bluuebunny/crossref_metadata_2025 huggingface dataset:
The clinical features of papillary thyroid cancer in Hashimoto’s thyroiditis patients from an area with a high prevalence of Hashimoto’s disease
Authors: Zhang Ling , Li Hui , Ji Qing-hai , Zhu Yong-xue , Wang Zhuo-ying , Wang Yu , Huang Cai-ping , Shen Qiang , Li Duan-shu , Wu Yi
Published: December 2012

Background

The goal of this study was to identify the clinicopathological factors of co-existing papillary thyroid cancer (PTC) in patients with Hashimoto’s thyroiditis (HT) and provide information to aid in the diagnosis of such patients.

Methods

This study included 6109 patients treated in a university-based tertiary care cancer hospital over a 3-year period. All of the patients were categorised based on their final diagnosis. Several clinicopathological factors, such as age, gender, nodular size, invasive status, central compartment lymph node metastasis (CLNM) and serum thyroid-stimulating hormone (TSH) level, were compared between the various groups of patients.

Results

There were 653 patients with a final diagnosis of HT. More PTC was found in those with HT (58.3%; 381 of 653) than those without HT (2416 of 5456; 44.3%; p < 0.05). The HT patients with co-occurring PTC were more likely to be younger, be female, have smaller nodules and have higher TSH levels than those without PTC. A multivariate analysis indicated that the presence of HT and higher TSH levels were risk factors for a diagnosis of PTC. In the PTC patients, the presence of HT or another benign nodule was a protective factor for CLNM, whereas no significant association was found for TSH levels.

Conclusion

PTC and HT have a close relationship in this region of highly prevalent HT disease. Based on the results of our study, we hypothesise that long-term HT leads to elevated serum TSH, which is the real risk factor for thyroid cancer.
Alternative dosing of dual PI3K and MEK inhibition in cancer therapy
Authors: Jokinen Elina , Laurila Niina , Koivunen Jussi P
Published: December 2012

Background

PI3K/AKT/mTOR and RAS/RAF/MEK/ERK pathways are thought to be the central transducers of oncogenic signals in solid malignancies, and there has been a lot of enthusiasm for developing inhibitors of these pathways for cancer therapy. Some preclinical models have suggested that combining inhibitors of both parallel pathways may be more efficacious, but it remains unknown whether dual inhibition with high enough concentrations of the drugs to achieve meaningful target inhibition is tolerable in a clinical setting. Furthermore, the predictive factors for dual inhibition are unknown.

Methods

Non-small cell lung cancer (NSCLC) cell lines (n=12) with the most frequent oncogenic backgrounds (K-Ras mut n=3, EGFR mut n=3, ALK translocated n=3, and triple-negative n=3) were exposed to PI3K inhibitors (ZSTK474, PI-103) or MEK inhibitor (CI-1040) alone or in combination and analysed with an MTS growth/cytotoxicity assay and statistically by combination index analysis. The activity of the intracellular signaling pathways in response to the inhibitor treatments was analysed with a western blot using phospho-specific antibodies to AKT, ERK1/2, S6, and 4E-BPI. For the differential dosing schedule experiments, additional breast and colon cancer cell lines known to be sensitive to dual inhibition were included.

Results

Two of the 12 NSCLC cell lines tested, H3122 (ALK translocated) and H1437 (triple-negative), showed increased cytotoxicity upon dual MEK and PI3K inhibition. Furthermore, MDA-MB231 (breast) and HCT116 (colon), showed increased cytotoxicity upon dual inhibition, as in previous studies. Activation of parallel pathways in the dual inhibition-sensitive lines was also noted in response to single inhibitor treatment. Otherwise, no significant differences in downstream intracellular pathway activity (S6 and 4E-BPI) were noted between PI3K alone and dual inhibition other than the increased cytotoxicity of the latter. In the alternative dosing schedules two out of the four dual inhibition-sensitive cell lines showed similar cytotoxicity to continuous PI3K and short (15min) MEK inhibition treatment.

Conclusions

Therapy with a dual PI3K and MEK inhibitor combination is more efficient than either inhibitor alone in some NSCLC cell lines. Responses to dual inhibition were not associated with any specific oncogenic genotype and no other predictive factors for dual inhibition were noted. The maximal effect of the dual PI3K and MEK inhibition can be achieved with alternative dosing schedules which are potentially more tolerable clinically.
Indigenous populations health protection: A Canadian perspective
Authors: Richardson Katya L , Driedger Michelle S , Pizzi Nick J , Wu Jianhong , Moghadas Seyed M
Published: December 2012

The disproportionate effects of the 2009 H1N1 pandemic on many Canadian Aboriginal communities have drawn attention to the vulnerability of these communities in terms of health outcomes in the face of emerging and reemerging infectious diseases. Exploring the particular challenges facing these communities is essential to improving public health planning. In alignment with the objectives of the Pandemic Influenza Outbreak Research Modelling (Pan-InfORM) team, a Canadian public health workshop was held at the Centre for Disease Modelling (CDM) to: (i) evaluate post-pandemic research findings; (ii) identify existing gaps in knowledge that have yet to be addressed through ongoing research and collaborative activities; and (iii) build upon existing partnerships within the research community to forge new collaborative links with Aboriginal health organizations. The workshop achieved its objectives in identifying main research findings and emerging information post pandemic, and highlighting key challenges that pose significant impediments to the health protection and promotion of Canadian Aboriginal populations. The health challenges faced by Canadian indigenous populations are unique and complex, and can only be addressed through active engagement with affected communities. The academic research community will need to develop a new interdisciplinary framework, building upon concepts from ‘Communities of Practice’, to ensure that the research priorities are identified and targeted, and the outcomes are translated into the context of community health to improve policy and practice.
Glucan-rich polysaccharides from Pleurotus sajor-caju (Fr.) Singer prevents glucose intolerance, insulin resistance and inflammation in C57BL/6J mice fed a high-fat diet
Authors: Kanagasabapathy Gowri , Kuppusamy Umah Rani , Abd Malek Sri Nurestri , Abdulla Mahmood Ameen , Chua Kek-Heng , Sabaratnam Vikineswary
Published: December 2012

