bluuebunny/crossref_metadata_2025 huggingface dataset:
SPIB, a novel immunohistochemical marker for human blastic plasmacytoid dendritic cell neoplasms: characterization of its expression in major hematolymphoid neoplasms
Authors: Montes-Moreno Santiago , Ramos-Medina Rocio , Martínez-López Azahara , Barrionuevo Cornejo Carlos , Parra Cubillos Alejandro , Quintana-Truyenque Shirley , Rodriguez Pinilla Socorro María , Pajares Raquel , Sanchez-Verde Lydia , Martinez-Torrecuadrada Jorge , Roncador Giovanna , Piris Miguel Angel
Published: November 2012

SPIB is an Ets transcription factor that is expressed exclusively in mature B cells, T-cell progenitors, and plasmacytoid dendritic cells. In the present study, we developed a novel mAb against the SPIB protein and characterized its expression in major hematolymphoid neoplasms, including a series of 45 cases of blastic plasmacytoid dendritic cell (BPDC) neoplasms and their potential cutaneous mimics. We found that SPIB is expressed heterogeneously among B- and T-cell lymphoma types. Interestingly, SPIB is expressed in a large proportion of nongerminal center type DLBCLs. In cutaneous neoplasms, SPIB is overexpressed in all BPDC neoplasms, but none of its cutaneous mimics. SPIB remains overexpressed in all cases that lack 1 or 2 of the markers used for BPDC neoplasms (ie, CD4, CD56, TCL1, and CD123). We conclude that SPIB expression can be used as a tool for diagnosing BPDC neoplasms, but it needs to be tested in conjunction with the growing arsenal of markers for human plasmacytoid dendritic cells.
Cleaved cytokeratin-18 is a mechanistically informative biomarker in idiopathic pulmonary fibrosis
Authors: Cha Seung-Ick , Ryerson Christopher J , Lee Joyce S , Kukreja Jasleen , Barry Sophia S , Jones Kirk D , Elicker Brett M , Kim Dong Soon , Papa Feroz R , Collard Harold R , Wolters Paul J
Published: November 2012

Background

Stress of the endoplasmic reticulum (ER) leading to activation of the unfolded protein response (UPR) and alveolar epithelial cell (AEC) apoptosis may play a role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Our objectives were to determine whether circulating caspase-cleaved cytokeratin-18 (cCK-18) is a marker of AEC apoptosis in IPF, define the relationship of cCK-18 with activation of the UPR, and assess its utility as a diagnostic biomarker.

Methods

IPF and normal lung tissues were stained with the antibody (M30) that specifically binds cCK-18. The relationship between markers of the UPR and cCK-18 was determined in AECs exposed in vitro to thapsigargin to induce ER stress. cCK-18 was measured in serum from subjects with IPF, hypersensitivity pneumonitis (HP), nonspecific interstitial pneumonia (NSIP), and control subjects.

Results

cCK-18 immunoreactivity was present in AECs of IPF lung, but not in control subjects. Markers of the UPR (phosphorylated IRE-1α and spliced XBP-1) were more highly expressed in IPF type II AECs than in normal type II AECs. Phosphorylated IRE-1α and cCK-18 increased following thapsigargin-induced ER stress. Serum cCK-18 level distinguished IPF from diseased and control subjects. Serum cCK-18 was not associated with disease severity or outcome.

Conclusions

cCK-18 may be a marker of AEC apoptosis and UPR activation in patients with IPF. Circulating levels of cCK-18 are increased in patients with IPF and cCK-18 may be a useful diagnostic biomarker.
Predictors for health facility delivery in Busia district of Uganda: a cross sectional study
Authors: Anyait Agnes , Mukanga David , Oundo George Bwire , Nuwaha Fred
Published: November 2012

Background

Among the factors contributing to the high maternal morbidity and mortality in Uganda is the high proportion of pregnant women who do not deliver under supervision in health facilities. This study aimed to identify the independent predictors of health facility delivery in Busia a rural district in Uganda with a view of suggesting measures for remedial action.

Methods

In a cross sectional survey, 500 women who had a delivery in the past two years (from November 16 2005 to November 15 2007) were interviewed regarding place of delivery, demographic characteristics, reproductive history, attendance for antenatal care, accessibility of health services, preferred delivery positions, preference for disposal of placenta and mother’s autonomy in decision making. In addition the household socio economic status was assessed. The independent predictors of health facility delivery were identified by comparing women who delivered in health facilities to those who did not, using bivariate and binary logistic regression analysis.

Results

Eight independent predictors that favoured delivery in a health facility include: being of high socio-economic status (adjusted odds ratio [AOR] 2.8 95% Confidence interval [95% CI]1.2–6.3), previous difficult delivery (AOR 4.2, 95% CI 3.0–8.0), parity less than four (AOR 2.9, 95% CI 1.6–5.6), preference of supine position for second stage of labour (AOR 5.9, 95% CI 3.5–11.1) preferring health workers to dispose the placenta (AOR 12.1, 95% CI 4.3–34.1), not having difficulty with transport (AOR 2.0, 95% CI 1.2–3.5), being autonomous in decision to attend antenatal care (AOR 1.9, 95% CI 1.1–3.4) and depending on other people (e.g. spouse) in making a decision of where to deliver from (AOR 2.4, 95% CI 1.4–4.6). A model with these 8 variables had an overall correct classification of 81.4% (chi square = 230.3, P < 0.001).

