The journey from pain to power: A meta-ethnography on women’s experiences of vaginal birth after caesarean

Publication date: Available online 24 June 2017
Source:Women and Birth
Author(s): Hazel Keedle, Virginia Schmied, Elaine Burns, Hannah Grace Dahlen
BackgroundVaginal birth after caesarean can be a safe and satisfying option for many women who have had a previous caesarean, yet rates of vaginal birth after caesarean remain low in the majority of countries. Exploring women's experiences of vaginal birth after caesarean can improve health practitioners' understanding of the factors that facilitate or hinder women in the journey to have a vaginal birth after caesarean.MethodsThis paper reports on a meta-ethnographic review of 20 research papers exploring women's experience of vaginal birth after caesarean in a variety of birth locations. Meta-ethnography utilises a seven-stage process to synthesise qualitative research.ResultsThe overarching theme was 'the journey from pain to power'. The theme 'the hurt me' describes the previous caesarean experience and resulting feelings. Women experience a journey of 'peaks and troughs' moving from their previous caesarean to their vaginal birth after caesarean. Achieving a vaginal birth after caesarean was seen in the theme 'the powerful me,' and the resultant benefits are described in the theme 'the ongoing journey'.ConclusionWomen undergo a journey from their previous caesarean with different positive and negative experiences as they move towards their goal of achieving a vaginal birth after caesarean. This 'journey from pain to power' is strongly influenced by both negative and positive support provided by health care practitioners. Positive support from a health care professional is more common in confident practitioners and continuity of care with a midwife.



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Clinical utility of soluble interleukin-2 receptor in hemophagocytic syndromes: a systematic scoping review

Abstract

The serum-soluble interleukin-2 receptor (sIL-2r) level is considered an important diagnostic test and disease marker in hemophagocytic syndromes/hemophagocytic lymphohistiocytosis (HPS/HLH). However, this cytokine receptor is rarely measured in clinical practice and has been excluded from recent diagnostic/classification criteria such as the HScore and macrophage activation syndrome (MAS) 16. We performed a systematic scoping review of 64 articles (1975–2016) examining the clinical utility of sIL-2r in HPS/HLH. Twenty-two articles describe sIL-2r as a sensitive diagnostic marker for HLH, but only three distinct datasets actually address sensitivity. The original HLH-2004 Guidelines reported sensitivity of 93% and specificity of 100% for sIL-2r ≥ 2400, based on a pediatric dataset (n = 152) which is published for the first time in this review. Two pediatric studies reported sensitivity of 89% for sIL-2r ≥ 2400 in diagnosis of MAS complicating juvenile idiopathic arthritis (JIA) (n = 27) and 88% for secondary HLH in acute liver failure (n = 9). Twenty articles described sIL-2r as a dynamic marker of disease activity that falls with response to treatment, and 15 described high initial sIL-2r levels >10,000 U/mL as a poor prognostic marker. The ability of sIL-2r to distinguish between subtypes of HPS/HLH was inconsistent. This review confirms the importance of soluble IL-2r as a diagnostic and disease marker in HPS/HLH, but also reveals the need for more primary data about its performance characteristics, particularly in adults. More emphasis should be made in including this simple, inexpensive test in clinical practice and studies of HPS/HLH.

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Effect of exercising at minimum recommendations of the multiple sclerosis exercise guideline combined with structured education or attention control education – secondary results of the step it up randomised controlled trial

Recent exercise guidelines for people with multiple sclerosis (MS) recommend a minimum of 30 min moderate intensity aerobic exercise and resistance exercise twice per week. This trial compared the secondary ou...

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A large choledochocystolithiasis mimicking Mirizzi syndrome

An 18-year-old man presented with spontaneous severe epigastric pain, progressing and radiating to back since 3 days. It was associated with epigastric tenderness, bilious vomiting and jaundice. He had been intermittently experiencing these symptoms for the last 1 year. No known comorbid. Ultrasound showed a poorly visualised heterogeneous focus at porta hepatis; considering poor visualisation, this might represent an enlarged calcified lymph node or cystic duct calculus causing extrinsic compression or a large sludge ball within the common bile duct (CBD), leading to dilatation of common hepatic duct and intrahepatic biliary system. Subsequent magnetic resonance cholangiopancreatography revealed a focal saccular dilatation of middle part of CBD, a type I-B choledochal cyst, large heterogeneous focus seen within it representing choledochocystolithiasis. Later, CT was performed for further characterisation of surrounding anatomy and pathology, which confused the appearance of choledochocystolithiasis for Mirizzi syndrome. Later, surgery and histopathology confirmed type I-B choledochocystolithiasis and chronic cholecystitis.

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Bilateral recurrent pyosalpinx in a sexually inactive 12-year-old girl secondary to rare variant of Mullerian duct anomaly

Pyosalpinx is a severe sequel of chronic pelvic inflammatory disease, whereby the fallopian tubes become filled with pus.^{1 2} Pyosalpinx often affects sexually active women and rarely is seen in celibate adolescent girls.³ We report a case of a 12-year-old girl with no prior sexual history who presented to our emergency department with complaints of severe right lower quadrant pain of 1-day duration. Ultrasonography and CT scan of the abdomen and pelvis revealed free fluid collections in the pelvis without visualisation of the appendix. A preoperative diagnosis of acute ruptured appendicitis was given and she was taken to the operating room. Peroperative findings included bilaterally distended, pus-filled pyosalpinges. A definitive diagnosis of bilateral pyosalpinx was then made. Two-week antibiotic therapy was successful but the patient returned with recurrent pyosalpinx and a pelvic abscess 9 weeks later.

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Maternal serum anti-Müllerian hormone in Sudanese women with preeclampsia

A case–control study was conducted at Omdurman Maternity Tertiary Hospital, Sudan, during the period from May to August 2014 to investigate AMH level in women with preeclampsia compared to healthy controls. Th...

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Isolation, speciation and antifungal susceptibility testing of Candida isolates from various clinical specimens at a tertiary care hospital, Nepal

Candida species are responsible for various clinical infections ranging from mucocutaneous infection to life threatening invasive diseases along with increased resistance to antifungal...

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Determinants of modern contraceptive practice in Yaoundé-Cameroon: a community based cross sectional study

Despite numerous efforts put in place to increase modern contraceptive use in Cameroon as a means to fight maternal and infant mortality, the prevalence of modern contraception has shown only a slow increase a...

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Assignment of sigma factors of RNA polymerase to promoters in Corynebacterium glutamicum

Corynebacterium glutamicum is an important industrial producer of various amino acids and other metabolites. The C. glutamicum genome encodes seven sigma subunits (factors) of RNA polymer...

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Meta-barcoding in combination with palynological inference is a potent diagnostic marker for honey floral composition

Identification of floral samples present in honey is important in order to determine the medicinal value, enhance the production of honey as well as to conserve the honey bees. Traditional approaches for study...

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Rising temperature stimulates the biosynthesis of water-soluble fluorescent yellow pigments and gene expression in Monascus ruber CGMCC10910

Monascus species can produce secondary metabolites that have a polyketide structure. In this study, four types of extracellular water-soluble yellow pigments (Y1–Y4) were generated by sub...

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Agaricus bisporus production on substrates pasteurized by self-heating

The aim of this work was to determine if the self-heating pasteurization procedure is technically applicable to the cultivation of Agaricus bisporus. Firstly the substrates alone (corncob, Pangola grass and a mix...

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A clinical utility assessment of the automatic measurement method of the quality of Meibomian glands

Meibomian gland dysfunction (MGD) is one of the most common diseases observed in clinics and is the leading cause of evaporative dry eye. Today, diagnostics of MGD is not fully automatic yet and is based on a ...

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Development of stereo endoscope system with its innovative master interface for continuous surgical operation

Although robotic laparoscopic surgery has various benefits when compared with conventional open surgery and minimally invasive surgery, it also has issues to overcome and one of the issues is the discontinuous...

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Ultrastructure of bioscaffolds derived from bovine articular cartilage as an experimental model to support blastema cells

Abstract

Decellularized cartilage extracellular matrix (ECM)-derived bioscaffolds have been designed as they provide a unique opportunity to carry out research on the mechanisms of chondrogenesis and its regulation. These scaffolds are used as a model in order to emulate different aspects relating to the formation, degeneration, and regeneration of the cartilage. This project has studied the interaction between the decellularized bovine articular cartilage and the blastema cells derived from the punched rabbit's ear. Articular cartilage was dissected in fragments with 10 mm length and 2 mm thickness. Then, they were chemically decellularized with 2% sodium dodecyl sulfate (SDS) for 2 h. The tissue rings derived from the rabbit's ear were assembled with the decellularized scaffolds and they were placed in a culture media for 30 days. These samples were fixed, sectioned, and microscopically studied. Micrographs of SEM electron microscopy and DAPI staining confirmed the decellularization of the scaffolds. FTIR analysis confirmed the preservation of ECM components including collagen II and proteoglycans. The optical microscopy observations confirmed migration, adherence, and penetration of the blastema cells into the scaffolds. The electron microscopy studies demonstrated that the blastema cells beside the scaffolds have triggered mutual interactions and merely progressed toward chondrogenic differentiation. The main objective is to identify and comprehend the interaction between cartilage matrix and blastema cells. The proposed model is an ideal model for fundamental studies in cartilage tissue engineering. The principles of tissue engineering must be taken in to account while studying such interactions.

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6-shogaol, a neuroactive compound of ginger (jahe gajah) induced neuritogenic activity via NGF responsive pathways in PC-12 cells

Ginger is a popular spice and food preservative. The rhizomes of the common ginger have been used as traditional medicine to treat various ailments. 6-Shogaol, a pungent compound isolated from the rhizomes of jah...

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Prevalence of Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium and Ureaplasma urealyticum infections using a novel isothermal simultaneous RNA amplification testing method in infertile males

The purpose of this study was to evaluate the prevalence of Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium and Ureaplasma urealyticum infections in infertile men that consulted our outpatient...

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Structural and functional insight into pan-endopeptidase inhibition by α2-macroglobulins

Journal Name: Biological Chemistry
Issue: Ahead of print


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Autophagy and multidrug resistance in cancer

Multidrug resistance (MDR) occurs frequently after long-term chemotherapy, resulting in refractory cancer and tumor recurrence. Therefore, combatting MDR is an important issue. Autophagy, a self-degradative sy...

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Dynamics of Helicobacter pylori infection as a determinant of progression of gastric precancerous lesions: 16-year follow-up of an eradication trial

Objective

To evaluate the long-term effect of cumulative time exposed to Helicobacter pylori infection on the progression of gastric lesions.

Design

795 adults with precancerous gastric lesions were randomised to receive anti-H. pylori treatment at baseline. Gastric biopsies were obtained at baseline and at 3, 6, 12 and 16 years. A total of 456 individuals attended the 16-year visit. Cumulative time of H. pylori exposure was calculated as the number of years infected during follow-up. Multivariable logistic regression models were used to estimate the risk of progression to a more advanced diagnosis (versus no change/regression) as well as gastric cancer risk by intestinal metaplasia (IM) subtype. For a more detailed analysis of progression, we also used a histopathology score assessing both severity and extension of the gastric lesions (range 1–6). The score difference between baseline and 16 years was modelled by generalised linear models.

