bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment Decisions at the Time of Miscarriage Diagnosis
Authors: Schreiber Courtney A. , Chavez Veronica , Whittaker Paul G. , Ratcliffe Sarah J. , Easley Ebony , Barg Frances K.
Published: November 2016

OBJECTIVE:

To describe the factors patients and physicians prioritize during first-trimester miscarriage management and assess what drives satisfaction with care.

METHODS:

We conducted a mixed-methods study of clinically stable women seeking surgical, medical, or expectant miscarriage treatment. Women with first-trimester fetal demise or anembryonic gestation (N=55) completed demographic and psychosocial surveys. Using purposive sampling, 45 (82%) completed in-depth interviews. Fifteen obstetricians were interviewed. Participants described factors that informed their counseling (physicians) or decision-making (patients). Content analysis used an integrated approach with inductively and deductively derived codes. Patient-derived themes were stratified by treatment choice. Associations between variables and treatment choices were analyzed.

RESULTS:

Thirty-four women (62%) received surgical management, 19 (35%) received medical, and two (4%) received expectant. Physicians expected that women with prior pregnancies have strong management preferences, and indeed, multigravid patients were less likely to change their initial treatment choice after counseling than primigravid patients (12% compared with 42%, odds ratio [OR] 0.18, 95% confidence interval [CI] 0.04–0.81, P=.03). Physicians favored patient-centered decisions and patients chose the treatment that they thought would least affect other responsibilities. Those ultimately receiving surgical management had a higher monthly income (adjusted OR 1.30, 95% CI 1.04–1.63, P=.023) and more social support (adjusted OR 2.45, 95% CI 1.07–5.61, P=.035) than the medical group. The surgical group cited loss acceptance, a favorable perception of surgery, and a desire to expedite the miscarriage as decisive factors. The medical group endorsed control over, and timed completion of, the miscarriage in a more intimate setting, an aversion to surgery or anesthesia, and a perception of improved fertility preservation as decisive factors. Regardless of treatment choice, satisfaction with treatment was linked to a supportive clinical team and expeditious resolution.

CONCLUSION:

Prior pregnancy experiences, obligations, and sociodemographic factors influence miscarriage management decision-making. Structured counseling, especially for primigravid patients, could improve both the physician and the patient experience with miscarriage care.
Prevalence of Human Papillomavirus in Self-Collected Cervicovaginal Swabs in Young Women in the United States Between 2003 and 2012
Authors: Tarney Christopher M. , Klaric John , Beltran Thomas , Pagan Megan , Han Jasmine
Published: November 2016

OBJECTIVE:

To evaluate whether there was a change in prevalence of human papillomavirus (HPV) in the United States correlated with the introduction of HPV vaccines in both vaccinated and unvaccinated women.

METHODS:

We performed a retrospective review of prevalence data for women aged 18–29 years living in the United States using the National Health and Nutrition Examination Surveys, which is an ongoing series of cross-sectional surveys. Participants provided responses to standardized questions and self-collected cervicovaginal swabs in which a Linear Array HPV Assay was used to determine HPV prevalence. A total of 783 women from the prevaccine era (2003–2004) and 1,526 from the postvaccine era (2007–2012) were analyzed.

RESULTS:

Among women aged 18–29 years, the prevalence of vaccine-type HPV declined among women receiving one or more doses of vaccine (P=.003): 10.1% (95% confidence interval [CI] 7.1–13.8%) in the prevaccine era to 4.2% (95% CI 3.3–10.9%) in the postvaccine era. There was no change in prevalence of nonvaccine-type HPV among women receiving one or more doses of vaccine (P>.05). There was also no change in prevalence of vaccine-type HPV among unvaccinated women from the prevaccine era 10.1% (95% CI 7.1–13.8%) to 8.8% (95% CI 5.6–12.9%) in the postvaccine era (P=.4). Vaccine coverage increased to 31.5% of eligible women aged 18–29 years as of 2011–2012.

CONCLUSION:

Six years after introduction of HPV vaccination in the United States, there has been a decrease in the prevalence of vaccine-type HPV among women correlated with receiving one or more vaccine doses with no change in nonvaccine-type HPV. Furthermore, there has been no change in prevalence of vaccine-type HPV among unvaccinated women.
Balloon Kyphoplasty for Managing Intractable Pain in Pediatric Pathologic Vertebral Fractures
Authors: Hoashi Jane S. , Thomas Stefanie M. , Goodwin Ryan C. , Gurd David P. , Hanna Rabi , Kuivila Thomas E.
Published: November 2016

Background:

Vertebral compression fractures are a common result of osteoporosis and osteopenia secondary to steroid use and chemotherapy treatment. Balloon kyphoplasty is a treatment option with good to excellent results well described in adults. Although a few recent studies have been published regarding the use of kyphoplasty in children, no formal indication exists for the pediatric population. The purpose of this study is to describe the outcomes of 3 chronically ill children with intractable pain from vertebral compression fractures, managed with kyphoplasty.

Methods:

We retrospectively reviewed 3 pediatric patients who underwent balloon kyphoplasty for vertebral compression fractures secondary to chronic illness. Patient variables included age, sex, primary diagnosis and treatments, levels of vertebral fracture, and time elapsed from initial therapy to fracture. A numeric rating scale of 0 to 10 was used for patient-reported pain, before and after kyphoplasty. Preoperative and postoperative analgesic use and physical function were also described. Surgical variables included levels of kyphoplasty, operative time, and procedure-related complications.

