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- Seeking to close the loopholes in transplant touri...
- Sequential and urgent coronary artery bypass surge...
- Early effects of renal replacement therapy on card...
- Mitochondrial Metabolism: Yin and Yang for Tumor P...
- Editorial Board and Contents
- DNA damage response inhibitors: mechanisms and pot...
- Reply to the Letter to the Editor Concerning: ‘Cha...
- A Survey of Australian Dysphagia Practice Patterns
- Table of contents
- Masthead
- Table of contents
- Granuloma annulare can occur on a scar, mimicking ...
- Masthead
- Oral administration of milk-derived phospholipids ...
- Granuloma annulare can occur on a scar, mimicking ...
- Oral administration of milk-derived phospholipids ...
- Plantar keratoderma climatericum: Successful impro...
- Plantar keratoderma climatericum: Successful impro...
- Temporal remodeling of pial collaterals and functi...
- A comparison between the neural correlates of lase...
- Spike-contrast: A novel time scale independent and...
- StimTrack: An open-source software for manual tran...
- Editorial Board/Aims & Scope
- Intraindividual homogeneity of 18F-FDG PET/CT para...
- Patient-oriented toxicity endpoints after head and...
- Appraisal of the AJCC 8th edition pathologic stagi...
- Oropharyngeal lymphoma: A US population based anal...
- Chemotherapy in head and neck osteosarcoma: Adjuva...
- Long-term results of a phase II study of gemcitabi...
- A randomized, open-label, Phase III clinical trial...
- Pre-diagnostic dynamic HPV16 IgG seropositivity an...
- Poor oral health affects survival in head and neck...
- Chemoradiotherapy for locally advanced squamous ce...
- Incidence and dosimetric parameters for brainstem ...
- Epigenetic therapy regulates the expression of ALD...
- Demographic and clinicopathological characteristic...
- Transoral bisected resection for T1-2 oral tongue ...
- Prevalence of high-risk human papillomavirus infec...
- Rationale for neoadjuvant immunotherapy in head an...
- Snail and Axin2 expression predict the malignant t...
- Genomic characterization of tobacco/nut chewing HP...
- Predictors of survival in head and neck mucosal me...
- The influence of immune status, age, and sex on Ma...
- Pediatric vasculitis: a single center experience
- Methane oxidation in lead-contaminated mineral soi...
- The sustainable arable land use pattern under the ...
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- Response of magnetic properties to metal depositio...
- Beyond classic dermoscopic patterns of dermatofibr...
- Detection of Malignancy Among Suspicious Thyroid N...
- Detection of Malignancy Among Suspicious Thyroid N...
- Needle migration and dosimetric impact in high-dos...
- The Influence of Sleep Disorders on Voice Quality
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- Synthesis and biological evaluation of novel synth...
- Bifunctional aryliodonium salts for highly efficie...
- New 5-HT1A, 5HT2A and 5HT2C receptor ligands conta...
- Prostate cancer post-prostatectomy radiotherapy: C...
- What is the optimal number of library plans in ART...
- Heart dose associated with overall survival in loc...
- A pediatric case with peripheral facial nerve pals...
- CACNA1A-related early-onset encephalopathy with my...
- A targeted next-generation sequencing panel reveal...
- A targeted next-generation sequencing panel reveal...
- Human CD40L-expressing type 3 innate lymphoid cell...
- High prevalence of severe asthma in a large random...
- TLR7/8 agonists stimulate plasmacytoid dendritic c...
- Th1 Signatures Are Present in the Lower Airways of...
- An unusual case of temporal bone encephalomeningoc...
- An unusual case of temporal bone encephalomeningoc...
- Influence and mechanism of 5-aminolevulinic acid-p...
- Effect of albumin on the fluorescence quantum yiel...
- Neurosurgical Microscopic Solid Laser-based Light ...
- Photodynamic therapy in combination with Ranibizum...
- Incidence rate of breakthrough varicella observed ...
- Stalking a lethal superbug by whole-genome sequenc...
- Methodology minute: A guide for infection preventi...
- The photosynthetic responses to stocking depth and...
- Monitoring of Incremental Changes in Maximum Inter...
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- Invited review: A systematic review and qualitativ...
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- Interpretive Summaries, October 2017
- Lowering rumen-degradable protein maintained energ...
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! # Ola via Alexandros G.Sfakianakis on Inoreader
Η λίστα ιστολογίων μου
Τρίτη 19 Σεπτεμβρίου 2017
Sequential and urgent coronary artery bypass surgery followed by kidney transplantation in a highly sensitized patient with unstable angina.
Early effects of renal replacement therapy on cardiovascular comorbidity in children with end-stage kidney disease: findings from the 4C-T Study.
http://ift.tt/2hf0wMZ
Mitochondrial Metabolism: Yin and Yang for Tumor Progression
Publication date: October 2017
Source:Trends in Endocrinology & Metabolism, Volume 28, Issue 10
Author(s): Lorea Valcarcel-Jimenez, Edoardo Gaude, Veronica Torrano, Christian Frezza, Arkaitz Carracedo
Altered metabolism is a distinct feature of cancer cells. During transformation, the entire metabolic network is rewired to efficiently convert nutrients to biosynthetic precursors to sustain cancer cell growth and proliferation. Whilst the molecular underpinnings of this metabolic reprogramming have been described, its role in tumor progression is still under investigation. Importantly, the mitochondrion is a central actor in many of the metabolic processes that are altered in tumors. Yet, we have only begun to understand the dualities of mitochondrial function during cancer metastasis and therapy resistance. Paradoxically, mitochondrial metabolism can be both advantageous and detrimental to these processes, highlighting the need for a better understanding of the molecular and microenvironmental cues that define the role of this fascinating organelle. In this review article, we present an updated view on the different mitochondrial metabolic strategies adopted by cancer cells to overcome the many hurdles faced during tumor progression.
http://ift.tt/2ypbHXC
Editorial Board and Contents
Publication date: October 2017
Source:Trends in Endocrinology & Metabolism, Volume 28, Issue 10
http://ift.tt/2xQDUcN
DNA damage response inhibitors: mechanisms and potential applications in cancer therapy
Source:Cancer Treatment Reviews
Author(s): Laura Carrassa, Giovanna Damia
Over the last decade the unravelling of the molecular mechanisms of the DNA damage response pathways and of the genomic landscape of human tumors have paved the road to new therapeutic approaches in oncology. It is now clear that tumors harbour defects in different DNA damage response steps, mainly signalling and repair, rendering them more dependent on the remaining pathways. We here focus on the proteins ATM, ATR, CHK1 and WEE1, reviewing their roles in the DNA damage response and as targets in cancer therapy. In the last decade specific inhibitors of these proteins have been designed, and their potential antineoplastic activity has been explored both in monotherapy strategies against tumors with specific defects (synthetic lethality approach) and in combination with radiotherapy or chemotherapeutic or molecular targeted agents. The preclinical and clinical evidence of antitumor activity of these inhibitors emanating from these research efforts will be critically reviewed. Lastly, the potential therapeutic feasibility of combining together such inhibitors with the aim to target particular subsets of tumors will be also discussed. .
http://ift.tt/2figrcE
Reply to the Letter to the Editor Concerning: ‘Changes in Swallowing-Related Quality of Life After Endoscopic Treatment for Zenker’s Diverticulum Using SWAL-QOL Questionnaire’
http://ift.tt/2wFoov8
A Survey of Australian Dysphagia Practice Patterns
Abstract
Dysphagia assessment and rehabilitation practice is complex, and significant variability in speech-language pathology approaches has been documented internationally. The aim of this study was to evaluate swallowing-related assessment and rehabilitation practices of SLPs currently working in Australia. One hundred and fifty-four SLPs completed an online questionnaire administered via QuickSurveys from May to July 2015. Results were analysed descriptively. The majority of clinicians had accessed post-graduate training in dysphagia management and assessment (66.23%). Referral and screening were typically on an ad hoc basis (74.03%). Clinical swallow examination (CSE) and Videofluoroscopic Swallowing Study were used by 93.51 and 88.31% of respondents, respectively. CSE was the assessment that predominantly informed clinical decision-making (52.63%). Clinicians typically treated clients with dysphagia for 30 min per session (46.10%), with recommendations of repetition of exercises inconsistent across settings. Outcome measures were utilised by many (67.53%), which however were typically informal. Results indicate variable practice patterns for dysphagia assessment and management across Australia. This variability may reflect the heterogeneous nature of dysphagia and the varying needs of patients accessing different services.
http://ift.tt/2hhfy1b
Masthead
http://ift.tt/2xQ0gLj
Masthead
http://ift.tt/2xQ0gLj
Oral administration of milk-derived phospholipids inhibits penetration of cutaneous nerve fibres into epidermis in a mouse model of acute dry skin
Summary
The density of intraepidermal nerve fibres has been shown to be higher in itchy dry skin than in healthy skin, suggesting that epidermal hyperinnervation is at least partly involved in peripheral itch sensitization. We investigated whether oral administration of milk-derived phospholipids (MPLs) would inhibit epidermal hyperinnervation in a mouse model of dry skin. We found that the number of intraepidermal nerve fibres was significantly lower in the MPL group than in the control group. Expression of nerve growth factor (NGF) levels in the epidermis was significantly decreased by oral administration of MPLs, whereas expression of semaphorin (Sema)3A, a nerve repulsion factor, was increased in the MPL group. These results suggest that dietary MPLs attenuate the penetration of nerve fibres into the epidermis by reducing epidermal NGF levels and increasing Sema3A level. Thus, dietary MPLs may have beneficial effects in the prevention and/or alleviation of dry skin-induced itch by reducing intraepidermal nerve fibre density.
