Publication date: Available online 3 December 2015
Source:Critical Reviews in Oncology/Hematology
Author(s): A. Mirabile, M. Airoldi, C. Ripamonti, A. Bolner, B. Murphy, E. Russi, G. Numico, L. Licitra, P. Bossi
Pain in head and neck cancer represents a major issue, before, during and after the oncological treatments.The most frequent cause of pain is chemo/radiation related oral mucositis, which involves 80% of the patients and worsens their quality of life inhibiting speaking, eating, drinking or swallowing and sometimes reducing the treatment compliance, the maximum dose intensity and thus the potential efficacy of treatment. Nevertheless pain is still often under estimated and undertreated. An Italian multidisciplinary group of head and neck cancer specialists met with the aim of reaching a consensus on pain management in this setting. The Delphi Appropriateness method was used for the consensus. External expert reviewers evaluated the final statements. The paper contains 30 consensus-reached statements about pain management in HNC patients and offers a review of recent literature in these topics.
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Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Πέμπτη 3 Δεκεμβρίου 2015
Pain management in head and neck cancer patients undergoing chemo-radiotherapy: clinical practical recommendations.
An approach to the diagnosis of spindle cell lesions of the breast
Although most breast spindle cell lesions (BSCLs) are rare, they constitute a wide spectrum of diseases, ranging from reactive processes to aggressive malignant tumours. Despite their varied histogenesis and behaviour, some lesions show an overlap of morphological features, making accurate diagnosis a challenging task, particularly in needle core biopsies. Clinical history and immunohistochemistry can help in making a correct diagnosis in morphologically challenging cases. To make an accurate diagnosis, it is important to maintain a wide differential diagnosis and be familiar with the diverse morphological appearances of these different entities. BSCLs can generally be classified into bland-looking and malignant-looking categories. In the former, the commonest diagnosis is scarring. However, it is important to distinguish low-grade spindle cell metaplastic breast carcinoma from other benign entities, as the management is clearly different. In the malignant category, it is important to differentiate metaplastic carcinoma from other malignant primary and metastatic malignant spindle cell tumours of the breast, such as malignant phyllodes tumour, angiosarcoma, and melanoma. This review focuses on the classification and histological and molecular diagnosis of various BSCLs, with an emphasis on the diagnostic approach, including in core biopsies.
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Sentinel lymph nodes for breast carcinoma: an update on current practice
Sentinel lymph node (SLN) biopsy has been established as the standard of care for axillary staging in patients with invasive breast carcinoma and clinically negative lymph nodes (cN0). Historically, all patients with a positive SLN underwent axillary lymph node dissection (ALND). The ACOSOG Z0011 trial showed that women with T1–T2 disease and cN0 who undergo breast-conserving surgery and whole-breast radiotherapy can safely avoid ALND. The main goal of SLN examination should be to detect all macrometastases (>2 mm). Gross sectioning of SLNs at 2-mm intervals and microscopic examination of one haematoxylin and eosin-stained section from each SLN block is the preferred method for pathological evaluation of SLNs. The role and timing of SLN biopsy for patients who have received neoadjuvant chemotherapy is controversial, and continues to be explored in clinical trials. SLN biopsies from patients with invasive breast carcinoma who have received neoadjuvant chemotherapy pose particular challenges for pathologists.
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The cancer genetics and pathology of male breast cancer
Male breast cancer (MBC) is an uncommon and poorly understood disease. Recent molecular studies have shown important differences from female breast cancer which are likely to influence treatment strategies from the current female-based management towards a more tailored approach. Significantly more MBCs than female breast cancers arise with an underlying germline cancer predisposition, and display a vastly different penetrance compared with females. Furthermore, the genophenotypical association of basal-like cancer with BRCA1 present in female breast cancer is not observed in male breast cancer. Differences in somatic changes between male and female breast cancer have also been reported, with particular enrichment of PIK3CA mutations and a paucity of TP53 mutations. In general, chromosomal-based changes, in particular regions of gains, are seen more frequently in male than female breast cancer and methylation is seen less frequently. Clinically, several molecular subtypes with prognostic relevance have been described, including chromosomal complex high and methylation high groups, and subgroups with profiling signatures pertaining to epithelial mesenchymal transition and hormonal therapy insensitivity. As with female breast cancer, attention to male specific multicentre trials based on the individual characteristics are needed, together with establishment of reliable preclinical models to understand more clearly the pathogenesis of male breast cancer and improve the general poor outcome of this disease.
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Markers of metastatic carcinoma of breast origin
This review summarizes the three major breast-associated markers that can be of assistance in evaluating metastatic carcinomas for which a breast primary diagnosis is entertained. These markers include gross cystic disease fluid protein-15 (GCDFP-15), mammaglobin, and GATA3. The first two are cytoplasmic markers that show comparable sensitivities for breast cancer, although relatively few of the published studies have employed the same antibodies against the target molecule, making direct comparisons challenging. GATA3 is a nuclear transcription factor that shows superior sensitivity to GCDFP-15 and mammaglobin. However, the specificity of GATA3 can pose challenges, inasmuch as carcinomas of the bladder and other sites can show significant levels of positivity. Determination of the optimal panel of antibodies employed in a given clinical setting will thus depend on the non-breast tumours included in the differential diagnosis.