Results:

The primary diagnoses were relapsed rhabdomyosarcoma, abdominal desmoplastic small round cell tumor, and IPEX-like (immune dysregulation, polyendrocrinopathy, enteropathy, X-linked) syndrome. All 3 patients were males, aged 12, 12, and 13, respectively, at the time of kyphoplasty. Pain scores were 8 to 9 preoperatively in 2 patients, severely affecting their physical function including independent walking. Excruciating back pain was a contributing factor to the respiratory distress of the third patient, who required elective intubation. All of the patients reported significant pain relief (range, 0 to 2) and improved physical function with kyphoplasty. The third patient was successfully extubated 1 week postoperatively and eventually returned to baseline activity. There were no complications related to kyphoplasty.

Conclusions:

Balloon kyphoplasty seems to be safe in terminally ill children and may be a useful tool for managing intractable pain due to vertebral compression fractures.

Level of Evidence:

Level IV—retrospective case series.
How Does Hyperkyphotic Early-Onset Scoliosis Respond to Growing Rod Treatment?
Authors: Chen Zhonghui , Qiu Yong , Zhu Zezhang , Li Song , Chen Xi , Sun Xu
Published: November 2016

Background:

Growing rods (GRs) pose a higher risk of kyphosis gain while improving coronal deformity with intermittent distractions in early-onset scoliosis (EOS), but in turn, increased kyphosis may also affect GR correction outcomes. However, there is a paucity of data regarding the effect of GRs on the sagittal spinal profiles in hyperkyphotic EOS. Thus, we aim to demonstrate how hyperkyphotic EOS responds to GRs treatment.

Methods:

Forty patients treated with GRs for EOS were included and categorized into a normal kyphosis (N) group [20 degrees≤thoracic kyphosis (TK)≤50 degrees] or hyperkyphosis group (K) group (TK≥50 degrees). Radiographic measurements were performed before and after the index surgery and at the last follow-up. The complications were identified and classified using the surgical complications grading system.

Results:

The N group included 13 patients with dual GRs and 6 patients with a single GR. The K group consisted of 17 patients with dual GRs and 4 patients with a single GR. The mean age at surgery in the N and K groups was 6.2±1.8 and 6.4±2.1 years, respectively. The N and K groups, respectively, had an average number of lengthenings of 4.2±2.0 and 4.3±2.3, with an average follow-up of 4.7±1.9 and 4.6±2.1 years, respectively. In the K group, TK was markedly reduced after the index surgery and slightly increased during follow-up, whereas changes in TK in the N group were not significant. The complication rate in the K group was significantly higher than in the N group (81.0% vs. 47.4%, P=0.046). The most common implant-related and alignment-related complication in both groups was rod fracture (17.5%) and proximal junctional kyphosis (22.5%), respectively. The complication events in the N group were 5 with grade I and 5 with grade IIA, whereas in the K group there were 8 with grade I and 11 with grade IIA.

Conclusions:

GRs can effectively correct hyperkyphotic EOS, with the sagittal profile being successfully restored to normal range. However, hyperkyphotic EOS tends to experience more complications such as rod fracture and PJK.

Level of Evidence:

Level III.
Free Functional Muscle Transfer Tendon Insertion Secondary Advancement Procedure to Improve Elbow Flexion
Authors: Sechachalam Sreedharan , O’Byrne Anne , MacQuillan Anthony
Published: November 2016

One method of restoring elbow flexion in patients with brachial plexus injuries is through the use of free functional muscle transfer. Most of our patients achieve good outcome, resulting in improved usefulness of the affected limb. However, a minority of our patients have successful reinnervation of the transferred muscle but with a suboptimal strength and range of motion (ROM) of elbow flexion. In this subset of patients, we perform a secondary procedure to improve the moment arm of the muscle on the elbow joint. This involves advancing the transferred muscle distally along the radius. The technique of the advancement procedure is described. We also report on our initial series of 5 patients who underwent this advancement procedure. In one patient, there was improvement in strength alone. In another, there was improvement of the ROM alone. The remaining 3 patients had improvement of both strength and ROM.
Effect of the lymphocyte-to-monocyte ratio on the clinical outcome of chemotherapy administration in advanced melanoma patients
Authors: Leontovich Alexey A. , Dronca Roxana S. , Nevala Wendy K. , Thompson Michael A. , Kottschade Lisa A. , Ivanov Leonid V. , Markovic Svetomir N.
Published: November 2016

Skin cancer affects more individuals in the USA than any other malignancy and malignant melanoma is particularly deadly because of its metastatic potential. Melanoma has been recognized as one of the most immunogenic malignancies; therefore, understanding the mechanisms of tumor–immune interaction is key for developing more efficient treatments. As the tumor microenvironment shows an immunosuppressive action, immunotherapeutic agents promoting endogenous immune response to cancer have been tested (interleukin-2, anticytotoxic-T-lymphocyte-associated antigen 4, and antiprogrammed cell death protein 1 monoclonal antibodies) as well as combinations of cytotoxic chemotherapy agents and inhibitors of angiogenesis (taxol/carboplatin/avastin). However, clinical outcomes are variable, with only a minority of patients achieving durable complete responses. The variability of immune homeostasis, which may be more active or more tolerant at any given time, in cancer patients and the interaction of the immune system with the tumor could explain the inconsistency in clinical outcomes among these patients. Recently, the role of the lymphocyte-to-monocyte-ratio (LMR) in the peripheral blood has been investigated and has been proven to be an independent predictor of survival in different hematological malignancies and in solid tumors. In melanoma, our group has validated the significance of LMR as a predictor of relapse after resection of advanced melanoma. In this study, we examined the dynamics in the immune system of patients with advanced melanoma by performing serial multiday concentration measurements of cytokines and immune cell subsets in the peripheral blood. The analysis of outcomes of chemotherapy administration as related to LMR on the day of treatment initiation showed that progression-free survival was improved in the patients who received chemotherapy on the day when LMR was elevated.
Agminated Clear Cell Tumor: An Impostor of PEComa and Distinctive Dermal Clear Cell Mesenchymal Neoplasm
Authors: Teixeira Ana Isabel , Soares-Almeida Luís , Kutzner Heinz
Published: November 2016