http://ift.tt/2ycNNgR
Oral administration of milk-derived phospholipids inhibits penetration of cutaneous nerve fibres into epidermis in a mouse model of acute dry skin
Summary
The density of intraepidermal nerve fibres has been shown to be higher in itchy dry skin than in healthy skin, suggesting that epidermal hyperinnervation is at least partly involved in peripheral itch sensitization. We investigated whether oral administration of milk-derived phospholipids (MPLs) would inhibit epidermal hyperinnervation in a mouse model of dry skin. We found that the number of intraepidermal nerve fibres was significantly lower in the MPL group than in the control group. Expression of nerve growth factor (NGF) levels in the epidermis was significantly decreased by oral administration of MPLs, whereas expression of semaphorin (Sema)3A, a nerve repulsion factor, was increased in the MPL group. These results suggest that dietary MPLs attenuate the penetration of nerve fibres into the epidermis by reducing epidermal NGF levels and increasing Sema3A level. Thus, dietary MPLs may have beneficial effects in the prevention and/or alleviation of dry skin-induced itch by reducing intraepidermal nerve fibre density.
http://ift.tt/2ycNNgR
Plantar keratoderma climatericum: Successful improvement with a topical estriol cream
Summary
Keratoderma climatericum affects menopausal women, and the diagnosis relies on typical clinical findings and exclusion of other potential causes of acquired keratoderma. Although its pathophysiology is still unknown, there has been speculation about its relation to hormonal dysregulation (possibly a local estrogen deficiency) since the 1930s. A female patient with long-lasting keratoderma climatericum was initially prescribed a topical 50% urea ointment and clobetasol propionate 0.05% ointment, with just a slight improvement after 2 months of daily use. The patient was started on topical estriol 0.125 mg/g vaginal cream applied on the plantar surface after her daily shower and application of the same topical 50% urea ointment and clobetasol propionate 0.05% ointment on alternate nights. There was a marked improvement under this regimen with total and fast control of the pruritus. At 6-month follow-up the patient retained total symptomatic control and was just applying the estriol cream and the 50% urea containing ointment. We report a case of a difficult to treat plantar keratoderma that markedly improved after adding a daily topical application of a vaginal cream containing estriol 0.125 mg/g. Trials that determine the efficacy and safety of topical estrogens for keratoderma climatericum are warranted.
http://ift.tt/2ycGmGp
Plantar keratoderma climatericum: Successful improvement with a topical estriol cream
Summary
Keratoderma climatericum affects menopausal women, and the diagnosis relies on typical clinical findings and exclusion of other potential causes of acquired keratoderma. Although its pathophysiology is still unknown, there has been speculation about its relation to hormonal dysregulation (possibly a local estrogen deficiency) since the 1930s. A female patient with long-lasting keratoderma climatericum was initially prescribed a topical 50% urea ointment and clobetasol propionate 0.05% ointment, with just a slight improvement after 2 months of daily use. The patient was started on topical estriol 0.125 mg/g vaginal cream applied on the plantar surface after her daily shower and application of the same topical 50% urea ointment and clobetasol propionate 0.05% ointment on alternate nights. There was a marked improvement under this regimen with total and fast control of the pruritus. At 6-month follow-up the patient retained total symptomatic control and was just applying the estriol cream and the 50% urea containing ointment. We report a case of a difficult to treat plantar keratoderma that markedly improved after adding a daily topical application of a vaginal cream containing estriol 0.125 mg/g. Trials that determine the efficacy and safety of topical estrogens for keratoderma climatericum are warranted.
http://ift.tt/2ycGmGp
Temporal remodeling of pial collaterals and functional deficits in a murine model of ischemic stroke
Source:Journal of Neuroscience Methods
Author(s): Benjamin Okyere, Miranda Creasey, Yeonwoo Lebovitz, Michelle H. Theus
BackgroundLeptomeningeal anastomoses play a critical role in regulating reperfusion following cerebrovascular obstruction; however, methods to evaluate their temporospatial remodeling remains under investigation.New methodWe combined arteriole-specific vessel painting with histological evaluation to assess the density and diameter of inter-collateral vessels between the middle cerebral artery and anterior cerebral artery (MCA-ACA) or posterior cerebral artery (MCA-PCA) in a murine model of permanent middle cerebral artery occlusion (pMCAO).ResultsWhile the overall density was not influenced by pMCAO, the size of MCA-ACA and MCA-PCA vessels had significantly increased 2days post-pMCAO and peaked by 4days compared to the un-injured hemisphere. Using a combination of vessel painting and immunofluorescence, we uniquely observed an induction of cellular division and a remodeling of the smooth muscle cells within the collateral niche following post-pMCAO on whole mount tissue sections. Vessel painting was also applied to pMCAO-injured Cx3cr1GFP mice, in order to identify the spatial relationship between Cx3cr1-positive peripheral-derived monocyte/macrophages and the vessel painted collaterals. Our histological findings were supplemented with analysis of cerebral blood flow using laser Doppler imaging and behavioral changes following pMCAO.Comparison with existing methodsCompared to polyurethane and latex methods for collateral labeling, this new method provides detailed cell-type specific analysis within the collateral niche at the microscopic level, which has previously been unavailable.ConclusionsThis simple and reproducible combination of techniques is the first to dissect the temporospatial remodeling of pial collateral arterioles. The method will advance investigations into the underlying mechanisms governing the intricate processes of arteriogenesis.
http://ift.tt/2xlxZLl
A comparison between the neural correlates of laser and electric pain stimulation and their modulation by expectation
Source:Journal of Neuroscience Methods
Author(s): E.J. Hird, A.K.P. Jones, D. Talmi, W. El-Deredy
BackgroundPain is modulated by expectation. Event-related potential (ERP) studies of the influence of expectation on pain typically utilise laser heat stimulation to provide a controllable nociceptive-specific stimulus. Painful electric stimulation has a number of practical advantages, but is less nociceptive-specific. We compared the modulation of electric versus laser-evoked pain by expectation, and their corresponding pain-evoked and anticipatory ERPs.New MethodWe developed understanding of recognised methods of laser and electric stimulation. We tested whether pain perception and neural activity induced by electric stimulation was modulated by expectation, whether this expectation elicited anticipatory neural correlates, and how these measures compared to those associated with laser stimulation by eliciting cue-evoked expectations of high and low pain in a within-participant design.ResultsDespite sensory and affective differences between laser and electric pain, intensity ratings and pain-evoked potentials were modulated equivalently by expectation, though ERPs only correlated with pain ratings in the laser pain condition. Anticipatory correlates differentiated pain intensity expectation to laser but not electric pain.Comparison with Existing MethodPrevious studies show that laser-evoked potentials are modulated by expectation. We extend this by showing electric pain-evoked potentials are equally modulated by expectation, within the same participants. We also show a difference between the pain types in anticipation.ConclusionsThough laser-evoked potentials express a stronger relationship with pain perception, both laser and electric stimulation may be used to study the modulation of pain-evoked potentials by expectation. Anticipatory-evoked potentials are elicited by both pain types, but they may reflect different processes.
http://ift.tt/2wFoTWb
Spike-contrast: A novel time scale independent and multivariate measure of spike train synchrony
Source:Journal of Neuroscience Methods
Author(s): Manuel Ciba, Takuya Isomura, Yasuhiko Jimbo, Andreas Bahmer, Christiane Thielemann
BackgroundSynchrony within neuronal networks is thought to be a fundamental feature of neuronal networks. In order to quantify synchrony between spike trains, various synchrony measures were developed. Most of them are time scale dependent and thus require the setting of an appropriate time scale. Recently, alternative methods have been developed, such as the time scale independent SPIKE-distance by Kreuz et al..New MethodIn this study, a novel time-scale independent spike train synchrony measure called Spike-contrast is proposed. The algorithm is based on the temporal "contrast" (activity vs. non-activity in certain temporal bins) and not only provides a single synchrony value, but also a synchrony curve as a function of the bin size.ResultsFor most test data sets synchrony values obtained with Spike-contrast are highly correlated with those of the SPIKE-distance (Spearman correlation value of 0.99). Correlation was lower for data containing multiple time scales (Spearman correlation value of 0.89). When analyzing large sets of data, Spike-contrast performed faster.Comparison of existing MethodSpike-contrast is compared to the SPIKE-distance algorithm. The test data consisted of artificial spike trains with various levels of synchrony, including Poisson spike trains and bursts, spike trains from simulated neuronal Izhikevich networks, and bursts made of smaller bursts (sub-bursts).ConclusionsThe high correlation of Spike-contrast with the established SPIKE-distance for most test data, suggests the suitability of the proposed measure. Both measures are complementary as SPIKE-distance provides a synchrony profile over time, whereas Spike-contrast provides a synchrony curve over bin size.
http://ift.tt/2xlPHy0
StimTrack: An open-source software for manual transcranial magnetic stimulation coil positioning
Publication date: Available online 19 September 2017
Source:Journal of Neuroscience Methods
Author(s): Emilia Ambrosini, Simona Ferrante, Mark van de Ruit, Stefano Biguzzi, Vera Colombo, Marco Monticone, Giorgio Ferriero, Alessandra Pedrocchi, Giancarlo Ferrigno, Michael J. Grey
BackgroundDuring Transcranial Magnetic Stimulation (TMS) experiments researchers often use a neuronavigation system to precisely and accurately maintain coil position and orientation.New methodThis study aimed to develop and validate an open-source software for TMS coil navigation. StimTrack uses an optical tracker and an intuitive user interface to facilitate the maintenance of position and orientation of any type of coil within and between sessions. Additionally, online access to navigation data is provided, hereby adding e.g. the ability to start or stop the magnetic stimulator depending on the distance to target or the variation of the orientation angles.ResultsStimTrack allows repeatable repositioning of the coil within 0.7mm for translation and <1° for rotation. Stimulus-response (SR) curves obtained from 19 healthy volunteers were used to demonstrate that StimTrack can be effectively used in a typical experiment. An excellent intra and inter-session reliability (ICC >0.9) was obtained on all parameters computed on SR curves acquired using StimTrack.Comparison with existing methodStimTrack showed a target accuracy similar to that of a commercial neuronavigation system (BrainSight, Rogue Research Inc.). Indeed, small differences both in position (∼0.2mm) and orientation (<1°) were found between the systems. These differences are negligible given the human error involved in landmarks registration.ConclusionsStimTrack, available as supplementary material, is found to be a good alternative for commercial neuronavigation systems facilitating assessment changes in corticospinal excitability using TMS. StimTrack allows researchers to tailor its functionality to their specific needs, providing added value that benefits experimental procedures and improves data quality.
