RR=1.76 (95% CI 1.66–1.88) for cardiovascular mortality and RR=2.26 (95% CI: 1.7-3.02) for stroke. There was no statistically significant evidence of publication bias.

Conclusion:

Type 2 diabetes increases mortality approximately two-fold increase and macrovascular disease is the principal cause of death.
The interplay of mediascapes and cityscapes in a sports mega-event
Authors: Kolamo Sami , Vuolteenaho Jani
Published: July 2013

Drawing on critical literature on the neoliberal practices of event and place branding, the article addresses the interplay of mediascapes and cityscapes in the making of the South African football spectacle in 2010. In analysing the world’s biggest football mega-event, orchestrated by FIFA (Fédération Internationale de Football Association) in collaboration with the South African hosts and mainly multinational sponsors, the article first addresses the manifestations of branding in the built environment, from flamboyant stadium architecture to transport and media technological infrastructures. Next, it scrutinizes people’s expected and actual acts and roles in the urban stages of the tournament. Ordinary South Africans were exhorted to co-create the tournament brand in the role of wildly celebrating ideal fans. As the flipside to and prerequisite for the emotionally captivating images circulated in the global mass media, the event-led enclaves of the tournament in the urban space were actually cleansed of people, symbols and actions that threatened the harmonious place brand.
The will to religion: Obligatory religious citizenship
Authors: Beaman Lori G.
Published: July 2013

This article takes up the problematic of the ‘new normal’ and its necessary twin, the ‘will to religion’. The notion of the ‘new normal’ describes the shift to the persistent presence, indeed requirement, for religious assessment in all manner of public and institutional life. The idea of the will to religion reflects a broadly Foucauldian perspective on the care of the self and the requirement to confess—in this instance to confess one’s belonging to a religious category. The article calls for a robust attention to the discursive construction of a normal in which we are all religious, and to which values are constituted as ‘universal’ or that we owe our moral and intellectual condition to religion. The article points to four consequences of this shift to a ‘new normal’ in which we are all religious, including the essentialization of religious identities, the overemphasis on religion, the infiltration of particular measures of religiosity, and the spread of religious freedom protectionism.
Lines that matter, lines that don't: Religion, boundaries, and the meaning of difference
Authors: Fuist Todd Nicholas , Josephsohn Thomas J.
Published: July 2013

Recent work in cultural sociology has noted the importance of boundaries for understanding intergroup relations. Within the sociology of religion, this has manifested in research into interreligious conflict and cooperation. However, the current literature often assumes that boundaries have fixed qualities and generate clear consequences for group interaction. In this article, we draw on two data sets, comprising interviews and ethnographic data on ten different religious groups from a variety of faith traditions, to demonstrate that cultural resources, including religious beliefs, may be used to assess the meaning and saliency of boundaries. Particular qualities of boundaries shape how social actors understand and interpret group difference, suggesting that boundaries themselves are a site of struggle. Finally, we use the concept of relational principles as a heuristic device to organize and understand the different ways that our subjects manage and assess competing boundaries.
The Miraculous Cure of a Sarcoma of the Pelvis: Cure of Vittorio Micheli at Lourdes
Authors: Neilan Barbara A.
Published: July 2013

In April 1962, Vittorio Micheli, a soldier in the Italian Army, developed rapidly increasing pain in his left buttock region. X-rays of the left hip showed osteolysis involving the ilium and the roof of the acetabulum. A biopsy of the gluteal muscle showed cells of a sarcomatous character. He was not deemed to be a candidate for medical intervention, so neither radiotherapy nor chemotherapy was offered to him. In May 1963, racked with pain and unable to walk, he made a pilgrimage to Lourdes, following which he was cured of his sarcoma. His case was reviewed by the International Medical Committee of Lourdes in 1969 and in 1971. There was unanimous agreement that this was a medically inexplicable cure.
Another Response to Todd Salzman and Michael Lawler's The Sexual Person
Authors: Flaman Paul
Published: July 2013

In their book, which has received mixed responses, Salzman and Lawler develop a “revisionist” approach to Catholic sexual ethics. They invite respectful dialogue. In this article I offer another response and attempt to engage in such dialogue by addressing both some things they say which I agree with and some things they say which I find problematic in certain ways. This includes their treatments of experience, science, and the Bible as these relate to homosexuality, and their approach to Christian sexual ethics and how they apply this to homosexuality and some other sexual issues. While Salzman and Lawler attempt to undermine a number of traditional Christian and official Catholic norms on these subjects, I offer some evidence and arguments in support of these norms. In this way I hope to contribute in a small way to the understanding of sexual persons and ethics.
Contingency nature of Helicobacter bizzozeronii oxygen-insensitive NAD(P)H-nitroreductase (HBZC1_00960) and its role in metronidazole resistance
Authors: Kondadi Pradeep Kumar , Pacini Claudia , Revez Joana , Hänninen Marja-Liisa , Rossi Mirko
Published: July 2013