Results

Individuals who were continuously infected with H. pylori for 16 years had a higher probability of progression to a more advanced diagnosis than those who cleared the infection and remained negative after baseline (p=0.001). Incomplete-type IM was associated with higher risk of progression to cancer than complete-type (OR, 11.3; 95% CI 1.4 to 91.4). The average histopathology score increased by 0.20 units/year (95% CI 0.12 to 0.28) among individuals continuously infected with H. pylori. The effect of cumulative time of infection on progression in the histopathology score was significantly higher for individuals with atrophy (without IM) than for individuals with IM (p<0.001).

Conclusions

Long-term exposure to H. pylori infection was associated with progression of precancerous lesions. Individuals infected with H. pylori with these lesions may benefit from eradication, particularly those with atrophic gastritis without IM. Incomplete-type IM may be a useful marker for the identification of individuals at higher risk for cancer.

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Increased risk of acute arterial events in young patients and severely active IBD: a nationwide French cohort study

Objective

Magnitude and independent drivers of the risk of acute arterial events in IBD are still unclear. We addressed this question in patients with IBD compared with the general population at a nationwide level.

Design

Using the French National Hospital Discharge Database from 2008 to 2013, all patients aged 15 years or older and diagnosed with IBD were identified and followed up until 31 December 2013. The rates of incident acute arterial events were calculated and the impact of time with active disease (period around hospitalisation for IBD flare or IBD-related surgery) on the risk was assessed by Cox regression adjusted for traditional cardiovascular risk factors.

Results

Among 210 162 individuals with IBD (Crohn's disease (CD), n=97 708; UC, n=112 454), 5554 incident acute arterial events were identified. Both patients with CD and UC had a statistically significant overall increased risk of acute arterial events (standardised incidence ratio (SIR) 1.35; 95% CI 1.30 to 1.41 and SIR 1.10; 95 CI 1.06 to 1.13, respectively). The highest risk was observed in patients under the age of 55 years, both in CD and UC. The 3-month periods before and after IBD-related hospitalisation were associated with an increased risk of acute arterial events in both CD and UC (HR 1.74; 95 CI 1.44 to 2.09 and 1.87; 95% CI 1.58 to 2.22, respectively).

Conclusion

Patients with IBD are at increased risk of acute arterial events, with the highest risk in young patients. Disease activity may also have an independent impact on the risk.

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IRTKS is correlated with progression and survival time of patients with gastric cancer

Background and objectives

IRTKS functions as a novel regulator of tumour suppressor p53; however, the role of IRTKS in pathogenesis of gastric cancer is unclear.

Design

We used immunohistochemistry to detect IRTKS levels in 527 human gastric cancer specimens. We generated both IRTKS-deficient and p53-deficient mice to observe survival time of these mice and to isolate mouse embryonic fibroblasts (MEFs) for evaluating in vivo tumorigenicity. Co-immunoprecipitation was used to study the interaction among p53, MDM2 and IRTKS, as well as the ubiquitination of p53.

Results

IRTKS was significantly overexpressed in human gastric cancer, which was conversely associated with wild-type p53 expression. Among patients with wild-type p53 (n=206), those with high IRTKS expression (n=141) had a shorter survival time than those with low IRTKS (n=65) (p=0.0153). Heterozygous p53^+/– mice with IRTKS deficiency exhibited significantly delayed tumorigenesis and an extended tumour-free survival time. p53^+/– MEFs without IRTKS exhibited attenuated in vivo tumorigenicity. IRTKS depletion upregulated p53 and its target genes, such as BAX and p21. Intriguingly, IRTKS overexpression promoted p53 ubiquitination and degradation in MEFs and gastric cancer cells. Under DNA damage conditions, IRTKS was phosphorylated at Ser331 by the activated Chk2 kinase and then dissociated from p53, along with the p53-specific E3 ubiquitin ligase MDM2, resulting in attenuated p53 ubiquitination and degradation.

Conclusion

IRTKS overexpression is negatively correlated with progression and overall survival time of patients with gastric cancer with wild-type p53 through promotion of p53 degradation via the ubiquitin/proteasome pathway.

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Highly Multiplexed, Super-resolution Imaging of T Cells Using madSTORM

We demonstrate a method to image multiple molecules within heterogeneous nano-structures at single molecule accuracy using sequential binding and elution of fluorescently labeled antibodies.

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Treatment delay and fatal outcomes of pulmonary tuberculosis in advanced age: a retrospective nationwide cohort study

Studies focusing on pulmonary tuberculosis in advanced age (≥80 years) are lacking. This study aimed to explore treatment delay, outcomes and their predictors in this group.

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A splitting algorithm for a novel regularization of Perona-Malik and application to image restoration

In this paper, we focus on a numerical method of a problem called the Perona-Malik inequality which we use for image denoising. This model is obtained as the limit of the Perona-Malik model and the p-Laplacian op...

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Percutaneous coronary intervention patients and cardiologists experiences of the informed consent process in Northern England: a qualitative study

Objective

Informed consent is central to ethical medical practice, but little is known about how the process takes place in clinical practice. Percutaneous coronary intervention (PCI) is a common revascularisation procedure. Studies report that patients overestimate benefits, forget the risks and are unaware of alternative treatments. The aim of this study was to describe PCI patients' and cardiologists' experiences of the informed consent process in acute care settings.

Design/setting/participants

A qualitative study with a maximum variation sample of elective and acute PCI patients and cardiologists taking their consent, recruited from a district general hospital and tertiary centre. In-depth interviews were conducted, and consent discussions were audio recorded. Data collection, coding and theorising occurred simultaneously.

Findings

Forty-one (26 male) patients scheduled for elective (20) or urgent (21) PCI and 19 cardiologists (5 female) participated. Despite diversity in patients' experiences of informed consent, elective and acute patients experienced a common four-stage process of consent. Most patients made the decision to have treatment at PCI referral and took a passive role in the discussions we recorded. They recognised cardiologists as experts, trusted the medical system to 'fix' their health problem and were unaware of their role in the informed consent process. Informed consent discussions functioned as a formal 'event',enabling cardiologists to check patients' understanding and enabling patients to access treatment.

Conclusions

The configuration of services and patients' perceptions of their role in informed consent underpin a mismatch between legal and ethical principles of informed consent and current practice. The variation in patients' experiences of the current place of informed consent in service delivery represents a missed opportunity for cardiologists to work in decision-making partnerships with patients. In light of recent changes in the law, a new approach to informed consent is required.

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A retrospective cohort study of high-impact users among patients with cerebrovascular conditions

Objective

To apply group-based trajectory modelling (GBTM) to the hospital administrative data to evaluate, model and visualise trends and changes in the frequency of long-term hospital care use of the subgroups of patients with cerebrovascular conditions.

Design

A retrospective cohort study of patients with cerebrovascular conditions.

Settings

Secondary care of all patients with cerebrovascular conditions admitted to English National Hospital Service hospitals.

Participants

All patients with cerebrovascular conditions identified through national administrative data (Hospital Episode Statistics) and subsequent emergency hospital admissions followed up for 4 years.

Main outcome measure

Annual number of emergency hospital readmissions.

Results

GBTM model classified patients with intracranial haemorrhage (n=2605) into five subgroups, whereas ischaemic stroke (n=34 208) and transient ischaemic attack (TIA) (n=20 549) patients were shown to have two conventional groups, low and high impact. The covariates with significant association with high-impact users (17.1%) among ischaemic stroke were epilepsy (OR 2.29), previous stroke (OR 2.18), anxiety/depression (OR 1.63), procedural complication (OR 1.43), admission to intensive therapy unit (ITU) or high dependency unit (HDU) (OR 1.42), comorbidity score (OR 1.36), urinary tract infections (OR 1.32), vision loss (OR 1.32), chest infections (OR 1.25), living alone (OR 1.25), diabetes (OR 1.23), socioeconomic index (OR 1.20), older age (OR 1.03) and prolonged length of stay (OR 1.00). The covariates associated with high-impact users among TIA (20.0%) were thromboembolic event (OR 3.67), previous stroke (OR 2.51), epilepsy (OR 2.25), hypotension (OR 1.86), anxiety/depression (OR 1.63), amnesia (OR 1.62), diabetes (OR 1.58), anaemia (OR 1.55), comorbidity score (OR 1.39), atrial fibrillation (OR 1.27), living alone (OR 1.25), socioeconomic index (OR 1.13), older age (OR 1.04) and prolonged length of stay (OR 1.02). The high-impact users (0.5%) among intracranial haemorrhage were strongly associated with thromboembolic event (OR 20.3) and inversely related to older age (OR 0.58).

Conclusion

GBTM effectively assessed trends in the use of hospital care by the subgroups of patients with cerebrovascular conditions. High-impact users persistently had higher annual readmission during the follow-up period.

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Thinker, Soldier, Scribe: cross-sectional study of researchers' roles and author order in the Annals of Internal Medicine

Objective

How researchers' contributions relate to author order on the byline remains unclear. We sought to identify researchers' contributions associated with author order, and to explore the existence of author profiles.

Design

Observational study.

Setting

Published record.

Participants

1139 authors of 119 research articles published in 2015 in the Annals of Internal Medicine.

Primary outcomes

Presence or absence of 10 contributions, reported by each author, published in the journal.

Results

On average, first authors reported 7.1 contributions, second authors 5.2, middle authors 4.0, penultimate authors 4.5 and last authors 6.4 (p<0.001). The first author made the greatest contributions to drafting the article, designing the study, analysing and interpreting the data, and providing study materials or patients. The second author contributed to data analysis as well and to drafting the article. The last author was most involved in obtaining the funding, critically revising the article, designing the study and providing support. Factor analysis yielded three author profiles—Thinker (study design, revision of article, obtaining funding), Soldier (providing material or patients, providing administrative and logistical support, collecting data) and Scribe (analysis and interpretation of data, drafting the article, statistical expertise). These profiles do not strictly correspond to byline position.

Conclusions

First, second and last authors of research articles made distinct contributions to published research. Three authorship profiles can be used to summarise author contributions. These findings shed light on the organisation of clinical research teams and may help researchers discuss, plan and report authorship in a more transparent way.

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A cross-sectional study on the prevalence and associated risk factors for workplace violence against Chinese nurses

Objectives

The purpose of the present study was to explore the characteristics of workplace violence that Chinese nurses at tertiary and county–level hospitals encountered in the 12 months from December 2014 to January 2016, to identify and analyse risk factors for workplace violence, and to establish the basis for future preventive strategies.

Design

A cross–sectional study.

Setting

A total of 44 tertiary hospitals and 90 county–level hospitals in 16 provinces (municipalities or autonomous regions) in China.

Methods

We used stratified random sampling to collect data from December 2014 to January 2016. We distributed 21 360 questionnaires, and 15 970 participants provided valid data (effective response rate=74.77%). We conducted binary logistic regression analyses on the risk factors for workplace violence among the nurses in our sample and analysed the reasons for aggression.