Graphical abstract
http://ift.tt/2wFvJLp
Intraindividual homogeneity of 18F-FDG PET/CT parameters in HPV-positive OPSCC
Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent malignancies and the 7th most common cause of cancer-induced mortality worldwide [1]. While incidence rates for cancer of the hypopharynx and larynx are decreasing, a significant increase in cancer of the oropharynx (OPSCC) has been observed [2]. Because of differences in risk factors, clinical course and outcome, HPV-positive tumours are considered to be a distinct entity and therefore have recently been added to the TNM/AJCC Cancer Staging Manual [3–7].
http://ift.tt/2jHBeYy
Patient-oriented toxicity endpoints after head and neck reirradiation with intensity modulated radiation therapy
Reirradiation (reRT) is a treatment option for select patients with recurrent or second primary squamous cell carcinoma of the head and neck (SCCHN) [1] and can result in prolonged disease control and even cure in select patients [2]. However, improvements in local-regional control rates must be balanced with the significant risks of treatment-related toxicity. Shared-decision making regarding the benefit of reRT must involve a discussion of possible side effects of treatment and the time course over which these side effects are likely to occur.
http://ift.tt/2wvWSoF
Appraisal of the AJCC 8th edition pathologic staging modifications for HPV−positive oropharyngeal cancer, a study of the National Cancer Data Base
The American Joint Commission on Cancer (AJCC) 7th edition staging manual for oropharyngeal cancer was designed before high-risk human papillomavirus positive oropharyngeal cancer (HPV+ OPSCC) became preeminent, an entity that's now expected to surpass incidence of HPV cervical cancer by 2020 [1]. As such, the 7th edition staging paradigm progressively lost its prognostic ability as HPV+ OPSCC boasts far better survival and treatment sensitivity than HPV−negative disease. Moreover, recent studies have demonstrated its prognostic inadequacy [2–5].
http://ift.tt/2jIZrxz
Oropharyngeal lymphoma: A US population based analysis
Head and neck lymphomas arise from lymph nodes as well as extranodal locations including, Waldeyer ring, the sinonasal tract, nasopharynx and salivary glands [1]. The oropharynx contains the palatine tonsils as well as the base of tongue (BOT), both of these locations are part of Waldeyer's ring and are comprised of lymphoid tissue [2]. B cells proliferate and mature at these locations, which represent the first contact point for exogenous antigens entering the aerodigestive tract [3]. Lymphomas are subdivided into Hodgkin's lymphoma (HL) and Non-Hodgkin's lymphoma (NHL), with extranodal NHL being the second most common primary head and neck malignancy after squamous cell carcinoma [4].
http://ift.tt/2wwXsTh
Chemotherapy in head and neck osteosarcoma: Adjuvant chemotherapy improves overall survival
Osteosarcoma is a common bone malignancy characterized by osteoid formation by highly malignant osteoblasts [1], osteosarcoma occurs commonly in the extremity of children and adolescents and rarely in the head and neck sites, only 6% to 10% of all osteosarcomas are reported to occur in head and neck sites [2,3]. The tumor is aggressive and often presents with high histological grade [4] and propensity towards lung metastasis [5]. Surgery is the main therapeutic modality for cure. However; many trials indicate the benefit of adjuvant chemotherapy in improving survival of these patients [6].
http://ift.tt/2jGAbYM
Long-term results of a phase II study of gemcitabine and cisplatin chemotherapy combined with intensity-modulated radiotherapy in locoregionally advanced nasopharyngeal carcinoma
Two-thirds of nasopharyngeal carcinoma (NPC) patients who present with stage III-IVA-B are potentially eligible for curative chemoradiotherapy. In the 2DRT era, concurrent chemoradiotherapy (CCRT) was the standard treatment in locoregionally advanced NPC since the publication of the landmark Intergroup 0099 study [1]. Several subsequential clinical trials also confirmed the effectiveness of this treatment modality [2–4]. The current NCCN guidelines recommend that CCRT followed by adjuvant chemotherapy (AC) for locoregionally advanced NPC, originate from the results of these studies.
http://ift.tt/2wwmku8
A randomized, open-label, Phase III clinical trial of nivolumab vs. therapy of investigator’s choice in recurrent squamous cell carcinoma of the head and neck: A subanalysis of Asian patients versus the global population in checkmate 141
Carcinoma of the head and neck accounts for ≥600,000 new cases and >300,000 deaths each year globally [1]. In Japan, the incidence of invasive oral, pharynx, and larynx cancers was estimated at 24,557 in 2012 [2]. The incidence of carcinoma of the head and neck is also increasing. In South Korea, the incidence of all carcinomas of the head and neck has increased since 1998, except for laryngeal cancer [3]. In Taiwan, among solid cancers, oropharyngeal cancer had the fourth greatest increase in incidence from 2002 to 2012, with an average annual percentage increase of 5% [4].
http://ift.tt/2jGFesp
Pre-diagnostic dynamic HPV16 IgG seropositivity and risk of oropharyngeal cancer
Human papillomavirus (HPV) is associated with a subset of head and neck squamous cell carcinomas (HNSCC) [1], with a strong association with cancers of the oropharynx (OPC), including cancers of the tonsils and base of tongue [2]. It is now estimated that HPV type 16 is associated with 65–80% of OPC [3,4] and incidence rates of HPV-related OPC are rapidly rising [5].
http://ift.tt/2wwDjfV
Poor oral health affects survival in head and neck cancer
Squamous cell carcinoma of the head and neck (HNSCC) contributes substantially to the global burden of cancer [1–3]. It is the sixth most common cancer worldwide [4], and the fifth most common cancer in the United States, affecting approximately 40,000 new patients each year [1]. It encompasses cancers of the oral cavity, oropharynx, and larynx among others. While the mortality rate for HNSCC has improved recently, it still has poorer survival rates than some other common malignancies such as breast, cervical, and colorectal cancers [5,6].
http://ift.tt/2jGFho5
Chemoradiotherapy for locally advanced squamous cell carcinoma of the oropharynx: Does completion of systemic therapy affect outcomes?
Locally advanced squamous cell carcinoma of the oropharynx (LA-OPC), defined as stage III–IVB disease per the current American Joint Committee on Cancer (AJCC) 7th edition staging manual, remains difficult to treat [1]. Recommended treatment options are diverse but universally include radiation therapy with the potential addition of preceding surgical resection, induction chemotherapy, and concurrent systemic agents [2,3]. In the setting of definitive radiation therapy for LA-OPC, multiple clinical trials have demonstrated significant advantage to the addition of concurrent systemic therapies, namely improving local control, disease-free survival, and overall survival [4–10].
http://ift.tt/2wx4B64
Incidence and dosimetric parameters for brainstem necrosis following intensity modulated radiation therapy in nasopharyngeal carcinoma
Nasopharyngeal carcinoma (NPC) is a malignancy of the nasopharyngeal epithelium with a distinct epidemiology compared to other head and neck squamous cell carcinomas. The incidence of NPC is extremely high (15–50 per 100,000) in southern China, but extremely low in most other countries [1].
http://ift.tt/2jJKqLV
Epigenetic therapy regulates the expression of ALDH1 and immunologic response: Relevance to the prognosis of oral cancer
Oral squamous cell carcinoma (OSCC) is the most malignant tumor of the head and neck [1]. Despite considerable advances in treatment, about 50% of patients with locally advanced disease relapse with local or distant disease progression [2,3]. Investigating specific molecular markers related to the capacity for tumor invasion and treatment sensitivity could provide new insights for the identification of innovative treatments.
http://ift.tt/2wwQv4q
Demographic and clinicopathological characteristics of nasopharyngeal carcinoma and survival outcomes according to age at diagnosis: A population-based analysis
Though rare in Japan and western countries, nasopharyngeal carcinoma (NPC) is endemic in southern China, Southeast Asia and Southern Africa. In general, the incidence of NPC in endemic and non-endemic areas has stabilised in recent decades [1,2]; however, the age distribution varies between endemic and non-endemic areas. The age distribution of NPC is unimodal in endemic areas, peaking in individuals aged 45–59-years-old [1,2]. However, in low risk populations, the age distribution is bimodal, with a first peak in young adolescents (aged 15–19) and a second peak in individuals aged 65–79 [1].
http://ift.tt/2jHBd6W
Transoral bisected resection for T1-2 oral tongue squamous cell carcinoma to secure adequate deep margin
To investigate the clinical usefulness of transoral bisected resection (TBR) asa new method to secure adequate deep resection margin in T1-2 oral tongue squamous cell carcinomas (SCC).
http://ift.tt/2wwmaTy
Prevalence of high-risk human papillomavirus infection and cancer gene mutations in nonmalignant tonsils
Head and neck squamous cell carcinoma (SCC) accounts for approximately 600,000 new cancer cases each year [1]. The main risk factors are tobacco and alcohol use. In many developed countries, however, the majority of newly diagnosed tonsillar SCCs are associated with high-risk human papillomavirus (HPV) infection, predominantly HPV type 16 [2,3]. Compared to individuals with HPV negative tonsillar SCC, those with HPV positive disease have better prognosis, and they are often younger with no significant history of tobacco or alcohol use [4–6].
http://ift.tt/2jHMm7Y
Rationale for neoadjuvant immunotherapy in head and neck squamous cell carcinoma
In patients with locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN), current treatment guidelines recommend surgery with post-operative adjuvant therapy or definitive chemoradiotherapy (CRT) as standard of care. Despite these intensive multimodality treatments, recurrence of disease persists asa key cause for treatment failure. Recurrent disease is especially problematic in human papillomavirus (HPV)-unrelated SCCHN.