Genomic analysis of a metronidazole resistant H. bizzozeronii strain revealed a frame length extension of the oxygen-insensitive NAD(P)H-nitroreductase HBZC1_00960 (RdxA), associated with the disruption of the C-terminal cysteine-containing conserved region (IACLXALGK). This was the result of the extension (from C8 to C9) of a simple sequence cytosine repeat (SSCR) located in the 3’ of the gene. A 3' SSCR is also present in the rdxA homolog of H. heilmannii sensu stricto, but not in H. pylori. We showed that in the majority of in vitro spontaneous H. bizzozeronii metronidazole resistant mutants, the extension of the 3′ SSCR of rdxA was the only mutation observed. In addition, we observed that H. bizzozeronii ΔrdxA mutant strain showed the same MIC value of metronidazole observed in the spontaneous mutants. These data indicate that loss of function mutations in rdxA and in particular the disruption of the conserved region IACLXALGK is associated with reduced susceptibility to metronidazole in H. bizzozeronii. Slipped-strand mispairing of the SSCR located in the 3′ of the H. bizzozeronii rdxA appears to be the main mechanism. We also observed that H. bizzozeronii acquires resistance to metronidazole at high mutation rate, and that serial passages in vitro without selection induced an increased level of susceptibility. In conclusion, contrary to what was previously described in H. pylori, the H. bizzozeronii rdxA appears to be a contingency gene which undergoes phase variation. The contingency nature of rdxA should be carefully considered when metronidazole is used in the treatment of H. heilmannii-associated gastritis.
Prevalence and risk factors of posterior vitreous detachment in a Chinese adult population: the Handan eye study
Authors: Shen Zhijun , Duan Xinrong , Wang Fenghua , Wang Ningli , Peng Yi , Liu David TL , Peng Xiaoyan , Li Sizhen , Liang Yuanbo
Published: July 2013

Background

To describe the prevalence and associations of posterior vitreous detachment (PVD) in a rural adult Chinese population.

Methods

All eligible subjects were requested to carry out a comprehensive eye examination; PVD was a pre-specified outcome variable and was determined via biomicroscopical examination (slit-lamp biomicroscopy) with a +90-D preset lens after mydriasis. Prevalence was standardized to China population census (2000).

Results

5890 (86.2%) subjects completed the examination of slit-lamp biomicroscopy with a +90-D lens. PVD was present in 160 participants (2.7%); the standardized prevalence was 2.0% (95% confidence interval [CI], 1.6-2.3%). PVD developed increasingly with age (P for trend < 0.001) for both men and women. Using a multivariate regression model, older people were found to run a higher risk of developing PVD than younger people, and women were found to have a higher risk than men (OR, 2.9; 95% CI, 1.5-5.9). Diabetes, hypertension, smoking, drinking, and intraocular pressure (IOP) were not significantly associated with PVD.

Conclusions

About one in fifty people is found to have PVD in this population-based study. Age and female are independently associated with PVD occurrence.
Diet, iron biomarkers and oxidative stress in a representative sample of Mediterranean population
Authors: Romeu Marta , Aranda Nuria , Giralt Montserrat , Ribot Blanca , Nogues Maria Rosa , Arija Victoria
Published: July 2013

Background

The consumption pattern characterized by high consumption of vegetables, fruit, fish, olive oil and red wine has been associated with improvements in the total antioxidant capacity of individuals and reduced incidence of diseases related to oxidation. Also, high body iron levels may contribute to increase the oxidative stress by the generation of reactive oxygen species. The objective of this study is to analyze the relationship between antioxidant and pro-oxidant factors obtained from the diet and iron biomarkers on lipoprotein oxidation and total antioxidant capacity in a representative sample of the Mediterranean population.

Methods

Cross-sectional prospective study, carried out with 815 randomly selected subjects (425 women and 390 men). Dietary assessment (3-day food records), iron biomarkers (serum ferritin, serum iron and transferrin saturation), biochemical markers of lipoperoxidation (TBARS), antioxidant capacity (ORAC) and CRP (C-Reactive Protein) were determined. Multiple Linear Regression (MLR) models were applied to analyze the association between diet factors and iron biomarkers on TBARS and ORAC levels.

Results

We observed that lipoperoxidation measured by TBARS increased by age but no differences were observed by sex. Antioxidant capacity measured by ORAC is independent of age and sex. In general, increasing age, tobacco, heme iron intake from meat and fish and transferrin saturation were independently and positively associated with TBARS, while non-heme iron was negatively associated. Vegetables, vitamin C intake and serum ferritin were positively associated with ORAC, whereas saturated fatty acids and meat intake were negatively associated.

Conclusions

In our general population, we observed that oxidative stress is related to aging, but antioxidant capacity is not. The highest intake of dietary non-heme iron, vegetables and vitamin C intake exerts a protective effect against oxidation while the highest intake of dietary heme iron from meat and fish and saturated fatty acids are associated with increased oxidative stress. High levels of circulating iron measured by transferrin saturation are associated with increased oxidative stress in women however its association with the higher levels of serum ferritin is controversial.
TMEM16A alternative splicing coordination in breast cancer
Authors: Ubby Ifeoma , Bussani Erica , Colonna Antonio , Stacul Giuseppe , Locatelli Martina , Scudieri Paolo , Galietta Luis , Pagani Franco
Published: July 2013

Background

TMEM16A, also known as Anoctamin-1, is a calcium-activated chloride channel gene overexpressed in many tumors. The role of TMEM16A in cancer is not completely understood and no data are available regarding the potential tumorigenic properties of the multiple isoforms generated by alternative splicing (AS).