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Phyllodes tumours of the breast: a consensus review
Phyllodes tumours constitute an uncommon but complex group of mammary fibroepithelial lesions. Accurate and reproducible grading of these tumours has long been challenging, owing to the need to assess multiple stratified histological parameters, which may be weighted differently by individual pathologists. Distinction of benign phyllodes tumours from cellular fibroadenomas is fraught with difficulty, due to overlapping microscopic features. Similarly, separation of the malignant phyllodes tumour from spindle cell metaplastic carcinoma and primary breast sarcoma can be problematic. Phyllodes tumours are treated by surgical excision. However, there is no consensus on the definition of an appropriate surgical margin to ensure completeness of excision and reduction of recurrence risk. Interpretive subjectivity, overlapping histological diagnostic criteria, suboptimal correlation between histological classification and clinical behaviour and the lack of robust molecular predictors of outcome make further investigation of the pathogenesis of these fascinating tumours a matter of active research. This review consolidates the current understanding of their pathobiology and clinical behaviour, and includes proposals for a rational approach to the classification and management of phyllodes tumours.
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Biomarker assessment and molecular testing for prognostication in breast cancer
Current treatment of breast cancer incorporates clinical, pathological and molecular data. Oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) define prognosis and identify tumours for targeted therapy, and remain the sole established single-molecule biomarkers defining the minimum breast cancer pathology data set. Ki67 remains one of the most promising yet controversial biomarkers in breast cancer, implemented routinely in some, but not all, pathology departments. Beyond the single-molecule biomarkers, a host of multigene expression tests have been developed to interrogate the driver pathways and biology of individual breast cancers to predict clinical outcome more accurately. A minority of these assays have entered into clinical practice. This review focuses on the established biomarkers of ER, PR and HER2, the controversial but clinically implemented biomarker Ki67 and the currently marketed gene expression signatures.
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E-cadherin immunohistochemistry in breast pathology: uses and pitfalls
E-cadherin immunohistochemistry is used commonly in surgical pathology practice to help distinguish lobular carcinoma in situ from ductal carcinoma in situ and invasive lobular carcinoma from invasive ductal carcinoma in histologically problematic or indeterminate cases. However, the interpretation of E-cadherin immunostains is not always straightforward. Failure to recognize the pitfalls and limitations of E-cadherin immunostains can lead to an erroneous diagnosis which may result in inappropriate patient management, particularly for patients with in-situ lesions. In this paper we review the uses and, particularly, the pitfalls in the interpretation of E-cadherin immunostains in distinguishing lobular from ductal lesions of the breast.
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Pathological criteria and practical issues in papillary lesions of the breast – a review
Papillary lesions of the breast include a broad spectrum of lesions, ranging from benign papilloma, papilloma with atypical ductal hyperplasia (ADH) or ductal carcinoma in situ (DCIS) to papillary carcinoma. The accurate diagnosis of mammary papillary lesions is a challenge for pathologists, owing to the overlapping features among these lesions. In this review, some of the diagnostic criteria of papillary lesions are discussed, with special emphasis on some key morphological features, namely fibrovascular cores, epithelial proliferation in a solid pattern, intraductal papilloma complicated by ADH or DCIS, and invasion and its mimics. The roles of immunohistochemistry, and the interpretation of myoepithelial cell markers, hormone receptors, and high molecular weight cytokeratin, are addressed. Finally, novel biomarkers and genetic aberrations in papillary lesions are summarized.
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Breast cancer stem cells: are we ready to go from bench to bedside?
Since the discovery of breast cancer stem cells (BCSCs) more than 10 years ago, a body of exciting research has developed. The intrinsic properties of BCSCs, including self-renewal and the ability to give rise to heterogeneous progeny, make BCSCs a likely source of tumour initiation, heterogeneity, progression and metastasis. BCSCs are also inherently resistant to conventional therapies and are therefore thought to contribute to disease recurrence. In this review, we will focus on both the challenges and recent advances in the characterization of BCSCs with respect to phenotype, molecular signature and their role in the behaviour of the different molecular subtypes of breast cancer. Of most importance is our ability to translate our growing knowledge base into the development of targeted therapies with the goal of reducing adverse outcomes in breast cancer patients.
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Ductal carcinoma in situ – update on risk assessment and management
Ductal carcinoma in situ (DCIS) accounts for ~20–25% of breast cancers. While DCIS is not life-threatening, it may progress to invasive carcinoma over time, and treatment intended to prevent invasive progression may itself cause significant morbidity. Accurate risk assessment is therefore necessary to avoid over- or undertreatment of an individual patient. In this review we will outline the evidence for current management of DCIS, discuss approaches to DCIS risk assessment and challenges facing identification of novel DCIS biomarkers.