Background

Pleurotus sajor-caju (P. sajor-caju) has been extremely useful in the prevention of diabetes mellitus due to its low fat and high soluble fiber content for thousands of years. Insulin resistance is a key component in the development of diabetes mellitus which is caused by inflammation. In this study, we aimed to investigate the in vivo efficacy of glucan-rich polysaccharide of P. sajor-caju (GE) against diabetes mellitus and inflammation in C57BL/6J mice fed a high-fat diet.

Methods

Diabetes was induced in C57BL/6J mice by feeding a high-fat diet. The mice were randomly assigned to 7 groups (n=6 per group). The control groups in this study were ND (for normal diet) and HFD (for high-fat diet). The treated groups were ND240 (for normal diet) (240 mg/kg b.w) and HFD60, HFD120 and HFD240 (for high-fat), where the mice were administrated with three dosages of GE (60, 120, 240 mg GE/kg b.w respectively). Metformin (2 mg/kg b.w) served as positive control. The glucose tolerance test, glucose and insulin levels were measured at the end of 16 weeks. Expressions of genes for inflammatory markers, GLUT-4 and adiponectin in the adipose tissue of the mice were assessed. One-way ANOVA and Duncan’s multiple range tests (DMRT) were used to determine the significant differences between groups.

Results

GE treated groups improved the glucose tolerance, attenuated hyperglycemia and hyperinsulinemia in the mice by up-regulating the adiponectin and GLUT-4 gene expressions. The mice in GE treated groups did not develop insulin resistance. GE also down-regulated the expression of inflammatory markers (IL-6, TNF-α, SAA2, CRP and MCP-1) via attenuation of nuclear transcription factors (NF-κB).

Conclusion

Glucan-rich polysaccharide of P. sajor-caju can serve as a potential agent for prevention of glucose intolerance, insulin resistance and inflammation.
Use of next generation sequencing technologies in research and beyond: are participants with mental health disorders fully protected?
Authors: Groisman Iris Jaitovich , Mathieu Ghislaine , Godard Beatrice
Published: December 2012

Background

Next Generation Sequencing (NGS) is expected to help find the elusive, causative genetic defects associated with Bipolar Disorder (BD). This article identifies the importance of NGS and further analyses the social and ethical implications of this approach when used in research projects studying BD, as well as other psychiatric ailments, with a view to ensuring the protection of research participants.

Methods

We performed a systematic review of studies through PubMed, followed by a manual search through the titles and abstracts of original articles, including the reviews, commentaries and letters published in the last five years and dealing with the ethical and social issues raised by NGS technologies and genomics studies of mental disorders, especially BD. A total of 217 studies contributed to identify the themes discussed herein.

Results

The amount of information generated by NGS renders individuals suffering from BD particularly vulnerable, and increases the need for educational support throughout the consent process, and, subsequently, of genetic counselling, when communicating individual research results and incidental findings to them. Our results highlight the importance and difficulty of respecting participants’ autonomy while avoiding any therapeutic misconception. We also analysed the need for specific regulations on the use and communication of incidental findings, as well as the increasing influence of NGS in health care.

Conclusions

Shared efforts on the part of researchers and their institutions, Research Ethics Boards as well as participants’ representatives are needed to delineate a tailored consent process so as to better protect research participants. However, health care professionals involved in BD care and treatment need to first determine the scientific validity and clinical utility of NGS-generated findings, and thereafter their prevention and treatment significance.
Haemoglobin variants and Plasmodium falciparum malaria in children under five years of age living in a high and seasonal malaria transmission area of Burkina Faso
Authors: Bougouma Edith C , Tiono Alfred B , Ouédraogo Alphonse , Soulama Issiaka , Diarra Amidou , Yaro Jean-Baptiste , Ouédraogo Espérance , Sanon Souleymane , Konaté Amadou T , Nébié Issa , Watson Nora L , Sanza Megan , Dube Tina JT , Sirima Sodiomon B
Published: December 2012

Background

Genetic factors play a key role in determining resistance/susceptibility to infectious disease. Susceptibility of the human host to malaria infection has been reported to be influenced by genetic factors, which could be confounders if not taken into account in the assessment of the efficacy of interventions against malaria. This study aimed to assess the relationship between haemoglobin genotypes and malaria in children under five years in a site being characterized for future malaria vaccine trials.

Methods

The study population consisted of 452 children living in four rural villages. Hb genotype was determined at enrolment. Clinical malaria incidence was evaluated over a one-year period using combined active and passive surveillance. Prevalence of infection was evaluated via bi-annual cross-sectional surveys. At each follow-up visit, children received a brief clinical examination and thick and thin blood films were prepared for malaria diagnosis. A clinical malaria was defined as Plasmodium falciparum parasitaemia >2,500 parasites/μl and axillary temperature ≥37.5°C or reported fever over the previous 24 hours.