Cutaneous clear cell tumors are a heterogeneous group of cutaneous neoplasms, which may show a wide range of histogenesis. We report the clinicopathological features of an agminated clear cell tumor, arising in a 67-year-old man, otherwise asymptomatic, with distinct histopathological and immunohistochemical features, which did not fit into any existing diagnostic categories. The patient presented with several skin-colored papules at the lateral and posterior aspects of the neck, which on histopathological examination showed circumscribed lobular aggregates of clear cells within the dermis. The immunohistochemical marker panel performed showed diffuse expression of vimentin, NKI-C3, and CD64 while revealing marked negativity for factor XIIIa, CD10, CD13, CD14, CD34, CD68, CD163, lysozyme, HMB45, Renal Cell Carcinoma antigen, calponin, h-caldesmon, Anti-alpha smooth muscle actin antibody [1 A4], S100, and pancytokeratin, leading the authors to postulate a monocytic origin.
Benefit of Postresection Adjuvant Chemotherapy for Stage III Colon Cancer in Octogenarians: Analysis of the National Cancer Database
Authors: Bergquist John R. , Thiels Cornelius A. , Spindler Blake A. , Shubert Christopher R. , Hayman Amanda V. , Kelley Scott R. , Larson David W. , Habermann Elizabeth B. , Pemberton John H. , Mathis Kellie L.
Published: November 2016

BACKGROUND:

Clinical trials demonstrate that postresection chemotherapy conveys survival benefit to patients with stage III colon cancer. It is unclear whether this benefit can be extrapolated to the elderly, who are underenrolled in clinical trials.

OBJECTIVE:

The purpose of this study was to determine outcomes of selected octogenarians with stage III colon cancer with/without postresection adjuvant therapy.

DESIGN:

This was a retrospective cohort study (2006–2011) using unadjusted Kaplan–Meier and adjusted Cox proportional hazards analyses of overall survival.

SETTING:

The study was conducted with the National Cancer Database.

PATIENTS:

We included patients 80 to 89 years of age who were undergoing curative-intent surgery for stage III colon cancer and excluded patients who received neoadjuvant therapy, died within 6 weeks of surgery, or had high comorbidity.

MAIN OUTCOME MEASURES:

Overall survival was the main measure.

RESULTS:

A total of 8141 octogenarians were included; 3483 (42.8%) received postresection chemotherapy, and 4658 (57.2%) underwent surgery alone. Patients receiving chemotherapy were younger (82.0 vs 84.0 years; p < 0.001), healthier (73.1% vs 70.4% with no comorbidities; p = 0.009), and more likely to have N2 disease (40.4% vs 32.8%; p < 0.001). Overall survival was improved in patients receiving adjuvant chemotherapy (median = 61.7 vs 35.0 months; p < 0.001). Subgroup analysis of patients offered chemotherapy but refusing (n = 1315) demonstrated overall survival worse than those receiving adjuvant chemotherapy (median = 42.7 vs 61.7 months; p < 0.001). Multivariable analysis adjusting for potential confounders showed therapy with surgery alone to be independently associated with increased mortality hazard (HR = 1.83; p < 0.001), and the mortality hazard remained elevated in patients who voluntarily refused adjuvant therapy (HR = 1.45; p < 0.001).

LIMITATIONS:

The study was limited by its retrospective, nonrandomized design.

CONCLUSIONS:

In selected octogenarians with stage III colon cancer, postresection adjuvant chemotherapy was associated with superior overall survival. However, less than half of the octogenarians with stage III colon cancer in the National Cancer Database received it. The remaining majority, who were all fit and survived ≥6 weeks postsurgery, could have derived benefit from adjuvant chemotherapy. This represents a substantial opportunity for quality improvement in treating octogenarians with stage III colon cancer.
Hospital Variability in Use of Adjuvant Chemotherapy for Patients with Stage 2 and 3 Colon Cancer
Authors: Daly Meghan C. , Hanseman Dennis J. , Abbott Daniel E. , Shah Shimul A. , Paquette Ian M.
Published: November 2016

BACKGROUND:

Following oncologic resection, adjuvant chemotherapy is associated with decreased recurrence and improved survival in stage 3 colon cancer. However, there is controversy regarding its use in stage 2 colon cancer with high-risk features (tumor depth T4, poorly differentiated, positive margin, and/or inadequate lymph node retrieval). Consensus guidelines recommend no adjuvant chemotherapy in the absence of these high-risk features (low-risk stage 2).

OBJECTIVE:

This study aimed to examine hospital characteristics associated with poor risk-adjusted, stage-specific guideline compliance for the use of adjuvant chemotherapy in stage 3 and low-risk stage 2 colon cancer.

DESIGN:

This was a retrospective study. Stepwise logistic regression was used to identify patient and hospital factors associated with administration of adjuvant chemotherapy. Hierarchical regression models were used to calculate risk- and reliability-adjusted rates of chemotherapy use and observed-to-expected ratios in each hospital’s stage 2 low-risk and stage 3 patients.