Methods

We evaluated TMEM16A AS pattern, isoforms distribution and Splicing Coordination (SC), in normal tissues and breast cancers, through a semi-quantitative PCR-assay that amplifies transcripts across three AS exons, 6b, 13 and 15.

Results

In breast cancer, we did not observe an association either to AS of individual exons or to specific TMEM16A isoforms, and induced expression of the most common isoforms present in tumors in the HEK293 Flp-In Tet-ON system had no effect on cellular proliferation and migration. The analysis of splicing coordination, a mechanism that regulates AS of distant exons, showed a preferential association of exon 6b and 15 in several normal tissues and tumors: isoforms that predominantly include exon 6b tend to exclude exon 15 and vice versa. Interestingly, we found an increase in SC in breast tumors compared to matched normal tissues.

Conclusions

As the different TMEM16A isoforms do not affect proliferation or migration and do not associate with tumors, our results suggest that the resulting channel activities are not directly involved in cell growth and motility. Conversely, the observed increase in SC in breast tumors suggests that the maintenance of the regulatory mechanism that coordinates distant alternative spliced exons in multiple genes other than TMEM16A is necessary for cancer cell viability.
Contemporary adjuvant polymethyl methacrylate cementation optimally limits recurrence in primary giant cell tumor of bone patients compared to bone grafting: a systematic review and meta-analysis
Authors: Zuo Dongqing , Zheng Longpo , Sun Wei , Fu Dong , Hua Yingqi , Cai Zhengdong
Published: July 2013

Background

Reports of recurrence following restructuring of primary giant cell tumor (GCT) defects using polymethyl methacrylate (PMMA) bone cementation or allogeneic bone graft with and without adjuvants for intralesional curettage vary widely. Systematic review and meta-analysis were conducted to investigate efficacy of PMMA bone cementation and allogeneic bone grafting following intralesional curettage for GCT.

Methods

Medline, EMBASE, Google Scholar, and Cochrane databases were searched for studies reporting GCT of bone treatment with PMMA cementation and/or bone grafting with or without adjuvant therapy following intralesional curettage of primary GCTs. Pooled risk ratios and 95% confidence intervals (CIs) for local recurrence risks were calculated by fixed-effects methods.

Results

Of 1,690 relevant titles, 6 eligible studies (1,293 patients) spanning March 2008 to December 2011 were identified in published data. Treatment outcomes of PMMA-only (n= 374), bone graft-only (n= 436), PMMA with or without adjuvant (PMMA + adjuvant;n= 594), and bone graft filling with or without adjuvant (bone graft + adjuvant;n= 699) were compared. Bone graft-only patients exhibited higher recurrence rates than PMMA-treated patients (RR 2.09, 95% CI (1.64, 2.66), Overall effect: Z = 6.00;P<0.001), and bone graft + adjuvant patients exhibited higher recurrence rates than PMMA + adjuvant patients (RR 1.66, 95% CI (1.21, 2.28), Overall effect: Z = 3.15,P= 0.002).

Conclusions

Local recurrence was minimal in PMMA cementation patients, suggesting that PMMA is preferable for routine clinical restructuring in eligible GCT patients. Relationships between tumor characteristics, other modern adjuvants, and recurrence require further exploration.
Lifestyle factors and reproductive health: taking control of your fertility
Authors: Sharma Rakesh , Biedenharn Kelly R , Fedor Jennifer M , Agarwal Ashok
Published: July 2013

Approximately 10 to 15% of couples are impacted by infertility. Recently, the pivotal role that lifestyle factors play in the development of infertility has generated a considerable amount of interest. Lifestyle factors are the modifiable habits and ways of life that can greatly influence overall health and well-being, including fertility. Many lifestyle factors such as the age at which to start a family, nutrition, weight, exercise, psychological stress, environmental and occupational exposures, and others can have substantial effects on fertility; lifestyle factors such as cigarette smoking, illicit drug use, and alcohol and caffeine consumption can negatively influence fertility while others such as preventative care may be beneficial. The present literature review encompasses multiple lifestyle factors and places infertility in context for the couple by focusing on both males and females; it aims to identify the roles that lifestyle factors play in determining reproductive status. The growing interest and amount of research in this field have made it evident that lifestyle factors have a significant impact on fertility.
Some discussion on the existence of common fixed points for a pair of maps
Authors: Patel Deepesh K , Kumam Poom , Gopal Dhananjay
Published: July 2013

In this paper, the concepts of conditionally sequential absorbing and pseudo-reciprocal continuous maps are introduced in connection to giving a brief discussion on the role of various types of commutativity (e.g., weakly compatible, occasionally weakly compatible, subcompatible, pseudo-compatible, etc.) and continuity-type conditions (e.g., reciprocal, weak reciprocal, g-reciprocal, conditionally reciprocal, subsequential and sequential continuity of type

(

A
g

)

and

(

A
f

)

) in the context of existence of common fixed points of a pair of maps. Here, the utility of newly introduced maps (i.e., conditionally sequential absorbing and pseudo-reciprocal continuous) in view of common fixed points for a pair of maps satisfying contractive as well as nonexpansive Lipschitz-type conditions is shown.