Results

Frequencies of Hb genotypes were 73.2% AA; 15.0% AC; 8.2% AS; 2.2% CC; 1.1% CS and 0.2% SS. Prevalence of infection at enrolment ranged from 61.9%-54.1% among AA, AC and AS children. After one year follow-up, clinical malaria incidence (95% CI) (episodes per person-year) was 1.9 (1.7-2.0) in AA, 1.6 (1.4-2.1) in AC, and 1.7 (1.4-2.0) in AS children. AC genotype was associated with lower incidence of clinical malaria relative to AA genotype among children aged 1–2 years [rate ratio (95% CI) 0.66 (0.42-1.05)] and 2–3 years [rate ratio (95% CI) 0.37 (0.18-0.75)]; an association of opposite direction was however apparent among children aged 3–4 years. AS genotype was associated with lower incidence of clinical malaria relative to AA genotype among children aged 2–3 years [rate ratio (95% CI) 0.63 (0.40-1.01)].

Conclusions

In this cohort of children, AC or AS genotype was associated with lower risk of clinical malaria relative to AA genotype only among children aged one to three years. It would be advisable for clinical studies of malaria in endemic regions to consider haemoglobin gene differences as a potentially important confounder, particularly among younger children.
NF-κB is activated in response to temozolomide in an AKT-dependent manner and confers protection against the growth suppressive effect of the drug
Authors: Caporali Simona , Levati Lauretta , Graziani Grazia , Muzi Alessia , Atzori Maria Grazia , Bonmassar Enzo , Palmieri Giuseppe , Ascierto Paolo A , D’Atri Stefania
Published: December 2012

Background

Most DNA-damaging chemotherapeutic agents activate the transcription factor nuclear factor κB (NF-κB). However, NF-κB activation can either protect from or contribute to the growth suppressive effects of the agent. We previously showed that the DNA-methylating drug temozolomide (TMZ) activates AKT, a positive modulator of NF-κB, in a mismatch repair (MMR) system-dependent manner. Here we investigated whether NF-κB is activated by TMZ and whether AKT is involved in this molecular event. We also evaluated the functional consequence of inhibiting NF-κB on tumor cell response to TMZ.

Methods

AKT phosphorylation, NF-κB transcriptional activity, IκB-α degradation, NF-κB2/p52 generation, and RelA and NF-κB2/p52 nuclear translocation were investigated in TMZ-treated MMR-deficient (HCT116, 293TLα-) and/or MMR-proficient (HCT116/3-6, 293TLα+, M10) cells. AKT involvement in TMZ-induced activation of NF-κB was addressed in HCT116/3-6 and M10 cells transiently transfected with AKT1-targeting siRNA or using the isogenic MMR-proficient cell lines pUSE2 and KD12, expressing wild type or kinase-dead mutant AKT1. The effects of inhibiting NF-κB on sensitivity to TMZ were investigated in HCT116/3-6 and M10 cells using the NF-κB inhibitor NEMO-binding domain (NBD) peptide or an anti-RelA siRNA.

Results

TMZ enhanced NF-κB transcriptional activity, activated AKT, induced IκB-α degradation and RelA nuclear translocation in HCT116/3-6 and M10 but not in HCT116 cells. In M10 cells, TMZ promoted NF-κB2/p52 generation and nuclear translocation and enhanced the secretion of IL-8 and MCP-1. TMZ induced RelA nuclear translocation also in 293TLα+but not in 293TLα-cells. AKT1 silencing inhibited TMZ-induced IκB-α degradation and NF-κB2/p52 generation. Up-regulation of NF-κB transcriptional activity and nuclear translocation of RelA and NF-κB2/p52 in response to TMZ were impaired in KD12 cells. RelA silencing in HCT116/3-6 and M10 cells increased TMZ-induced growth suppression. In M10 cells NBD peptide reduced basal NF-κB activity, abrogated TMZ-induced up-regulation of NF-κB activity and increased sensitivity to TMZ. In HCT116/3-6 cells, the combined treatment with NBD peptide and TMZ produced additive growth inhibitory effects.

Conclusion

NF-κB is activated in response to TMZ in a MMR- and AKT-dependent manner and confers protection against drug-induced cell growth inhibition. Our findings suggest that a clinical benefit could be obtained by combining TMZ with NF-κB inhibitors.
Fecal microbial determinants of fecal and systemic estrogens and estrogen metabolites: a cross-sectional study
Authors: Flores Roberto , Shi Jianxin , Fuhrman Barbara , Xu Xia , Veenstra Timothy D , Gail Mitchell H , Gajer Pawel , Ravel Jacques , Goedert James J
Published: December 2012

Background

High systemic estrogen levels contribute to breast cancer risk for postmenopausal women, whereas low levels contribute to osteoporosis risk. Except for obesity, determinants of non-ovarian systemic estrogen levels are undefined. We sought to identify members and functions of the intestinal microbial community associated with estrogen levels via enterohepatic recirculation.

Methods

Fifty-one epidemiologists at the National Institutes of Health, including 25 men, 7 postmenopausal women, and 19 premenopausal women, provided urine and aliquots of feces, using methods proven to yield accurate and reproducible results. Estradiol, estrone, 13 estrogen metabolites (EM), and their sum (total estrogens) were quantified in urine and feces by liquid chromatography/tandem mass spectrometry. In feces, β-glucuronidase and β-glucosidase activities were determined by realtime kinetics, and microbiome diversity and taxonomy were estimated by pyrosequencing 16S rRNA amplicons. Pearson correlations were computed for each loge estrogen level, loge enzymatic activity level, and microbiome alpha diversity estimate. For the 55 taxa with mean relative abundance of at least 0.1%, ordinal levels were created [zero, low (below median of detected sequences), high] and compared to loge estrogens, β-glucuronidase and β-glucosidase enzymatic activity levels by linear regression. Significance was based on two-sided tests with α=0.05.