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Recommendations for excision following core needle biopsy of the breast: a contemporary evaluation of the literature
Pathologists frequently encounter non-malignant histological findings in percutaneous core needle biopsies (CNBs). Standards for the management of patients with lesions such as atypical ductal hyperplasia, atypical lobular hyperplasia, and lobular carcinoma in situ, as well as other benign lesions, are not well defined, and recommendations for surgical biopsy or continued clinical and radiological follow-up are inconsistent. The frequency with which these lesions are 'upgraded' to carcinoma in excision specimens is widely variable in the literature. Many CNB studies lack careful radiological–pathological correlation, clear criteria for excision, and clinical follow-up for patients on whom excision was not performed. This review of the recent literature emphasizes studies with radiological–pathological correlation, with the goal of developing a contemporary, evidence-based approach to the management of non-malignant lesions of the breast diagnosed on CNB. The data supporting an emerging consensus on which lesions may not require excision are highlighted. The management of non-malignant lesions diagnosed on magnetic resonance imaging-guided CNB is also discussed.
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Alternative treatment of restless legs syndrome: an overview of the evidence for mind–body interventions, lifestyle interventions, and neutraceuticals
Publication date: January 2016
Source:Sleep Medicine, Volume 17
Author(s): Danny Bega, Roneil Malkani
Conventional pharmacologic treatment of restless legs syndrome (RLS) may be limited in some people. Up to 65% of patients with RLS regularly use alternative practices for symptom relief. We reviewed the current clinical evidence, and we proposed physiologic basis for various alternative practices for RLS including mind–body interventions (conventional exercise, yoga, and acupuncture), non-pharmacologic lifestyle interventions (pneumatic compression devices [PCDs], light therapy, and cognitive–behavioral therapy [CBT]), and neutraceuticals (vitamins, valerian, and Chinese herbs). Based on the available evidence, regular physical activity should be recommended for the treatment of RLS symptoms. Oral iron supplementation should be considered for people with RLS who have low ferritin levels, although criteria to identify probable responders, and optimal formulations and durations of treatment are needed. Supplementation for low levels of vitamins E, C, and D could be considered, although evidence specifically in RLS is limited, and it is unclear if levels should routinely be checked in patients with RLS. Insufficient evidence exists for yoga, acupuncture, PCDs, near-infrared light therapy, CBT, valerian, or Chinese herbs, but preliminary studies on each of these suggest that high-quality randomized controlled trials may be warranted to support and verify the data presented.
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Significant association between systolic and diastolic blood pressure elevations and periodic limb movements in patients with idiopathic restless legs syndrome
Publication date: January 2016
Source:Sleep Medicine, Volume 17
Author(s): Werner Cassel, Karl Kesper, Axel Bauer, Frank Grieger, Erwin Schollmayer, Lars Joeres, Claudia Trenkwalder
ObjectiveA new and unique methodology was developed to evaluate the association between periodic limb movements (PLMs) and nocturnal blood pressure (BP) excursions in patients with restless legs syndrome (RLS).MethodsAll data were collected at baseline of the ENCORE (Effects of Neupro on Cardiovascular Observations in Patients with Restless Legs Syndrome) study, a placebo-controlled polysomnographic study of rotigotine in patients with idiopathic RLS. Continuous beat-by-beat BP and heart rate assessments were performed during a full night of polysomnography. All BP elevations occurring with and without PLMs were systematically identified and analyzed.ResultsPatients (n = 89) had a mean total of 508.9 ± 405.7 PLMs, 788.4 ± 261.9 systolic BP elevations, and 349.7 ± 242.9 diastolic BP elevations during the night. Higher time-adjusted frequencies of systolic BP elevations [mean difference (95% confidence interval, CI): 543.0 (487.2, I); p < 0.0001] and diastolic BP elevations (205.8 (169.3, I); p < 0.0001) were observed with PLMs than without PLMs. A peak in the frequency of PLM onset coincided with BP elevation onset.ConclusionOur methodology allowed the first evaluation of the total number of nocturnal PLM-associated BP elevations occurring in patients with RLS. Our data clearly indicate an interdependence between BP elevations and PLMs, and they have clinical relevance as BP variability is a potential cardiovascular risk factor.
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LCA-based indicators for recycling: a case study on plastic waste treatment in Flanders
The last decades, waste management strategies are shifting from waste disposal to recycling, considering waste as resources. To quantitatively monitor the progress in this transition, a wide range of indicators has been developed. One of these indicators developed by the European Commission is the recyclability benefit rate (RBR), defined as the ratio of the environmental benefits that can be achieved from recycling over the environmental losses related to virgin production and disposal. These environmental benefits and losses are expressed in terms of environmental impacts obtained through Life Cycle Assessment (LCA). To assess the usefulness of this indicator, we applied it on two cases of plastic waste treatment in Flanders, Belgium: closed-loop recycling (case A) and open-loop recycling (case B). The environmental impact of resource consumption is quantified as the Cumulative Exergy Extraction of the Natural Environment (CEENE). Case A considers plastic waste from electronic appliances. The recycled plastic is of good quality and can be used in products similar to the original product. The average RBR of case A is 58%. Case B considers plastic household waste. The recycled plastic is of lower quality, making it only useable for other products, e.g. street benches, in which it substitutes other materials, e.g. wood. Here, the indicator had to be further adapted for open-loop recycling. The outcome is an average RBR of 13%. This value is rather low because more mass of the recycled plastic is needed to meet the same quality requirements as the substituted material. By further developing the indicator for open-loop recycling, it was possible to quantify the environmental sustainability of plastic recycling in Flanders. These quantitative results may be useful for policy makers, e.g. in legislation on subsidies and levies.