http://ift.tt/2wwm6Di
Snail and Axin2 expression predict the malignant transformation of oral leukoplakia
Oral leukoplakias (OL) are common whitish patches of the oral cavity having a well-documented potential risk of malignant transformation [1–3]. The prevalence of OL is approximately 1% in all ages, the annual rate of malignant transformation of untreated lesions having been reported as 2–3% [1]. Meanwhile, the risk of recurrence after the surgical treatment of non-homogeneous leukoplakia has been estimated at up to 20%, and oral squamous cell carcinomas (OSCC) developed from OL demonstrate poor clinical outcomes [2].
http://ift.tt/2jIO7S8
Genomic characterization of tobacco/nut chewing HPV-negative early stage tongue tumors identify MMP10 asa candidate to predict metastases
Tongue cancer is the most predominant form of oral cancer in developed countries with a varying incidence in developing countries [1]. The major etiological factors associated with tongue cancer include tobacco related products, alcohol and human papilloma virus (HPV) infections [2]. These factors lend to variability across populations, particularly in the Indian subcontinent wherein chewing betel-quid comprising betel leaf (Piper betel), areca nut (Areca catechu) and slaked lime (predominantly calcium hydroxide) is a part of the tradition [3].
http://ift.tt/2wvrVRL
Predictors of survival in head and neck mucosal melanoma
Mucosal melanomas are among the most lethal of head and neck cancers. Although they can arise from any mucosa-lined surface, mucosal melanomas most commonly occur in the sinonasal regions of the head and neck [1]. In comparison to cutaneous, acral, and ocular melanomas, mucosal melanoma exhibits an aggressive clinical course with poor prognosis [2–5]. Diagnosis is often delayed given few and nonspecific presenting symptoms mimicking more common benign processes [6]. Furthermore, head and neck mucosal melanomas (HNMMs) have relatively high rates of local, regional, and distant metastases despite aggressive multimodality therapy [7].
http://ift.tt/2jIRXL8
The influence of immune status, age, and sex on Majocchi granuloma: a review of 52 cases from a tertiary level hospital and published Korean cases in literature
Abstract
Background
Majocchi granuloma (MG) is a rare dermal and subcutaneous granulomatous inflammation caused by dermatophytes. The detailed characteristics of MG are not fully elucidated. This study investigated the influence of systemic immune status, age, and sex on the clinical, demographic, mycological, and therapeutic characteristics of MG in Korea.
Methods
We analyzed cases of histopathologically diagnosed MG at our tertiary referral center from January 2001 to December 2016. We also analyzed all Korean MG cases published in Korean and English literature to date. The different features based on immune status, age, and sex were compared. P < 0.05 were considered statistically significant.
Results
We enrolled 52 patients, 33 (63.5%) were male and 19 (36.5%) were female. The mean age was 45.4 ± 23.1 years. Immunosuppression was reported in 13 cases (26.5%). Statistical analysis showed that the immune status affects the anatomical location and clinical manifestation. Age has an influence on involved sites and identified fungal species. The frequent fungal pathogens were different based on sex.
Conclusion
The results of our study revealed that distinctive features of MG exist based on immune status, age, and sex.
http://ift.tt/2fiosyz
Pediatric vasculitis: a single center experience
Abstract
Background
Existing studies of children with vasculitis are limited. The aim of this study was to assess the epidemiology, clinical manifestations, laboratory findings, course, and outcome of Greek children presenting with vasculitic rash.
Methods
The relevant data included in the study were collected retrospectively using a standardized form from children who were admitted into our department between 2003 and 2013, with the provisional diagnosis of vasculitis of the skin.
Results
The study sample consisted of 95 children (58 boys, 37 girls) with a mean age of 5.9 years. In total, 76 out of 95 (80%) of the children were diagnosed with Henoch-Schönlein purpura, 10/95 (10.5%) with hypersensitivity vasculitis, 6/95 (6.3%) with urticarial vasculitis, and 3/95 (3.1%) with acute hemorrhagic edema of infancy. The mean age of the children was 5.7 years for Henoch-Schönlein purpura, 9 years for hypersensitivity vasculitis, 5.1 years for urticarial vasculitis, and 0.5 years for acute hemorrhagic edema of infancy.
Conclusions
(i) The most common vasculitis presenting with skin rash in children is Henoch-Schönlein purpura; (ii) hypersensitivity vasculitis occurs in older children more often when compared to other types of vasculitis; (iii) urticarial vasculitis lesions may be a sign of severe underlying disease; therefore a thorough examination of these patients is warranted; (iv) Despite relapses, the overall prognosis of patients with pediatric skin vasculitides is good, with the exception of those with the urticarial vasculitis type.
http://ift.tt/2xvqH8m
Methane oxidation in lead-contaminated mineral soils under different moisture levels
Abstract
Methane (CH4) oxidation in soil reduces the concentration of this greenhouse gas due to the activity of methanotrophic bacteria. This process is influenced by chemical and physical parameters of soil. We tested the methanotrophic activity of selected mineral soils (Mollic Gleysol, Haplic Podzol, Eutric Cambisol) contaminated with lead (Pb) under different soil water potentials (pF 0; 2.2; 3.2). The heavy metal was added as PbCl2 in two doses. Together with the initial content of Pb in soils, the final contents of heavy metal in different soils were 11.6 and 30.8 mg kg−1 in Eutric Cambisol, 7.1 and 26.3 mg kg−1 in Haplic Podzol, and 12.2 and 31.4 mg kg−1 in Mollic Gleysol (dry mass of the soil is specified in all cases). The results showed relatively low sensitivity of methane oxidation to the addition of the heavy metal. The major factor controlling this process was soil water content, which in most cases turned out to be the most optimal at pF = 2.2.
http://ift.tt/2xw85F9
The sustainable arable land use pattern under the tradeoff of agricultural production, economic development, and ecological protection—an analysis of Dongting Lake basin, China
Abstract
To find a solution regarding sustainable arable land use pattern in the important grain-producing area during the rapid urbanization process, this study combined agricultural production, locational condition, and ecological protection to determine optimal arable land use. Dongting Lake basin, one of the major grain producing areas in China, was chosen as the study area. The analysis of land use transition, the calculation of arable land barycenter, the landscape indices of arable land patches, and the comprehensive evaluation of arable land quality(productivity, economic location, and ecological condition) were adopted in this study. The results showed that (1) in 1990–2000, the arable land increased by 11.77%, and the transformation between arable land and other land use types actively occurred; in 2000–2010, the arable land decreased by 0.71%, and more ecological area (forestland, grassland, and water area) were disturbed and transferred into arable land; (2) urban expansion of the Changsha-Zhuzhou-Xiangtan city cluster (the major economy center of this area) induced the northward movement of the arable land barycenter; (3) the landscape fragmentation and decentralization degree of arable land patches increased during 1990–2010; (4) potential high-quality arable land is located in the zonal area around Dongting Lake, which contains the Li County, Linli County, Jinshi County, Taoyuan County, Taojiang County, Ningxiang County, Xiangxiang County, Shaoshan County, Miluo County, and Zhuzhou County. The inferior low-quality arable land is located in the northwestern Wuling mountainous area, the southeastern hilly area, and the densely populated big cities and their surrounding area. In the optimized arable land use pattern, the high-quality land should be intensively used, and the low-quality arable land should be reduced used or prohibitively used. What is more, it is necessary to quit the arable land away from the surrounding area of cities appropriately, in order to allow more space for urban expansion. This study could provide guidance for sustainable arable land use by both satisfying the future agricultural production and the local economic development, which can be used for the other major grain-producing areas in this rapid developing country.
http://ift.tt/2fhJSf1
Aquatic environmental assessment of Lake Balaton in the light of physical-chemical water parameters
Abstract
One of the issues of the Hungarian Water Management Strategy is the improvement and upgrading of the water of Lake Balaton. The Water Framework Directive (WFD) specifies and sets forth the achievement of the good ecological status. However, the assessment of the water quality of the lake as a complex system requires a comprehensive monitoring and evaluation procedure. Measurements were carried out around the Lake Balaton at ten different locations/sites and 13 physical-chemical parameters were monitored at each measurement site.
For the interpretation of the water chemistry parameters the Aquatic Environmental Assessment (AEA) method devised by authors was used for the water body of the Lake Balaton. The AEA method can be used for all types of the water bodies since it is flexible and using individual weighting procedure for the water chemistry parameters comprehensive information can be obtain. The AEA method was compared with existing EIA methods according to a predefined criterion system and proved to be the most suitable tool for evaluating the environmental impacts in our study.
On the basis of the results it can be concluded that the status of the quality of studied area on the Lake Balaton can be categorized as proper quality (from the outcome of the ten measurement sites this conclusion was reached at seven sites).
http://ift.tt/2xvnUfk
Response of magnetic properties to metal deposition on urban green in Nanjing, China
Abstract
Environmental magnetism is a simple and fast method that can be used to assess heavy metal pollution in urban areas from the relationships between magnetic properties and heavy metal concentrations. Leaves of Osmanthus fragrans, one of the most widely distributed evergreen trees in Nanjing, China, were collected from four different district types, i.e., residential, educational, traffic, and industrial. The magnetic properties and heavy metal concentrations were measured both for unwashed (dust-loaded) and washed leaves. Scanning electron microscopy with energy-dispersive X-ray spectroscopy confirmed that unwashed leaves accumulated much dust due to atmospheric deposition. The value of magnetic properties and heavy metal concentrations in unwashed leaves was significantly higher than those of washed leaves, indicating that these characteristics were mainly derived from atmospheric particulate matter. Saturation isothermal remanent magnetization (SIRM) values obtained from unwashed and washed leaves ranged from 209.14 × 10−6 to 877.85 × 10−6 Am2 kg−1 and from 69.50 × 10−6 to 501.28 × 10−6 Am2 kg−1, respectively. High concentrations of heavy metals, such as Pb and Fe, the Tomlinson pollution load index, and the SIRM of unwashed leaves occurred in the traffic and industrial districts. A preliminary principal component analysis identified the source categories and suggested that industrial activities may be more related to the release of particulate matter rich in Fe. The heavy metal concentrations and pollution load index showed significant positive correlations with the low-frequency magnetic susceptibility and SIRM of unwashed leaves, indicating that these properties can be used to semi-quantify atmospheric heavy metal pollution. Our study suggests that it is possible to employ magnetic measurements as a useful tool for the monitoring and assessment of atmospheric heavy metal pollution.