MSC:47H10, 54H25.
Investigational treatment suspension and enhanced cell-mediated immunity at rebound followed by drug-free remission of simian AIDS
Authors: Shytaj Iart Luca , Chirullo Barbara , Wagner Wendeline , Ferrari Maria G , Sgarbanti Rossella , Corte Alessandro Della , LaBranche Celia , Lopalco Lucia , Palamara Anna Teresa , Montefiori David , Lewis Mark G , Garaci Enrico , Savarino Andrea
Published: July 2013

Background

HIV infection persists despite antiretroviral treatment (ART) and is reignited as soon as therapies are suspended. This vicious cycle is fueled by the persistence of viral reservoirs that are invulnerable to standard ART protocols, and thus therapeutic agents able to target these reservoirs are needed. One such agent, auranofin, has recently been shown to decrease the memory T-cell reservoir in chronically SIVmac251-infected macaques. Moreover, auranofin could synergize with a fully suppressive ART protocol and induce a drug-free post-therapy containment of viremia.

Results

We administered buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis currently in clinical trials for cancer, in combination with auranofin to chronically SIVmac251-infected macaques under highly-intensified ART (H-iART). The ART/auranofin/BSO therapeutic protocol was followed, after therapy suspension, by a significant decrease of viral RNA and DNA in peripheral blood as compared to pre-therapy levels. Drug-free post-therapy control of the infection was achieved in animals with pre-therapy viral loads ranging from values comparable to average human set points to levels largely higher. This control was dependent on the presence CD8+ cells and associated with enhanced levels of cell-mediated immune responses.

Conclusions

The level of post-therapy viral set point reduction achieved in this study is the largest reported so far in chronically SIVmac251-infected macaques and may represent a promising strategy to improve over the current “ART for life” plight.
Alternative Imaging Modalities in Ischemic Heart Failure (AIMI-HF) IMAGE HF Project I-A: study protocol for a randomized controlled trial
Authors: O’Meara Eileen , Mielniczuk Lisa M , Wells George A , deKemp Robert A , Klein Ran , Coyle Doug , Mc Ardle Brian , Paterson Ian , White James A , Arnold Malcolm , Friedrich Matthias G , Larose Eric , Dick Alexander , Chow Benjamin , Dennie Carole , Haddad Haissam , Ruddy Terrence , Ukkonen Heikki , Wisenberg Gerald , Cantin Bernard , Pibarot Philippe , Freeman Michael , Turcotte Eric , Connelly Kim , Clarke James , Williams Kathryn , Racine Normand , Garrard Linda , Tardif Jean-Claude , DaSilva Jean , Knuuti Juhani , Beanlands Rob ,   the IMAGE HF investigators
Published: July 2013

Background

Ischemic heart disease (IHD) is the most common cause of heart failure (HF); however, the role of revascularization in these patients is still unclear. Consensus on proper use of cardiac imaging to help determine which candidates should be considered for revascularization has been hindered by the absence of clinical studies that objectively and prospectively compare the prognostic information of each test obtained using both standard and advanced imaging.

Methods/Design

This paper describes the design and methods to be used in the Alternative Imaging Modalities in Ischemic Heart Failure (AIMI-HF) multi-center trial. The primary objective is to compare the effect of HF imaging strategies on the composite clinical endpoint of cardiac death, myocardial infarction (MI), cardiac arrest and re-hospitalization for cardiac causes.

In AIMI-HF, patients with HF of ischemic etiology (n = 1,261) will follow HF imaging strategy algorithms according to the question(s) asked by the physicians (for example, Is there ischemia and/or viability?), in agreement with local practices. Patients will be randomized to either standard (SPECT, Single photon emission computed tomography) imaging modalities for ischemia and/or viability or advanced imaging modalities: cardiac magnetic resonance imaging (CMR) or positron emission tomography (PET). In addition, eligible and consenting patients who could not be randomized, but were allocated to standard or advanced imaging based on clinical decisions, will be included in a registry.

Discussion

AIMI-HF will be the largest randomized trial evaluating the role of standard and advanced imaging modalities in the management of ischemic cardiomyopathy and heart failure. This trial will complement the results of the Surgical Treatment for Ischemic Heart Failure (STICH) viability substudy and the PET and Recovery Following Revascularization (PARR-2) trial. The results will provide policy makers with data to support (or not) further investment in and wider dissemination of alternative ‘advanced’ imaging technologies.