Conclusions

These data suggest that in order to increase health facility deliveries there is need for reaching women of low social economic status and of higher parity with suitable interventions aimed at reducing barriers that make women less likely to deliver in health units such as ensuring availability of transport and involving spouses in the birth plan.
Tumorigenic potential of pituitary tumor transforming gene (PTTG) in vivoinvestigated using a transgenic mouse model, and effects of cross breeding with p53 (+/−) transgenic mice
Authors: Fong Miranda Y , Farghaly Hanan , Kakar Sham S
Published: November 2012

Background

Pituitary tumor-transforming gene (PTTG) is an oncogene that is overexpressed in variety of tumors and exhibits characteristics of a transforming gene. Previous transgenic mouse models to access the tumorigenic potential in the pituitary and ovary have resulted in dysplasia without formation of visible tumors, possibly due to the insufficient expression of PTTG. PTTG expression level is critical for ovarian tumorigenesis in a xenograft model. Therefore, the tumorigenic function of PTTG in vivo remains unclear. We generated a transgenic mouse that overexpresses PTTG driven by the CMV promoter to determine whether PTTG functions as a transforming oncogene that is capable of initiating tumorigenesis.

Methods

Transgenic animals were generated by microinjection of PTTG transgene into the male pronucleus of FVB 0.5 day old embryos. Expression levels of PTTG in tissues of transgenic animals were analyzed using an immunohistochemical analysis. H&E staining and immunohistostaining were performed to examine the type of tumor in transgenic and PTTG transgenic/p53+/- animals.

Results

PTTG transgenic offspring (TgPTTG) were monitored for tumor development at various ages. H&E analysis was performed to identify the presence of cancer and hyperplastic conditions verified with the proliferation marker PCNA and the microvessel marker CD31. Immunohistochemistry was performed to determine transgene expression, revealing localization to the epithelium of the fallopian tube, with more generalized expression in the liver, lung, kidney, and spleen. At eight months of age, 2 out of 15 TgPTTG developed ovarian cancer, 2 out of 15 developed benign tumors, 2 out of 15 developed cervical dysplasia, and 3 out of 15 developed adenomyosis of the uterus. At ten months of age, 2 out of 10 TgPTTG developed adenocarcinoma of the ovary, 1 out of 10 developed a papillary serous adenocarcinoma, and 2 out of 10 presented with atypia of ovarian epithelial cells. Tumorigenesis is a multi-step process, often requiring multiple oncogenes and/or inactivation of tumor suppressor genes. Therefore, to understand the contribution of p53 to PTTG induced tumorigenesis, we crossbred TgPTTG to p53+/− mice and maintained those 8 to 10 months. TgPTTG/p53+/− animals developed sarcomas faster than p53+/− alone as well as different tumor types in addition to cervical carcinomas in situ in 10 out of 17 females.

Conclusions

We conclude that while PTTG is a functional transforming oncogene, it requires an additional partner to effectively promote tumorigenesis through the loss of p53 include or between function or modulation.
Let-7 miRNA-binding site polymorphism in the KRAS 3′UTR; colorectal cancer screening population prevalence and influence on clinical outcome in patients with metastatic colorectal cancer treated with 5-fluorouracil and oxaliplatin +/− cetuximab
Authors: Kjersem Janne B , Ikdahl Tone , Guren Tormod , Skovlund Eva , Sorbye Halfdan , Hamfjord Julian , Pfeiffer Per , Glimelius Bengt , Kersten Christian , Solvang Hiroko , Tveit Kjell M , Kure Elin H
Published: November 2012

Background

Recent studies have reported associations between a variant allele in a let-7 microRNA complementary site (LCS6) within the 3′untranslated region (3′UTR) of KRAS (rs61764370) and clinical outcome in metastatic colorectal cancer (mCRC) patients receiving cetuximab. The variant allele has also been associated with increased cancer risk. We aimed to reveal the incidence of the variant allele in a colorectal cancer screening population and to investigate the clinical relevance of the variant allele in mCRC patients treated with 1st line Nordic FLOX (bolus 5-fluorouracil/folinic acid and oxaliplatin) +/− cetuximab.

Methods

The feasibility of the variant allele as a risk factor for CRC was investigated by comparing the LCS6 gene frequencies in 197 CRC patients, 1060 individuals with colorectal polyps, and 358 healthy controls. The relationship between clinical outcome and LCS6 genotype was analyzed in 180 mCRC patients receiving Nordic FLOX and 355 patients receiving Nordic FLOX + cetuximab in the NORDIC-VII trial (NCT00145314).

Results

LCS6 frequencies did not vary between CRC patients (23%), individuals with polyps (20%), and healthy controls (20%) (P = 0.50). No statistically significant differences were demonstrated in the NORDIC-VII cohort even if numerically increased progression-free survival (PFS) and overall survival (OS) were found in patients with the LCS6 variant allele (8.5 (95% CI: 7.3-9.7 months) versus 7.8 months (95% CI: 7.4-8.3 months), P = 0.16 and 23.5 (95% CI: 21.6-25.4 months) versus 19.5 months (95% CI: 17.8-21.2 months), P = 0.31, respectively). Addition of cetuximab seemed to improve response rate more in variant carriers than in wild-type carriers (from 35% to 57% versus 44% to 47%), however the difference was not statistically significant (interaction P = 0.16).