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Cholinergic deafferentation of the hippocampus causes non-temporally graded retrograde amnesia in an odor discrimination task
Source:Behavioural Brain Research, Volume 299
Author(s): Jenny R. Köppen, Sarah L. Stuebing, Megan L. Sieg, Ashley A. Blackwell, Philip A. Blankenship, Joseph L. Cheatwood, Douglas G. Wallace
Dementia of the Alzheimer's type (DAT) is a neurodegenerative disorder marked by loss of hippocampal cholinergic tone and significant memory impairments, specifically for memories acquired prior to disease onset. The nature of this relationship, however, remains debated. The current study used the string pulling task to evaluate the temporal effects of odor discrimination learning in animals with selective cholinergic lesions to determine the role of the septohippocampal cholinergic system in mnemonic function. Rats with 192-IgG-Saporin lesions to the medial septum had a higher number of correct responses in the reversal training when compared to sham rats, suggesting an inability to retrieve the previously learned discrimination; however, no temporal gradient was observed. Furthermore, there were no group differences when learning a novel odor discrimination, demonstrating the ability for all rats to form new memories. These results establish a role for the cholinergic medial septum projections in long-term memory retrieval. The current study provides a behavioral assessment technique to investigate factors that influence mnemonic deficits associated with rodent models of DAT.
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Integration of trauma and rehabilitation services is the answer to more cost-effective care
Abstract
Background
The pathway from acute trauma care to inpatient rehabilitation has not been previously studied in New South Wales (NSW), Australia. This study aimed to examine the outcomes of patients transferred from a trauma service to its 'in-house' rehabilitation service (Group A) compared with outcomes of patients transferred from a designated trauma centre to an external rehabilitation service (Group B). This is carried out to identify any inefficiencies, delays and opportunities for improvement.
Methods
This is a retrospective cohort study using linked registry data. This study included all patients admitted after a motor vehicle collision to trauma services in NSW over the period of 2009–2012, who required inpatient rehabilitation. Those requiring specialized brain or spinal injury rehabilitation or those who went to private rehabilitation units were excluded.
Results
There were 249 patients in this cohort with majority (59%) in Group A and the remainder in Group B. There was no significant difference between the age of the patients, injury severity or acute length of stay (LOS) between the two groups. Admission and discharge functional independence measure scores were also similar between the two groups. There was a significant difference in the LOS in rehabilitation (30 days for Group A compared with 40 days in Group B, P = 0.02).
Conclusions
Transferring patients to an external rehabilitation service from a designated trauma service is less efficient than providing the same care by the 'in-house' rehabilitation service. There may be opportunities to improve the efficiency of trauma management and reduce costs.
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Routine multidisciplinary cerebrovascular meetings do not reduce aneurysm clipping case load: a cohort study
Abstract
Background
Structured multidisciplinary care is an increasingly popular tool in the management of many complex disease processes; however, there is little published data regarding the effects of such a process on management of intracranial aneurysms and neurosurgical case loads. There is some resistance in the neurosurgical community to routine involvement of interventional neuroradiologists in the care of patients with intracranial aneurysms due to concerns regarding maintenance of neurosurgical case loads and training capabilities. At our tertiary Australian hospital, we have implemented a weekly multidisciplinary cerebrovascular meeting (MDCVM) facilitating routine discussion of these cases between neurosurgeons and interventional neuroradiologists.
Methods
This study identified management modalities for ruptured and unruptured cerebral aneurysms diagnosed at our centre for a 2-year period before and after the implementation of MDCVM culminating in a 4-year retrospective cohort study. The pre- and post-MDCVM cohorts were well matched for demographics with 162 and 224 patients, respectively.
Results
There is no significant difference in percentage or absolute numbers of endovascular or surgical cases in the pre-MDCVM (103; 73.0% versus 38; 27.0%, respectively) or post-MDCVM cohorts (105; 79.5% versus 27; 20.5%, respectively), reflecting a maintained surgical case load after the implementation of MDCVM (P = 0.21). There were no significant differences in any confounding variables including age, sex, aneurysm size/location, Fisher or World Federation of Neurosurgical Societies (WFNS) grade.
Conclusions
Implementation of MDCVM did not impact on active management case loads with consistent numbers and percentages for both endovascular and microsurgical management.
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Short-term outcomes of local infiltration anaesthetic in total knee arthroplasty: a randomized controlled double-blinded controlled trial
Abstract
Background
The primary objective of the study was to determine if local infiltration anaesthetic (LIA) reduced total length of hospital stay in total knee arthroplasty (TKA) patients. The study also examined whether LIA improves early pain management, patient satisfaction and range of motion in TKA patients.