Results

The prevalence of workplace violence was 65.8%; of this, 64.9% was verbal violence, and physical violence and sexual harassment accounted for 11.8% and 3.9%, respectively. Frequent workplace violence occurred primarily in emergency and paediatric departments. Respondents reported that patients' relatives were the main perpetrators in tertiary and county–level hospitals. Logistic regression analysis showed that respondents' age, department, years of experience and direct contact with patients were common risk factors at different levels of hospitals.

Conclusions

Workplace violence is frequent in China's tertiary and county–level hospitals; its occurrence is especially frequent in the emergency and paediatric departments. It is necessary to cope with workplace violence by developing effective control strategies at individual, hospital and national levels.

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Effects of a peer support programme for youth social services employees experiencing potentially traumatic events: a protocol for a prospective cohort study

Introduction

The use of peer support programmes to help workers experiencing potentially traumatic events (PTE) has increased in high-risk organisations in the last decades. However, the scientific evidence of its effectiveness is still very limited. This paper aims to describe the protocol of a prospective cohort study that assesses the efficacy of a peer support programme among youth social services employees exposed to a PTE at work on psychological well-being, work functioning and needs of support.

Methods and analysis

This is a mixed-methods prospective study that will examine workers' evolution four times over a 12-month period in Canada. This study involves: (1) quantitative data obtained through self-administrated questionnaires among 222 workers, and (2) qualitative in-depth interviews with a subsample of 45 workers. This study will compare findings from a cohort who received the support of a peer following a PTE (peer support–experimental protocol) as part of the experimental protocol of the Montreal Youth Social Services-University Institute (MYSS-UI), the second group of workers did not ask for the peer support (no peer support-experimental protocol) but was part of MYSS-UI, and the third group received standard organisational support from the Monteregie Youth Social Services (MYSS) (standard organisational protocol).

Ethics and dissemination

The protocol and informed consent form complied with the ethics guidelines of the MYSS-UI. The Research Ethics Board of MYSS-UI and MYSS reviewed and accepted the protocol as required. The results of the study will be published in peer-reviewed journals, presented at research and general public conferences, disseminated via a public report for the institute that funded the project and for all workers. Results of this study will influence decision making regarding intervention policies following PTE and peer support interventions may be expanded throughout the youth social services in Canada and worldwide.

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Observed and projected trends in paediatric health resources and services in China between 2003 and 2030: a time-series study

Objectives

The two-child policy took effect in China on 1 January 2016, thus officially ending the one-child policy. The resultant growth in the population will create a considerable demand for public services such as paediatric healthcare, even while there are limited paediatric resources. We estimated the relationship between paediatric health resources and services and child mortality to determine the degree of the deficiency of such resources in China. Projecting the quantity of paediatric health resource allocation and service supply through 2030 will help provide data reference for future policy decision making.

Design

Time-series study.

Setting

The People's Republic of China.

Participants

Paediatric patients whose data were recorded between 2003 and 2012 from the National Health and Family Planning Commission of the People's Republic of China.

Primary and secondary outcome measures

Child mortality and paediatric health resources and services data were entered into a cubic polynomial regression model to project paediatric health resources and services to 2030.

Results

Child mortality decreased throughout the past decade. Furthermore, the number of paediatric beds, paediatricians and nurses increased between 2003 and 2012, although the proportions increased rather slowly. Both the number and proportion of paediatric outpatients and inpatients increased rapidly. The observed and model-predicted values matched well (adjusted R²=93.8% for paediatric beds; adjusted R²=96.6% for paediatric outpatient visits). Overall, the projection indicated that paediatric beds, paediatricians and nurses will reach 460 148, 233 884 and 184 059 by 2030, respectively. Regarding paediatric services, the number of paediatric outpatient visits and inpatients is expected to reach upwards of 449.95 million and 21.83 million by 2030, respectively.

Conclusions

Despite implementation of the two-child policy, resource allocation in paediatrics has many deficiencies. Proper measures should be taken to actively respond to the demand for paediatric health services.

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Developing implementation strategies for firearm safety promotion in paediatric primary care for suicide prevention in two large US health systems: a study protocol for a mixed-methods implementation study

Introduction

The promotion of safe firearm practices, or firearms means restriction, is a promising but infrequently used suicide prevention strategy in the USA. Safety Check is an evidence-based practice for improving parental firearm safety behaviour in paediatric primary care. However, providers rarely discuss firearm safety during visits, suggesting the need to better understand barriers and facilitators to promoting this approach. This study, Adolescent Suicide Prevention In Routine clinical Encounters, aims to engender a better understanding of how to implement the three firearm components of Safety Check as a suicide prevention strategy in paediatric primary care.

Methods and analysis

The National Institute of Mental Health-funded Mental Health Research Network (MHRN), a consortium of 13 healthcare systems across the USA, affords a unique opportunity to better understand how to implement a firearm safety intervention in paediatric primary care from a system-level perspective. We will collaboratively develop implementation strategies in partnership with MHRN stakeholders. First, we will survey leadership of 82 primary care practices (ie, practices serving children, adolescents and young adults) within two MHRN systems to understand acceptability and use of the three firearm components of Safety Check (ie, screening, brief counselling around firearm safety and provision of firearm locks). Then, in collaboration with MHRN stakeholders, we will use intervention mapping and the Consolidated Framework for Implementation Research to systematically develop and evaluate a multilevel menu of implementation strategies for promoting firearm safety as a suicide prevention strategy in paediatric primary care.

Ethics and dissemination

Study procedures have been approved by the University of Pennsylvania. Henry Ford Health System and Baylor Scott & White institutional review boards (IRBs) have ceded IRB review to the University of Pennsylvania IRB. Results will be submitted for publication in peer-reviewed journals.

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Treatments for gestational diabetes: a systematic review and meta-analysis

Objective

To investigate the effectiveness of different treatments for gestational diabetes mellitus (GDM).

Design

Systematic review, meta-analysis and network meta-analysis.

Methods

Data sources were searched up to July 2016 and included MEDLINE and Embase. Randomised trials comparing treatments for GDM (packages of care (dietary and lifestyle interventions with pharmacological treatments as required), insulin, metformin, glibenclamide (glyburide)) were selected by two authors and double checked for accuracy. Outcomes included large for gestational age, shoulder dystocia, neonatal hypoglycaemia, caesarean section and pre-eclampsia. We pooled data using random-effects meta-analyses and used Bayesian network meta-analysis to compare pharmacological treatments (ie, including treatments not directly compared within a trial).

Results

Forty-two trials were included, the reporting of which was generally poor with unclear or high risk of bias. Packages of care varied in their composition and reduced the risk of most adverse perinatal outcomes compared with routine care (eg, large for gestational age: relative risk0.58 (95% CI 0.49 to 0.68; I²=0%; trials 8; participants 3462). Network meta-analyses suggest that metformin had the highest probability of being the most effective treatment in reducing the risk of most outcomes compared with insulin or glibenclamide.

Conclusions

Evidence shows that packages of care are effective in reducing the risk of most adverse perinatal outcomes. However, trials often include few women, are poorly reported with unclear or high risk of bias and report few outcomes. The contribution of each treatment within the packages of care remains unclear. Large well-designed and well-conducted trials are urgently needed.

Trial registration number

PROSPERO CRD42013004608.

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Patients as partners in Enhanced Recovery After Surgery: A qualitative patient-led study

Objectives

Explore the experience of patients undergoing colorectal surgery within an Enhanced Recovery After Surgery (ERAS) programme. Use these experiential data to inform the development of a framework to support ongoing, meaningful patient engagement in ERAS.

Design

Qualitative patient-led study using focus groups and narrative interviews. Data were analysed iteratively using a Participatory Grounded Theory approach.

Setting

Five tertiary care centres in Alberta, Canada, following the ERAS programme.

Participants

Twenty-seven patients who had undergone colorectal surgery in the last 12 months were recruited through purposive sampling. Seven patients participated in a codesign focus group to set and prioritise the research direction. Narrative interviews were conducted with 20 patients.

Results

Patients perceived that an ERAS programme should not be limited to the perioperative period, but should encompass the journey from diagnosis to recovery. Practical recommendations to improve the patient experience across the surgical continuum, and enhance patient engagement within ERAS included: (1) fully explain every protocol, and the purpose of the protocol, both before surgery and while in-hospital, so that patients can become knowledgeable partners in their recovery; (2) extend ERAS guidelines to the presurgery phase, so that patients can be ready emotionally, psychologically and physically for surgery; (3) extend ERAS guidelines to the recovery period at home to avoid stressful situations for patients and families; (4) consider activating a programme where experienced patients can provide peer support; (5) one size does not fit all; personalised adaptations within the standardised pathway are required.

Drawing upon these data, and through consultation with ERAS Alberta stakeholders, the ERAS team developed a matrix to guide sustained patient involvement and action throughout the surgical care continuum at three levels: individual, unit and ERAS system.

Conclusion

This patient-led study generated new insights into the needs of ERAS patients and informed the development of a framework to improve patient experiences and outcomes.

http://ift.tt/2u00YQ7

Targeting metabolic reprogramming in KRAS-driven cancers

Abstract

Mutations of KRAS are found in a variety of human malignancies, including in pancreatic cancer, colorectal cancer, and non-small cell lung cancer at high frequency. To date, no effective treatments that target mutant variants of KRAS have been introduced into clinical practice. In recent years, a number of studies have shown that the oncogene KRAS plays a critical role in controlling cancer metabolism by orchestrating multiple metabolic changes. One of the metabolic hallmarks of malignant tumor cells is their dependency on aerobic glycolysis, known as the Warburg effect. The role of KRAS signaling in the regulation of aerobic glycolysis has been reported in several types of cancer. KRAS-driven cancers are characterized by altered metabolic pathways involving enhanced nutrients uptake, enhanced glycolysis, enhanced glutaminolysis, and elevated synthesis of fatty acids and nucleotides. However, Just how mutated KRAS can coordinate the metabolic shift to promote tumor growth and whether specific metabolic pathways are essential for the tumorigenesis of KRAS-driven cancers are questions which remain to be answered. In this context, the aim of this review is to summarize current data on KRAS-related metabolic alterations in cancer cells. Given that cancer cells rely on changes in metabolism to support their growth and survival, the targeting of metabolic processes may be a potential strategy for treating KRAS-driven cancers.

http://ift.tt/2s2BbdO

The hydrophobic side chain of oseltamivir influences type A subtype selectivity of Neuraminidase inhibitors

Abstract

Neuraminidase, which plays a critical role in the influenza virus life cycle, is a target for new therapeutic agents. The study of structure–activity relationships revealed that the C-5 position amino group of oseltamivir was pointed to 150-cavity of the neuraminidase in group-1. This cavity is important for selectivity of inhibitors against N1 versus N2 NA. A serial of influenza neuraminidase inhibitors with the oseltavimir scaffold containing lipophilic side chains at the C-5 position have been synthesized and evaluated for their influenza neuraminidase inhibitory activity and selectivity. The results indicated that compound 13o (H5N1 IC₅₀ = 0.1 ±0.04μM,H3N2 IC₅₀ = 0.26±0.18 μM) showed better inhibitory activity and selectivity against the group-1 neuraminidase. This study may provide a clue to design of better group-1 neuraminidase inhibitors.

This article is protected by copyright. All rights reserved.