http://ift.tt/2fipgU7
Beyond classic dermoscopic patterns of dermatofibromas: a prospective research study
The usual stereotypical dermoscopic pattern associated with dermatofibromas is a pigment network and central white patch. However, this pattern may be difficult to diagnose in some variant cases. We aimed to d...
http://ift.tt/2xdPWw8
Detection of Malignancy Among Suspicious Thyroid Nodules
Thyroid , Vol. 0, No. 0.
http://ift.tt/2hhHylc
Detection of Malignancy Among Suspicious Thyroid Nodules
Thyroid , Vol. 0, No. 0.
http://ift.tt/2hhHylc
Needle migration and dosimetric impact in high-dose-rate brachytherapy for prostate cancer evaluated by repeated MRI
Source:Brachytherapy
Author(s): Simon Buus, Maria Lizondo, Steffen Hokland, Susanne Rylander, Erik M. Pedersen, Kari Tanderup, Lise Bentzen
PurposeTo quantify needle migration and dosimetric impact in high-dose-rate brachytherapy for prostate cancer and propose a threshold for needle migration.Methods and MaterialsTwenty-four high-risk prostate cancer patients treated with an HDR boost of 2 × 8.5 Gy were included. Patients received an MRI for planning (MRI1), before (MRI2), and after treatment (MRI3). Time from needle insertion to MRI3 was ∼3 hours. Needle migration was evaluated from coregistered images: MRI1-MRI2 and MRI1-MRI3. Dose volume histogram parameters from the treatment plan based on MRI1 were related to parameters based on needle positions in MRI2 or MRI3. Regression was used to model the average needle migration per implant and change in D90 clinical target volume, CTVprostate+3mm. The model fit was used for estimating the dosimetric impact in equivalent dose in 2 Gy fractions for dose levels of 6, 8.5, 10, 15, and 19 Gy.ResultsNeedle migration was on average 2.2 ± 1.8 mm SD from MRI1-MRI2 and 5.0 ± 3.0 mm SD from MRI1-MRI3. D90 CTVprostate+3mm was robust toward average needle migration ≤3 mm, whereas for migration >3 mm D90 decreased by 4.5% per mm. A 3 mm of needle migration resulted in a decrease of 0.9, 1.7, 2.3, 4.8, and 7.6 equivalent dose in 2 Gy fractions for dose levels of 6, 8.5, 10, 15, and 19 Gy, respectively.ConclusionsSubstantial needle migration in high-dose-rate brachytherapy occurs frequently in 1–3 hours following needle insertion. A 3-mm threshold of needle migration is proposed, but 2 mm may be considered for dose levels ≥15 Gy.
http://ift.tt/2ycSyXK
The Influence of Sleep Disorders on Voice Quality
To verify the influence of sleep quality on the voice.
http://ift.tt/2fhNOMD
Synthesis, computational studies and enzyme inhibitory kinetics of substituted methyl[2-(4-dimethylamino-benzylidene)-hydrazono)-4-oxo-thiazolidin-5-ylidene]acetates as mushroom tyrosinase inhibitors
Publication date: Available online 18 September 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Pervaiz Ali Channar, Aamer Saeed, Fayaz Ali Larik, Muhammad Rafiq, Zaman Ashraf, Farukh Jabeen, Tanzeela Abdul Fattah
The present article describes the synthesis and enzyme inhibitory kinetics of methyl[2-(arylmethylene-hydrazono)-4-oxo-thiazolidin-5-ylidene]acetates 5a–j as mushroom tyrosinase inhibitors. The title compounds were synthesized via cyclocondensation of thiosemicarbazones 3a–j with dimethyl but-2-ynedioate (DMAD) 4 in good yields under solvent-free conditions. The synthesized compounds were evaluated for their potential to inhibit the activity of mushroom tyrosinase. It was unveiled that compounds 5i showed excellent enzyme inhibitory activity with IC50 3.17µM while IC50 of standard kojic acid is 15.91µM. The presence of heterocyclic pyridine ring in compound 5i play important role in enzyme inhibitory activity as rest of the functional groups are common in all synthesized compounds. The enzyme inhibitory kinetics of the most potent derivative 5i determined by Lineweaver-Burk plots and Dixon plots showed that it is non-competitive inhibitor with Ki value 1.5 µM. It was further investigated that the wet lab results are in good agreement with the computational results. The molecular docking of the synthesized compounds was performed against tyrosinase protein (PDBID 2Y9X) to delineate ligand-protein interactions at molecular level. The docking results showed that the major interacting residues are His244, His85, His263, Val 283, His 296, Asn260, Val248, His260, His261 and Phe264 which are located in active binding site of the protein. The molecular modeling demonstrates that the oxygen atom of the compound 5i coordinated with the key residues in the active site of mushroom tyrosinase contribute significantly against inhibitory ability and diminishing the human melanin synthesis. These results evident that compound 5i is a lead structure in developing most potent mushroom tyrosinase inhibitors.
Graphical abstract
http://ift.tt/2xdCpV5
Design, synthesis and biological evaluation of 2-phenylquinoline-4-carboxamide derivatives as a new class of tubulin polymerization inhibitors
Publication date: Available online 18 September 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Li Zhu, Kaixiu Luo, Ke Li, Yi Jin, Jun Lin
A novel series of 2-phenylquinoline-4-carboxamide derivatives was synthesized, characterized and evaluated for its antiproliferative activity against five cancer cell lines, Hela, SK-OV-3, HCT116, A549 and MDA-MB-468, and a normal human fetal lung fibroblastic cell line, MRC-5. Among them, compound 7b displayed potent cytotoxic activity in vitro against SK-OV-3 and HCT116 cell lines with IC50 values of 0.5 and 0.2 μM, respectively. In general, the antiproliferative activity was correlated with the binding property of the colchicine binding site and inhibitory effect on tubulin polymerization. In addition, immunofluorescence and flow cytometry analysis revealed that selected compounds caused disruption of the mitotic spindle assembly and G2/M phase arrest of the cell cycle, which correlated with proliferation inhibitory activity. Molecular docking analysis demonstrated the interaction of 7b at the colchicine binding site of tubulin. These results indicate these compounds are promising inhibitors of tubulin polymerization for the potent treatment of cancer.
Graphical abstract
http://ift.tt/2xcT5fu
Synthesis and biological evaluation of novel synthetic chalcone derivatives as anti-tumor agents targeting Cat L and Cat K
Publication date: Available online 17 September 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Yali Wang, Situ Xue, Ruolan Li, Zhihui Zheng, Hong Yi, Zhuorong Li
A series of chalcone derivatives bearing benzamide or benzenesulfonamide moieties were synthesized and evaluated for their anti-tumor effect on HCT116, MCF7 and 143B cell lines in vitro. SAR analysis showed that compounds bearing a benzenesulfonamide group had greater potency than those bearing a benzamide group. It was also shown that compounds with a mono-methyl or mono-halogen group at the 3-position on the terminal phenyl ring were more effective than those with trifluoromethyl or methoxy groups. Compound 8e exhibited the most potent anti-tumor activities against HCT116, MCF7 and 143B cell lines, with IC50 values of 0.597, 0.886 and 0.791 μM, respectively. Molecular docking studies and enzymatic assays demonstrated that the anti-tumor activity of compound 8e might be regulated by Cat L and Cat K.
Graphical abstract
http://ift.tt/2xcSR88
Bifunctional aryliodonium salts for highly efficient radioiodination and astatination of antibodies
Publication date: Available online 19 September 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): F. Guérard, L. Navarro, Y.-S. Lee, A. Roumesy, C. Alliot, M. Chérel, M.W. Brechbiel, J.-F. Gestin
In this report we describe the development of an alternative approach to arylstannane chemistry for radiolabeling antibodies with radioiodine or astatine based on aryliodonium salts precursors. Bifunctional aryliodonium salts were designed and tested for the synthesis of 125I and 211At labeled prosthetic groups for bioconjugation. The nature of the electron rich aryl group was varied and its impact on the regioselectivity of radiohalogenation was evaluated. Unexpectedly, whereas the 2-thienyl group provided the best regioselectivity towards the radioiodination of the aryl moiety of interest (98:2), it was less selective for astatination (87:13); the anisyl group providing the best regioselectivity in this case (94:6). Under optimized conditions, both radioiodination and astatination could be performed very efficiently in mild conditions (radiochemical yields > 85%). The ionic nature of the precursors was exploited to develop an efficient purification approach: the HPLC step that is usually necessary in conventionnal approaches to optimize removal of organotin toxic precursors and side products was replaced by a filtration through a silica cartridge with a significantly reduced loss of radiolabeled product. The purified radioiodinated and astatinated prosthetic groups were then conjugated efficiently to an anti-CD138 monoclonal antibody (75-80% conjugation yield). By using this novel and simple radiohalogenation procedure, higher overall radiochemical yields of astatination were obtained in comparison with the use of an arylstannane precursor and procedures of the litterature for labeling the same antibody. Overall, due to their simplicity of use and high robustness, these new precursors should simplify the labeling of proteins of interest with iodine and astatine radioisotopes for imaging and therapeutic applications.