Conclusions

The LCS6 variant allele does not seem to be a risk factor for development of colorectal polyps or CRC. No statistically significant effect of the LCS6 variant allele on response rate, PFS or OS was found in mCRC patients treated with 1st line Nordic FLOX +/− cetuximab.
Current iodine nutrition status and progress toward elimination of iodine deficiency disorders in Jazan, Saudi Arabia
Authors: Alsanosy Rashad Mohammed Ali , Gaffar Abdelrahim Mutwakel , Khalafalla Husam Eldin Elsawi , Mahfouz Mohamed Salih , Zaid Abdel Naser Shaaban , Bani Ibrahim Ahmed
Published: November 2012

Background

The term iodine deficiency disorders (IDD) refers to all the effects of iodine deficiency on growth and development in human and animal populations that can be prevented by correction of the iodine deficiency. The objective of this paper was to determine the iodine nutrition status among schoolchildren in the Jazan Region of the Kingdom of Saudi Arabia (KSA), by measuring urinary iodine concentrations and by clinical assessments of goiter rate.

Methods

A school-based cross-sectional survey was conducted in the Jazan region of southwestern KSA from May to November 2010. A total of 311 children, aged 6–13 years, drawn from 12 schools, were selected by a three-stage cluster random sampling method. Data on sociodemographic characteristics were collected using a structured questionnaire. Urine samples were collected and physical examinations were conducted to determine the presence or absence of goiter. Data were analyzed using SPSS version 17.0. Chi square and independentt-tests were used for proportions and mean comparisons between groups.

Results

Out of 360 selected children, 311 were examined. There were 131 males (42%) and 180 females (58%). The median urinary iodine concentration (UIC) of the study group was 421 μg/L. The study population proportion with UIC > 300 μg/L was 74% with a higher proportion among males and urban populations. The proportion of children with UIC of 100–300 μg/L was only 21% and was significantly higher among females compared with males (p< 0.001). Only about 3% of the children had a median UIC less than 50 μg/L. The prevalence of total goiter rate (TGR) among the sample of schoolchildren in Jazan was 11%, with significant variations between rural and urban populations and by gender.

Conclusions

The present study demonstrates a remarkable achievement in Universal Salt Iodization (USI) and IDD elimination goals in the Jazan area. However, UIC levels reflect excessive iodine intake and may put the population at risk of adverse health consequences like iodine-induced hyperthyroidism and autoimmune thyroid diseases.
Respiratory symptoms and illnesses among brick kiln workers: a cross sectional study from rural districts of Pakistan
Authors: Shaikh Shiraz , Nafees Asaad Ahmed , Khetpal Vikash , Jamali Abid Ali , Arain Abdul Manan , Yousuf Akram
Published: November 2012

Background

Occupational risk factors are one of the major causes of respiratory illnesses and symptoms, and account for 13% of chronic obstructive pulmonary disease and 11% of asthma worldwide. Majority of brick kilns in Pakistan use wood and coal for baking the bricks which makes the brick kiln workers susceptible to high exposure of air pollution. This study was designed to describe frequency of chronic respiratory symptoms and illnesses and study the association between these symptoms and different types of work.

Methods

This was a questionnaire based cross sectional survey conducted among the brick kiln workers in Larkana and Dadu districts, Sindh, Pakistan. A total of 340 adult men were assessed using translated version of the American Thoracic Society Division of Lung Disease (ATS-DLD) questionnaire. Logistic regression analysis was done to determine the relationship between various socio-demographic and occupational factors (age, education, type of work, number of years at work, smoking status), and the respiratory symptoms and illnesses (chronic cough, chronic phlegm, wheeze, Chronic Bronchitis and asthma).

Results

Results of the study show that 22.4% workers had chronic cough while 21.2% reported chronic phlegm. 13.8% had two or more attacks of shortness of breath with wheezing. 17.1% workers were suffering from Chronic Bronchitis while 8.2% reported physician diagnosed asthma. Amongst the non-smoking workers 8.9% had Chronic Bronchitis. Multivariate analysis found that workers involved in brick baking were more likely to have Chronic Bronchitis (OR= 3.7, 95% CI 1.1-11.6, p=<0.05) and asthma (OR= 3.9, 95% CI 1.01-15.5, p=<0.05) compared to those involved in carriage and placement work.

Conclusion

A high frequency of respiratory symptoms and illnesses was observed among brick kiln workers. Age, nature of work and smoking were strong predictors of developing these symptoms and illnesses.
National, regional, and global trends in adult overweight and obesity prevalences
Authors: Stevens Gretchen A , Singh Gitanjali M , Lu Yuan , Danaei Goodarz , Lin John K , Finucane Mariel M , Bahalim Adil N , McIntire Russell K , Gutierrez Hialy R , Cowan Melanie , Paciorek Christopher J , Farzadfar Farshad , Riley Leanne , Ezzati Majid ,   the Global Burden of Metabolic Risk Factors of Chronic Diseases Collaborating Group (Body Mass Index)
Published: November 2012

Background

Overweight and obesity prevalence are commonly used for public and policy communication of the extent of the obesity epidemic, yet comparable estimates of trends in overweight and obesity prevalence by country are not available.

Methods

We estimated trends between 1980 and 2008 in overweight and obesity prevalence and their uncertainty for adults 20 years of age and older in 199 countries and territories. Data were from a previous study, which used a Bayesian hierarchical model to estimate mean body mass index (BMI) based on published and unpublished health examination surveys and epidemiologic studies. Here, we used the estimated mean BMIs in a regression model to predict overweight and obesity prevalence by age, country, year, and sex. The uncertainty of the estimates included both those of the Bayesian hierarchical model and the uncertainty due to cross-walking from mean BMI to overweight and obesity prevalence.