A series of oseltamivir derivatives were prepared. Most of them have better NA inhibitory activity and selectivity which indicated C-5 amino of oseltamivir was an important point to modify for finding novel influenza NA inhibitors

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Synthesis of novel and functionally selective non-competitive muscarinic antagonists as chemical probes

Abstract

Muscarinic receptors are known to play important biological roles and are drug targets for several human diseases. In a pilot study, novel muscarinic antagonists were synthesized and used as chemical probes to obtain additional information of the muscarinic pharmacophore. The design of these ligands made use of current orthosteric and allosteric models of drug-receptor interactions together with chemical motifs known to achieve muscarinic receptor selectivity. This approach has led to the discovery of several non-competitive muscarinic ligands that strongly bind at a secondary receptor site. These compounds were found to be non-competitive antagonists that completely abolished carbachol activation in functional assays. Several of these compounds antagonized functional response to carbachol with great potency at M₁ and M₄ than at the rest of receptor subtypes.

This article is protected by copyright. All rights reserved.

Synthesis of various functionally selective muscarinic antagonists that bind to all five receptor subtypes with similar affinity. Complete inhibition of the orthosteric antagonist [³H]NMS suggests steric interaction between tested compounds and [³H]NMS while antagonism of carbachol induced functional response suggests non-competitive interaction as potency of functional antagonism pK_B is greater than affinity of the compounds pK_I.

http://ift.tt/2t6klu0

HOXB7 accelerates the malignant progression of hepatocellular carcinoma by promoting stemness and epithelial-mesenchymal transition

Abstract

Background

Homeobox B7 (HOXB7) has been identified associated with poor prognosis of hepatocellular carcinoma (HCC). However, the specific mechanism by which HOXB7 promotes the malignant progression of HCC remains to be determined.

Methods

Immunohistochemistry (IHC) was used to detect the expression level of HOXB7 in 77-paired HCC tissue samples, and the correlation between HOXB7 and HCC prognosis was assessed. The location of HOXB7 was confirmed by immunofluorescence. Cell Titer-Blue assay was used to assess the proliferation of hepatoma cells. The stem-like properties of hepatoma cells were analysed by sphere formation and clone formation assays. The effect of HOXB7 on expression of cancer stem cell markers was evaluated. Transwell and wound-healing assays were performed to estimate the invasion and migration abilities of hepatoma cells. A xenograft tumor model was established in nude mice to assess the role of HOXB7 in tumor growth. Bioluminescence imaging was used to survey the effect of HOXB7 on the metastatic ability of hepatoma cells in vivo.

Results

Higher expression of HOXB7 was detected in HCC tissues compared with noncancerous tissues and significantly associated with poor prognosis of HCC. In addition, HOXB7 knockdown suppressed the cell proliferation, clone formation, sphere formation, invasion and migration of hepatoma cells in vitro; conversely, these biological abilities of hepatoma cells were enhanced by HOXB7 overexpression. Moreover, the cancer stem cell markers EPCAM and NANOG were up-regulated by HOXB7. The role of HOXB7 in promoting tumor growth and metastasis was verified in vivo. Further investigation revealed that c-Myc and Slug expression was elevated by HOXB7 and the AKT pathway was activated.

Conclusion

Overexpression of HOXB7 was significantly correlated with poor prognosis of HCC. HOXB7 up-regulated c-Myc and Slug expression via the AKT pathway to promote the acquisition of stem-like properties and facilitate epithelial-mesenchymal transition of hepatoma cells, accelerating the malignant progression of HCC.

http://ift.tt/2t2zkFc

PRC1 contributes to tumorigenesis of lung adenocarcinoma in association with the Wnt/β-catenin signaling pathway

Abstract

Background

Protein regulator of cytokinesis-1 (PRC1) belongs to the microtubule-associated proteins (MAPs) family, and is involved in cytokinesis. Recent investigations suggest PRC1 involvement in human carcinogenesis, including breast carcinoma, hepatocellular carcinoma and etc. However, whether PRC1 contributes to lung adenocarcinoma tumorigenesis remains unknown.

Methods

Quantitative reverse-transcription polymerase chain reaction (qRT-PCR), Western blotting and Immunohistochemical staining (IHC) were used to evaluate and contrast the PRC1 expression profile in lung adenocarcinoma and adjacent normal lung tissues. We examined the clinical use of PRC1 in lung adenocarcinoma prognosis. Additionally, the tumorigenesis impact of PRC1 in lung adenocarcinoma cells was verified via in vitro and in vivo metastasis and tumorigenesis assays. Notably, Next Generation Sequencing (NGS) was performed to investigate the molecular mechanism underlying the oncogenic role of PRC1 in lung adenocarcinoma.

Results

PRC1 mRNA and protein expressions were upregulated in lung adenocarcinoma tissues compared to adjacent normal lung tissues. PRC1 protein overexpression correlated with lymph node metastasis and was an independent poor prognostic factor for lung adenocarcinoma patients. Our data implied that PRC1 depletion limited the proliferation and invasion of lung adenocarcinoma cells in vitro and lowered tumor development and lung metastasis in vivo. Remarkably, limiting PRC1 substantially prompted G2/M phase cell cycle arrest and apoptosis. Mechanistically, by conducting NGS on PRC1-depleted A549 cells and control cells, we discovered that PRC1 expression was significantly correlated with the Wnt signaling pathway.

Conclusions

This investigation offers confirmation that PRC1 is a prognostic and promising therapeutic biomarker for people with lung adenocarcinoma and takes on a key part in the activation of the Wnt/β-catenin pathway in lung adenocarcinoma development.

http://ift.tt/2s1ZvfX

Stereotactic radiosurgery versus whole-brain radiotherapy after intracranial metastasis resection: a systematic review and meta-analysis

Abstract

Background

In patients with one to three brain metastases who undergo resection, options for post-operative treatments include whole-brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS) of the resection cavity. In this meta-analysis, we sought to compare the efficacy of each post-operative radiation modality with respect to tumor recurrence and survival.

Methods

Pubmed, Embase and Cochrane databases were searched through June 2016 for cohort studies reporting outcomes of SRS or WBRT after metastasis resection. Pooled effect estimates were calculated using fixed-effect and random-effect models for local recurrence, distant recurrence, and overall survival.

Results

Eight retrospective cohort studies with 646 patients (238 with SRS versus 408 with WBRT) were included in the analysis. Comparing SRS to WBRT, the overall crude risk ratio using the fixed-effect model was 0.59 for local recurrence (95%-CI: 0.32–1.09, I²: 3.35%, P-heterogeneity = 0.36, 3 studies), 1.09 for distant recurrence (95%-CI: 0.74–1.60, I²: 50.5%, P-heterogeneity = 0.13; 3 studies), and 2.99 for leptomeningeal disease (95% CI 1.55–5.76; I²: 14.4% p-heterogeneity: 0.28; 2 studies). For the same comparison, the risk ratio for median overall survival was 0.47 (95% CI: 0.41–0.54; I²: 79.1%, P-heterogeneity < 0.01; 4 studies) in a fixed-effect model, but was no longer significant (0.63; 95%-CI: 0.40–1.00) in a random-effect model. SRS was associated with a lower risk of leukoencephalopathy (RR: 0.15, 95% CI: 0.07–0.33, 1 study), yet with a higher risk of radiation-necrosis (RR: 19.4, 95% CI: 1.21–310, 1 study).

Conclusion

Based on retrospective cohort studies, the results of this study suggest that SRS of the resection cavity may offer comparable survival and similar local and distant control as adjuvant WBRT, yet may be associated with a higher risk for developing leptomeningeal disease. Future research on SRS should focus on achieving a better understanding of the various factors that may favor SRS over WBRT.

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PC-FACS

PC-FACS (Fast Article Critical Summaries for Clinicians in Palliative Care) provides hospice and palliative care clinicians with concise summaries of the most important findings from more than 100 medical and scientific journals. If you have colleagues who would benefit from receiving PC-FACS, please encourage them to join the AAHPM at aahpm.org. Comments from readers are welcomed at pc-facs@aahpm.org.

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A constant companion: immune recognition and response to cytomegalovirus with aging and implications for immune fitness

Abstract

Approximately 50% of individuals aged 6–49 years in the United States are infected with cytomegalovirus (CMV), with seroprevalence increasing with age, reaching 85–90% by 75–80 years according to Bate et al. (Clin Infect Dis 50 (11): 1439-1447, 2010) and Pawelec et al. (Curr Opin Immunol 24:507-511, 2012). Following primary infection, CMV establishes lifelong latency with periodic reactivation. Immunocompetent hosts experience largely asymptomatic infection, but CMV can cause serious illness in immunocompromised populations, such as transplant patients and the elderly. Control of CMV requires constant immune surveillance, and recent discoveries suggest this demand alters general features of the immune system in infected individuals. Here, we review recent advances in the understanding of the immune response to CMV and the role of CMV in immune aging and fitness, while highlighting the importance of potential confounding factors that influence CMV studies. Understanding how CMV contributes to shaping "baseline" immunity has important implications for a host's ability to mount effective responses to diverse infections and vaccination.

http://ift.tt/2sBVGMT

CMV immune evasion and manipulation of the immune system with aging

Abstract

Human cytomegalovirus (HCMV) encodes numerous proteins and microRNAs that function to evade the immune response and allow the virus to replicate and disseminate in the face of a competent innate and acquired immune system. The establishment of a latent infection by CMV, which if completely quiescent at the level of viral gene expression would represent an ultimate in immune evasion strategies, is not sufficient for lifelong persistence and dissemination of the virus. CMV needs to reactivate and replicate in a lytic cycle of infection in order to disseminate further, which occurs in the face of a fully primed secondary immune response. Without reactivation, latency itself would be redundant for the virus. It is also becoming clear that latency is not a totally quiescent state, but is characterized by limited viral gene expression. Therefore, the virus also needs immune evasion strategies during latency. An effective immune response to CMV is required or viral replication will cause morbidity and ultimately mortality in the host. There is clearly a complex balance between virus immune evasion and host immune recognition over a lifetime. This poses the important question of whether long-term evasion or manipulation of the immune response driven by CMV is detrimental to health. In this meeting report, three groups used the murine model of CMV (MCMV) to examine if the contribution of the virus to immune senescence is set by the (i) initial viral inoculum, (ii) inflation of T cell responses, (iii) or the balance between functionally distinct effector CD4+ T cells. The work of other groups studying the CMV response in humans is discussed. Their work asks whether the ability to make immune responses to new antigens is compromised by (i) age and HCMV carriage, (ii) long-term exposure to HCMV giving rise to an overall immunosuppressive environment and increased levels of latent virus, or (iii) adapted virus mutants (used as potential vaccines) that have the capacity to elicit conventional and unconventional T cell responses.

http://ift.tt/2s70yWO

Intratumoral treatment with radioactive beta-emitting microparticles: a systematic review

Abstract

Purpose

The purpose of this study was to review the role of radioactive microparticles (1–100 μm) for the treatment of solid tumors and provide a comprehensive overview of the feasibility, safety, and efficacy.