SETTINGS:

Data were retrieved from the National Cancer Database.

PATIENTS:

Patients selected were adults treated with oncologic resection for stage 2 to 3 colon cancer between 2004 and 2010.

MAIN OUTCOME MEASURES:

The primary outcome measured was receipt of adjuvant chemotherapy.

RESULTS:

A total of 167,345 patients were identified at 1395 hospitals. The mean overall risk-adjusted adjuvant chemotherapy rate was 65.3% for stage 3 and 15.2% for low-risk stage 2. Analysis of low outlier hospitals for stage 3 colon cancer, where adjuvant chemotherapy was underutilized, demonstrated that 62.8% were low-volume centers and 51.4% were community centers. Of high outlier hospitals for stage 2 low-risk disease, where adjuvant chemotherapy was overutilized, 87.2% were low-volume hospitals and 67.2% were community centers.

LIMITATIONS:

Selection bias and the inability to compare specific chemotherapy regimens were limitations of this study.

CONCLUSIONS:

Following oncologic resection, administration of adjuvant chemotherapy for low-risk stage 2 and stage 3 disease varies substantially among hospitals in the United States. Outlier hospitals were most likely to be low-volume community centers.
Biomarker-Based Scoring System for Prediction of Tumor Response After Preoperative Chemoradiotherapy in Rectal Cancer by Reverse Transcriptase Polymerase Chain Reaction Analysis
Authors: Hur Hyuk , Tulina Inna , Cho Min Soo , Min Byung Soh , Koom Woong Sub , Lim Joon Seok , Ahn Joong Bae , Kim Nam Kyu
Published: November 2016

BACKGROUND:

Numerous molecular markers have been investigated to predict tumor response after preoperative chemoradiotherapy for rectal cancer.

OBJECTIVE:

This study aimed to evaluate the predictive value of biomarkers for the prediction of tumor response after preoperative chemoradiotherapy.

DESIGN & SETTING:

Tumor specimens have been collected prospectively from 80 patients with rectal cancer who underwent curative resection at 8 weeks after completing preoperative chemoradiotherapy.

MAIN OUTCOME MEASURES:

With the use of reverse transcriptase polymerase chain reaction analysis, mRNA expression levels of 7 candidate biomarkers (p53, p21, Ki-67, VEGF, CD133, CD24, and CD44) were evaluated from fresh tumor samples collected before preoperative chemoradiotherapy. The correlation between biomarker expression levels and the pathologic response was assessed based on histopathological staging (pTNM) and tumor regression grade.

RESULTS:

The mRNA expression levels of 4 biomarkers (p53, p21, Ki67, and CD133) significantly correlated with tumor regression grade response and pathologic complete response. Patients showing low expression of p53 and/or high expression of p21, Ki67, and CD133 exhibited a significantly greater tumor regression grade response and pathologic complete response rate. A scoring system devised so that 1 point was given for each biomarker whose expression level correlated with pathologic complete response (score range: 0–4) showed that 9 of 62 patients with scores of 0 to 2 achieved pathologic complete response, whereas 15 of 18 patients with scores of 3 to 4 achieved pathologic complete response (14.5% vs 83.3%, p < 0.001). For prediction of pathologic complete response, the scoring system showed 62.5% sensitivity, 94.6% specificity, an 83.3% positive predictive value, and an 85.5% negative predictive value.

LIMITATIONS:

Small patient numbers have limitations related to the reproducibility and ability to provide quantitative information. In addition, this study lacks test and validation sets.

CONCLUSIONS:

The pretreatment mRNA expression levels of 4 biomarkers correlated with pathologic tumor response after intraoperative chemoradiotherapy in rectal cancer. Furthermore, the scoring system combining values of biomarker expression might have predictive power with high positive and negative predictive values.
Sex differences in episodic memory in early midlife: impact of reproductive aging
Authors: Rentz Dorene M. , Weiss Blair K. , Jacobs Emily G. , Cherkerzian Sara , Klibanski Anne , Remington Anne , Aizley Harlyn , Goldstein Jill M.
Published: November 2016

Objective:

Few have characterized cognitive changes with age as a function of menopausal stage relative to men, or sex differences in components of memory in early midlife. The study aim was to investigate variation in memory function in early midlife as a function of sex, sex steroid hormones, and reproductive status.

Methods:

A total of 212 men and women aged 45 to 55 were selected for this cross-sectional study from a prenatal cohort of pregnancies whose mothers were originally recruited in 1959 to 1966. They underwent clinical and cognitive testing and hormonal assessments of menopause status. Multivariate general linear models for multiple memory outcomes were used to test hypotheses controlling for potential confounders. Episodic memory, executive function, semantic processing, and estimated verbal intelligence were assessed. Associative memory and episodic verbal memory were assessed using Face-Name Associative Memory Exam (FNAME) and Selective Reminding Test (SRT), given increased sensitivity to detecting early cognitive decline. Impacts of sex and reproductive stage on performance were tested.

Results:

Women outperformed men on all memory measures including FNAME (β = −0.30, P < 0.0001) and SRT (β = −0.29, P < 0.0001). Furthermore, premenopausal and perimenopausal women outperformed postmenopausal women on FNAME (initial learning, β= 0.32, P = 0.01) and SRT (recall, β= 2.39, P = 0.02). Across all women, higher estradiol was associated with better SRT performance (recall, β = 1.96, P = 0.01) and marginally associated with FNAME (initial learning, β = 0.19, P = 0.06).