Results

The global age-standardized prevalence of obesity nearly doubled from 6.4% (95% uncertainty interval 5.7-7.2%) in 1980 to 12.0% (11.5-12.5%) in 2008. Half of this rise occurred in the 20 years between 1980 and 2000, and half occurred in the 8 years between 2000 and 2008. The age-standardized prevalence of overweight increased from 24.6% (22.7-26.7%) to 34.4% (33.2-35.5%) during the same 28-year period. In 2008, female obesity prevalence ranged from 1.4% (0.7-2.2%) in Bangladesh and 1.5% (0.9-2.4%) in Madagascar to 70.4% (61.9-78.9%) in Tonga and 74.8% (66.7-82.1%) in Nauru. Male obesity was below 1% in Bangladesh, Democratic Republic of the Congo, and Ethiopia, and was highest in Cook Islands (60.1%, 52.6-67.6%) and Nauru (67.9%, 60.5-75.0%).

Conclusions

Globally, the prevalence of overweight and obesity has increased since 1980, and the increase has accelerated. Although obesity increased in most countries, levels and trends varied substantially. These data on trends in overweight and obesity may be used to set targets for obesity prevalence as requested at the United Nations high-level meeting on Prevention and Control of NCDs.
Schwann cell myelination requires Dynein function
Authors: Langworthy Melissa M , Appel Bruce
Published: November 2012

Background

Interaction of Schwann cells with axons triggers signal transduction that drives expression of Pou3f1 and Egr2 transcription factors, which in turn promote myelination. Signal transduction appears to be mediated, at least in part, by cyclic adenosine monophosphate (cAMP) because elevation of cAMP levels can stimulate myelination in the absence of axon contact. The mechanisms by which the myelinating signal is conveyed remain unclear.

Results

By analyzing mutations that disrupt myelination in zebrafish, we learned that Dynein cytoplasmic 1 heavy chain 1 (Dync1h1), which functions as a motor for intracellular molecular trafficking, is required for peripheral myelination. In dync1h1 mutants, Schwann cell progenitors migrated to peripheral nerves but then failed to express Pou3f1 and Egr2 or make myelin membrane. Genetic mosaic experiments revealed that robust Myelin Basic Protein expression required Dync1h1 function within both Schwann cells and axons. Finally, treatment of dync1h1 mutants with a drug to elevate cAMP levels stimulated myelin gene expression.

Conclusion

Dync1h1 is required for retrograde transport in axons and mutations of Dync1h1 have been implicated in axon disease. Our data now provide evidence that Dync1h1 is also required for efficient myelination of peripheral axons by Schwann cells, perhaps by facilitating signal transduction necessary for myelination.
Adoptive Transfer of Epstein-Barr Virus (EBV) Nuclear Antigen 1–Specific T Cells As Treatment for EBV Reactivation and Lymphoproliferative Disorders After Allogeneic Stem-Cell Transplantation
Authors: Icheva Vanya , Kayser Simone , Wolff Daniel , Tuve Sebastian , Kyzirakos Christina , Bethge Wolfgang , Greil Johann , Albert Michael H. , Schwinger Wolfgang , Nathrath Michaela , Schumm Michael , Stevanovic Stefan , Handgretinger Rupert , Lang Peter , Feuchtinger Tobias
Published: November 2012

Purpose

Reactivation of Epstein-Barr virus (EBV) after allogeneic stem-cell transplantation (SCT) can lead to severe life-threatening infections and trigger post-transplantation lymphoproliferative disease (PTLD). Since EBV-specific T cells could prevent PTLD, cellular immunotherapy has been a promising treatment option. However, generation of antigen-specific T-cell populations has been difficult within a short time frame.

Patients and Methods

To improve availability in urgent clinical conditions, we developed a rapid protocol for isolation of polyclonal EBV nuclear antigen 1 (EBNA-1) –specific T cells by using an interferon gamma (IFN-γ) capture technique.

Results

We report on the use of adoptive transfer of EBNA-1–specific T cells in 10 pediatric and adult patients with EBV viremia and/or PTLD after SCT. No acute toxicity or graft-versus-host disease (GVHD) of more than grade 2 occurred as a result of adoptive T-cell transfer. In vivo expansion of transferred EBNA-1–specific T cells was observed in eight of 10 patients after a median of 16 days following adoptive transfer that was associated with clinical and virologic response in seven of them (70%). None of the responders had EBV-associated mortality. Within clinical responders, three patients were disease free by the day of last follow-up (2 to 36 months), three patients died of other infectious complications, and one patient died as a result of relapse of malignancy. EBV-related mortality was observed in two of 10 patients, and another patient had ongoing viremia without clinical symptoms at last follow-up.

Conclusion

Adoptive ex vivo transfer of EBNA-1–specific T cells is a feasible and well-tolerated therapeutic option, representing a fast and efficient procedure to achieve reconstitution of antiviral T-cell immunity after SCT.
Postoperative Adjuvant Chemotherapy Use in Patients With Stage II/III Rectal Cancer Treated With Neoadjuvant Therapy: A National Comprehensive Cancer Network Analysis
Authors: Khrizman Polina , Niland Joyce C. , ter Veer Anna , Milne Dana , Bullard Dunn Kelli , Carson William E. , Engstrom Paul F. , Shibata Stephen , Skibber John M. , Weiser Martin R. , Schrag Deborah , Benson Al B.
Published: November 2012

Purpose

Practice guidelines recommend that patients who receive neoadjuvant chemotherapy and radiation for locally advanced rectal cancer complete postoperative adjuvant systemic chemotherapy, irrespective of tumor downstaging.

Patients and Methods

The National Comprehensive Cancer Network (NCCN) Colorectal Cancer Database tracks longitudinal care for patients treated at eight specialty cancer centers across the United States and was used to evaluate how frequently patients with rectal cancer who were treated with neoadjuvant chemotherapy also received postoperative systemic chemotherapy. Patient and tumor characteristics were examined in a multivariable logistic regression model.