Methods
We conducted a randomized controlled double-blinded study. Fifty patients undergoing TKA were randomized to receive either placebo or LIA at the time of surgery and on the first day post-operatively. Pain scores, level of satisfaction and range of motion were recorded preoperatively and post-operatively.
Results
There was no statistical difference between the groups for length of stay, post-operative pain scores, satisfaction scores or range of motion 6 weeks post-operatively.
Conclusion
This randomized double-blinded trial did not demonstrate a decrease in pain or reduction of length of stay due to local infiltration analgesia.
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Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome
New England Journal of Medicine, Volume 373, Issue 23, Page 2247-2257, December 2015.
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Pylephlebitis as a Complication of Diverticulitis
New England Journal of Medicine, Volume 373, Issue 23, Page 2270-2270, December 2015.
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Retraction: Ahimastos AA, Dart AM, Kingwell BA. Angiotensin II blockade in Marfan’s syndrome. N Engl J Med 2008;359:1732
New England Journal of Medicine, Volume 373, Issue 23, Page 2280-2280, December 2015.
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Ending the HIV–AIDS Pandemic — Follow the Science
New England Journal of Medicine, Volume 373, Issue 23, Page 2197-2199, December 2015.
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Tenuous Tether
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Individual Responsibility and Community Solidarity — The Swiss Health Care System
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Back to Nature
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Cardiac Complications in Patients Undergoing Major Noncardiac Surgery
New England Journal of Medicine, Volume 373, Issue 23, Page 2258-2269, December 2015.
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Tenuous Tether
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Cystine Crystals in Bone Marrow
New England Journal of Medicine, Volume 373, Issue 23, December 2015.
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Intensive Supportive Care plus Immunosuppression in IgA Nephropathy
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Prenatal Factors in Cerebral Palsy
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Estimating the Long-Term Treatment Benefits of Sacubitril–Valsartan
New England Journal of Medicine, Volume 373, Issue 23, Page 2289-2290, December 2015.
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Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome
New England Journal of Medicine, Volume 373, Issue 23, Page 2247-2257, December 2015.
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Report from Paris
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Cytomegalovirus reactivation and its clinical impact in patients with solid tumors
Abstract
Cytomegalovirus reactivation can be life threatening. However, little evidence on its incidence in solid cancers is available. Therefore our single center Cytomegalovirus polymerase chain reaction database with altogether 890 CMV positive blood serum samples of mainly hematological and oncological patients was retrospectively analyzed to examine the occurrence of Cytomegalovirus reactivation in patients with solid tumors, resulting in 107 patients tested positive for Cytomegalovirus reactivation. Seventeen patients with solid cancer and a positive CMV-PCR test were identified, of which eight patients had clinically relevant CMV disease and received prompt antiviral treatment. Five patients fully recovered, but despite prompt antiviral treatment three patients died. Among these three patients two had significant co-infections (in one case EBV and in the other case Aspergillus) indicating that that CMV reactivation was at least one factor contributing to sepsis. The patient with the EBV co-infection was treated in an adjuvant therapy setting for breast cancer and died due to Cytomegalovirus and Epstein-Barr virus associated pneumonia despite intensive therapy. The other two patients had progressive disease of an underlying pancreatic cancer at the time of CMV diagnosis. One patient died due to attendant uncontrollable Aspergillus pneumonia, the other patient most likely died independent from CMV disease because of massively progressive underlying disease.
Cytomegalovirus reactivation and disease might be underestimated in routine clinical practice. In our retrospective analysis we show that approximately 50 % of our patients suffering from solid cancers with a positive Cytomegalovirus polymerase chain reaction also had clinically relevant Cytomegalovirus disease requiring antiviral therapy.
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Preventing Foodborne Staphylococcal Disease – Hygiene Matters!
Although meat products are an important source of foodborne disease caused by Staphylococcus aureus, Kadariya et al. (2014) note that other foodstuffs such as sandwich fillings, bakery goods, salad items and dairy can also transmit this microbe. Since contamination mostly arises opportunistically from improper handling practices in the retail food chain, producers can take steps Read the rest of this article
The post Preventing Foodborne Staphylococcal Disease – Hygiene Matters! appeared first on Accelerating Science.
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Defenders of the image. Painted collectors’ cabinets and the display of display in Counter-Reformation Antwerp
This article considers the collections of painters and the invention of the typical Antwerp-genre of the gallery picture. It holds that these pictures were a 'defense of the image' and must be understood in Antwerp's Counter Reformation context, in the aftermath of the iconoclastic furies of the sixteenth century. Quintessential to both iconoclasm and the culture of collecting were issues of display and materiality. The paintings of cabinets suggest that some Antwerp artists were defenders of the image in a time when images and other man-made objects were at the forefront of intellectual debate. The gallery paintings can be related to a widespread debate on materiality that, implicitly or explicitly, extended from scholarly publications to workshops and collectors' rooms.