Methods

A systematic search was performed in MEDLINE, EMBASE, and The Cochrane Library (January 2017) by combining synonyms for the determinants "tumor," "injection," and "radionuclide." Data on injection technique, toxicity, tumor response, and survival were collected.

Results

The search yielded 7271 studies, and 37 were included for analysis. Twelve studies were performed in human patients and 25 animal studies. The studies were heterogeneous in patient population, tumors, follow-up time, and treatment characteristics. The direct intratumoral injection of radioactive microparticles resulted in a response rate of 71% in a variety of tumors and uncomplicated procedures with high cumulative doses of >19,000 Gy were reported.

Conclusion

The large variety of particles, techniques, and treated tumors in the studies provided an important insight into issues concerning efficacy, safety, particle and isotope choice, and other concepts for future research. Animal studies showed efficacy and a dose response. Most studies in humans concluded that intratumoral treatment with radioactive beta-emitting microparticles is relatively safe and effective. Conflicting evidence about safety and efficacy might be explained by the considerable variation in the treatment characteristics. Larger particles had a better retention which resulted in higher anti-tumor effect. Leakage seems to follow the path of least resistance depending on anatomical structures. Subsequently, a grid-like injection procedure with small volume depots is advised over a single large infusion. Controlled image-guided treatment is necessary because inadequate local delivery and inhomogeneous dose distribution result in reduced treatment efficacy and in potential complications.

http://ift.tt/2s2mAyL

Cancers, Vol. 9, Pages 72: Epigenetic Regulation of the Epithelial to Mesenchymal Transition in Lung Cancer

Lung cancer is the leading cause of cancer deaths worldwide. It is an aggressive and devastating cancer because of metastasis triggered by enhanced migration and invasion, and resistance to cytotoxic chemotherapy. The epithelial to mesenchymal transition (EMT) is a fundamental developmental process that is reactivated in wound healing and a variety of diseases including cancer where it promotes migration/invasion and metastasis, resistance to treatment, and generation and maintenance of cancer stem cells. The induction of EMT is associated with reprogramming of the epigenome. This review focuses on major mechanisms of epigenetic regulation mainly in lung cancer with recent data on EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit ), the catalytic subunit of the PRC2 (Polycomb Group PcG), that behaves as an oncogene in lung cancer associated with gene repression, non-coding RNAs and the epitranscriptome.

http://ift.tt/2s2a4iK

Balloon enteroscopy versus spiral enteroscopy for small-bowel disorders: a systematic review and meta-analysis

Two novel enteroscopic procedures, balloon enteroscopy (BE) and spiral enteroscopy (SE), have revolutionized the diagnostic and therapeutic approach to small-bowel disorders. These disorders that historically required surgical interventions are now investigated and managed nonsurgically. There are only a few weakly powered studies comparing the outcomes of SE and BE. We conducted a systematic review and meta-analysis to compare the efficacy and safety of these 2 procedures.

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The outcome of low-frequency intravitreal bevacizumab therapy for macular edema in retinal vein occlusions

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Clinical utility of cyclosporine (CsA) ophthalmic emulsion 0.05% for symptomatic relief in people with chronic dry eye: a review of the literature

http://ift.tt/2tFt2ZT

The signs of ocular-surface disorders after switching from latanoprost to tafluprost/timolol fixed combination: a prospective study

http://ift.tt/2t67aK4

Value of upper endoscopic biopsies in predicting medical refractoriness in pediatric patients with ulcerative colitis

Refractory ulcerative colitis (UC) occurs in patients who experience a severe disease manifestation that is unresponsive to medical therapy. The assessment of upper endoscopic microscopic findings and its correlation with refractory UC has not been fully studied in pediatric patients, and is the focus of this study. Medical records of UC patients treated at a tertiary pediatric center between 2000 and 2014 were reviewed. Endoscopic biopsies of the upper gastrointestinal tract of patients meeting a priori inclusion criteria were compared between refractory UC patients and non-refractory UC patients for active inflammation.

http://ift.tt/2t6duBp

Unusual high-grade features in pediatric diffuse leptomeningeal glioneuronal tumor: comparison with a typical low-grade example

Diffuse leptomeningeal glioneuronal tumor, a recent addition to the WHO classification system, typically presents in the pediatric population with signs and symptoms related to elevated intracranial pressure and imaging characteristics that may mimic infectious etiologies. The tumor is usually low-grade and tends to harbor BRAF rearrangement/duplication in up to 75% of cases, BRAF V600E mutation in a smaller subset of cases, and loss of chromosomal arm 1p in approximately 50-60% of cases, with ~20% of those showing loss of both 1p and 19q (codeletion).

http://ift.tt/2t5JfdP

Influence of inspiratory resistive loading on expiratory muscle fatigue in healthy humans

Abstract

Expiratory resistive loading elicits inspiratory as well as expiratory muscle fatigue, suggesting parallel co-activation of the inspiratory muscles during expiration. It is unknown whether the expiratory muscles are similarly co-activated to the point of fatigue during inspiratory resistive loading (IRL). The purpose of this study was to determine whether IRL elicits expiratory as well as inspiratory muscle fatigue. Healthy male subjects (n = 9) underwent isocapnic IRL (60% maximal inspiratory pressure, 15 breaths∙min⁻¹, 0.7 inspiratory duty cycle) to task failure. Abdominal and diaphragm contractile function was assessed at baseline and at 3, 15 and 30 min post-IRL by measuring gastric twitch pressure (P_ga,tw) and transdiaphragmatic twitch pressure (P_di,tw) in response to potentiated magnetic stimulation of the thoracic and phrenic nerves, respectively. Fatigue was defined as a significant reduction from baseline in P_ga,tw or P_di,tw. Throughout IRL, there was a time-dependent increase in cardiac frequency and mean arterial blood pressure, suggesting activation of the respiratory muscle metaboreflex. P_di,tw was significantly lower than baseline (34.3 ± 9.6 cmH₂O) at 3 min (23.2 ± 5.7 cmH₂O, P < 0.001), 15 min (24.2 ± 5.1 cmH₂O, P < 0.001) and 30 min post-IRL (26.3 ± 6.0 cmH₂O, P < 0.001). P_ga,twwas not significantly different from baseline (37.6 ± 17.1 cmH₂O) at 3 min (36.5 ± 14.6 cmH₂O), 15 min (33.7 ± 12.4 cmH₂O) and 30 min post-IRL (32.9 ± 11.3 cmH₂O). IRL elicits objective evidence of diaphragm, but not abdominal, muscle fatigue. Agonist-antagonist interactions for the respiratory muscles appear to be more important during expiratory versus inspiratory loading.

This article is protected by copyright. All rights reserved

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Fluoxetine induces apoptosis through endoplasmic reticulum stress via mitogen-activated protein kinase activation and histone hyperacetylation in SK-N-BE(2)-M17 human neuroblastoma cells

Abstract

Fluoxetine (FLX) is an antidepressant drug that belongs to the class of selective serotonin reuptake inhibitors. FLX is known to induce apoptosis in multiple types of cancer cells. In this study, the molecular mechanisms underlying the anti-cancer effects of FLX were investigated in SK-N-BE(2)-M17 human neuroblastoma cells. FLX induced apoptotic cell death, activation of caspase-4, -9, and -3, and expression of endoplasmic reticulum (ER) stress-associated proteins, including C/EBP homologous protein (CHOP). Inhibition of ER stress by treatment with the ER stress inhibitors, salubrinal and 4-phenylbutyric acid or CHOP siRNA transfection reduced FLX-induced cell death. FLX induced phosphorylation of mitogen-activated protein kinases (MAPKs) family, p38, JNK, and ERK, and an upstream kinase apoptosis signal kinase 1 (ASK1). Inhibition of MAPKs and ASK1 reduced FLX-induced cell death and CHOP expression. We then showed that FLX reduced mitochondrial membrane potential (MMP) and ER stress inhibitors as well as MAPK inhibitors ameliorated FLX-induced loss of MMP. Interestingly, FLX induced hyperacetylation of histone H3 and H4, upregulation of p300 histone acetyltransferase (HAT), and downregulation of histone deacetylases (HDACs). Treatment with a HAT inhibitor anacardic acid or p300 HAT siRNA transfection blocked FLX-induced apoptosis in SK-N-BE(2)-M17 cells. However, FLX did not induce histone acetylation and anacardic acid had no protective effect on FLX-induced cell death and CHOP expression in MYCN non-amplified SH-SY5Y human neuroblastoma and MYCN knockdowned SK-N-BE(2)-M17 cells. These findings suggest that FLX induces apoptosis in neuroblastoma through ER stress and mitochondrial dysfunction via the ASK1 and MAPK pathways and through histone hyperacetylation in a MYCN-dependent manner.

http://ift.tt/2tFFTLy

Disseminated histoplasmosis in a patient with HIV diagnosed by simple bedside investigations

Description

A 41-year-old HIV-infected woman presented with prolonged fever at another hospital. Besides low CD4 count (8 cell/mm³) and pancytopaenia, blood cultures, chest radiograph, chest–whole abdominal CT and bone marrow examination were unremarkable. Empirical treatment for tuberculosis was given. One week later, she developed rash and was transferred to our hospital. Physical examination showed multiple pruritic erythematous purplish maculopapular rashes with central necrotic areas predominantly on face, back-chest wall and both forearms (figure 1). Peripheral blood smear (figure 2) and skin scraping (figure 3) revealed multiple intracellular yeast-like organisms suggestive of Histoplasma capsulatum. Intravenous amphotericin B was given, followed by oral itraconazole. Her condition improved after 2 weeks of treatment. Antiretroviral medications were initiated 1 month later.

Figure 1

Multiple pruritic erythematous purplish maculopapular rashes with some central necrotic areas predominantly on the (A) face, (B) back-chest wall and (C,D) both forearms.

...

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Down syndrome and Moyamoya disease: unusual cause of stroke

Down syndrome is a frequent clinical entity, being considered one of the most frequent chromosomal aberrations. It is characterised by a typical clinical phenotype and is associated with a heterogeneous group of organ and system-specific abnormalities. The cardiovascular system is commonly affected and if so, it may be associated with an increased morbidity and mortality. Cerebrovascular events in patients with Down syndrome are multifactorial, being possibly related to congenital heart disease, vascular malformations and traditional cardiovascular risk factors. Moyamoya disease is a rare chronic occlusive vascular disease causing stenosis of the distal portion of the internal carotid artery, which has been associated with Down syndrome. The authors report the case of a 26-year-old woman with Down syndrome who presented with an acute stroke secondary to Moyamoya disease. The case is noteworthy for the rarity of this clinicopathological entity, and serves as a reminder for the possible association between these two conditions.

http://ift.tt/2s24CMU

Microcephaly in infantile Sandhoff's disease

Description

We evaluated a boy aged 16 months with developmental arrest at the age of 6 months followed by neuroregression and recurrent generalised seizures. Perinatal and family history was not contributory. He was first born to non-consanguineous parents by term, uncomplicated vaginal delivery and weighed 2.8 kg at birth. On examination, he was unable to hold neck, fixate, coo or smile and showed no interest in the surroundings. His weight was 9.5 kg (between 15th and 50th centile), length 78 cm (between 15th and 50th centile) and head circumference 44.4 cm (below 3rd centile) with normal head circumference of father (54 cm) and mother (51 cm). He also had hyperacusis, bilateral cherry-red spot, generalised hypotonia, brisk muscle stretch reflexes, bilateral Babinski's sign and no organomegaly. In view of infantile-onset neuroregression, microcephaly, seizures, cherry-red spot and spasticity, clinical diagnoses of GM2 (Tay-Sach's and Sandhoff's disease), GM1 gangliosidosis and Krabbe's disease were considered initially. Skull radiograph showed J-shaped...