Results

Between September 2005 and December 2010, 2,073 patients with stage II/III rectal cancer were enrolled in the database. Of these, 1,193 patients receiving neoadjuvant chemoradiotherapy were in the analysis, including 203 patients not receiving any adjuvant chemotherapy. For those seen by a medical oncologist, the most frequent reason chemotherapy was not recommended was comorbid illness (25 of 50, 50%); the most frequent reason chemotherapy was not received even though it was recommended or discussed was patient refusal (54 of 74, 73%). After controlling for NCCN Cancer Center and clinical TNM stage in a multivariable logistic model, factors significantly associated with not receiving adjuvant chemotherapy were age, Eastern Cooperative Oncology Group performance status ≥ 1, on Medicaid or indigent compared with private insurance, complete pathologic response, presence of re-operation/wound infection, and no closure of ileostomy/colostomy.

Conclusion

Even at specialty cancer centers, a sizeable minority of patients with rectal cancer treated with curative-intent neoadjuvant chemoradiotherapy do not complete postoperative chemotherapy. Strategies to facilitate the ability to complete this third and final component of curative intent treatment are necessary.
Effect on Survival of Longer Intervals Between Confirmed Diagnosis and Treatment Initiation Among Low-Income Women With Breast Cancer
Authors: McLaughlin John M. , Anderson Roger T. , Ferketich Amy K. , Seiber Eric E. , Balkrishnan Rajesh , Paskett Electra D.
Published: November 2012

Purpose

To determine the impact of longer periods between biopsy-confirmed breast cancer diagnosis and the initiation of treatment (Dx2Tx) on survival.

Patients and Methods

This study was a noninterventional, retrospective analysis of adult female North Carolina Medicaid enrollees diagnosed with breast cancer from January 1, 2000, through December, 31, 2002, in the linked North Carolina Central Cancer Registry–Medicaid Claims database. Follow-up data were available through July 31, 2006. Cox proportional hazards regression models were constructed to evaluate the impact on survival of delaying treatment ≥ 60 days after a confirmed diagnosis of breast cancer.

Results

The study cohort consisted of 1,786 low-income, adult women with a mean age of 61.6 years. A large proportion of the patients (44.3%) were racial minorities. Median time from biopsy-confirmed diagnosis to treatment initiation was 22 days. Adjusted Cox proportional hazards regression showed that although Dx2Tx length did not affect survival among those diagnosed at early stage, among late-stage patients, intervals between diagnosis and first treatment ≥ 60 days were associated with significantly worse overall survival (hazard ratio [HR], 1.66; 95% CI, 1.00 to 2.77; P = .05) and breast cancer–specific survival (HR, 1.85; 95% CI, 1.04 to 3.27; P = .04).

Conclusion

One in 10 women waited ≥ 60 days to initiate treatment after a diagnosis of breast cancer. Waiting ≥ 60 days to initiate treatment was associated with a significant 66% and 85% increased risk of overall and breast cancer–related death, respectively, among late-stage patients. Interventions designed to increase the timeliness of receiving breast cancer treatments should target late-stage patients, and clinicians should strive to promptly triage and initiate treatment for patients diagnosed at late stage.
Preoperative Delays in the US Medicare Population With Breast Cancer
Authors: Bleicher Richard J. , Ruth Karen , Sigurdson Elin R. , Ross Eric , Wong Yu-Ning , Patel Sameer A. , Boraas Marcia , Topham Neal S. , Egleston Brian L.
Published: November 2012

Purpose

Although no specific delay threshold after diagnosis of breast cancer has been demonstrated to affect outcome, delays can cause anxiety, and surgical waiting time has been suggested as a quality measure. This study was performed to determine the interval from presentation to surgery in Medicare patients with nonmetastatic invasive breast cancer who did not receive neoadjuvant chemotherapy and factors associated with a longer time to surgery.

Methods

Medicare claims linked to Surveillance, Epidemiology, and End Results data were reviewed for factors associated with delay between the first physician claim for a breast problem and first therapeutic surgery.

Results

Between 1992 and 2005, 72,586 Medicare patients with breast cancer had a median interval (delay) between first physician visit and surgery of 29 days, increasing from 21 days in 1992 to 32 days in 2005. Women (29 days v 24 days for men; P < .001), younger patients (29 days; P < .001), blacks and Hispanics (each 37 days; P < .001), patients in the northeast (33 days; P < .001), and patients in large metropolitan areas (32 days; P < .001) had longer delays. Patients having breast conservation and mastectomies had adjusted median delays of 28 and 30 days, respectively, with simultaneous reconstruction adding 12 days. Preoperative components, including imaging modalities, biopsy type, and clinician visits, were also each associated with a specific additional delay.

Conclusion

Waiting times for breast cancer surgery have increased in Medicare patients, and measurable delays are associated with demographics and preoperative evaluation components. If such increases continue, periodic assessment may be required to rule out detrimental effects on outcomes.
Parenteral Hydration in Patients With Advanced Cancer: A Multicenter, Double-Blind, Placebo-Controlled Randomized Trial
Authors: Bruera Eduardo , Hui David , Dalal Shalini , Torres-Vigil Isabel , Trumble Joseph , Roosth Joseph , Krauter Susan , Strickland Carol , Unger Kenneth , Palmer J. Lynn , Allo Julio , Frisbee-Hume Susan , Tarleton Kenneth
Published: November 2012

Purpose

The vast majority of patients with cancer at the end of life receive parenteral hydration in hospitals and no hydration in hospice, with limited evidence supporting either practice. In this randomized controlled trial, we determined the effect of hydration on symptoms associated with dehydration, quality of life, and survival in patients with advanced cancer.