Results

In men and postmenopausal women, levels of total urinary estrogens (as well as most individual EM) were very strongly and directly associated with all measures of fecal microbiome richness and alpha diversity (R≥0.50, P≤0.003). These non-ovarian systemic estrogens also were strongly and significantly associated with fecal Clostridia taxa, including non-Clostridiales and three genera in the Ruminococcaceae family (R=0.57−0.70, P=0.03−0.002). Estrone, but not other EM, in urine correlated significantly with functional activity of fecal β-glucuronidase (R=0.36, P=0.04). In contrast, fecal β-glucuronidase correlated inversely with fecal total estrogens, both conjugated and deconjugated (R≤-0.47, P≤0.01). Premenopausal female estrogen levels, which were collected across menstrual cycles and thus highly variable, were completely unrelated to fecal microbiome and enzyme parameters (P≥0.6).

Conclusions

Intestinal microbial richness and functions, including but not limited to β-glucuronidase, influence levels of non-ovarian estrogens via enterohepatic circulation. Thus, the gut microbial community likely affects the risk for estrogen-related conditions in older adults. Understanding how Clostridia taxa relate to systemic estrogens may identify targets for interventions.

Trial registration

Not applicable.
Wip1 and p53 contribute to HTLV-1 Tax-induced tumorigenesis
Authors: Zane Linda , Yasunaga Junichiro , Mitagami Yu , Yedavalli Venkat , Tang Sai-Wen , Chen Chia-Yen , Ratner Lee , Lu Xiongbin , Jeang Kuan-Teh
Published: December 2012

Background

Human T-cell Leukemia Virus type 1 (HTLV-1) infects 20 million individuals world-wide and causes Adult T-cell Leukemia/Lymphoma (ATLL), a highly aggressive T-cell cancer. ATLL is refractory to treatment with conventional chemotherapy and fewer than 10% of afflicted individuals survive more than 5 years after diagnosis. HTLV-1 encodes a viral oncoprotein, Tax, that functions in transforming virus-infected T-cells into leukemic cells. All ATLL cases are believed to have reduced p53 activity although only a minority of ATLLs have genetic mutations in their p53 gene. It has been suggested that p53 function is inactivated by the Tax protein.

Results

Using genetically altered mice, we report here that Tax expression does not achieve a functional equivalence of p53 inactivation as that seen with genetic mutation of p53 (i.e. a p53

−/−
genotype). Thus, we find statistically significant differences in tumorigenesis between Tax

+

p53

+/+

versus Tax

+

p53

−/−
mice. We also find a role contributed by the cellular Wip1 phosphatase protein in tumor formation in Tax transgenic mice. Notably, Tax

+

Wip1
−/−
mice show statistically significant reduced prevalence of tumorigenesis compared to Tax

+

Wip1
+/+
counterparts.

Conclusions

Our findings provide new insights into contributions by p53 and Wip1 in the in vivo oncogenesis of Tax-induced tumors in mice.
WIP1 deficiency inhibits HTLV-1 Tax oncogenesis: novel therapeutic prospects for treatment of ATL?
Authors: Gillet Nicolas , Carpentier Alexandre , Barez Pierre-Yves , Willems Luc
Published: December 2012

Attenuation of p53 activity appears to be a major step in Human T-lymphotropic virus type 1 (HTLV-1) Tax transformation. However, p53 genomic mutations are late and rather infrequent events in HTLV-1 induced Adult T cell leukemia (ATL). The paper by Zane et al. shows that a mediator of p53 activity, Wild-type p53-induced phosphatase 1 (Wip1), contributes to Tax-induced oncogenesis in a mouse model. Wip1 may therefore be a novel target for therapeutic approaches.
Number of rare germline CNVs and TP53 mutation types
Authors: Silva Amanda G , Achatz Maria Isabel Waddington , Krepischi Ana CV , Pearson Peter L , Rosenberg Carla
Published: December 2012

Background

The Li-Fraumeni syndrome (LFS), an inherited rare cancer predisposition syndrome characterized by a variety of early-onset tumors, is caused by different highly penetrant germline mutations in the TP53 gene; each separate mutation has dissimilar functional and phenotypic effects, which partially clarifies the reported heterogeneity between LFS families. Increases in copy number variation (CNV) have been reported in TP53 mutated individuals, and are also postulated to contribute to LFS phenotypic variability. The Brazilian p.R337H TP53 mutation has particular functional and regulatory properties that differ from most other common LFS TP53 mutations, by conferring a strikingly milder phenotype.

Methods

We compared the CNV profiles of controls, and LFS individuals carrying either p.R337H or DNA binding domain (DBD) TP53 mutations by high resolution array-CGH.

Results

Although we did not find any significant difference in the frequency of CNVs between LFS patients and controls, our data indicated an increased proportion of rare CNVs per genome in patients carrying DBD mutations compared to both controls (p=0.0002***) and p.R337H (0.0156*) mutants.