Graphical abstract
http://ift.tt/2xcSI4A
New 5-HT1A, 5HT2A and 5HT2C receptor ligands containing a picolinic nucleus: Synthesis, in vitro and in vivo pharmacological evaluation
Publication date: Available online 17 September 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Ferdinando Fiorino, Elisa Magli, Ewa Kędzierska, Antonio Ciano, Angela Corvino, Beatrice Severino, Elisa Perissutti, Francesco Frecentese, Paola Di Vaio, Irene Saccone, Angelo A. Izzo, Raffaele Capasso, Paola Massarelli, Ilaria Rossi, Jolanta Orzelska-Gòrka, Jolanta Helena Kotlińska, Vincenzo Santagada, Giuseppe Caliendo
Picolinamide derivatives, linked to an arylpiperazine moiety, were prepared and their affinity to 5-HT1A, 5-HT2A and 5-HT2C receptors was evaluated. The combination of structural elements (heterocyclic nucleus, alkyl chain and 4-substituted piperazine), known to play critical roles in affinity for serotoninergic receptors, and the proper selection of substituents led to compounds with high specificity and affinity towards serotoninergic receptors. In binding studies, several molecules showed high affinity in nanomolar and subnanomolar range at 5-HT1A, 5-HT2A and 5-HT2C receptors and moderate or no affinity for other relevant receptors (D1, D2, α1 and α2). N-(2-(4-(pyrimidin-2-yl)piperazin-1-yl)ethyl)picolinamide (3o) with Ki = 0.046 nM, was the most affine and selective derivative for the 5-HT1A receptor compared to other serotoninergic dopaminergic and adrenergic receptors. N-(2-(4-(2-methoxyphenyl)piperazin-1-yl)ethyl)picolinamide (3b), instead, showed a subnanomolar affinity towards 5-HT2A with Ki = 0.0224 nM, whereas N-(2-(4-(bis(4-fluorophenyl)methyl)piperazin-1-yl)ethyl)picolinamide (3s) presented an attractive 5-HT2C affinity with Ki = 0.8 nM. Moreover, the compounds having better affinity and selectivity binding profiles towards 5-HT2A were selected and tested on rat ileum, to determine their effect on 5HT induced contractions. Those more selective towards 5-HT1A receptors were studied in vivo on several behavioral tests.
Graphical abstract
http://ift.tt/2xdGDfI
Prostate cancer post-prostatectomy radiotherapy: CT vs MRI for vesico-urethral anastomosis target delineation
Source:Radiotherapy and Oncology
Author(s): Daryl Lim Joon, Adeline Lim, Michal Schneider, Chee-Yan Hiew, Nathan Lawrentschuk, Shomik Sengupta, Farshad Foroudi, Trish Jenkins, David Angus, Morikatsu Wada, Michael Chao, Vincent Khoo
BackgroundVesico-urethral anastomosis (VUA) is critical to the clinical target volume (CTV) in post-prostatectomy radiotherapy (PPRT), as it is the commonest site of recurrence. Typically, this is performed on a CT alone but guidelines recommend MRI.ObjectiveTo evaluate the VUA spatial differences between CT (ctVUA) and MRI (mrVUA) and analyse its impact on the CT defined CTV (ctCTV) as recommended by published guidelines.Materials and methodsWe identified 34 patients with a co-registered simulation CT and T2 weighted MRI. The VUA was located on CT and MRI whilst blinded to the opposing scan. The differences were analysed using Wilcoxon's Signed Rank Test. The mrVUA coverage was investigated using three ctCTV margins of 5mm, 8mm and 12mm.ResultsMedian age was 63years with 59% having pT3a disease and median Gleason score of 7. The mrVUA was coincident with the ctVUA in 12% and inferior in 88%. Median difference was 5mm (0–10mm) (P<0.0001). Only a ctCTV margin of 12mm would have encompassed all mrVUAs. A ctCTV margin of 8mm and 5mm resulted in 12% and 38% cases where the VUA was excluded from the ctCTV.ConclusionsMRI is important for the accurate delineation of VUA for PPRT.
http://ift.tt/2jIGLhy
What is the optimal number of library plans in ART for locally advanced cervical cancer?
Source:Radiotherapy and Oncology
Author(s): E. Nováková, S.T. Heijkoop, S. Quint, A.G. Zolnay, J.W.M. Mens, J. Godart, B.J.M. Heijmen, M.S. Hoogeman
PurposeLibrary-of-plans ART is used to manage daily anatomy changes in locally advanced cervical cancer. In our institute, the library contains 2 VMAT plans for patients with large cervix-uterus motion. Increasing this number could be beneficial for tissue sparing, but is burdensome while the dosimetric gain is yet unclear. This study's aim is to determine the optimal number of plans at an individual patient level.Material and methodsData of 14 treated patients were analyzed. Plan libraries were created containing 1–4 VMAT plans. Pre-treatment extent of uterus motion was defined by the 99th percentile of the Hausdorff distance (HD99). For dosimetric evaluations, OARs were contoured in daily CBCT scans, plan selection was simulated, and the V45Gy and V40Gy parameters were recorded.ResultsModerate to strong correlations were found between HD99 and the volume of spared OARs. All patients benefitted from adding a 2nd plan, as is the clinical practice. For patients with a HD99 between 30 and 50mm, a 3-plan library reduced the composite V40Gy with 11–21ml compared to a 2-plan library.ConclusionPatients with large uterus motion (HD99>30mm) would benefit from an extension of the plan library to 3. HD99 is an easy-to-implement criteria to select those patients pre-treatment.
http://ift.tt/2xdUxhH
Heart dose associated with overall survival in locally advanced NSCLC patients treated with hypofractionated chemoradiotherapy
Source:Radiotherapy and Oncology
Author(s): Barbara Stam, Erik van der Bijl, Judi van Diessen, Maddalena M.G. Rossi, Angela Tijhuis, José S.A. Belderbos, Eugène Damen, Jan-Jakob Sonke
Association of heart dose and overall survival was investigated in a cohort including 469 locally-advanced NSCLC patients receiving daily low-dose hypofractionated chemo-radiotherapy. Significant associations were found over a range of dose parameters. Multivariate analysis showed significant associations of heart_V2Gy:HR=1.007%−1 (95% CI:1.002–1.013; p=0.006), age:HR=1.026year−1 (1.011–1.042; p=0.001) and GTV volume:HR=1.001cc−1 (1.000–1.002; p=0.006) with overall survival.
http://ift.tt/2jJS7lg
A pediatric case with peripheral facial nerve palsy caused by a granulomatous lesion associated with cat scratch disease
Source:Brain and Development
Author(s): Chizuko Nakamura, Yuji Inaba, Keiko Tsukahara, Mie Mochizuki, Emi Sawanobori, Yozo Nakazawa, Kouki Aoyama
BackgroundCat scratch disease is a common infectious disorder caused by Bartonella henselae that is transmitted primarily by kittens. It typically exhibits a benign and self-limiting course of subacute regional lymphadenopathy and fever lasting two to eight weeks. The most severe complication of cat scratch disease is involvement of the nervous system, such as encephalitis, meningitis, and polyneuritis. Peripheral facial nerve palsy associated with Bartonella infection is rare; few reported pediatric and adult cases exist and the precise pathogenesis is unknown.Case reportA previously healthy 7-year-old boy presented with fever, cervical lymphadenopathy, and peripheral facial nerve palsy associated with serologically confirmed cat scratch disease. The stapedius muscle reflex was absent on the left side and brain magnetic resonance imaging revealed a mass lesion at the left internal auditory meatus. The patient's symptoms and imaging findings were gradually resolved after the antibiotics and corticosteroids treatment.ConclusionsThe suspected granulomatous lesion was considered to have resulted from the host's immune reaction to Bartonella infection and impaired the facial nerve. This is the first case report providing direct evidence of peripheral facial nerve palsy caused by a suspected granulomatous lesion associated with cat scratch disease and its treatment course.
http://ift.tt/2xlbNRy
CACNA1A-related early-onset encephalopathy with myoclonic epilepsy: A case report
Source:Brain and Development
Author(s): Takuya Hayashida, Yoshiaki Saito, Atsushi Ishii, Hiroyuki Yamada, Ayako Itakura, Toshinori Minato, Tetsuhiro Fukuyama, Yoshihiro Maegaki, Shinichi Hirose
We report a one-year-old boy with early-onset myoclonic epilepsy, developmental arrest, and hyperekplexia during early infancy. He presented with refractory myoclonic/tonic seizures since birth. Electroencephalography revealed multifocal spikes, and rhythmic activities that occurred simultaneous with aggravation of myoclonus accompanied by tonic upper limb elevation. Brain magnetic resonance imaging revealed progressive cerebral atrophy with periventricular signal change and thin corpus callosum at one year of age. A de novo heterozygous missense mutation in the CACNA1A gene was confirmed. This patient was the most severe phenotype of CACNA1A-related early-onset encephalopathy among previous reports.
http://ift.tt/2wFaKbj
A targeted next-generation sequencing panel reveals novel mutations in Japanese patients with primary ciliary dyskinesia
Primary ciliary dyskinesia (PCD) is a rare genetic disorder caused by functional impairment of cilia throughout the body. The early diagnosis of PCD is important for the prevention of long-term sequelae; however, this is often challenging because of the phenotypic heterogeneity of PCD and difficulty in genetic analysis. The majority of PCD patients in Japan are not diagnosed properly. To diagnose PCD more accurately, we developed a targeted next-generation sequencing (NGS) panel.
http://ift.tt/2wvooTj
A targeted next-generation sequencing panel reveals novel mutations in Japanese patients with primary ciliary dyskinesia
Primary ciliary dyskinesia (PCD) is a rare genetic disorder caused by functional impairment of cilia throughout the body. The early diagnosis of PCD is important for the prevention of long-term sequelae; however, this is often challenging because of the phenotypic heterogeneity of PCD and difficulty in genetic analysis. The majority of PCD patients in Japan are not diagnosed properly. To diagnose PCD more accurately, we developed a targeted next-generation sequencing (NGS) panel.
http://ift.tt/2wvooTj
Human CD40L-expressing type 3 innate lymphoid cells induce IL-10-producing immature transitional regulatory B cells
ILC3-mediated induction of Breg cells is a novel, innate immunoregulatory mechanism that may contribute to the maintenance of immune tolerance and become insufficient in allergy, as the frequency of ILC3s is reduced in allergic diseases.
http://ift.tt/2hfQBTN
High prevalence of severe asthma in a large random population study
Every third asthmatic showed at least one sign of asthma severity which indicates that there are still many unmet needs in managing this disease. Asthma severity phenotypes are very diverse prompting an individualized approach to patients.