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Perforated duodenal diverticulum: a rare complication in a common condition

The authors present a rare case of perforated duodenal diverticulum diagnosed in an 80-year-old Caucasian woman with vomiting and abdominal pain localised to the epigastrium. CT scan showed thickening of the second portion of the duodenum with retroperitoneal fat stranding and perihepatic free fluid, with a presumptive diagnosis of a duodenal perforation. A laparotomy was performed which showed a perforated diverticulum in the second portion of the duodenum. A diverticulectomy with single-layer closure was performed, without complications. The postoperative course was uneventful.

http://ift.tt/2s2sr7h

The Esophageal Epithelial Barrier in Health and Disease

Dysfunction in the esophageal epithelial barrier function is a major source for morbidity. In order to better understand the pathophysiologic pathways of the diseases associated with barrier dysfunction, including gastroesophageal reflux disease (GERD), eosinophilic esophagitis (EoE), Barrett's esophagus (BE) and obesity, it is important to understand the esophageal epithelial embryologic development, microscopic anatomy with a special focus on the barrier structure and function, extra-epithelial defense mechanisms and how these change in the diseased state.

http://ift.tt/2t5u985

Prehospital advanced cardiac life support for out-of-hospital cardiac arrest: a cohort study

Abstract

Objectives

Out-of-hospital advanced cardiac life support (ACLS) has not consistently shown a positive impact on survival. Extracorporeal cardiopulmonary resuscitation (E-CPR) could render prolonged on-site resuscitation (ACLS or basic cardiac life support [BCLS]) undesirable in selected cases. The objectives of this study were to evaluate, in patients suffering from out-of-hospital cardiac arrest (OHCA) and in a subgroup of potential E-CPR candidates, the association between the addition of prehospital ACLS to BCLS and survival to hospital discharge, prehospital return of spontaneous circulation (ROSC) and delay from call to hospital arrival.

Methods

This cohort study targets adult patients treated for OHCA between April 2010 and December 2015 in the city of Montreal, Canada. We defined potential E-CPR candidates using clinical criteria previously described in the literature (65 years of age or younger, initial shockable rhythm, absence of return of spontaneous circulation after 15 minutes of prehospital resuscitation and emergency medical services witnessed collapse or witnessed collapse with bystander cardiopulmonary resuscitation). Associations were evaluated using multivariate regression models.

Results

A total of 7134 patients with OHCA were included, 761 (10.7%) of whom survived to discharge. No independent association between survival to hospital discharge and the addition of prehospital ACLS to BCLS was found in either the entire cohort [adjusted odds ratio (AOR) 1.05 (95% confidence interval 0.84-1.32), p=0.68] or amongst the 246 potential E-CPR candidates [AOR 0.82 (95% confidence interval 0.36-1.84), p=0.63]. The addition of prehospital ACLS to BCLS was associated with a significant increase in the rate of prehospital ROSC in all patients experiencing OHCA (AOR 3.92 [95% CI 3.38-4.55], p<0.001) and in potential E-CPR candidates (AOR 3.48 [95% CI 1. 76-6.88], p<0.001) as compared to isolated prehospital BCLS. Delay from call to hospital arrival was longer in the ACLS group than in the BCLS group (difference=16 min [95% CI 15-16], p<0.001).

Conclusions

In a tiered-response urban emergency medical service setting, prehospital ACLS is not associated with an improvement in survival to hospital discharge in patients suffering from OHCA and in potential E-CPR candidates, but with an improvement in prehospital ROSC and with longer delay to hospital arrival.

This article is protected by copyright. All rights reserved.

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Randomized Controlled Double-Blind Trial Comparing Haloperidol Combined with Conventional Therapy to Conventional Therapy Alone in Patients with Symptomatic Gastroparesis

Abstract

Objective

Gastroparesis is a debilitating condition that causes nausea, vomiting, and abdominal pain. Management includes analgesics and antiemetics, but symptoms are often refractory. Haloperidol has been utilized in the palliative care setting for similar symptoms. The study objective was to determine whether haloperidol as an adjunct to conventional therapy would improve symptoms in gastroparesis patients presenting to the emergency department.

Methods and trial design

This was a randomized, double-blind, placebo-controlled trial of adult emergency department patients with acute exacerbation of previously diagnosed gastroparesis. The treatment group received 5 mg haloperidol plus conventional therapy (determined by the treating physician). The control group received a placebo plus conventional therapy. The severity of each subject's abdominal pain and nausea were assessed before intervention and every 15 minutes thereafter for 1 hour using a 10-point scale for pain and a 5-point scale for nausea. Primary outcomes were decreased pain and nausea 1 hour after treatment.

Results and Adverse Effects

Of the 33 study patients, 15 were randomized to receive haloperidol. Before treatment, the mean intensity of pain was 8.5 in the haloperidol group and 8.28 in the placebo group; mean pretreatment nausea scores were 4.53 and 4.11, respectively. One hour after therapy, the mean pain and nausea scores in the haloperidol group were 3.13 and 1.83 compared to 7.17 and 3.39 in the placebo group. The reduction in mean pain intensity therapy was 5.37 in the haloperidol group (p ≤0.001) compared to 1.11 in the placebo group (p =0 .11). The reduction in mean nausea score was 2.70 in the haloperidol group (p ≤ 0.001) and 0.72 in the placebo group (p = 0.05). Therefore, the reductions in symptom scores were statistically significant in the haloperidol group but not in the placebo group. No adverse events were reported.

Conclusions

Haloperidol as an adjunctive therapy is superior to placebo for acute gastroparesis symptoms.

This article is protected by copyright. All rights reserved.

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The Association of Health Literacy with Preventable ED Visits: A Cross-Sectional Study

Abstract

Background

Policy-makers argue that emergency department (ED) visits for conditions preventable with high-quality outpatient care contribute to waste in the healthcare system. However, access to ambulatory care is uneven, especially for vulnerable populations like minorities, the poor and those with limited health literacy. The impact of limited health literacy on ED visits that are preventable with timely, high-quality ambulatory care is unknown.

Objective

To determine the association of health literacy and preventable ED visits.

Methods

We conducted an observational cross-sectional study of potentially preventable ED visits (outcome) among adults (≥18 years old) in an ED serving an urban community. We assessed health literacy (predictor) through structured interviews with the Rapid Estimate of Adult Literacy in Medicine (REALM). We recorded age, sex, race, employment, payer, marital and health status, and number of comorbidities through structured interviews or electronic record review. We identified potentially preventable ED visits in the two years prior to the index ED visit by applying Agency for Healthcare Research and Quality technical specifications to identify ambulatory care sensitive conditions using ED discharge diagnoses in hospital administrative data. We used Poisson regression to evaluate the number of preventable ED visits among patients with limited (REALM < 61), versus adequate (REALM ≥ 61), health literacy after adjusting for covariates.

Results

Of 1,201 participants, 709 (59%) were female, 370 (31%) were African American, mean age was 41.6 years, and 394 (33%) had limited health literacy. Out of 4,444 total ED visits, 423 (9.5%) were potentially preventable. Of these, 260 (61%) resulted in hospital admission and 163 (39%) were treat-and-release. After adjusting for covariates, patients with limited literacy had 2.3 (95% CI 1.7-3.1) times the number of potentially preventable ED visits resulting in hospital admission compared to individuals with adequate health literacy, 1.4 (95%CI 1.0-2.0) times the number of treat-and-release visits, and 1.9 (95% CI 1.5-2.4) times the number of total preventable ED visits.

Conclusions

Our results suggest that the ED may be an important site to deploy universal literacy-sensitive precautions and to test literacy-sensitive interventions with the goal of reducing the burden of potentially preventable ED visits on patients and the healthcare system.

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Neurology Concepts: Young Women and Ischemic Stroke: Evaluation and Management in the Emergency Department

Abstract

Objective

Ischemic stroke is a leading cause of morbidity and mortality worldwide. While the incidence of ischemic stroke is highest in older populations, incidence of ischemic stroke in adults has been rising particularly rapidly among young (e.g. premenopausal) women. The evaluation and timely diagnosis of ischemic stroke in young women presents a challenging situation in the emergency department, due to a range of sex-specific risk factors and to broad differentials. The goals of this concepts paper are to summarize existing knowledge regarding the evaluation and management of young women with ischemic stroke in the acute setting.

Methods

A panel of 6 board certified emergency physicians, 1 with fellowship training in stroke and 1 with training in sex and gender based medicine, along with 1 vascular neurologist were co-authors involved in the paper. Each author used various search strategies (e.g PubMed, Psycinfo, and Google Scholar) for primary research, and review articles related to their section. The references were reviewed and evaluated for relevancy and included based on review by the lead authors

Results

Estimates on the incidence of ischemic stroke in premenopausal women range from 3.65 to 8.9 per 100,000 in the United States. Several risk factors for ischemic stroke exist for young women including oral contraceptive (OCP) use and migraine with aura. Pregnancy and the postpartum period (up to 12 weeks) is also an important transient state during which risks for both ischemic stroke and cerebral hemorrhage are elevated, accounting for 18% of strokes in women under 35. Current evidence regarding the management of acute ischemic stroke in young women is also summarized including use of thrombolytic agents (e.g. tPA) in both pregnant and nonpregnant individuals.

Conclusion

Unique challenges exist in the evaluation and diagnosis of ischemic stroke in young women. There are still many opportunities for future research aimed at improving detection and treatment of this population.

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Shape Analysis of the Cervical Spinous Process

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Cancers, Vol. 9, Pages 71: Exosomal MicroRNAs in Breast Cancer towards Diagnostic and Therapeutic Applications

Soon after the discovery of microRNAs over 15 years ago, a myriad of research groups around the world sought to develop clinical applications in breast cancer for these short, noncoding, regulatory RNAs. While little of this knowledge has translated into the clinic, the recent research explosion on cell-to-cell communication via exosomes and other extracellular vesicles has rekindled interest in microRNA-based clinical applications. microRNAs appear to be a preferential and important cargo of exosomes in mediating biological effects in recipient cells. This review highlights recent studies on the biology of exosomal microRNAs (exo-miRNAs) and discusses potential clinical applications. From a diagnostic perspective, circulating exo-miRNAs may represent breast cancer cell content and/or tumor microenvironmental reactions to cancer cell growth. Thus, serum or plasma analysis of exo-miRNAs could be useful for early disease detection or for monitoring treatment response and disease progression. From a therapeutic perspective, exo-miRNAs derived from different cell types have been implicated in supporting or restraining tumor growth, conferring drug resistance, and preparing the metastatic niche. Strategies to interfere with the loading or delivery of tumor-promoting exo-miRNAs or to replenish tumor-suppressive miRNAs via exosomal delivery are under investigation. These recent studies provide new hope and opportunities, but study design limitations and technical challenges will need to be overcome before seriously considering clinical application of exo-miRNAs.