Trial registration

NCT01288560
Renal collecting duct carcinoma with extensive coagulative necrosis mimicking anemic infarct: report of a case and the literature review
Authors: Xu Qinqin , Cao Qinghua , Liu Ni , Fang Ziwen , Ye Ziyin , Peng Tingsheng
Published: July 2013

Collecting duct carcinoma (CDC) with a mass of coagulative necrosis is very rare. We report here a case of CDC with extensive geographic coagulative necrosis mimicking anemic infarct with tumor cells embedded around the necrotic foci in a 73-years-old man. Histopathological examination showed that tumor nests near the necrotic foci were arranged as angulated tubules, tubulopapillary and glandular structures. Neoplastic cells had moderate to abundant eosinophilic cytoplasm and large hyperchromatic nuclei with prominent nucleoli as Fuhrman nuclear grade 3 or 4. The tumor cells were positive for pan-Cytokeratin, Vimentin, E-cadherin, CD10, and CK7, confirming the diagnosis as CDC. The patient is still alive 6 months later from nephrectomy, a long time following up is needed to learn the prognosis. Conclusively, morphology from different portions of the lesion, immunohistochemical stain and the combination analysis of the radiological features is essential to make a precise pathological diagnosis of CDC. And CDC should also be distinguished from clear cell renal cell carcinoma, renal medullary carcinoma, urothelial carcinoma with glandular differentiation, renal neuroendocrine tumor, renal epithelioid angiomyolipoma, renal pigmented paraganglioma and renal mesenchymal chondrosarcoma etc.

Virtual Slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1264270525975030
A comparison of dosimetric parameters between tomotherapy and three-dimensional conformal radiotherapy in rectal cancer
Authors: Yu Mina , Lee Joo Hwan , Jang Hong Seok , Jeon Dong Min , Cheon Jae Suk , Lee Hyo Chun , Lee Jong Hoon
Published: July 2013

Purpose

Tomotherapy for intensity-modulated radiation has been demonstrated to reduce unnecessary irradiations to adjacent organs at risk (OARs). The purpose of this study was to compare the dosimetric parameters between Tomotherapy and three-dimensional conformal radiotherapy (3D-CRT) in rectal cancer patients.

Materials and methods

We redesigned three-dimensional conformal plans for 20 rectal cancer patients who had received short-course preoperative radiotherapy with Tomotherapy. The target coverage for 3D-CRT and Tomotherapy was evaluated with the following including the mean dose, VnGy, Dmin, Dmax, radiation conformality index (RCI), and radical dose homogeneity index (rDHI).

Results

The mean PTV dose for Tomotherapy is significantly higher than that observed for the 3D-CRT (p = 0.043). However, there is no significant difference in the V23.25Gy, V26.25Gy, V27.5Gy, and RCI values between Tomotherapy and 3D-CRT. However, the average rDHI (p < 0.001) value for Tomotherapy was significantly lower than that reported for the 3D-CRT. Tomotherapy significantly lowered the mean level of irradiation doses to the bladder, small bowel, and femur heads as compared to 3D-CRT.

Conclusions

Tomotherapy could produce a favorable target coverage and significant dose reduction for the OARs at the expense of acceptable dose inhomogeneity of the PTV compared with 3D-CRT in rectal cancer patients.
Fertility preservation in female classic galactosemia patients
Authors: van Erven Britt , Gubbels Cynthia S , van Golde Ron J , Dunselman Gerard A , Derhaag Josien G , de Wert Guido , Geraedts Joep P , Bosch Annet M , Treacy Eileen P , Welt Corrine K , Berry Gerard T , Rubio-Gozalbo M Estela
Published: July 2013

Almost every female classic galactosemia patient develops primary ovarian insufficiency (POI) as a diet-independent complication of the disease. This is a major concern for patients and their parents, and physicians are often asked about possible options to preserve fertility. Unfortunately, there are no recommendations on fertility preservation in this group. The unique pathophysiology of classic galactosemia with a severely reduced follicle pool at an early age requires an adjusted approach. In this article recommendations for physicians based on current knowledge concerning galactosemia and fertility preservation are made. Fertility preservation is only likely to be successful in very young prepubertal patients. In this group, cryopreservation of ovarian tissue is currently the only available technique. However, this technique is not ready for clinical application, it is considered experimental and reduces the ovarian reserve. Fertility preservation at an early age also raises ethical questions that should be taken into account. In addition, spontaneous conception despite POI is well described in classic galactosemia. The uncertainty surrounding fertility preservation and the significant chance of spontaneous pregnancy warrant counseling towards conservative application of these techniques. We propose that fertility preservation should only be offered with appropriate institutional research ethics approval to classic galactosemia girls at a young prepubertal age.
Down-regulation of miR-181c in imatinib-resistant chronic myeloid leukemia
Authors: Mosakhani Neda , Mustjoki Satu , Knuutila Sakari
Published: July 2013