Conclusions

The larger accumulation of rare CNVs in DBD mutants may contribute to the reported anticipation and severity of the syndrome; likewise the fact that p.R337H individuals do not present the same magnitude of rare CNV accumulation may also explain the maintenance of this mutation at relatively high frequency in some populations.
Novel biomarker combination improves the diagnosis of serious bacterial infections in Malawian children
Authors: Irwin Adam D , Marriage Fiona , Mankhambo Limangeni A , Group IPD Study , Jeffers Graham , Kolamunnage-Dona Ruwanthi , Guiver Malcolm , Denis Brigitte , Molyneux Elizabeth M , Molyneux Malcolm E , Day Philip J , Carrol Enitan D
Published: December 2012

Background

High throughput technologies offer insight into disease processes and heightens opportunities for improved diagnostics. Using transcriptomic analyses, we aimed to discover and to evaluate the clinical validity of a combination of reliable and functionally important biomarkers of serious bacterial infection (SBI).

Methods

We identified three previously reported biomarkers of infection (neutrophil gelatinase-associated lipocalin (NGAL), granulysin and resistin) and measured gene expression using quantitative real-time PCR. Protein products related to the three transcripts were measured by immunoassays.

Results

Relative gene expression values of NGAL and resistin were significantly increased, and expression of granulysin significantly decreased in cases compared to controls. Plasma concentrations of NGAL and resistin were significantly increased in children with confirmed SBI compared to children with no detectable bacterial infection (NBI), and to controls (287 versus 128 versus 62 ng/ml and 195 versus 90 versus 18 ng/ml, respectively, p < 0.05). Plasma protein concentrations of NGAL and resistin were significantly increased in non-survivors compared to survivors (306 versus 211 and 214 versus 150 ng/ml, p = 0.02). The respective areas under the curve (AUC) for NGAL, resistin and procalcitonin in predicting SBI were 0.79, 0.80 and 0.86, whilst a combination of NGAL, resistin and procalcitonin achieved an AUC of 0.90.

Conclusions

We have demonstrated a unique combination of diagnostic biomarkers of SBI using transcriptomics, and demonstrated translational concordance with the corresponding protein. The addition of NGAL and resistin protein measurement to procalcitonin significantly improved the diagnosis of SBI.
Tracking the mechanical dynamics of human embryonic stem cell chromatin
Authors: Hinde Elizabeth , Cardarelli Francesco , Chen Aaron , Khine Michelle , Gratton Enrico
Published: December 2012

Background

A plastic chromatin structure has emerged as fundamental to the self-renewal and pluripotent capacity of embryonic stem (ES) cells. Direct measurement of chromatin dynamics in vivo is, however, challenging as high spatiotemporal resolution is required. Here, we present a new tracking-based method which can detect high frequency chromatin movement and quantify the mechanical dynamics of chromatin in live cells.

Results

We use this method to study how the mechanical properties of chromatin movement in human embryonic stem cells (hESCs) are modulated spatiotemporally during differentiation into cardiomyocytes (CM). Notably, we find that pluripotency is associated with a highly discrete, energy-dependent frequency of chromatin movement that we refer to as a ‘breathing’ state. We find that this ‘breathing’ state is strictly dependent on the metabolic state of the cell and is progressively silenced during differentiation.

Conclusions

We thus propose that the measured chromatin high frequency movements in hESCs may represent a hallmark of pluripotency and serve as a mechanism to maintain the genome in a transcriptionally accessible state. This is a result that could not have been observed without the high spatial and temporal resolution provided by this novel tracking method.
Mentha longifolia syrup in secondary amenorrhea: a double-blind, placebo-controlled, randomized trials
Authors: Mokaberinejad Roshanak , Zafarghandi Nafiseh , Bioos Soodabeh , Dabaghian Fataneh Hashem , Naseri Mohsen , Kamalinejad Mohammad , Amin Gholamreza , Ghobadi Ali , Tansaz Mojgan , Akhbari Ali , Hamiditabar Mohammadali
Published: December 2012

Background

Amenorrhea is defined as the cessation of menses. Hormone therapy is the most common treatment. Due to the contraindications and side effects of it and the increasing demand for alternative medicine substitutes, Mentha longifolia L. was used in this study. Mentha longifolia L. is a known medication in Iranian traditional medicine to induce menstrual bleeding in women with secondary amenorrhea and oligomenorrhea.

Methods

A double-blind, randomized, placebo-controlled, multicenter study was conducted in 120 women with secondary amenorrhea and oligomenorrhea. Treatment consisted of sequential oral syrup, 45 ml (15 ml three times a day) for 2 weeks. If the patients did not have menstruation after 2 weeks of taking the medication, we would wait for two more weeks. If the patients had menstruation at each stage of using the drug, we started it one week after the end of menstruation. But if the patients had not menstruate after four weeks (two-week using of drug and waiting for two more weeks), the previous steps were repeated. The drug and placebo were repeated in three cycles of menstruation. Bleeding was documented by the patient on diary cards. The primary outcome variable was the occurrence (yes/no) of bleeding during the first treatment cycle. The secondary efficacy outcome was the regularity of bleeding pattern during the three cycles of the study.

Results

The number of women with bleeding during the first cycle were higher in the drug group as in the placebo group (68.3% vs. 13.6%; p < 0.001). The regularity of bleeding throughout the study was markedly better in the drug group compared with those given placebo (33.3% vs. 3.3%; p < 0.001). No notable complication or side effect was reported in relation to Mentha longifolia L. syrup.