Patients and Methods

We randomly assigned 129 patients with cancer from six hospices to receive parenteral hydration (normal saline 1 L per day) or placebo (normal saline 100 mL per day) daily over 4 hours. The primary outcome was change in the sum of four dehydration symptoms (fatigue, myoclonus, sedation and hallucinations, 0 = best and 40 = worst possible) between day 4 and baseline. Secondary outcomes included Edmonton Symptom Assessment Scale (ESAS), Memorial Delirium Assessment Scale (MDAS), Nursing Delirium Screening Scale (NuDESC), Unified Myoclonus Rating Scale (UMRS), Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F), Dehydration Assessment Scale, creatinine, urea, and overall survival. Intention-to-treat analysis was conducted to examine the change by day 4 ± 2 and day 7 ± 2 between groups.

Results

The hydration (n = 63) and placebo (n = 66) groups had similar baseline characteristics. We found no significant differences between the two groups for change in the sum of four dehydration symptoms (−3.3 v −2.8, P = .77), ESAS (all nonsignificant), MDAS (1 v 3.5, P = .084), NuDESC (0 v 0, P = .13), and UMRS (0 v 0, P = .54) by day 4. Results for day 7, including FACIT-F, were similar. Overall survival did not differ between the two groups (median, 21 v 15 days, P = .83).

Conclusion

Hydration at 1 L per day did not improve symptoms, quality of life, or survival compared with placebo.
Active Aging for Individuals with Intellectual Disability: Meaningful Community Participation Through Employment, Retirement, Service, and Volunteerism
Authors: Fesko Sheila Lynch , Hall Allison Cohen , Quinlan Jerrilyn , Jockell Catherine
Published: November 2012

As individuals with intellectual and developmental disabilities become more engaged in community employment, it will be critical to consider how their employment experience changes as they age. Similar to other seniors, individuals will need to consider whether they want to maintain their employment, reduce their work commitment, or retire completely. If they do choose to retire, what activities will they choose to engage in, and what service or supports might be necessary? This article considers the issues faced by all aging workers in regard to retirement planning and active aging as well as specific strategies for individuals with intellectual and developmental disabilities to remain active and engaged. Recommendations for service options, policy consideration, and future research are also discussed.
Correlation of structure, composition and local mechanical properties in the dorsal carapace of the edible crab Cancer pagurus
Authors: Fabritius Helge-Otto , Karsten Eva Simone , Balasundaram Keerthika , Hild Sabine , Huemer Katja , Raabe Dierk
Published: November 2012

The exoskeleton of crustaceans is formed by the cuticle, a chitin-protein-based nano-composite with hierarchical organization over at least eight levels. On the molecular level, it consists of chitin associated with proteins forming fibres, which are organized in the form of twisted plywood. On the higher levels, the twisted plywood organization is modified and forms skeletal elements with elaborate functions. The load-bearing parts of crustacean cuticle are reinforced with both crystalline and amorphous biominerals. During evolution, all parts of the exoskeleton were optimized to fulfill different functions according to different ecophysiological strains faced by the animals. This is achieved by modifications in microstructure and chemical composition. In order to understand the relationship between structure, composition, mechanical properties and function we structurally characterized cuticle from the dorsal carapace of the edible crab Cancer pagurus using light and scanning electron microscopy (SEM). The local chemical composition was investigated using energy dispersive X-ray spectroscopy (EDX) and confocal m-Raman spectroscopy. Nanoindentation tests were performed to study the resulting local mechanical properties. The results show local differences in structure on several levels of the structural hierarchy in combination with a very heterogeneous mineralization. The distal exocuticle is mineralized with calcite, followed by a layer containing a magnesium, phosphate and carbonate rich phase and ACC in the proximal part. The endocuticle contains magnesian calcite and ACC in special regions below the exocuticle. Structure and mineral phase are reflected in the local stiffness and hardness of the respective cuticle regions. The heterogeneity of structural organization and mechanical properties suggests remarkable consequences for the mechanical behaviour of the bulk material.
The Saccharomyces cerevisiae F-Box Protein Dia2 Is a Mediator of S-Phase Checkpoint Recovery from DNA Damage
Authors: Fong Chi Meng , Arumugam Ashwini , Koepp Deanna M
Published: November 2012

Cell-cycle progression is monitored by checkpoint pathways that pause the cell cycle when stress arises to threaten the integrity of the genome. Although activation of checkpoint pathways has been extensively studied, our understanding of how cells resume the cell cycle when the stress is resolved is relatively limited. In this study, we identify the Saccharomyces cerevisiae F-box protein Dia2 as a novel player in the S-phase checkpoint recovery pathway. Dia2 is required for robust deactivation of the Rad53 checkpoint kinase and timely completion of DNA replication during recovery from DNA damage induced by methyl methanesulfonate (MMS). Aiming to identify the substrate of SCFDia2 (Skp1/Cul1/F-box Dia2) in checkpoint recovery, we performed a genetic screen to identify suppressors of dia2Δ cells. The screen identified a new checkpoint-defective allele of MRC1 truncated at the C terminus. We found that checkpoint-defective mrc1 alleles suppress the MMS sensitivity and the checkpoint recovery defect of dia2Δ cells. In addition, Dia2 contributes to Mrc1 degradation during S-phase checkpoint recovery. Furthermore, induced degradation of checkpoint-functional Mrc1 partially rescues the checkpoint recovery defect of dia2Δ cells. We propose a model in which Dia2 mediates Mrc1 degradation to help cells resume the cell cycle during recovery from MMS-induced DNA damage in S-phase.
Dysfunctional Mitochondria Modulate cAMP-PKA Signaling and Filamentous and Invasive Growth of Saccharomyces cerevisiae
Authors: Aun Anu , Tamm Tiina , Sedman Juhan
Published: November 2012