Conclusions:

This study demonstrated that, in early midlife, women outperformed age-matched men across all memory measures, but sex differences were attenuated for postmenopausal women. Initial learning and memory retrieval were particularly vulnerable, whereas memory consolidation and storage were preserved. Findings underscore the significance of the decline in ovarian estradiol production in midlife and its role in shaping memory function.
Interacting Neural Processes of Feeding, Hyperactivity, Stress, Reward, and the Utility of the Activity-Based Anorexia Model of Anorexia Nervosa
Authors: Ross Rachel A. , Mandelblat-Cerf Yael , Verstegen Anne M.J.
Published: November 2016

Anorexia nervosa (AN) is a psychiatric illness with minimal effective treatments and a very high rate of mortality. Understanding the neurobiological underpinnings of the disease is imperative for improving outcomes and can be aided by the study of animal models. The activity-based anorexia rodent model (ABA) is the current best parallel for the study of AN. This review describes the basic neurobiology of feeding and hyperactivity seen in both ABA and AN, and compiles the research on the role that stress-response and reward pathways play in modulating the homeostatic drive to eat and to expend energy, which become dysfunctional in ABA and AN.
Screening History in 313 Cases of Invasive Cancer: A Retrospective Review of Cervical Cancer Screening in Alberta, Canada
Authors: Mema Silvina C. , Nation Jill , Yang Huiming , Waghray Ranjit , Sun Maggie C. , Xu Linan , Kliewer Gordon
Published: November 2016

Objective

To examine the screening history of invasive cervical cancer (ICC) cases in Alberta, Canada to identify areas for improvement of the population-based cervical cancer screening program.

Methods

Retrospective review of ICC cases diagnosed in 2 cities in Alberta between 2007 and 2012. Cancer morphology and staging were elicited from the Alberta Cancer Registry; cancer screening history and Pap test results were extracted from the Provincial Cervical Cancer Screening database. Women were classified as adequately screened, underscreened, and unscreened depending on time from last screening Pap test to diagnosis.

Results

Of the 280 cases that occurred in women eligible for screening, 125 (44.6%) were adequately screened, 18 (6.4%) were underscreened, and 137 (49%) were unscreened. Among the adequately screened, 71 (56.8%) had normal Pap test results, but 48 (38%) had less than 3 previous Pap tests (p = .003). Cancer stages I to II were diagnosed in 48.8% and 44.1% of adequately screened and unscreened women and cancer stages III to IV in 30.6% and 66.1% in each group, respectively (p = .0058). Squamous cell carcinoma (SCC) was diagnosed in 189 women (67.5%). The proportion of SCCs was similar in adequately screened and unscreened women.

Conclusions

The proportion of SCCs and advanced stages of ICC seems to be decreased. The results of quality improvement initiatives such as enhanced surveillance of high-grade Pap test results and histology-cytology correlation will be monitored and are expected to result in better outcomes for adequately screened women.
An overview of the recent findings in the cultivation of Leishmania
Authors: Nasiri Vahid
Published: November 2016

The cultivation of parasites of the genusLeishmaniahas been a subject of much interest due to the necessity of performing biochemical and immunological studies with isolated parasites in an effort to develop future therapeutic and preventive tools. Foetal calf serum (FCS) as the main part ofLeishmaniaspp. cultivation media is highly expensive, and reliable supply of it is very difficult to obtain. Here, we take an overview of the new replacements for FCS in the cultivation process ofLeishmaniaspp. and probability of optimizing them for parasites culture procedure. A precise review was conducted based on the database resources, and no restrictions were placed on date, design or language of publications and literature search was performed using Cochrane library, PubMed, Scopus, Google scholar and IranMedex. All considerable information about new replacements for FCS in the cultivation process ofLeishmaniaparasites was searched, evaluated and discussed. The aim of this article was to introduce and discuss new replacements for FCS in the cultivation process ofLeishmaniaparasites to give an overview about these candidates. According to this review, several novel replacements such as human and animal urine, animals’ milk, hydatid cyst fluid, chicken, sheep and lyophilized rabbit serum have been evaluated for cultivation ofLeishmaniaspp., and efficiency of some of them were confirmed and established and resulted in new formulation of media. We could conclude that future research will be done to study about effective elements of those suitable replacements to find new commercial culture media.
Use of Orally Disintegrating Olanzapine During Electroconvulsive Therapy for Prevention of Postictal Agitation
Authors: HERMIDA ADRIANA P. , JANJUA A. UMAIR , TANG YILANG , SYRE SHARYN R. , JOB GREGORY , MCDONALD WILLIAM M.
Published: November 2016

A major medical problem for patients undergoing electroconvulsive therapy (ECT) is the occurrence of postictal agitation (PIA). This phenomenon is associated with confusion and disorientation that can have severe clinical implications for the safety of the patient and health care professionals. Many different pharmacological strategies have been used to prevent PIA. We present data on 40 patients who suffered from PIA after a course of ECT and evaluate the prophylactic use of orally disintegrating olanzapine in the prevention of PIA in subsequent ECT treatments.
Antipsychotic Selection for Acute Agitation and Time to Repeat Use in a Psychiatric Emergency Department
Authors: GOMEZ SETH , DOPHEIDE JULIE
Published: November 2016

Background:

Early recognition and treatment of agitated patients is essential to avoid violence in the psychiatric emergency department (ED). Antipsychotics have established efficacy in managing agitation, yet little is known about how the choice of initial antipsychotic impacts time to repeat use and length of stay (LOS) in the psychiatric ED.