Conclusion

In conclusion, Mentha longifolia L. syrup is a safe, well-tolerated, and effective choice in inducing bleeding and maintaining regular bleeding in women with secondary amenorrhea and oligomenorrhea.
RNAi-mediated abrogation of trehalase expression does not affect trehalase activity in sugarcane
Authors: O’Neill Brian P , Purnell Matthew P , Nielsen Lars K , Brumbley Stevens M
Published: December 2012

To engineer trehalose metabolism in sugarcane (Saccharumspp. hybrids) two transgenes were introduced to the genome: trehalose-6-phosphate synthase- phosphatase (TPSP), to increase trehalose biosynthesis and an RNAi transgene specific for trehalase, to abrogate trehalose catabolism. In RNAi-expressing lines trehalase expression was abrogated in many plants however no decrease in trehalase activity was observed. In TPSP lines trehalase activity was significantly higher. No events of co-integration of TPSP and RNAi transgenes were observed. We suggest trehalase activity is essential to mitigate embryonic lethal effects of trehalose metabolism and discuss the implications for engineering trehalose metabolism.
FMR1 CGG allele size and prevalence ascertained through newborn screening in the United States
Authors: Tassone Flora , Iong Ka Pou , Tong Tzu-Han , Lo Joyce , Gane Louise W , Berry-Kravis Elizabeth , Nguyen Danh , Mu Lisa Y , Laffin Jennifer , Bailey Don B , Hagerman Randi J
Published: December 2012

Background

Population screening for FMR1 mutations has been a topic of considerable discussion since the FMR1 gene was identified in 1991. Advances in understanding the molecular basis of fragile X syndrome (FXS) and in genetic testing methods have led to new, less expensive methodology to use for large screening endeavors. A core criterion for newborn screening is an accurate understanding of the public health burden of a disease, considering both disease severity and prevalence rate. This article addresses this need by reporting prevalence rates observed in a pilot newborn screening study for FXS in the US.

Methods

Blood spot screening of 14,207 newborns (7,312 males and 6,895 females) was conducted in three birthing hospitals across the United States beginning in November 2008, using a PCR-based approach.

Results

The prevalence of gray zone alleles was 1:66 females and 1:112 males, while the prevalence of a premutation was 1:209 females and 1:430 males. Differences in prevalence rates were observed among the various ethnic groups; specifically higher frequency for gray zone alleles in males was observed in the White group compared to the Hispanic and African-American groups. One full mutation male was identified (>200 CGG repeats).

Conclusions

The presented pilot study shows that newborn screening in fragile X is technically feasible and provides overall prevalence of the premutation and gray zone alleles in the USA, suggesting that the prevalence of the premutation, particularly in males, is higher than has been previously reported.
Residual statics estimation by sparsity maximization
Authors: Gholami Ali
Published: December 2012

Residual statics estimation in complex areas is one of the main challenging problems in seismic data processing. It is well known that the result of this processing step has a profound effect on the quality of final reconstructed image. A novel method is presented to compensate for surface-consistent residual static corrections based on sparsity maximization, which has proved to be a powerful tool in the analysis and processing of signals and related problems. The method is based on the hypothesis that residual static time shift represents itself by noise-like features in the Fourier or curvelet domain. Residual time shift corrections are then retrieved by optimizing the sparsity in these domains. Here, the statics model is considered as a maximizer of [Formula: see text]-norm ([Formula: see text]) of the data coefficients in the sparse domain, and a fast and efficient algorithm is presented to iteratively solve the corresponding nonlinear optimization problem. Applications on synthetic and real data show very high performance of the presented algorithm.
Employment outcome for people with schizophrenia in rural v. urban China: population-based study
Authors: Yang Lawrence H. , Phillips Michael R. , Li Xianyun , Yu Gary , Zhang Jingxuan , Shi Qichang , Song Zhiqiang , Ding Zhijie , Pang Shutao , Susser Ezra
Published: December 2012

Background

Although outcomes among people with schizophrenia differ by social context, this has rarely been examined across rural v. urban settings. For individuals with schizophrenia, employment is widely recognised as a critical ingredient of social integration.

Aims

To compare employment for people with schizophrenia in rural v. urban settings in China.

Method

In a large community-based study in four provinces representing 12% of China's population, we identified 393 people with schizophrenia (112 never treated). We used adjusted Poisson regression models to compare employment for those living in rural (n = 297) v. urban (n = 96) settings.

Results

Although rural and urban residents had similar impairments due to symptoms, rural residents were three times more likely to be employed (adjusted relative risk 3.27, 95% Cl 2.11-5.07, P<0.001).

Conclusions

People with schizophrenia have greater opportunities to use their capacities for productive work in rural than urban settings in China. Contextual mechanisms that may explain this result offer a useful focus for future research.
Elements of an engaged clinical ethics: a qualitative analysis of hospice clinical ethics committee discussions
Authors: Hunt Geoffrey , Gannon Craig , Gallagher Ann
Published: December 2012

Social, legal and health-care changes have created an increasing need for ethical review within end-of-life care. Multiprofessional clinical ethics committees (CECs) are increasingly supporting decision-making in hospitals and hospices. This paper reports findings from an analysis of formal summaries from CEC meetings, of one UK hospice, spanning four years. Using qualitative content analysis, five themes were identified: timeliness of decision-making, holistic care, contextual openness, values diversity and consensual understanding. The elements of an engaged clinical ethics in a hospice context is not generally acknowledged nor its elements articulated. Findings from this study have the potential to explain some of the most challenging ethical problems and to contribute to their resolution. It may also guide future deliberation and raise CEC members’ awareness of the recurrent issues and values of their CEC practice.
Hypokalaemia: Common Things Occur Commonly — a Retrospective Survey
Authors: Reid Alasdair , Jones Gareth , Isles Chris
Published: December 2012

Summary

Objectives

To define the causes of hypokalaemia in an unselected adult population.

Design

Retrospective survey of biochemistry database.

Setting

District general hospital in southwest Scotland.