Mitochondrial metabolism is targeted by conserved signaling pathways that mediate external information to the cell. However, less is known about whether mitochondrial dysfunction interferes with signaling and thereby modulates the cellular response to environmental changes. In this study, we analyzed defective filamentous and invasive growth of the yeast Saccharomyces cerevisiae strains that have a dysfunctional mitochondrial genome (rho mutants). We found that the morphogenetic defect of rho mutants was caused by specific downregulation of FLO11, the adhesin essential for invasive and filamentous growth, and did not result from general metabolic changes brought about by interorganellar retrograde signaling. Transcription of FLO11 is known to be regulated by several signaling pathways, including the filamentous-growth-specific MAPK and cAMP-activated protein kinase A (cAMP-PKA) pathways. Our analysis showed that the filamentous-growth-specific MAPK pathway retained functionality in respiratory-deficient yeast cells. In contrast, the cAMP-PKA pathway was downregulated, explaining also various phenotypic traits observed in rho mutants. Thus, our results indicate that dysfunctional mitochondria modulate the output of the conserved cAMP-PKA signaling pathway.
Muscle-enhancing Behaviors Among Adolescent Girls and Boys
Authors: Eisenberg Marla E. , Wall Melanie , Neumark-Sztainer Dianne
Published: November 2012

OBJECTIVE:

Media images of men and women have become increasingly muscular, and muscle-enhancing techniques are available to youth. Identifying populations at risk for unhealthy muscle-enhancingbehaviors is of considerable public health importance. The current study uses a large and diverse population-based sample of adolescents to examine the prevalence of muscle-enhancing behaviors and differences across demographic characteristics, weight status, and sports team involvement.

METHODS:

Survey data from 2793 diverse adolescents (mean age = 14.4) were collected at 20 urban middle and high schools. Use of 5 muscle-enhancing behaviors was assessed (changing eating, exercising, protein powders, steroids and other muscle-enhancing substances), and a summary score reflecting use of 3 or more behaviors was created. Logistic regression was used to test for differences in each behavior across age group, race/ethnicity, socioeconomic status, BMI category, and sports team participation.

RESULTS:

Muscle-enhancing behaviors were common in this sample for both boys and girls. For example, 34.7% used protein powders or shakes and 5.9% reported steroid use. Most behaviors were significantly more common among boys. In models mutually adjusted for all covariates, grade level, Asian race, BMI category, and sports team participation were significantly associated with the use of muscle-enhancing behaviors. For example, overweight (odds ratio = 1.45) and obese (odds ratio = 1.90) girls had significantly greater odds of using protein powders or shakes than girls of average BMI.

CONCLUSIONS:

The use of muscle-enhancing behaviors is substantially higher than has been previously reported and is cause for concern. Pediatricians and other health care providers should ask their adolescent patients about muscle-enhancing behaviors.
Evisceration of Small Bowel After Cauterization of an Umbilical Mass
Authors: Kondrich Janienne , Woo Theodore , Ginsburg Howard B. , Levine Deborah A.
Published: November 2012

The omphalomesenteric duct (OMD), a temporary structure essential to fetal development, normally involutes completely by week 8 or 9 of gestation. On occasion, the OMD persists, the clinical presentations of which vary widely. We describe a case of a 6-week-old male with a patent OMD remnant that was initially treated as an umbilical granuloma, which then potentially allowed for prolapse of the small bowel through the umbilical ring. The patient required resection of the incarcerated bowel but had an otherwise uneventful and complete recovery.
Immobilization of magnesium ammonium phosphate crystals within microchannels for efficient ammonia removal
Authors: Masuda Takanobu , Ogino Isao , Mukai Shin R.
Published: November 2012

Magnesium ammonium phosphate was formed in flow-through microchannels of silica monoliths using two different methods to fabricate materials that show efficient ammonia adsorption performance from wastewater with low hydraulic resistance. Magnesium ammonium phosphate crystals in these materials release ammonia when heated at 378 K, yielding primarily magnesium hydrogen phosphate. When this material was used for ammonia removal from an aqueous solution containing 100 ppm ammonia in a flow system, the material readily removed ammonia, decreasing the ammonia concentration to 25 ppm. The material can be reactivated by the same procedure and used again for ammonia removal. Hydrodynamic resistance through the lengths of the materials depend on the shape of the immobilized crystals, showing that needle-like crystals are more effective to cause less resistance than plate-like particles. The material containing needle-like crystals causes only approximately one-eighth of the hydraulic resistance that a packed column consisted of spherical particles with a typical bed porosity of 0.5 does. Thus, these results demonstrate the high applicability of the material for ammonia removal from wastewater in a continuous process.
Long-term performance evaluation of EBPR process in tropical climate: start-up, process stability, and the effect of operational pH and influent C:P ratio
Authors: Ong Y. H. , Chua A. S. M. , Lee B. P. , Ngoh G. C.
Published: November 2012