Objective:

To describe the impact of initial antipsychotic selection on time to repeat use and LOS in the psychiatric ED.

Methods:

A chart review identified 388 cases in which patients were administered an antipsychotic for agitation in the psychiatric ED between July 1 and August 31, 2014. Time to repeat use and LOS were compared for intramuscular (IM) haloperidol, other IM antipsychotics, and oral second-generation antipsychotics (SGAs) using the Kruskal-Wallis or Wilcoxon-Mann-Whitney test.

Results:

Of the 388 cases, 31% (n=122) required repeat medications. Mean time to repeat use for IM haloperidol was 20.1±18.4 hours, which was not significantly different from mean time to repeat use in the groups receiving other IM antipsychotics or oral SGAs (P=0.35). The mean LOS was 29.7±28.7 hours for IM haloperidol, 30.3±36.9 hours for other IM antipsychotics, and 22.6±28.0 hours for oral SGAs. Significant differences in LOS between repeat and nonrepeat users of IM haloperidol and other IM antipsychotics were observed, but not among those who received oral SGAs.

Conclusions:

Mean time to repeat use ranged from 14 to 20 hours with IM haloperidol, other IM antipsychotics, and oral SGAs without significant differences in time to repeat use in the 3 different groups. Repeat users of IM antipsychotics had a significantly longer LOS in the ED compared with nonrepeat users of IM antipsychotics. However, patients who were initially administered oral SGAs did not have longer LOS in the ED even if a repeat dose was given.
Evaluation of Bipolar Disorder in Children and Adolescents Referred to a Mood Service: Diagnostic Pathways and Manic Dimensions
Authors: FERREIRA-MAIA ANA P. , BORONAT ALEXANDRE C. , BOARATI MIGUEL A. , FU-I LEE , WANG YUAN-PANG
Published: November 2016

Objectives:

Few studies have examined pediatric mental health services for early-onset bipolar disorder (BD). The goal of this study was to describe diagnostic pathways and manic dimensions in BD among referred children and adolescents.

Methods:

Data were obtained from a review of the charts of 814 subjects, 2 to 17 years of age, with a complaint of mood disturbances who were referred between 2003 and 2012 to a university-based child and adolescent clinic that specializes in mood disorders. After screening, eligible participants (N=494) were systematically assessed and followed to determine diagnoses on the basis of criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision in accordance with the best-estimate approach. Manic symptoms were subjected to principal component analysis to investigate the dimensional bipolar profile of the sample.

Results:

Among the total help-seeking sample, approximately one third of the participants dropped out at intake and, after an average follow-up of 1.7 years, one third had been determined to meet criteria for BD and one third did not fulfill operational criteria for BD. The diagnostic status was changed in 35% of patients: approximately 10% were false positive (going from any bipolar diagnosis to a nonbipolar diagnosis) and approximately 25% were false negative (going from a nonbipolar diagnosis to any bipolar diagnosis). Most patients who converted to a bipolar diagnosis were initially labeled with major depressive disorder or attention-deficit/hyperactivity disorder and had a longer follow-up period. Relevant manic dimensions were elation, grandiosity, and disruption, which explained 41.4% of total variance.

Conclusions:

Regular reappraisal and follow-up of children and adolescents with mood disturbances provides a window for detection of BD (eg, of core manic dimensions). A coordinated and hierarchical connection among pediatric mental health services with different degrees of specialization is recommended.
Hopes and Expectations Regarding Genetic Testing for Schizophrenia Among Young Adults at Clinical High-Risk for Psychosis
Authors: FRIESEN PHOEBE , LAWRENCE RYAN E. , BRUCATO GARY , GIRGIS RAGY R. , DIXON LISA
Published: November 2016

Genetic tests for schizophrenia could introduce both risks and benefits. Little is known about the hopes and expectations of young adults at clinical high-risk for psychosis concerning genetic testing for schizophrenia, despite the fact that these youth could be among those highly affected by such tests. We conducted semistructured interviews with 15 young adults at clinical high-risk for psychosis to ask about their interest, expectations, and hopes regarding genetic testing for schizophrenia. Most participants reported a high level of interest in genetic testing for schizophrenia, and the majority said they would take such a test immediately if it were available. Some expressed far-reaching expectations for a genetic test, such as predicting symptom severity and the timing of symptom onset. Several assumed that genetic testing would be accompanied by interventions to prevent schizophrenia. Participants anticipated mixed reactions on finding out they had a genetic risk for schizophrenia, suggesting that they might feel both a sense of relief and a sense of hopelessness. We suggest that genetic counseling could play an important role in counteracting a culture of genetic over-optimism and helping young adults at clinical high-risk for psychosis understand the limitations of genetic testing. Counseling sessions could also invite individuals to explore how receiving genetic risk information might impact their well-being, as early evidence suggests that some psychological factors help individuals cope, whereas others heighten distress related to genetic test results.
CPK Measurements and ECT in Polymyositis: A Case Report
Authors: DELUCIA BENJAMIN , PATEL RACHIT , YACOUB ADEEB , FRANCIS ANDREW
Published: November 2016