Participants and main outcome measures

There were 187,704 measurements of urea and electrolytes in 2010. Sixty-one patients had serum potassium <2.5 mmol/L on at least one occasion.

Results

Average age of the patients was 71 (range 33–99) years. The most common causes were diarrhoea and/or vomiting (51% of cases), diuretic therapy (47%), nutritional causes including poor dietary intake, re-feeding syndrome and inadequate potassium supplementation when patients were nil by mouth (37%). In 25% of patients a transient and profound fall in serum potassium appeared to coincide with their acute illness. Acute alcohol intoxication and/or alcohol withdrawal were prominent features in 11% of patients. More than one cause was commonly present. There were no cases of Bartter's, Gitelman's or Liddle's syndromes or of hypokalaemic periodic paralysis in this study.

Conclusions

Severe hypokalaemia <2.5 mmol/L occurs at least once a week in a district general hospital with a catchment population of around 150,000, suggesting there may be around 300 cases a week in the UK (population around 50,000,000). Diuretics, vomiting and diarrhoea are commonly implicated as are nutritional causes, acute illness and alcohol. Bartter's, Gitelman's, Liddle's syndrome and hypokalaemic period paralysis are all extremely uncommon.
Dividing a Territory Among Several Facilities
Authors: Carlsson John Gunnar , Devulapalli Raghuveer
Published: December 2012

We consider the problem of dividing a geographic region into subregions so as to minimize the maximum workload of a collection of facilities over that region. We assume that the cost of servicing a demand point is a monomial function of the distance to its assigned facility and that demand points follow a continuous probability density. We show that, when our objective is to minimize the maximum workload of all facilities, the optimal partition consists of a collection of circular arcs that are induced by a multiplicatively weighted Voronoi diagram. When we require that all subregions have equal area, the optimal partition consists of a collection of hyperbolic or quartic curves. We show that, for both problems, the dual variables correspond to “prices” for a facility to serve a demand point, and our objective is to determine a set of prices such that the entire region is “purchased” by the facilities, i.e., that the market clears. This allows us to solve the partitioning problem quickly without discretizing the service region.
Efficient Analysis of Single Molecule Spectroscopic Data via MATLAB
Authors: Hill Caleb M. , Pan Shanlin
Published: December 2012

A MATLAB program is developed to help analyze single molecule spectroscopic data obtained with a standard inverted optical microscope. The described software has provisions to mitigate the effects of high background signals present in such data sets and greatly streamlines their analysis. Efficient single molecule image analysis and statistical blinking analysis are enabled with these programs to support single molecule imaging in an inverted configuration.
Long-Term Pegylated Liposomal Doxorubicin Use and Oromaxillary Squamous Cell Carcinoma in Endometrial Cancer
Authors: Matsuo Koji , Blake Erin A. , Yessaian Annie A. , Roman Lynda D.
Published: December 2012

A case of primary buccal squamous cell carcinoma arising in a patient with uterine papillary serous carcinoma after long-term pegylated liposomal doxorubicin treatment is presented.
Aggressive Squamous Cell Carcinoma of the Oral Tongue in a Woman With Metastatic Giant Cell Tumor Treated With Pegylated Liposomal Doxorubicin
Authors: Gu Ping , Wu Jennifer , Sheu Mike , Myssiorek David , Cohen Richard
Published: December 2012

An instance of squamous cell carcinoma resulting from long-term treatment with pegylated liposomal doxorubicin in a woman with no risk factors for this malignancy is reported.
Does Choice of Head Size and Neck Geometry Affect Stem Migration in Modular Large-Diameter Metal-on-Metal Total Hip Arthroplasty? A Preliminary Analysis
Authors: Georgiou CS , Evangelou KG , Theodorou EG , Provatidis CG , Megas PD
Published: December 2012

Due to their theoretical advantages, hip systems combining modular necks and large diameter femoral heads have gradually gained popularity. However, among others, concerns regarding changes in the load transfer patterns were raised. Recent stress analyses have indeed shown that the use of modular necks and big femoral heads causes significant changes in the strain distribution along the femur. Our original hypothesis was that these changes may affect early distal migration of a modular stem. We examined the effect of head diameter and neck geometry on migration at two years of follow-up in a case series of 116 patients (125 hips), who have undergone primary Metal-on-Metal total hip arthroplasty with the modular grit-blasted Profemur®E stem combined with large-diameter heads (>36 mm). We found that choice of neck geometry and head diameter has no effect on stem migration. A multivariate regression analysis including the potential confounding variables of the body mass index, bone quality, canal fill and stem positioning revealed only a negative correlation between subsidence and canal fill in midstem area. Statistical analysis, despite its limitations, did not confirm our hypothesis that choice of neck geometry and/or head diameter affects early distal migration of a modular stem. However, the importance of correct stem sizing was revealed.
Combined Association of Creatinine, Albuminuria, and Cystatin C with All-Cause Mortality and Cardiovascular and Kidney Outcomes
Authors: Waheed Salman , Matsushita Kunihiro , Astor Brad C. , Hoogeveen Ron C. , Ballantyne Christie , Coresh Josef
Published: December 2012

Background

Estimated GFR by serum creatinine (eGFRcreatinine) is a pivotal measure of kidney function in clinical practice but can be affected by several non-GFR determinants, resulting in misclassification. Combining multiple kidney markers to predict risk is an area of substantial interest.

Design, setting, participants, & measurements

This study followed 9489 adults from visit 4 (1996–1998) of the Atherosclerosis Risk in Communities Study for a median of 11.2 years, and assessed joint association of eGFRcreatinine, eGFRcystatin, and urinary albumin/creatinine ratio (ACR) with mortality, coronary heart disease, heart failure, AKI, and ESRD using Cox proportional hazards models. The predictive ability of ACR and eGFRcystatin beyond eGFRcreatinine was also investigated.