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Cycling to School and Body Composition, Physical Fitness, and Metabolic Syndrome in Children and Adolescents

To evaluate the association between cycling to/from school and body composition, physical fitness, and metabolic syndrome among a sample of Colombian children and adolescents.

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Metastatic Dissemination of a Neuroblastoma

A 4-year-old boy presented with a history of proptosis, periorbital ecchymosis ("raccoon eyes"), weight loss, headache, and vomiting for 2 months. On clinical examination, he presented with periorbital ecchymosis, subconjunctival hemorrhage (Figure 1), proptosis, and stiff neck. No other abnormality was found. The findings of a lumbar puncture were normal. Laboratory tests showed anemia and elevated alkaline phosphatase, phosphorus, and lactate dehydrogenase levels. Computed tomography (CT) of the brain showed a lobulated periorbital mass involving the roof and lateral wall of the left orbit, and "hair-on-end" spiculated periostitis of the orbits, sphenoid wings, and skull associated with bone destruction and irregular sutural diastasis (Figure 2; available at www.jpeds.com).

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Mutation in the FGFR1 tyrosine kinase domain or inactivation of PTEN is associated with acquired resistance to FGFR inhibitors in FGFR1-driven leukemia/lymphomas

Abstract

Stem cell leukemia/lymphoma syndrome (SCLL) is driven by constitutive activation of chimeric FGFR1 kinases generated by chromosome translocations. We have shown that FGFR inhibitors significantly suppress leukemia and lymphoma development in vivo, and cell viability in vitro. Since resistance to targeted therapies is a major reason for relapse, we developed FGFR1-overexpressing mouse and human cell lines that are resistant to the specific FGFR inhibitors AZD4547 and BGJ398, as well as non-specific inhibitors, such as ponatinib, TKI258 and E3810. Two mutually exclusive mechanisms for resistance were demonstrated; an activating V561M mutation in the FGFR1 kinase domain and mutational inactivation of PTEN resulting in increased PI3K/AKT activity. Ectopic expression of PTEN in the PTEN-mutant cells resensitizes them to FGFR inhibitors. Treatment of resistant cells with BGJ398, in combination with the BEZ235 PI3K inhibitor, shows an additive effect on growth in vitro and prolongs survival in xenograft models in vivo. These studies provide the first direct evidence for both the involvement of the FGFR1 V561M mutation and PTEN inactivation in the development of resistance in leukemias overexpressing chimeric FGFR1. These studies also provide a potential strategy to treat leukemias and lymphomas driven by FGFR1 activation that become resistant to FGFR1 inhibitors. This article is protected by copyright. All rights reserved.

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Genetic variants in microRNA-binding sites of DNA repair genes as predictors of recurrence in patients with squamous cell carcinoma of the oropharynx

Abstract

The incidence of squamous cell carcinoma of the oropharynx (SCCOP) continues to rise because of increasing rates of human papillomavirus (HPV) infection. Inherited polymorphisms in DNA repair pathways may influence the risk of SCCOP development and the prognosis of SCCOP. We sought to determine whether polymorphisms in microRNA (miRNA)-binding sites within 3ʹ-untranslated regions (3'UTRs) of genes in DNA repair pathways modulate the risk of SCCOP recurrence. We evaluated the associations between nine such polymorphisms and SCCOP recurrence in 1008 patients with incident SCCOP using the log-rank test and multivariable Cox models. In an analysis of all the patients, patients with variant genotypes of BRCA1 rs12516 and RAD51 rs7180135 had better disease-free survival (log-rank, P = 0.0002 and P = 0.0003, respectively) and lower risk of SCCOP recurrence (hazard ratio [HR], 0.5, 95% confidence interval [CI], 0.2-0.8, and HR, 0.5, 95% CI, 0.3-0.9, respectively) than patients with common homozygous genotypes of the two polymorphisms after multivariable adjustment. Moreover, in tumor HPV16-positive patients, patients with variant genotypes of the same two polymorphisms also had better disease-free survival (log-rank, P = 0.004 and P = 0.003, respectively) and lower recurrence risk (HR, 0.2, 95% CI, 0.1-0.6, and HR, 0.2, 95% CI, 0.0-0.7, respectively) than patients with common homozygous genotypes of the two polymorphisms. No such significant associations were found for other polymorphisms. These findings support significant roles of BRCA1 rs12516 and RAD51 rs7180135 in modifying the risk of recurrence of SCCOP, particularly HPV16-positive SCCOP. However, these results must be validated in larger studies. This article is protected by copyright. All rights reserved.

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Targeting STAT3 by HO3867 induces apoptosis in ovarian clear cell carcinoma

Abstract

Advanced ovarian clear cell carcinoma (OCCC) carries a very poor prognosis in large part secondary to the extremely high rate of resistance to standard platinum and taxane chemotherapy. STAT3 expression and activation has been shown to regulate tumor progression in various human cancers, though has not been well studied in OCCC. Preliminary work in our lab has demonstrated constitutive activation of STAT3 (pSTAT3Tyr705 or pSTAT3727) in OCCC cell lines as well as human OCCC tumor tissue samples. Significantly, pSTAT3 is expressed in the absence of other forms of activated STAT (pSTAT1, 2, 6). Therefore, this work was planned to investigate the role of STAT3 and examine the efficacy of a novel anti-cancer compound -HO-3867, which is an inhibitor of STAT3, using known OCCC cell lines. Results demonstrate that treatment with HO-3867 decreased expression of pSTAT3 Tyr705 as well pSTAT3 Ser727, while total STAT3 remained constant. STAT3 overexpression increased the migration capability in OVTOKO cells in vitro and led to an increased tumor size when injected in vivo. The inhibitory effect of HO-3867 on cell proliferation and cell survival was accompanied by increased apoptosis, within 24 h post treatment. Treatment with HO-3867 resulted in a decrease in Bcl-2 and increase of cleavage of caspase 3, caspase 7, and PARP, confirming induction of apoptosis after treatment with HO-3867. In addition, HO-3867 significantly inhibited formation of HUVEC cells capillary-like structures and invasion at both 5 and 10µM concentrations. STAT3 expression plays an important role in the spread of OCCC in vitro as well as in vivo. Thus, we can exploit the STAT3 pathway for targeted drug therapy. Inhibition of pSTAT3 using HO-3867in OCCC cell lines appears to be a promising therapy. This is of utmost importance given the poor response of OCCC to standard chemotherapy regimens. This article is protected by copyright. All rights reserved.

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Functional Analysis of p.Ala253_Leu254insAsn Mutation in PLS3 Responsible for X-linked Osteoporosis

ABSTRACT

Mutations in Plastin-3 (PLS3) have been identified as a cause of X-linked osteoporosis. To reveal the molecular mechanism of PLS3 on osteoporosis, we characterized the p.Ala253_Leu254insAsn mutation in PLS3. We first identified Lymphocyte cytosolic protein 1 (LCP1) as a binding partner of PLS3 and the mutation disrupted the interaction between them. We then confirmed the roles of PLS3 and LCP1 in the regulation of intracellular Ca²⁺, which was weakened by the mutant PLS3. Moreover, the interaction between PLS3 and LCP1 was enhanced under a low concentration of extracellular Ca²⁺. However, the mutation in PLS3 weakened the responsiveness. The reduced regulation on Ca²⁺ caused by p.Ala253_Leu254insAsn may be the possible molecular mechanism of osteoporosis.

Graphical Abstract

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Spectrum of mutations in cystinuria patients presenting with prenatal hyperechoic colon

ABSTRACT

Cystinuria is a heterogeneous, rare but important cause of inherited kidney stone disease due to mutations in two genes: SLC3A1 and SLC7A9. Antenatal hyperechoic colon has been reported in some patients as a non-pathological consequence of the intestinal transport defect. We report 83 patients affected by cystinuria: 44 presented prenatally with a hyperechoic colon (HEC group) and 39 with a classical postnatal form (CC group). SLC3A1 and SLC7A9 were sequenced. All patients were fully genotyped, and the relationship between the genotype and clinical features was analyzed. We identified mutations in SLC3A1 in 80% of the HEC group and in only 49% of the CC group. The SLC3A1 p.Thr216Met mutation was found in 21% of the alleles in the HEC group but was never found in the CC group. Most of the mutations found in the HEC group were considered severe mutations in contrast with the CC group. Twenty-five novel mutations were reported. This study shows a relationship between genotype and the clinical form of cystinuria, suggesting that only the patients with the most severe mutations presented with an HEC. These results emphasized the need for prenatal cystinuria screening using classical third-trimester ultrasound scan and the early management of suspected newborns.

Graphical Abstract

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Up-regulation of carcinoembryonic antigen-related cell adhesion molecule 1 in gastrointestinal cancer and its clinical relevance

Abstract

Serum carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is dysregulated in various malignant tumors and has been associated with tumor progression. However, the expression and regulatory mechanisms of serum CEACAM1 in gastrointestinal cancer are still unclear. The expression ratio of the CEACAM1-L and CEACAM1-S isoforms has seldom been investigated in gastrointestinal cancer. In this study, we intended to explore the expression and diagnostic value of CEACAM1 in gastrointestinal cancer. Serum CEACAM1 levels were measured by enzyme-linked immunosorbent assay. The protein expression and distribution of CEACAM1 in tumors were examined by immunohistochemical staining. The expression patterns and ratio of CEACAM1-L/S were analyzed by reverse transcription-polymerase chain reaction. The results showed that serum CEACAM1 levels were significantly higher in cancer patients than in healthy controls. CEACAM1 was found in secreted forms within the neoplastic glands, and its expression was more intense at the tumor invasion front. The CEACAM1-L/S (L:S) ratios were up-regulated during tumorigenesis. Our data suggest that the serum level of CEACAM1 may be used to discriminate gastrointestinal cancer patients from health controls.

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Ginseng saponin Rb1 enhances hematopoietic function and dendritic cells differentiation

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Local knockdown of Nav1.6 relieves pain behaviors induced by BmK I

Abstract

Voltage-gated sodium channels (VGSCs) in peripheral nociceptive sensory neurons are critical to transmit pain signals. BmK I purified from the venom of scorpion Buthus martensi Karsch (BmK) has been demonstrated to be the primary contributor of envenomation-associated pain. However, the role of distinct VGSCs such as Nav1.6 in the induction and maintenance of pain behaviors induced by BmK I was ambiguous. Herein, using molecular and behavioral approaches we investigated the mRNA and protein expression profiles of Nav1.6 in rat DRG after intraplantar injection of BmK I and tested the pain behaviors after knockdown of Nav1.6 in BmK I-treated rats. It was shown that during induction and maintenance of pain responses induced by BmK I, the expression of Nav1.6 in DRG was found to be significantly increased at both mRNA and protein levels. The percentage of co-localization of Nav1.6 and Isolectin B4, a molecular marker of small diameter non-peptidergic DRG neurons, was increased at the maintenance phase of pain responses. Furthermore, spontaneous pain and mechanical allodynia, but not thermal hyperalgesia induced by BmK I, were significantly alleviated after knockdown of Nav1.6. These data strongly suggest that Nav1.6 plays an indispensable role in the peripheral pain hypersensitivity induced by BmK I.