http://ift.tt/2hg9E3K
TLR7/8 agonists stimulate plasmacytoid dendritic cells to initiate a Th17-deviated acute contact dermatitis in humans
Stimulation of TLR7/8 in human skin induces an acute contact dermatitis with pDC as primary sensors and IL-23 as essential driver of the reaction, thus constituting a standardized, but limited model of human psoriasis.
http://ift.tt/2hfQAiH
Th1 Signatures Are Present in the Lower Airways of Children with Severe Asthma, Regardless of Allergic Status
A Th1 signature dominates the lower airways of children with severe asthma, regardless of allergic status. Our findings warrant further investigation of the contributions of Th1 cells to the development and maintenance of severe asthma.
http://ift.tt/2he4NQL
An unusual case of temporal bone encephalomeningocele occurring together with normal pressure hydrocephalus
Temporal bone encephalomeningoceles are uncommon clinical entities that can be challenging to diagnose and treat. Common presenting complaints include symptoms of aural fullness, hearing loss, clear otorrhea and meningitis. Common etiologies are chronic middle ear disease and trauma. A significant proportion of cases are spontaneous, which occurs in relation to benign intracranial hypertension. Normal pressure hydrocephalus associated with temporal bone encepahomeningoceles has not been previously described.
http://ift.tt/2xdHUTH
An unusual case of temporal bone encephalomeningocele occurring together with normal pressure hydrocephalus
Temporal bone encephalomeningoceles are uncommon clinical entities that can be challenging to diagnose and treat. Common presenting complaints include symptoms of aural fullness, hearing loss, clear otorrhea and meningitis. Common etiologies are chronic middle ear disease and trauma. A significant proportion of cases are spontaneous, which occurs in relation to benign intracranial hypertension. Normal pressure hydrocephalus associated with temporal bone encepahomeningoceles has not been previously described.
http://ift.tt/2xdHUTH
Influence and mechanism of 5-aminolevulinic acid-photodynamic therapy on the metastasis of esophageal carcinoma
Source:Photodiagnosis and Photodynamic Therapy, Volume 20
Author(s): Xiaona Zhang, Longmei Cai, Jingcai He, Xiaoyan Li, Libo Li, Xiaohua Chen, Ping Lan
BackgroudPhotodynamic therapy (PDT) for the treatment of esophageal cancer was more and more popularly used since it was approved for the treatment of advanced esophageal cancer in 1996. It has been reported to influence the tumor growth and metastasis via a variety of signaling pathways, but its mechanism remains to be further studied. This research studied the effects of ALA-PDT on esophageal carcinoma in vitro and in vivo, discovering its molecular regulating mechanism and the way to enhence the PDT effect.MethodsEca-109 cells were incubated with a medium containing EGFR tyrphostin AG1478 or PI3K inhibitor LY294002, then with ALA, and the cells were irradiated with the laser 6h later. The cell viability was measured with MTT assay, and the migration ability was detected by transwell experiments 24h post-ALA-PDT. The gene and protein expression on EGFR/PI3K/AKT signaling pathway was analyzed by realtime PCR and Western blotting respectively. Then, RFP-Eca-109 burdened nude mice model was constructed, and were treated with ALA-PDT when the tumor volume reached 150–350mm3. The gene and protein expression were analyzed 24h and 50days post-ALA-PDT.ResultsOur study showed that ALA-PDT respectively combined with AG1478, LY294002 could synergistically reduce the growth and migration ability of the Eca-109 cells in vitro and significantly down-regulate the protein expression of EGFR/PI3K and PI3K/AKT, meanwhile, significantly down-regulate the gene expression of EGFR when combining with AG1478. Forthermore, ALA-PDT could significantly decrease the tumor growth and metastasis and down-regulate the gene expression of EGFR and the protein expression of EGFR and PI3K in the tumor of mice.ConclusionThis study revealed a molecular mechanism of ALA-PDT and developed a new modality application of therapy, by combining ALA-PDT with small molecular inhibitors, for better effect in the clinical practice of esophageal carcinoma.
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Effect of albumin on the fluorescence quantum yield of porphyrin -based agents for fluorescent diagnostics
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Vladimir V. Zarubaev, Tatyana C. Kris'ko, Elelna V. Kriukova, Tatyana D. Muraviova
BackgroundAmong modern methods of diagnostics of tumors, the fluorescent methods are considered ones of the most prospective. Diagnostic agents (DAs) spread throughout the body by the bloodstream, so, the DA molecules are often transported by albumins and can be affected by these proteins. In our study we evaluate the effect of complex formation between bovine serum albumin (BSA) and three fluorescence DA's (Photolon, Photoditazin and Dimegin) on their fluorescent quantum yields.MethodsElectron absorption spectroscopy and fluorescence spectroscopy were carried out to calculate fluorescence quantum yields of the DAs using Rhodamine 6G as a standard fluorescent dye.ResultsFor all three DA's dissolved in phosphate buffer with pH 7.5 (close to that of blood) the addition of albumin resulted in bathochromic shift of the Soret band as well as change of amplitudes of absorption bands. Similar changes were observed for fluorescence spectra of all DAs that are connected with complex formation between DA and albumin. The presence of isobestic point suggests that DA can present in the solution only in two states, free and BSA-bound. Chlorine-based DA's demonstrate about 1.5-times higher fluorescence quantum yield in PBS than Dimegin. Nevertheless, the addition of BSA to the solutions of all DA's decreases sharply their fluorescence quantum yield to approximately equal values.ConclusionThe complex formation between DA and albumin equalize fluorescence efficacies of all studied DAs, so the results of photodymanic diagnostics using the specific DA will depend on other factors.
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Neurosurgical Microscopic Solid Laser-based Light Inhibits Photobleaching during Fluorescence-Guided Brain Tumor Removal with 5-Aminolevulinic Acid
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Fumitaka Matsuda, Naokado Ikeda, Yoshinaga Kajimoto, Naosuke Nonoguchi, Koji Takeuchi, Masao Fukumura, Shinji Kawabata, Motomasa Furuse, Tetsuo Sugano, Taku Sato, Kiyoshi Saito, Toshihiko Kuroiwa
BackgroundFluorescence image guided surgery (FIGS) with 5-aminolevulinic acid for malignant gliomas improves surgical outcome. One of the problems during FIGS is photobleaching under surgical microscopic white light. A solid laser-based white light source for neurosurgery that we developed does not include light with a wavelength of around 405nm, which is strongly absorbed by protoporphyrin IX. In the present study, we examined the efficacy of this light source to prevent the photobleaching of protoporphyrin IX-induced fluorescence.MethodsFilter papers transfused with protoporphyrin IX solution and a coronally sectioned F98 glioma rat model pretreated with 50mg/kg 5-aminolevulinic acid were continuously exposed to white light. One group was exposed to conventional xenon-based white light and another group was exposed to laser-based white light. Fluorescence at a wavelength of 635nm was measured with a radiospectrometer (in vitro study) and the relative fluorescence brightness was also measured in digital images (in vivo study) under excitation from violet blue light emitted from diodes every 5min.Results and conclusionEstimated time for 50% photobleaching was prolonged about two times in the laser-based white light exposure group compared with that in the xenon-based white light exposure group (9.1/18.7min). In the brain tumor rat model, it was also prolonged about 2.7 times (15.1/40.7min). A laser-based white light source may inhibit photobleaching during FIGS for malignant gliomas. This light source for neurosurgical microscopy has the potential to prolong the prognosis of malignant glioma patients.
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Photodynamic therapy in combination with Ranibizumab versus Ranibizumab monotherapy for polypoidal choroidal vasculopathy: A systematic review and meta-analysis
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Lei Liu, Yih-Chung Tham, Jingyang Wu, Song Yue, Ching-Yu Cheng
PurposeTo perform a systematic review and meta-analysis to compare the outcome and serious adverse effects of intravitreal ranibizumab (IVR) monotherapy vs. combined treatment of IVR and photodynamic therapy (PDT) on polypoidal choroidal vasculopathy (PCV).MethodsA computerized online search was performed using PubMed, EMBASE, Cochrane Library, Web of Science and China National Knowledge Infrastructure (CNKI) database. The quality of included studies was evaluated according to the Newcastle-Ottawa Scale. Stata 11.0 software was used to do the Meta-analysis.ResultsAfter a detailed systematic review, 4 articles (5 study samples) were included for this meta-analysis. PCV eyes treated with PDT combined with IVR achieved better best-corrected visual acuity (BCVA) than IVR monotherapy group throughout a follow-up of 12(th) month (weight mean difference [WMD] in BCVA, 0.132; 95% CI, 0.029-0.234, p=0.012). Further meta-analysis including studies with 24-month follow up period showed that BCVA at 24(th) month was also better in the combined treatment group than the monotherapy group (WMD in BCVA=0.234; 95% CI, 0.071-0.398, p=0.005). There were no significant differences both in serious ocular adverse effects and non-ocular adverse effects (p >0.05) between two groups.ConclusionsTreatment of PCV by PDT combine with IVR is valuable in improving visual acuity and maintaining long term effectiveness. Given the inherent limitations of the included researches, more future studies are needed to further validate and update the findings in this area.
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Incidence rate of breakthrough varicella observed in healthy children after 1 or 2 doses of varicella vaccine: Results from a meta-analysis
Source:American Journal of Infection Control
Author(s): Sui Zhu, Fangfang Zeng, Lan Xia, Hong He, Juying Zhang
BackgroundAlthough extensive varicella vaccination coverage has been reported in many countries, breakthrough varicella (BV) still occurs in healthy children. We performed a meta-analysis to understand whether 2 varicella vaccine doses are needed in children and, if so, to determine the best time to vaccinate.MethodsThe BV incidence rates after 1 or 2 doses of varicella vaccine were pooled using random effects, and 95% confidence intervals (CI) were used to estimate the risk factors after vaccination.ResultsA total of 27 original articles were included in this meta-analysis. The pooled average BV incidence rate in children vaccinated with 1 dose was 8.5 cases per 1,000 person years (PY) (95% confidence interval [CI], 5.3-13.7; random effects model) and 2.2 cases per 1,000 PY (95% CI, 0.5-9.3; random effects model) in children vaccinated with 2 doses. The pooled trend of the annual BV incidence rate from the first to eighth year fluctuated, with a peak annual incidence rate of 35.3 cases per 1,000 population in the fourth year. The meta-regression showed that design type, type of vaccine, and their interaction accounted for approximately 71.74% of the heterogeneity in the average BV incidence rate after 1 vaccine dose.ConclusionsTwo doses of varicella vaccine are more effective than a single dose, and 3-4 years between the first and second vaccinations may achieve higher efficacy.