The association of microRNA alterations with progression and treatment outcome has been revealed in different types of cancers. To find miRNAs involved in imatinib response we performed miRNA microarray followed by RT-qPCR verification of 9 available diagnostic bone marrow core biopsies from 9 CML patients including 4 imatinib-resistant and 5 imatinib-responder patients. Only one differentially expressed miRNA, miR-181c, was found when the imatinib-resistant group was compared with imatinib-responders. Significant down-regulation of miR-181c in imatinib-resistant versus imatinib-responders was confirmed by qRT-PCR. Some miR-181c target genes such as PBX3, HSP90B1, NMT2 and RAD21 have been associated with drug response.
Blood transfusion requirements for endoscopic sinonasal inverted papilloma resections
Authors: Habib Al-Rahim R , Hathorn Iain , Sunkaraneni Vishnu S , Srubiski Aviva , Javer Amin R
Published: July 2013

Background

Endoscopic resection of sinonasal Inverted Papilloma (SNIP) tumors has been shown to reduce intra-operative blood loss and recovery time compared to open approaches. The purpose of this study is to investigate the incidence and requirements of blood transfusion for endoscopic SNIP surgeries.

Methods

An individual retrospective cohort study of endoscopic SNIP surgeries over a 10-year period was performed. Age, sex, pre-existing co-morbidity, use of anti-coagulants, tumor type and stage, time of surgery, estimated blood loss and the requirement for blood transfusion were recorded.

Results

82 patients were included (57 males, 25 females). 4 (5%) Stage 1, 7 (8.5%) Stage 2, 62 (75.5%) Stage 3 and 9 (11%) Stage 4 SNIP tumors were identified according to the Krouse staging system. 3 (4%) patients required blood transfusion. 3 of the 9 (33%) Stage 4 tumors required blood transfusion. Stage 4 tumors were significantly associated with blood transfusion (p < 0.05). Higher staged tumors were associated with greater blood loss (p < 0.05) than lower staged cases. No other tumor stage required blood transfusion and no other pre-operative variable was associated with requirement for blood transfusion.

Conclusion

Endoscopic SNIP resections rarely require blood transfusions. No pre-operative factor other than tumor stage is associated with the requirement for blood transfusion. We would therefore suggest that only Stage 4 SNIP tumors require pre-operative type and screen.
Pyrene removal from contaminated soils by modified Fenton oxidation using iron nano particles
Authors: Jorfi Sahand , Rezaee Abbas , Moheb-ali Ghasem-ali , Jaafarzadeh Nemat alah
Published: July 2013

Background

The problems related to conventional Fenton oxidation, including low pH required and production of considerable amounts of sludge have led researchers to investigate chelating agents which might improve the operating range of pH and the use of nano iron particle to reduce the excess sludge. The pyrene removal from contaminated soils by modified Fenton oxidation at neutral pH was defined as the main objective of the current study.

Methods

Varying concentrations of H2O2 (0-500 mM) and iron nano oxide (0-60 mM), reaction times of 0.5-24 hours and variety of chelating agents including sodium pyrophosphate, sodium citrate, ethylene diamine tetraacetic, fulvic and humic acid were all investigated at pyrene concentration levels of 100 – 500 mg/kg.

Results

By applying the following conditions (H2O2 concentration of 300 mM, iron nano oxide of 30 mM, sodium pyrophosphate as chelating agent, pH 3 and reaction time of 6 hours) the pyrene removal efficiency at an initial concentration of 100 mg/kg was found to be 99%. As a result, the pyrene concentration was reduced from 100 to 93 mg/kg once the above optimum conditions are met.

Conclusions

In this research, the modified Fenton oxidation using iron nano oxide at optimum conditions is introduced as an efficient alternative method in lab scale for chemical remediation or pre-treatment of soils contaminated by pyrene at neutral pH.
Communication and Trust in the Care Provided to a Dying Parent: A Nationwide Study of Cancer-Bereaved Youths
Authors: Bylund Grenklo Tove , Kreicbergs Ulrika C. , Valdimarsdóttir Unnur A. , Nyberg Tommy , Steineck Gunnar , Fürst Carl Johan
Published: July 2013

Purpose

To assess children's trust in the care provided to a dying parent during the final week of life in relation to end-of-life medical information about disease, treatment, and death.

Methods

This nationwide population-based survey included 622 (73%) of 851 youths who, 6 to 9 years earlier, at age 13 to 16 years, lost a parent to cancer. We asked about the children's reception of end-of-life professional information and trust in the care provided. We also asked about depression and several potential risk factors of distrust in the care provided.

Results

A majority (82%) reported moderate/very much trust in the care provided. Compared with children who received end-of-life medical information before their loss, the risk of distrust in the care provided was higher in those who received no information (risk ratio [RR], 2.5; 95% CI, 1.5 to 4.1), in those who only received information afterward (RR, 3.2; 95% CI, 1.7 to 5.9), and in those who did not know or remember if end-of-life medical information was provided (RR, 1.7; 95% CI, 1.1 to 2.5). Those reporting distrust in the care provided had an RR of 2.3 (95% CI, 1.5 to 3.5) for depression. Furthermore, the risk of distrust in the care provided was higher among children reporting poor efforts to cure (RR, 5.1; 95% CI, 3.6 to 7.3), and/or a poor relationship with the surviving parent (RR, 2.9; 95% CI, 2.0 to 4.1).