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'Most rare workmen': optical practitioners in early seventeenth-century Delft
A special interest in optics among various seventeenth-century painters living in the Dutch city of Delft, has intrigued (art-)historians for a long time. Equally, the impressive career of the Delft microscopist Anthony van Leeuwenhoek has been studied by many historians of science. However, it has never been investigated who, at that time, had access to the mathematical and optical knowledge necessary for the impressive achievements of these Delft practitioners. We have tried to gain insight in Delft as a 'node' of optical knowledge by following the careers of three minor local figures in early-seventeenth-century Delft. We argue that through their work, products, discussions in the vernacular and exchange of skills, rather than via learned publications, these practitioners constituted a foundation on which the later scientific and artistic achievements of other Delft citizens were built. Our Delft case demonstrates that these practitioners were not simple and isolated craftsmen; rather they were crucial components in a network of scholars, savants, painters and rich virtuosi. Decades before Vermeer made his masterworks, or Van Leeuwenhoek started his famous microscopic investigations the intellectual atmosphere and artisanal knowledge in this city centred on optical topics.
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Recombinant Resilin-Based Bioelastomers for Regenerative Medicine Applications
The outstanding elasticity, excellent resilience at high-frequency, and hydrophilic capacity of natural resilin have motivated investigations of recombinant resilin-based biomaterials as a new class of bio-elastomers in the engineering of mechanically active tissues. Accordingly, here the comprehensive characterization of modular resilin-like polypeptide (RLP) hydrogels is presented and their suitability as a novel biomaterial for in vivo applications is introduced. Oscillatory rheology confirmed that a full suite of the RLPs can be rapidly cross-linked upon addition of the tris(hydroxymethyl phosphine) cross-linker, achieving similar in situ shear storage moduli (20 k ± 3.5 Pa) across various material compositions. Uniaxial stress relaxation tensile testing of hydrated RLP hydrogels under cyclic loading and unloading showed negligible stress reduction and hysteresis, superior reversible extensibility, and high resilience with Young's moduli of 30 ± 7.4 kPa. RLP hydrogels containing MMP-sensitive domains are susceptible to enzymatic degradation by matrix metalloproteinase-1 (MMP-1). Cell culture studies revealed that RLP-based hydrogels supported the attachment and spreading (2D) of human mesenchymal stem cells and did not activate cultured macrophages. Subcutaneous transplantation of RLP hydrogels in a rat model, which to our knowledge is the first such reported in vivo analysis of RLP-based hydrogels, illustrated that these materials do not elicit a significant inflammatory response, suggesting their potential as materials for tissue engineering applications with targets of mechanically demanding tissues such as vocal fold and cardiovascular tissues.
Resilin-like polypeptide-based hydrogels, a new class of elastomeric materials with modular design features, exhibit excellent mechanical properties, tunable enzymatic-mediated biodegradation, biological function as well as promising in vitro cytocompatibility and in vivo biocompatibility, demonstrating their potential in the engineering of mechanically active tissues.
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Periodic Nanoneedle and Buffer Zones Constructed on a Titanium Surface Promote Osteogenic Differentiation and Bone Calcification In Vivo
Rapid and effective bone mineralization at the bone/implant interface is required for successful orthopedic and dental implants. In this study, two periodic microscale functionalized zones on titanium (MZT) are created, namely, nanoneedle zones and buffer zones. The aim of this design is to provide spatially regulated topographical cues on titanium to enhance the efficacy of bone regeneration. This goal is achieved using a versatile and effective technique in which nanoneedle structures are hydrothermally constructed on the surface of titanium sheets, after which selective laser irradiation is used to construct buffer zones. The zonal structures of the MZT overcome the suppressive effect of the nanoneedle film on osteoblasts. Additionally, the MZT exhibits zone-selective apatite deposition and protein adsorption. The accelerated in vitro osteoblast differentiation and nodule deposition on the MZT are confirmed. Elemental analysis of the bone nodules formed by the osteoblasts growing on the titanium and MZT demonstrates they have different compositions. Histological and scanning electron microscope analysis of the bone formation on in vivo implants shows that this process is also enhanced by the MZT implant. The concept of constructing functionalized zones on titanium implant could facilitate future research on improving the design of orthopedic and dental implant surfaces.
The effects of constructing functionalized microscale zones on titanium bone implants (MZT) on osteogenesis are presented. The periodic nanoneedle zones promote protein adsorption and apatite deposition. The buffer zones of MZT are constructed to stimulate cell proliferation and provide hierarchical topographical cues to promote osteogenic differentiation at implants surface.