Results

Lower eGFRcreatinine and eGFRcystatin as well as elevated ACR were independently associated with risk for all outcomes. eGFRcreatinine <60 was not associated with risk of mortality, coronary heart disease, or heart failure if eGFRcystatin ≥60 with ACR <30 mg/g compared with those with all three markers above CKD cutoffs (i.e., eGFRcystatin ≥60, eGFRcreatinine ≥60, and ACR<30), whereas risk association with kidney outcomes remained: Hazard ratio (95% confidence interval), 0.96 (0.66, 1.39) for mortality, 0.85 (0.55, 1.31) for coronary heart disease, 0.99 (0.60, 1.63) for heart failure, 1.61 (0.92, 2.82) for AKI, and 3.53 (1.06, 11.68) for ESRD. Adding ACR to the fully adjusted model with eGFRcreatinine or adding eGFRcystatin to both eGFRcreatinine and ACR improved risk classification for all outcomes (P ≤ 0.01).

Conclusions

eGFRcystatin can be a useful confirmatory marker in those with eGFRcreatinine <60 and whose ACR is <30 mg/g. This approach improves risk classification, and provides reassurance to a large group of individuals with eGFRcreatinine <60.
Categorification of Hopf algebras of rooted trees
Authors: Kock Joachim
Published: December 2012

We exhibit a monoidal structure on the category of finite sets indexed by P-trees for a finitary polynomial endofunctor P. This structure categorifies the monoid scheme (over Spec ℕ) whose semiring of functions is (a P-version of) the Connes-Kreimer bialgebra H of rooted trees (a Hopf algebra after base change to ℤ and collapsing H 0). The monoidal structure is itself given by a polynomial functor, represented by three easily described set maps; we show that these maps are the same as those occurring in the polynomial representation of the free monad on P.
On restrictions of generic modules of tame algebras
Authors: Bautista Raymundo , Pérez Efrén , Salmerón Leonardo
Published: December 2012

Given a convex algebra ∧0 in the tame finite-dimensional basic algebra ∧, over an algebraically closed field, we describe a special type of restriction of the generic ∧-modules.
Decreasing ventricular infections through the use of a ventriculostomy placement bundle: experience at a single institution
Authors: Kubilay Zeynep , Amini Shahram , Fauerbach Loretta Litz , Archibald Lennox , Friedman William A. , Layon A. Joseph
Published: December 2012

Object

Ventricular infection after ventriculostomy placement carries a high mortality rate. Responding to ventriculostomy infection rates, a multidisciplinary performance improvement team was formed, a comprehensive protocol for ventriculostomy placement was developed, and the efficacy was evaluated.

Methods

A best-practice protocol was developed, including hand hygiene before the procedure; prophylactic antibiotics; sterile gloves changed between preparation, draping, and procedure; hair removal by clipping for dressing adherence; skin preparation using iodine povacrylex (0.7% available iodine) and isopropyl alcohol (74%); full body and head drape; full surgical attire for the surgeon and other bedside providers; and an antimicrobial-impregnated catheter. A checklist of critical components was used to confirm proper insertion and to monitor practice. Procedure-specific infection rates were calculated using the number of infections divided by the number of patients in whom an external ventricular drainage (EVD) device was inserted × 100 (%). Data were reported back to providers and to the committee. Bundle compliance was monitored over a 4-year period.

Results

At the authors' institution, 2928 ventriculostomies were performed between the beginning of the fourth quarter of 2006 and the end of the first quarter of 2012. Although the best-evidence bundle was applied to all patients, only 588 (20.1%) were checklist monitored (increasing from 7% to 23% over the study period). The infection rate for the 2 quarters before bundle implementation was 9.2%. During the study period, the rate decreased quarterly to 2.6% and then to 0%. Over a 4-year period, the rate was 1.06% (2007), 0.66% (2008), 0.15% (2009), and 0.34% (2010); it was 0% in 2011 and the first quarter of 2012. The overall EVD infection rate was 0.46% after bundle implementation.

Conclusions

Bundle implementation including an antimicrobial-impregnated catheter dramatically decreased EVD-related infections. Training and situational awareness of appropriate practice, assisted by the checklist, plus use of the antibiotic-impregnated catheter resulted in sustained reduction in ventriculitis.
Balantidium coli: an unrecognized cause of vertebral osteomyelitis and myelopathy
Authors: Dhawan Shashi , Jain Deepali , Mehta Veer Singh
Published: December 2012

Balantidium coli is a ciliated protozoan parasite that primarily infects primates and pigs. It is the largest protozoan to infect humans and is a well-known cause of diarrhea and dysentery. Extraintestinal disease is uncommon, and extraintestinal spread to the peritoneal cavity, appendix, genitourinary tract, and lung has rarely been reported. The authors describe a case of vertebral osteomyelitis with secondary cervical cord compression caused by B. coli. The patient was a 60-year-old immunocompetent man presenting with quadriplegia of short duration. Magnetic resonance imaging of the cervical spine showed extradural and prevertebral abscess at the C3–4 level. Drainage of the abscess, C3–4 discectomy, and iliac bone grafting were performed. Histologically B. coli was confirmed in an abscess sample. To the best of the authors' knowledge, involvement of bone by B. coli has never been reported, and this case is the first documented instance of cervical cord compression due to B. coli osteomyelitis of the spine in the literature.