Conclusion

Our study suggests that children's trust in the care provided to a dying parent was highest when they received end-of-life medical information before their loss.
Mcl1 regulates the terminal mitosis of neural precursor cells in the mammalian brain through p27Kip1
Authors: Hasan S. M. Mahmudul , Sheen Ashley D. , Power Angela M. , Langevin Lisa Marie , Xiong Jieying , Furlong Michael , Day Kristine , Schuurmans Carol , Opferman Joseph T. , Vanderluit Jacqueline L.
Published: July 2013

Cortical development requires the precise timing of neural precursor cell (NPC) terminal mitosis. Although cell cycle proteins regulate terminal mitosis, the factors that influence the cell cycle machinery are incompletely understood. Here we show in mice that myeloid cell leukemia 1 (Mcl1), an anti-apoptotic Bcl-2 protein required for the survival of NPCs, also regulates their terminal differentiation through the cell cycle regulator p27Kip1. A BrdU-Ki67 cell profiling assay revealed that in utero electroporation of Mcl1 into NPCs in the embryonic neocortex increased NPC cell cycle exit (the leaving fraction). This was further supported by a decrease in proliferating NPCs (Pax6+ radial glial cells and Tbr2+ neural progenitors) and an increase in differentiating cells (Dcx+ neuroblasts and Tbr1+ neurons). Similarly, BrdU birth dating demonstrated that Mcl1 promotes premature NPC terminal mitosis giving rise to neurons of the deeper cortical layers, confirming their earlier birthdate. Changes in Mcl1 expression within NPCs caused concomitant changes in the levels of p27Kip1 protein, a key regulator of NPC differentiation. Furthermore, in the absence of p27Kip1, Mcl1 failed to induce NPC cell cycle exit, demonstrating that p27Kip1 is required for Mcl1-mediated NPC terminal mitosis. In summary, we have identified a novel physiological role for anti-apoptotic Mcl1 in regulating NPC terminal differentiation.
Analysis of Gpr126 function defines distinct mechanisms controlling the initiation and maturation of myelin
Authors: Glenn Thomas D. , Talbot William S.
Published: July 2013

In peripheral nerves, Schwann cells form the myelin sheath, which allows the efficient propagation of action potentials along axons. The transcription factor Krox20 regulates the initiation of myelination in Schwann cells and is also required to maintain mature myelin. The adhesion G protein-coupled receptor (GPCR) Gpr126 is essential for Schwann cells to initiate myelination, but previous studies have not addressed the role of Gpr126 signaling in myelin maturation and maintenance. Through analysis of Gpr126 in zebrafish, we define two distinct mechanisms controlling the initiation and maturation of myelin. We show that gpr126 mutant Schwann cells elaborate mature myelin sheaths and maintain krox20 expression for months, provided that the early signaling defect is bypassed by transient elevation of cAMP. At the onset of myelination, Gpr126 and protein kinase A (PKA) function as a switch that allows Schwann cells to initiate krox20 expression and myelination. After myelination is initiated, krox20 expression is maintained and myelin maturation proceeds independently of Gpr126 signaling. Transgenic analysis indicates that the Krox20 cis-regulatory myelinating Schwann cell element (MSE) becomes active at the onset of myelination and that this activity is dependent on Gpr126 signaling. Activity of the MSE declines after initiation, suggesting that other elements are responsible for maintaining krox20 expression in mature nerves. We also show that elevated cAMP does not initiate myelination in the absence of functional Neuregulin 1 (Nrg1) signaling. These results indicate that the mechanisms regulating the initiation of myelination are distinct from those mediating the maturation and maintenance of myelin.
Apical constriction initiates new bud formation during monopodial branching of the embryonic chicken lung
Authors: Kim Hye Young , Varner Victor D. , Nelson Celeste M.
Published: July 2013

Branching morphogenesis sculpts the airway epithelium of the lung into a tree-like structure to conduct air and promote gas exchange after birth. In the avian lung, a series of buds emerges from the dorsal surface of the primary bronchus via monopodial branching to form the conducting airways; anatomically, these buds are similar to those formed by domain branching in the mammalian lung. Here, we show that monopodial branching is initiated by apical constriction of the airway epithelium, and not by differential cell proliferation, using computational modeling and quantitative imaging of embryonic chicken lung explants. Both filamentous actin and phosphorylated myosin light chain were enriched at the apical surface of the airway epithelium during monopodial branching. Consistently, inhibiting actomyosin contractility prevented apical constriction and blocked branch initiation. Although cell proliferation was enhanced along the dorsal and ventral aspects of the primary bronchus, especially before branch formation, inhibiting proliferation had no effect on the initiation of branches. To test whether the physical forces from apical constriction alone are sufficient to drive the formation of new buds, we constructed a nonlinear, three-dimensional finite element model of the airway epithelium and used it to simulate apical constriction and proliferation in the primary bronchus. Our results suggest that, consistent with the experimental results, apical constriction is sufficient to drive the early stages of monopodial branching whereas cell proliferation is dispensable. We propose that initial folding of the airway epithelium is driven primarily by apical constriction during monopodial branching of the avian lung.
ERF and ETV3L are retinoic acid-inducible repressors required for primary neurogenesis
Authors: Janesick Amanda , Abbey Rachelle , Chung Connie , Liu Sophia , Taketani Mao , Blumberg Bruce
Published: July 2013