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Peripheral NMDA Receptors Mediate Antidromic Nerve Stimulation-Induced Tactile Hypersensitivity in the Rat
We investigated the role of peripheral NMDA receptors (NMDARs) in antidromic nerve stimulation-induced tactile hypersensitivity outside the skin area innervated by stimulated nerve. Tetanic electrical stimulation (ES) of the decentralized L5 spinal nerve, which induced enlargement of plasma extravasation, resulted in tactile hypersensitivity in the L4 plantar dermatome of the hind-paw. When intraplantar (i.pl.) injection was administered into the L4 dermatome before ES, NMDAR and group-I metabotropic Glu receptor (mGluR) antagonists and group-II mGluR agonist but not AMPA/kainate receptor antagonist prevented ES-induced hypersensitivity. I.pl. injection of PKA or PKC inhibitors also prevented ES-induced hypersensitivity. When the same injections were administered after establishment of ES-induced hypersensitivity, hypersensitivity was partially reduced by NMDAR antagonist only. In naïve animals, i.pl. Glu injection into the L4 dermatome induced tactile hypersensitivity, which was blocked by NMDAR antagonist and PKA and PKC inhibitors. These results suggest that the peripheral release of Glu, induced by antidromic nerve stimulation, leads to the expansion of tactile hypersensitive skin probably via nociceptor sensitization spread due to the diffusion of Glu into the skin near the release site. In addition, intracellular PKA- and PKC-dependent mechanisms mediated mainly by NMDAR activation are involved in Glu-induced nociceptor sensitization and subsequent hypersensitivity.
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Information for Readers
Publication date: December 2015
Source:Annals of Allergy, Asthma & Immunology, Volume 115, Issue 6
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Instructions for Authors
Publication date: December 2015
Source:Annals of Allergy, Asthma & Immunology, Volume 115, Issue 6
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Developing Costimulatory Molecules for Immunotherapy of Diseases
Publication date: December 2015
Source:Annals of Allergy, Asthma & Immunology, Volume 115, Issue 6
Author(s): Fred H. Hsieh
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Table of Contents
Publication date: December 2015
Source:Annals of Allergy, Asthma & Immunology, Volume 115, Issue 6
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Editorial Board
Publication date: December 2015
Source:Annals of Allergy, Asthma & Immunology, Volume 115, Issue 6
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Allergen of the Month—Japanese Maple
Publication date: December 2015
Source:Annals of Allergy, Asthma & Immunology, Volume 115, Issue 6
Author(s): Richard W. Weber
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Bronchial thermoplasty: a review of the evidence
Publication date: Available online 2 December 2015
Source:Annals of Allergy, Asthma & Immunology
Author(s): Chelle Pope Wilhelm, Bradley E. Chipps
ObjectiveTo provide a review of the literature regarding bronchial thermoplasty in the treatment of asthma.Data SourcesPubMed was searched without time limitations using the key term bronchial thermoplasty alone and in combination with the key terms asthma and treatment of asthma. Other key terms included cost-effectiveness and bronchial thermoplasty, cost-effectiveness and omalizumab, and epidemiology and asthma.Study SelectionQualifying articles included clinical trials performed with bronchial thermoplasty and review articles outlining the procedure of bronchial thermoplasty.ResultsThree predominant clinical trials investigated bronchial thermoplasty as a treatment of asthma, with only 1 of these being placebo-controlled with a sham procedure. Two of these clinical trials had follow-up data published 5 years after bronchial thermoplasty. The efficacy of bronchial thermoplasty is promising for patients with asthma whose symptoms are not controlled despite medical therapy; however, evidence from the 1 sham-controlled clinical trial has been met with some concerns because the long-term follow-up of the sham-treated group was not reported. This review of the literature indicates that the procedure is safe and effective at least 5 years after the procedure. The phenotype of asthma that can be expected to respond best to bronchial thermoplasty has not been determined.ConclusionBronchial thermoplasty could be a safe and effective option for patients with severe asthma, particularly when symptoms are uncontrolled despite medical therapy. Further investigation should be performed to determine which phenotypes of asthma would benefit from the procedure.
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The recurrently wheezing preschool child—benign or asthma in the making?
Publication date: December 2015
Source:Annals of Allergy, Asthma & Immunology, Volume 115, Issue 6
Author(s): Leonard B. Bacharier
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Long-term omalizumab therapy for refractory chronic spontaneous urticaria: a real-life experience
Publication date: December 2015
Source:Annals of Allergy, Asthma & Immunology, Volume 115, Issue 6
Author(s): Luis Felipe Ensina, Alex Eustáquio de Lacerda, Ligia Maria de Oliveira Machado, Inês Camelo-Nunes, Dirceu Solé
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Author Index to Volume 115, 2015
Publication date: December 2015
Source:Annals of Allergy, Asthma & Immunology, Volume 115, Issue 6
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Methicillin-Resistant Staphylococcus Aureus
Saudi Journal of Medicine and Medical Sciences 2016 4(1):1-1
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Methicillin-Resistant Staphylococcus Aureus in Saudi Arabia: Genotypes distribution review
Saudi Journal of Medicine and Medical Sciences 2016 4(1):2-8
Methicillin-resistant Staphylococcus aureus (MRSA) infections in hospital have obviously imposed a significant burden of morbidity and mortality, and strain on healthcare resources. Here, we review the genotype distribution of these pathogens in the Kingdom of Saudi Arabia (KSA). A PubMed literature search (until May 2014) specified 12 articles that characterized MRSA clones in KSA. Only two regions (Riyadh and Damamm) were represented in ten articles. Data from these articles showed that the pandemic Vienna/Hungarian/Brazilian clone (CC8/ST239-III) is the most frequent in Saudi regions (Riyadh and Damamm). Several other clones such as Barnim/UK-EMRSA-15 (CC22-IV), Southwest Pacific clone (ST30-IV) and European community-associated-MRSA clone (CC80-IV) have been detected in the Riyadh region. A variety of MRSA clones is beginning to circulate in Saudi hospitals. Continued collection and molecular characterization of MRSA is crucial for the effective prevention and treatment.