To date, little information is known about the operation of the enhanced biological phosphorus removal (EBPR) process in tropical climates. Along with the global concerns on nutrient pollution and the increasing array of local regulatory requirements, the applicability and compliance accountability of the EBPR process for sewage treatment in tropical climates is being evaluated. A sequencing batch reactor (SBR) inoculated with seed sludge from a conventional activated sludge (CAS) process was successfully acclimatized to EBPR conditions at 28 °C after 13 days' operation. Enrichment of Candidatus Accumulibacter phosphatis in the SBR was confirmed through fluorescence in situ hybridization (FISH). The effects of operational pH and influent C:P ratio on EBPR were then investigated. At pH 7 or pH 8, phosphorus removal rates of the EBPR processes were relatively higher when operated at C:P ratio of 3 than C:P ratio of 10, with 0.019–0.020 and 0.011–0.012 g-P/g-MLVSS•day respectively. One-year operation of the 28 °C EBPR process at C:P ratio of 3 and pH 8 demonstrated stable phosphorus removal rate of 0.020 ± 0.003 g-P/g-MLVSS•day, corresponding to effluent with phosphorus concentration <0.5 mg/L. This study provides the first evidence on good EBPR activity at relatively high temperature, indicating its applicability in a tropical climate.
Biological activity of bleached kraft pulp mill effluents before and after activated sludge and ozone treatments
Authors: Lopes Alessandra Cunha , Mounteer Ann H. , Stoppa Teynha Valverde , Aquino Davi Santiago
Published: November 2012

Eucalyptus bleached kraft pulp production, an important sector of the Brazilian national economy, is responsible for generating large volume, high pollutant load effluents, containing a considerable fraction of recalcitrant organic matter. The objectives of this study were to quantify the biological activity of the effluent from a eucalyptus bleached kraft pulp mill, characterize the nature of compounds responsible for biological activity and assess the effect of ozone treatment on its removal. Primary and secondary effluents were collected bimonthly over the course of one year at a Brazilian bleached eucalypt kraft pulp mill and their pollutant loads (biochemical oxygen demand (BOD), chemical oxygen demand (COD), total organic carbon (TOC), adsorbable organic halogen (AOX), lignin, extractives) and biological activity (acute and chronic toxicity and estrogenic activity) quantified. The effluent studied did not present acute toxicity to Daphnia, but presented the chronic toxicity effects of algal growth inhibition and reduced survival and reproduction in Ceriodaphnia, as well as estrogenic activity. Chronic toxicity and estrogenic activity were reduced but not eliminated during activated sludge biological treatment. The toxicity identification evaluation revealed that lipophilic organic compounds (such as residual lignin, extractives and their byproducts) were responsible for the toxicity and estrogenic activity. Ozone treatment (50 mg/L O3) of the secondary effluent eliminated the chronic toxicity and significantly reduced estrogen activity.
Broadening of Generalized Anxiety Disorders Definition Does not Affect the Response to Psychiatric Care: Findings from the Observational ADAN Study
Authors: Álvarez Enrique , Carrasco Jose L , Olivares José M , López-Gómez Vanessa , Vilardaga Inma , Perez María
Published: November 2012

Objective:

To elucidate the consequences of broadening DSM-IV criteria for generalized anxiety disorder (GAD), we examined prospectively the evolution of GAD symptoms in two groups of patients; one group diagnosed according to DSM-IV criteria and the other, according to broader criteria.

Method:

Multicentre, prospective and observational study conducted on outpatient psychiatric clinics. Patients were selected from October 2007 to January 2009 and diagnosed with GAD according to DSM-IV criteria (DSM-IV group) or broader criteria. Broader criteria were considered 1-month of excessive or non-excessive worry and only 2 of the associated symptoms listed on DSM-IV for GAD diagnosis. Socio-demographic data, medical history and functional outcome measures were collected three times during a 6-month period.

Results:

3,549 patients were systematically recruited; 1,815 patients in DSM-IV group (DG) and 1,264 in broad group (BG); 453 patients did not fulfil inclusion criteria and were excluded. Most patients (87.9% in DG, 82.0% in BG) were currently following pharmacological therapies (mainly benzodiazepines) to manage their anxiety symptoms. The changes observed during the study were: 49.0% and 58.0%, respectively of patients without anxiety symptoms as per HAM-A scale at the 6 month visit (p=0.261) and 59.7% and 67.7%, respectively (p=0.103) of responder rates (> 50% reduction of baseline scoring).

Conclusion:

Broadening of GAD criteria does not seem to affect psychiatric care results in subjects with GAD, is able to identify the core symptoms of the disease according to the DSM-IV criteria and could lead to an earlier diagnosis.
Intramedullary Fixation of Diaphyseal Clavicle Fractures Using the Rockwood Clavicle Pin: Review of 86 Cases
Authors: Marlow William J , Ralte Peter , Morapudi Syam PK , Bassi Rashpal , Fischer Jochen , Waseem Mohammad
Published: November 2012

Aim:

This study reports the safety, efficacy and functional and patient centred outcomes of the largest published series of patients treated with the Rockwood clavicle pin (intramedullary device) to date.

Patients and Methods:

A retrospective review of case notes, radiographs and follow-up by questionnaire was conducted. 86 patients were operated upon, 70 for acute fractures (group A) and 16 for non-union (group B).Results: Rate of non-union was 2 (2.9%) in group A and 0 in group B. Mean Disability of the Arm, Shoulder and Hand (DASH) scores were 5.9 for group A and 8.7 for group B. Satisfaction was rated as good or excellent in 61 (96.8%) of responders and all patients would have the procedure again. Pin prominence was the predominant complication in both groups and all patients underwent a second procedure for metalwork removal.

Discussion:

Rockwood clavicle pins are as effective as plates in achieving union and maintaining length, however the advantages of this less invasive technique should be weighed against the common complication of pin prominence and the inconvenience of removal of metalwork in all cases.