Cells in the developing neural tissue demonstrate an exquisite balance between proliferation and differentiation. Retinoic acid (RA) is required for neuronal differentiation by promoting expression of proneural and neurogenic genes. We show that RA acts early in the neurogenic pathway by inhibiting expression of neural progenitor markers Geminin and Foxd4l1, thereby promoting differentiation. Our screen for RA target genes in early Xenopus development identified Ets2 Repressor Factor (Erf) and the closely related ETS repressors Etv3 and Etv3-like (Etv3l). Erf and Etv3l are RA responsive and inhibit the action of ETS genes downstream of FGF signaling, placing them at the intersection of RA and growth factor signaling. We hypothesized that RA regulates primary neurogenesis by inducing Erf and Etv3l to antagonize proliferative signals. Loss-of-function analysis showed that Erf and Etv3l are required to inhibit proliferation of neural progenitors to allow differentiation, whereas overexpression of Erf led to an increase in the number of primary neurons. Therefore, these RA-induced ETS repressors are key components of the proliferation-differentiation switch during primary neurogenesis in vivo.
An innate twist between Crick’s wobble and Watson-Crick base pairs
Authors: Ananth Prakash , Goldsmith Gunaseelan , Yathindra Narayanarao
Published: July 2013

Non-Watson-Crick pairs like the G·U wobble are frequent in RNA duplexes. Their geometric dissimilarity (nonisostericity) with the Watson-Crick base pairs and among themselves imparts structural variations decisive for biological functions. Through a novel circular representation of base pairs, a simple and general metric scheme for quantification of base-pair nonisostericity, in terms of residual twist and radial difference that can also envisage its mechanistic effect, is proposed. The scheme is exemplified by G·U and U·G wobble pairs, and their predicable local effects on helical twist angle are validated by MD simulations. New insights into a possible rationale for contextual occurrence of G·U and other non-WC pairs, as well as the influence of a G·U pair on other non-Watson-Crick pair neighborhood and RNA-protein interactions are obtained from analysis of crystal structure data. A few instances of RNA-protein interactions along the major groove are documented in addition to the well-recognized interaction of the G·U pair along the minor groove. The nonisostericity-mediated influence of wobble pairs for facilitating helical packing through long-range interactions in ribosomal RNAs is also reviewed.
Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction
Authors: Bronicki Lucas M. , Jasmin Bernard J.
Published: July 2013

Precise control of messenger RNA (mRNA) processing and abundance are increasingly being recognized as critical for proper spatiotemporal gene expression, particularly in neurons. These regulatory events are governed by a large number oftrans-acting factors found in neurons, most notably RNA-binding proteins (RBPs) and micro-RNAs (miRs), which bind to specificcis-acting elements or structures within mRNAs. Through this binding mechanism,trans-acting factors, particularly RBPs, control all aspects of mRNA metabolism, ranging from altering the transcription rate to mediating mRNA degradation. In this context the best-characterized neuronal RBP, the Hu/ELAVl family member HuD, is emerging as a key component in multiple regulatory processes—including pre-mRNA processing, mRNA stability, and translation—governing the fate of a substantial amount of neuronal mRNAs. Through its ability to regulate mRNA metabolism of diverse groups of functionally similar genes, HuD plays important roles in neuronal development and function. Furthermore, compelling evidence indicates supplementary roles for HuD in neuronal plasticity, in particular, recovery from axonal injury, learning and memory, and multiple neurological diseases. The purpose of this review is to provide a detailed overview of the current knowledge surrounding the expression and roles of HuD in the nervous system. Additionally, we outline the present understanding of the molecular mechanisms presiding over the localization, abundance, and function of HuD in neurons.
Did the elimination of lead from petrol reduce crime in the USA in the 1990s?
Authors: Hall Wayne
Published: July 2013

This article assesses the evidence for the hypothesis that a decline in all types of crime since the early 1990s in the USA was an unintended consequence of removing lead from petrol between 1975 and 1985. It describes ecological and econometric studies that have generally but not always found correlations between lead exposures in childhood and some types of crime 20 years later; a small number of epidemiological studies that have found a dose-response relationship between lead exposure in childhood and self-reported and officially recorded criminal offences in young adulthood; and evidence for the biological plausibility of a causal relationship. The major anomaly in the evidence is that the associations reported in ecological studies are much stronger (explaining 56-90% of the variation in crime rates) than the weaker relationships found in the cohort studies (that typically explain less than 1% of the variance in offending).  Suggestions are made for research that will better assess the contribution that reduced lead exposure has made to declining crime rates in the USA.