Inflammatory myopathies, including polymyositis (PM), may add risk to electroconvulsive therapy (ECT) due to muscle sensitivity to depolarizing neuromuscular agents. In addition, previously published case series have shown elevations in creatine phosphokinase (CPK), an index of PM disease severity, in patients without muscle disease receiving ECT. We report the case of a 74-year-old female who developed initial onset of depression after steroid treatment for biopsy-proven PM. After she failed to respond to trials of antidepressant medications, she was treated with 21 inpatient and outpatient sessions of ECT over 2 years. Each course of treatment was effective for her depression without worsening symptoms of muscle disease activity. Two previous cases have described the use of ECT in patients with inflammatory myopathies, but our case is the first to report maintenance phase treatment with CPK monitoring.
Use of an Analog Scale in the Treatment of Patients With Major Depressive Disorder to Optimize Assessment and Clinical Outcome
Authors: PRESKORN SHELDON H.
Published: November 2016

This column explains how a clinician can use an analog scale (1) to elucidate the course of major depressive disorder in a specific patient and (2) to assess response to treatment. This scale complements other standardized rating scales, such as the Montgomery-Asberg Depression Rating Scale (MADRS), because its anchors are tailored to each specific patient in terms of his or her worst depressive episode (ie, episode rated a 10) and how it has responded to treatment in the past, including whether the patient ever has achieved a full remission (ie, score of 0) following the initial onset of the disorder. The scale can then be used to assess how the patient in an acute or chronic active episode responds to new treatment, whether somatic and/or psychotherapeutic, and how that compares to historical responses to previous treatments. Going forward the scale can be used to assess the course of the patient’s illness (eg, episodic with full recovery or chronic with more severe episodes and increasing residual symptoms.) Through the use of this analog scale, the patient also develops a better understanding of his or her illness, including how episodes develop and resolve and whether there are factors (eg, interpersonal relationships) that either aggravate and/or are aggravated by the disorder. This simple scale, thus, fulfills many purposes, including history gathering, monitoring the usefulness of different treatment interventions, and patient education.
Small Bowel Gastrointestinal Stromal Tumors: Multidetector Computed Tomography Enhancement Pattern and Risk of Progression
Authors: Verde Franco , Hruban Ralph H. , Fishman Elliot K.
Published: November 2016

Objective

Small bowel gastrointestinal stromal tumors (SB-GISTs) are rare lesions with a variable appearance on computed tomography (CT). This case series analyzes the CT enhancement pattern with the histologic risk assessment of tumor progression.

Methods

Local institutional pathology database was searched for SB-GISTs from 2000 to 2015. Pathology reports and clinical notes were reviewed. Imaging was qualitatively reviewed for pattern of enhancement categorized into homogeneous or heterogeneous groups. Nonparametric statistical analysis was performed comparing enhancement to segment of bowel involved, presence of necrosis, tumor size, histologic grade (ie, G1 or G2), and histologic risk of progression (ie low, moderate, high). For simplicity, risk of progression was binned into low-risk or non–low-risk groups.

Results

Twenty-six pathology-proven, first presentation, nonmetastatic SB-GISTs were included into study. Seventeen were located in duodenum, 7 in jejunum, and 2 within the ileum. Dual phase (arterial and venous) CT imaging was available for 22 cases. Four cases did not have dual phase (three venous phase and one arterial phase only). Seventeen cases demonstrated heterogeneous enhancement and 9 cases homogeneous enhancement. Statistically significant difference was found between size versus enhancement groups (3.1 cm for homogeneous versus 6.8 cm for heterogeneous) (Mann-Whitney U test, n = 26, P = 0.002). Presence of necrosis versus enhancement group was statistically significant (Pearson χ2, P = 0.001). Low-risk and non–low-risk groups versus enhancement groups was very significant (P = 0.001). Bowel segment involvement and histologic grading versus enhancement group did not reach statistical significance (P = 0.174 and P = 0.07, respectively).

Conclusions

This case series reveals an important significant association between heterogeneous enhancement and non-low risk (ie, moderate/high) SB-GISTs. Beyond just describing the tumor, using enhancing pattern, the interpreting radiologist can preoperatively suggest additional prognostic information, potentially helpful for surgical planning.
Nodal signalling and asymmetry of the nervous system
Authors: Signore Iskra A. , Palma Karina , Concha Miguel L.
Published: November 2016

The role of Nodal signalling in nervous system asymmetry is still poorly understood. Here, we review and discuss how asymmetric Nodal signalling controls the ontogeny of nervous system asymmetry using a comparative developmental perspective. A detailed analysis of asymmetry in ascidians and fishes reveals a critical context-dependency of Nodal function and emphasizes that bilaterally paired and midline-unpaired structures/organs behave as different entities. We propose a conceptual framework to dissect the developmental function of Nodal as asymmetry inducer and laterality modulator in the nervous system, which can be used to study other types of body and visceral organ asymmetries. Using insights from developmental biology, we also present novel evolutionary hypotheses on how Nodal led the evolution of directional asymmetry in the brain, with a particular focus on the epithalamus. We intend this paper to provide a synthesis on how Nodal signalling controls left–right asymmetry of the nervous system.