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A New Marker for Regulatory Macrophages.

No abstract available

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Socio-environmental risk factors for medically-attended agricultural injuries in Wisconsin dairy farmers

Publication date: July 2017
Source:Injury, Volume 48, Issue 7
Author(s): Jeffrey J. VanWormer, Kathrine L. Barnes, Stephen C. Waring, Matthew C. Keifer
BackgroundAccidents are common in the agricultural industry, particularly among dairy farmers. How said farmers get hurt is well established, but far less is known about how distal, socio-environmental factors influence injuries. This study examined associations between medically-attended agricultural injuries and: (1) personal sociodemographic characteristics, and (2) farm environment features and general safety practices.MethodsA cross-sectional survey was implemented with linked data from electronic health records on prior agricultural injuries that occurred between 01/01/2002–12/31/2015. The sample included adult dairy producers who resided in north-central Wisconsin (USA) and were medically-homed to the Marshfield Clinic Health System. Multiple logistic regression was used to analyze associations between socio-environmental characteristics and agricultural injuries.ResultsThere were 620 dairy farmers in the analytical sample, with 50 medically-attended agricultural injuries observed during the 14-year study time period (5.7 injuries per 1000 dairy farmers per year). In the multivariable model, the odds of agricultural injury were significantly greater among farmers who have private individually-purchased health insurance (OR=4.25; 95% CI: 1.31, 13.84), do not live at their dairy operation (OR=2.91; CI: 1.27, 6.67), and do not provide safety training to their workers (OR=4.27; CI: 1.00, 18.21).ConclusionsDairy farmers in this analysis who did not live at their dairy operation, did not provide safety training to all their workers, or had individually-purchased health insurance were more apt to get injured, but more research is needed to confirm these findings in prospectively designed studies. How these factors can be directly addressed or otherwise used to better focus farm injury prevention initiatives should also be explored.



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The learning curve with a new cephalomedullary femoral nail

Publication date: July 2017
Source:Injury, Volume 48, Issue 7
Author(s): N.F. Fine, S.A. Sexton, D.H. Williams
IntroductionThe Cephalomedullary Nail (CMN) (Zimmer, Warsaw) was introduced in 2010 as part of a multicenter trial to evaluate its performance. At one year the CMN had results in keeping with other intramedullary devices with good union rates and low complication rates. In the second and third years of use an increased rate of implant failure was observed, towards the higher end of the 1–5% nail breakage rate seen in other studies. This study aims to evaluate if there any common features in this cohort of patients.Materials and methodsThis is a retrospective cohort study looking at patients who underwent femoral fracture fixation using the cephalomedullary nail between January 2011 and June 2014. The primary outcome measure was implant failure; secondary outcomes were; fracture reduction and bisphosphonate use.Results201 patients were included (135 female, 66 male) with an average age of 81 years. Ten (5%) nail breakages occurred in the study period at an average of 39 weeks (24–92); 9 were 125° nails 1 was a 130° nail and all fractured at the lag screw junction.ConclusionsImplant failure is a recognised complication of intramedullary nailing in cases of non-union. The increased rate of implant failure in our department required a change to a 130° CMN implant and a 3.2mm diameter guide wire for placement of the lag screw. We continue to monitor this difficult group of patients very closely.



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Lactated Ringer-based storage solutions are equally well suited for the storage of fresh osteochondral allografts as cell culture medium-based storage solutions

Publication date: July 2017
Source:Injury, Volume 48, Issue 7
Author(s): Afif Harb, Alexander von Horn, Kornelia Gocalek, Luisa Marilena Schäck, Jan Clausen, Christian Krettek, Sandra Noack, Claudia Neunaber
BackgroundDue to the rising interest in Europe to treat large cartilage defects with osteochondrale allografts, research aims to find a suitable solution for long-term storage of osteochondral allografts. This is further encouraged by the fact that legal restrictions currently limit the use of the ingredients from animal or human sources that are being used in other regions of the world (e.g. in the USA). Therefore, the aim of this study was A) to analyze if a Lactated Ringer (LR) based solution is as efficient as a Dulbecco modified Eagle's minimal essential medium (DMEM) in maintaining chondrocyte viability and B) at which storage temperature (4°C vs. 37°C) chondrocyte survival of the osteochondral allograft is optimally sustained.Methods300 cartilage grafts were collected from knees of ten one year‐old Black Head German Sheep. The grafts were stored in four different storage solutions (one of them DMEM-based, the other three based on Lactated Ringer Solution), at two different temperatures (4 and 37°C) for 14 and 56days. At both points in time, chondrocyte survival as well as death rate, Glycosaminoglycan (GAG) content, and Hydroxyproline (HP) concentration were measured and compared between the grafts stored in the different solutions and at the different temperatures.ResultsIndependent of the storage solutions tested, chondrocyte survival rates were higher when stored at 4°C compared to storage at 37°C both after short-term (14days) and long-term storage (56days). At no point in time did the DMEM-based solution show a superior chondrocyte survival compared to lactated Ringer based solution. GAG and HP content were comparable across all time points, temperatures and solutions.ConclusionLR based solutions that contain only substances that are approved in Germany may be just as efficient for storing grafts as the USA DMEM-based solution gold standard. Moreover, in the present experiment storage of osteochondral allografts at 4°C was superior to storage at 37°C.



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Editorial Board/Publication Information

Publication date: July 2017
Source:Injury, Volume 48, Issue 7





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Post wall fixation by lag screw only in associated both column fractures with posterior wall involvement

Publication date: July 2017
Source:Injury, Volume 48, Issue 7
Author(s): Hu Wang, Kandemir Utku, Yan Zhuang, Kun Zhang, Ya-hui Fu, Xing Wei, Peng-fei Wang, Yu-xuan Cong, Jin-lai Lei, Bin-fei Zhang
PurposeTo evaluate the quality of reduction, clinical outcomes and complications of associated both column acetabular fractures with posterior wall involvement that are treated through single ilioinguinal approach and fixation of posterior wall by lag screws only.MethodsWe conducted a retrospective review involving ninety-nine consecutive patients with associated both column fractures of acetabulum treated through single ilioinguinal approach. Patients were divided into two groups. The first group consisted of 35 patients presented with both column fractures with posterior wall involvement that fixation performed with lag screws. This group was compared to a second group of 64 patients with both column fractures without posterior wall involvement. The quality of reduction was assessed using criteria described by Matta. The size of posterior wall fragment was measured. Functional outcome was evaluated using Modified Postel Merle D'Aubigne score. Radiographs at the latest follow up were analyzed for arthritis (Kellgren-Lawrence classification), and femoral head avascular necrosis (Ficat/Arlet classification).ResultsThe study showed no significant differences in all preoperative variables (P>0.05). While intraoperative blood loss and operative time in group 1 were increased compared to group 2, the difference was not statistically significant (P>0.05). The height, relative depth and peripheral length of posterior wall respectively were 27.8±2.5mm (range: 24–35mm), 71.5±5.4% (range: 65–88%), 23.0±2.3mm (range: 17–28mm). The mean posterior wall fracture displacement is 5.0±3.2mm (range: 0–11mm). There was no difference regarding the quality of reduction between the two groups (P>0.05). The excellent to good clinical outcome was around 71.4% in the group 1 versus 73.4% in the group 2 at the final follow-up, this difference was not statistically significant (P>0.05). There was no difference in rate of complications between the two groups (P>0.05).ConclusionsLag screws fixation of posterior wall through single ilioinguinal approach in associated both column fractures of acetabulum is a safe and effective method. Our results shown that the presence of posterior wall fracture in cases of associated both column fractures does not compromise the clinical outcomes.



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Factors affecting fracture location in atypical femoral fractures: A cross-sectional study with 147 patients

Publication date: July 2017
Source:Injury, Volume 48, Issue 7
Author(s): Ji Wan Kim, Jung Jae Kim, Young-Soo Byun, Oog-Jin Shon, Hyoung Keun Oh, Ki Chul Park, Joon-Woo Kim, Chang-Wug Oh
IntroductionMany studies have tried to determine the characteristics of atypical femoral fractures (AFFs) through age-, sex-, and ethnicity-matched comparison with non-AFFs. However, we hypothesized that diaphyseal AFFs would have characteristics different from those of subtrochanteric AFFs. The aim of this study was to evaluate the clinical features of diaphyseal/subtrochanteric AFFs and determine the factors related to fracture location.Patients and methodsOne hundred forty-seven patients with AFF were enrolled, 114 patients (78%) had a history of bisphosphonate use. Forty-nine patients (33%) had bilateral lesion, and 35% of patients had thigh pain. Patients were divided into two groups according to fracture location: 52 patients (35.4%) with subtrochanteric AFF and 95 patients (64.6%) with diaphyseal AFF. The patient demographics and fracture characteristics of the two groups were compared. Multivariate logistic regression analysis was used to adjust for variables related to fracture location.ResultsThe patients in the diaphyseal AFFs group were older and had lower BMI, lower BMD, and larger lateral and anterior bowing. Multivariate analysis revealed that age greater than 65 years and low BMD were related with diaphyseal location. With greater lateral bowing angle, the AFF location was moved from the subtrochanteric area to the diaphyseal area.ConclusionThis study demonstrated that patients with diaphyseal AFFs had different characteristics compared with those with subtrochanteric AFFs.



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Modified dynamic hip screw loaded with autologous bone graft for treating Pauwels type-3 vertical femoral neck fractures

Publication date: July 2017
Source:Injury, Volume 48, Issue 7
Author(s): Deqing Luo, Weitao Zou, Yijiao He, Hang Xian, Lei Wang, Jiazuo Shen, Kejian Lian, Dasheng Lin
IntroductionManagement of Pauwels type-3 vertical femoral neck fractures has been a challenging clinical problem as they experience high shear forces and thus a greater risk of treatment failure. There is no apparent consensus on the optimal implant type for these injuries. We developed a modified dynamic hip screw (DHS), which was designed to a cage in the lag screw, loaded with autologous bone graft for the treatment of Pauwels type-3 vertical femoral neck fractures.MethodsBetween February 2010 and January 2012, 17 consecutive patients with Pauwels type-3 vertical femoral neck fractures were treated with the modified DHS loaded with autologous bone graft. All patients were followed up for a minimum of 24 months (range, 24–36 months). Surgical details, operative and postoperative complications, the rates of nonunion and osteonecrosis and the Harris hip score were evaluated.ResultsThere were thirteen men and four women with a mean age of 37.2 years (range, 27–52 years). There were no intraoperative complications related to this technology. All fractures healed within 14.1 weeks (range, 12 to 20 weeks). One patient required total hip replacement because of avascular necrosis of the femoral head at 27 months after surgery. According to the Harris hip score, eleven patients (64.7%) had excellent results, four (23.5%) had good results, one (5.9%) had moderate and one (5.9%) had poor result.ConclusionsThe modified DHS loaded with autologous bone graft appears to be a reliable implant for the treatment of Pauwels type-3 vertical femoral neck fractures with fewer complications.



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