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Cyclic vomiting syndrome
Saudi Journal of Medicine and Medical Sciences 2016 4(1):45-46
Cyclic vomiting syndrome (CVS) consists of recurrent paroxysms of severe nausea and vomiting separated by symptom-free periods. A 12-year-old boy presented with recurrent vomiting over a period of 3 years. Episodes occurred over a period of 6 months, and the patient remained normal for next 6 months. About 8 such episodes occurred in the last 6 months. Physical and neurological examinations were normal. All routine investigations were normal. He was started on cognitive behavioral therapy and cyproheptadine and improved gradually. CVS is considered a functional brain-gut disorder and is characterized by recurrent, sudden, stereotypical, disabling, discrete episodes of intense nausea and vomiting that can last a few hours to days interspersed with varying weeks of symptom-free intervals. Integrated treatment combining pharmacological, psychotherapeutic, psycho-educational and lifestyle aspects as well as family therapy provides the best chances of successful treatment.
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Pharmaceutical care in the community pharmacies of Saudi Arabia: Present status and possibilities for improvement
Saudi Journal of Medicine and Medical Sciences 2016 4(1):9-14
Pharmaceutical care can be given in all settings: The community, hospitals, long-term care, and the clinic. However, published literature indicates that there is a substantial barrier to implementing pharmaceutical care programs in community pharmacies. This review was conducted to discover gaps and limitations in pharmaceutical care services in community pharmacies in the Kingdom of Saudi Arabia (KSA). We searched PubMed and other available scientific website databases using the following key words to retrieve the relevant articles: Community Pharmacy, Healthcare System, Pharmaceutical Care, KSA. Two authors independently screened the titles and abstracts of promising articles. They discarded irrelevant studies and retained studies, and reviews that held the promise of relevant data or information. The review revealed that only one out of the four studies conducted in KSA retrieved by the authors reported pharmaceutical care service other than dispensing. The same results were reported in other studies conducted in some developing countries. All pharmaceutical care services were reported in studies conducted in Europe. The authors came to the conclusion that in KSA, dispensing of medicines is the dominant service provided by community pharmacists and that there was very limited if not a total absence of other pharmaceutical care services.
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Sialolipoma of the superficial lobe of the parotid gland: A case report and literature review
Saudi Journal of Medicine and Medical Sciences 2016 4(1):38-41
Sialolipoma of the parotid gland is very rare. We report a case of a 38-year-old woman who presented with a painless, slowly growing, mobile lump of the parotid gland. Computed tomography revealed lipoma of the superficial lobe of the parotid gland. Superficial parotidectomy was performed with uneventful postoperative course. The histology showed sialolipoma. Review of the 25 reported cases (including our case) of parotid sialolipoma shows that this tumor is more common in the fifth decade of life, on the left side and the superficial lobe. It has a slight preference for men. Its clinical presentation mimics the standard (pure) parotid lipoma and other more common benign parotid tumors particularly pleomorphic adenoma and Warthin's tumor. Surgical excision is curative with minor complications and small recurrence rate. Histological examination is necessary to establish the diagnosis and to exclude malignancy.
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Acute back pain: A survey of primary health care physicians' awareness and knowledge of "red flag" signs
Saudi Journal of Medicine and Medical Sciences 2016 4(1):15-18
Background: The failure to detect "red flag" signs in patients presenting with acute low back pain can adversely affect the outcome of management. This can seriously affect the quality of life and productivity of the patient. Objective: The present questionnaire-based study was performed to assess the knowledge and awareness of red flag signs among primary health care physicians managing patients with acute back pain in Riyadh, Saudi Arabia. Materials and Methods: The study sample size was comprised of 80 subjects. The level of knowledge was assessed by means of a new structured self-administered questionnaire. The design of this questionnaire was based on the Agency for Health Care Research and Policy (AHCRP) guidelines for detection of red flag signs. Physicians were asked about red flag signs that indicate the presence of tumor, infection, spinal fracture, or cauda equina syndrome. Results: Sixty-eight (85% of total) physicians were aware of red flag signs. Of the 68 physicians who were aware of the red flag signs, 58 (72%) were aware of neurological deficit, 36 (45% of total) were aware of extremes of age (<10 years and >50 years), and 33 (41% of total) were aware of and routinely inquired about the history of spinal trauma, whereas only 24 (30% of total) were aware of and inquired about constitutional symptoms in their patients with acute back pain. Conclusion: Although low back pain is extremely common, knowledge and awareness of red flag signs of primary health care physicians managing patients with acute back pain in Riyadh appear to be inadequate. This indicates a lack of adherence to the international guidelines. Specific educational programs should target these deficiencies and increase awareness.
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Trivial head injury or not?
Saudi Journal of Medicine and Medical Sciences 2016 4(1):49-50
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