This article is part of the themed issue ‘Provocative questions in left–right asymmetry’.
Split hand/foot malformation genetics supports the chromosome 7 copy segregation mechanism for human limb development
Authors: Klar Amar J. S.
Published: November 2016

Genetic aberrations of several unlinked loci cause human congenital split hand/foot malformation (SHFM) development. Mutations of theDLX5(distal-less) transcription factor-encoding gene in chromosome 7 cause SHFM through haploinsufficiency, but the vast majority of cases result from heterozygous chromosomal aberrations of the region without mutating theDLX5gene. To resolve this paradox, we invoke a chromosomal epigenetic mechanism for limb development. It is composed of a monochromatid gene expression phenomenon that we discovered in two fission yeasts with the selective chromosome copy segregation phenomenon that we discovered in mouse cells. Accordingly, one daughter cell inherits both expressedDLX5copies while the other daughter inherits both epigenetically silenced ones from a single deterministic cell of the developing limb. Thus, differentiated daughter cells after further proliferation will correspondingly produce proximal/distal-limb tissues. Published results of a Chr. 7 translocation with a centromere-proximal breakpoint situated over 41 million bases away from theDLXlocus, centromeric andDLX5-region inversions have satisfied key genetic and developmental biology predictions of the mechanism. Further genetic tests of the mechanism are proposed. We propose that the DNA double helical structure itself causes the development of sister cells' gene regulation asymmetry. We also argue against the conventionally invoked morphogen model of development.

This article is part of the themed issue ‘Provocative questions in left–right asymmetry’.
Tractography-based connectomes are dominated by false-positive connections
Authors: Maier-Hein Klaus H. , Neher Peter , Houde Jean-Christophe , Côté Marc-Alexandre , Garyfallidis Eleftherios , Zhong Jidan , Chamberland Maxime , Yeh Fang-Cheng , Lin Ying-Chia , Ji Qing , Reddick Wilburn E. , Glass John O. , Chen David Qixiang , Feng Yuanjing , Gao Chengfeng , Wu Ye , Ma Jieyan , Renjie H , Li Qiang , Westin Carl-Fredrik , Deslauriers-Gauthier Samuel , González J. Omar Ocegueda , Paquette Michael , St-Jean Samuel , Girard Gabriel , Rheault François , Sidhu Jasmeen , Tax Chantal M.W. , Guo Fenghua , Mesri Hamed Y. , Dávid Szabolcs , Froeling Martijn , Heemskerk Anneriet M. , Leemans Alexander , Boré Arnaud , Pinsard Basile , Bedetti Christophe , Desrosiers Matthieu , Brambati Simona , Doyon Julien , Sarica Alessia , Vasta Roberta , Cerasa Antonio , Quattrone Aldo , Yeatman Jason , Khan Ali R. , Hodges Wes , Alexander Simon , Romascano David , Barakovic Muhamed , Auría Anna , Esteban Oscar , Lemkaddem Alia , Thiran Jean-Philippe , Cetingul H. Ertan , Odry Benjamin L. , Mailhe Boris , Nadar Mariappan S. , Pizzagalli Fabrizio , Prasad Gautam , Villalon-Reina Julio E. , Galvis Justin , Thompson Paul M. , Requejo Francisco De Santiago , Laguna Pedro Luque , Lacerda Luis Miguel , Barrett Rachel , Dell’Acqua Flavio , Catani Marco , Petit Laurent , Caruyer Emmanuel , Daducci Alessandro , Dyrby Tim B. , Holland-Letz Tim , Hilgetag Claus C. , Stieltjes Bram , Descoteaux Maxime
Published: November 2016

Fiber tractography based on non-invasive diffusion imaging is at the heart of connectivity studies of the human brain. To date, the approach has not been systematically validated in ground truth studies. Based on a simulated human brain dataset with ground truth white matter tracts, we organized an open international tractography challenge, which resulted in 96 distinct submissions from 20 research groups. While most state-of-the-art algorithms reconstructed 90% of ground truth bundles to at least some extent, on average they produced four times more invalid than valid bundles. About half of the invalid bundles occurred systematically in the majority of submissions. Our results demonstrate fundamental ambiguities inherent to tract reconstruction methods based on diffusion orientation information, with critical consequences for the approach of diffusion tractography in particular and human connectivity studies in general.
GARFIELD - GWAS Analysis of Regulatory or Functional Information Enrichment with LD correction
Authors: Iotchkova Valentina , Ritchie Graham R.S. , Geihs Matthias , Morganella Sandro , Min Josine L. , Walter Klaudia , Timpson Nicholas ,   UK10K Consortium, Dunham Ian , Birney Ewan , Soranzo Nicole
Published: November 2016

Loci discovered by genome-wide association studies (GWAS) predominantly map outside protein-coding genes. The interpretation of functional consequences of non-coding variants can be greatly enhanced by catalogs of regulatory genomic regions in cell lines and primary tissues. However, robust and readily applicable methods are still lacking to systematically evaluate the contribution of these regions to genetic variation implicated in diseases or quantitative traits. Here we propose a novel approach that leverages GWAS findings with regulatory or functional annotations to classify features relevant to a phenotype of interest. Within our framework, we account for major sources of confounding that current methods do not offer. We further assess enrichment statistics for 27 GWAS traits within regulatory regions from the ENCODE and Roadmap projects. We characterise unique enrichment patterns for traits and annotations, driving novel biological insights. The method is implemented in standalone software and R package to facilitate its application by the research community.
EthSEQ: ethnicity annotation from whole exome sequencing data
Authors: Romanel Alessandro , Zhang Tuo , Elemento Olivier , Demichelis Francesca
Published: November 2016

Whole exome sequencing (WES) is widely utilized both in translational cancer genomics studies and in the setting of precision medicine. Stratification of individual's ethnicity is fundamental for the correct interpretation of personal genomic variation impact. We implemented EthSEQ to provide reliable and rapid ethnicity annotation from whole exome sequencing individual's data and validated it on 1,000 Genome Project and TCGA data demonstrating high precision (>99%). EthSEQ can be integrated into any WES based processing pipeline and exploits multi-core capabilities. Source code, manual and other data is available athttp://demichelislab.unitn.it/EthSEQ.