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Stalking a lethal superbug by whole-genome sequencing and phylogenetics: Influence on unraveling a major hospital outbreak of carbapenem-resistant Klebsiella pneumoniae
Source:American Journal of Infection Control
Author(s): Thorsten Kaiser, Knut Finstermeier, Madlen Häntzsch, Sarah Faucheux, Martin Kaase, Tim Eckmanns, Sven Bercker, Udo X. Kaisers, Norman Lippmann, Arne C. Rodloff, Joachim Thiery, Christoph Lübbert
BackgroundFrom July 2010-April 2013, Leipzig University Hospital experienced the largest outbreak of a Klebsiella pneumoniae carbapenemase 2 (KPC-2)-producing Klebsiella pneumoniae (KPC-2-Kp) strain observed in Germany to date. After termination of the outbreak, we aimed to reconstruct transmission pathways by phylogenetics based on whole-genome sequencing (WGS).MethodsOne hundred seventeen KPC-2-Kp isolates from 89 outbreak patients, 5 environmental KPC-2-Kp isolates, and 24 K pneumoniae strains not linked to the outbreak underwent WGS. Phylogenetic analysis was performed blinded to clinical data and based on the genomic reads.ResultsA patient from Greece was confirmed as the source of the outbreak. Transmission pathways for 11 out of 89 patients (12.4%) were plausibly explained by descriptive epidemiology, applying strict definitions. Five of these and an additional 15 (ie, 20 out of 89 patients [22.5%]) were confirmed by phylogenetics. The rate of phylogenetically confirmed transmissions increased significantly from 8 out of 66 (12.1% for the time period before) to 12 out of 23 patients (52.2% for the time period after; P < .001) after implementation of systematic screening for KPC-2-Kp (33,623 screening investigations within 11 months). Using descriptive epidemiology, systematic screening showed no significant effect (7 out of 66 [10.6%] vs 4 out of 23 [17.4%] patients; P = .465). The phylogenetic analysis supported the assumption that a contaminated positioning pillow served as a reservoir for the persistence of KPC-2-Kp.ConclusionsEffective phylogenetic identification of transmissions requires systematic microbiologic screening. Extensive screening and phylogenetic analysis based on WGS should be started as soon as possible in a bacterial outbreak situation.
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Methodology minute: A guide for infection preventionists for sizing up systematic reviews
Source:American Journal of Infection Control
Author(s): Patti Grota, Linda McKinley, Emme Lopez
Systematic reviews have become a key strategy to identifying evidence-based practice guidelines in infection prevention. They are considered the highest level of evidence providing the most effective answers to practice questions. Infection preventionists need to become familiar with reading systematic reviews and learn to critically appraise the findings and implications for practice. A systematic literature review is a rigorous preplanned process established to answer a specific practice question. The preplanned methods are detailed in the final publication. There are several key components that should be outlined in systematic reviews, which are briefly reviewed here.
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The photosynthetic responses to stocking depth and algal mat density in the farmed seaweed Gracilaria lemaneiformis (Gracilariales, Rhodophyta)
Abstract
The branches and mass of Gracilaria lemaneiformis increase with growth season, and the thalli sink to deeper depths with increasing biomass density during maricultivation. The changing depth and algal mat density may affect the physiology of the algae. In the present study, the photosynthetic behaviors regarding different biomass densities in G. lemaneiformis thalli collected from different stocking depths were determined, to examine how photosynthesis of this farmed alga was affected by the growth depths and algal mat densities. Our results showed that the chlorophyll a (Chl a), carotenoids (Car), phycoerythrin (PE) contents, and irradiance-saturated maximum photosynthetic rates (P max) of the deeper layer-grown algae were significantly increased relative to the surface layer-grown algae. The P max, apparent photosynthetic efficiency (α) and dark respiration rate (R d) of G. lemaneiformis thalli, were reduced, whereas the irradiance saturation points (I k) were increased, with the increasing algal mat density. We proposed that appropriate measures are needed to trade off the stocking depth and biomass density, in an effort to maintain a relative high photosynthetic productivity during G. lemaneiformis maricultivation.
http://ift.tt/2xkYYGB
Monitoring of Incremental Changes in Maximum Interincisal Opening After Gap Arthroplasty Omits the Risk of Re-ankylosis
The aim of this clinical study was to prospectively measure the incremental changes in the MIO after 1 cm gap arthroplasty, compare these changes between unilateral and bilateral cases, and emphasize the importance of the monitoring of the MIO for at least 24 months.
http://ift.tt/2hheYQX
Blood plasma traits associated with genetic merit for feed utilization in Holstein cows
Publication date: October 2017
Source:Journal of Dairy Science, Volume 100, Issue 10
Author(s): C.D. Dechow, C.R. Baumrucker, R.M. Bruckmaier, J.W. Blum
The objective of this study was to evaluate the potential of selection for feed utilization on associated blood plasma metabolite and hormone traits. Dry matter intake (DMI) was recorded in 970 Holsteins from 11 commercial farms in Pennsylvania and used to derive dry matter efficiency (DME; fat-corrected milk yield/DMI), crude protein efficiency (CPE; protein yield/crude protein intake), and residual feed intake (RFI, defined as actual feed intake minus expected feed intake for maintenance and milk production, based on calculation of DMI adjusted for yield, body weight, and body condition score). Estimated breeding values for the 4 feed utilization traits (DMI, DME, CPE, and RFI), yield traits, body traits, and days open were standardized according to their respective genetic standard deviations. Up to 631 blood samples from 393 cows from 0 to 60 d in milk (DIM) were evaluated for blood plasma concentrations of glucose, nonesterified fatty acids (NEFA), β-hydroxybutyrate (BHB), creatinine, urea, growth hormone (GH), 3,5,3′-triiodothyronine (T3), and other parameters. Blood plasma traits were regressed on DIM, lactation number, herd, and standardized genetic merit. Cows with higher genetic merit for yield had significantly higher concentrations of GH, NEFA (milk and protein yield), and BHB (fat yield) from 31 to 60 DIM, but lower concentrations of glucose from 0 to 30 DIM, and T3 (milk yield, 0–60 DIM). The high GH–low glucose–low T3 concentration pattern was further accentuated for cows with genetic merit for enhanced feed efficiency (higher DME and lower RFI). Cows with a genetic tendency to be thin (low body condition score) also had elevated GH concentrations, but lower blood glucose, creatinine, and T3 concentrations. Those characteristics associated with enhanced feed efficiency (higher GH and lower glucose and T3 concentrations) were unfavorably associated with fertility, as indicated by elevated days open. Elevated NEFA and BHB concentrations were also associated with extended days open. Consideration of metabolic profiles when evaluating feed efficiency might be a method of maintaining high levels of health and reproductive fitness when selecting for feed efficiency.
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News and Announcements
Source:Journal of Dairy Science, Volume 100, Issue 10
http://ift.tt/2jIekjK
Invited review: A systematic review and qualitative analysis of treatments other than conventional antimicrobials for clinical mastitis in dairy cows
Publication date: October 2017
Source:Journal of Dairy Science, Volume 100, Issue 10
Author(s): D. Francoz, V. Wellemans, J.P. Dupré, J.P. Roy, F. Labelle, P. Lacasse, S. Dufour
Clinical mastitis is an important disease in dairies. Its treatment is mainly based on the use of antimicrobial drugs. Numerous non-antimicrobial drugs and treatment strategies have already been reported for clinical mastitis treatment, but data on their efficacy have never been collated in a systematic way. The objective of this systematic review was to identify treatments other than conventional antimicrobials for the treatment of clinical mastitis in lactating dairy cows. A systematic review was performed with studies written in English or French selected from CAB Abstracts, PubMed, and Web of Science from January 1970 to June 2014. Controlled clinical trials, observational studies, and experimental challenges were retained. Lactating dairy cows with clinical mastitis were the participant of interest. All treatments other than conventional antimicrobials for clinical mastitis during lactation were retained. Only studies comparing the treatment under investigation to a negative or positive control, or both, were included. Outcomes evaluated were clinical and bacteriological cure rates and milk production. Selection of the study, data extraction, and assessment of risk of bias was performed by 3 reviewers. Assessment of risk of bias was evaluated using the Cochrane Collaboration tool for systematic review of interventions. A total of 2,451 manuscripts were first identified and 39 manuscripts corresponding to 41 studies were included. Among these, 22 were clinical trials, 18 were experimental studies, and 1 was an observational study. The treatments evaluated were conventional anti-inflammatory drugs (n = 14), oxytocin with or without frequent milk out (n = 5), biologics (n = 9), homeopathy (n = 5), botanicals (n = 4), probiotics (n = 2), and other alternative products (n = 2). All trials had at least one unclear or high risk of bias. Most trials (n = 13) did not observe significant differences in clinical or bacteriological cure rates in comparison with negative or positive controls. Few studies evaluated the effect of treatment on milk yield. In general, the power of the different studies was very low, thus precluding conclusions on noninferiority or nonsuperiority of the treatments investigated. No evidence-based recommendations could be given for the use of an alternative or non-antimicrobial conventional treatment for clinical mastitis. However, probiotics and oxytocin with or without frequent milk out should not be recommended. We concluded that homeopathic treatments are not efficient for management of clinical mastitis.
http://ift.tt/2xcZrM3
Health-promoting benefits of low-fat akawi cheese made by exopolysaccharide-producing probiotic Lactobacillus plantarum isolated from camel milk
Source:Journal of Dairy Science, Volume 100, Issue 10
Author(s): Ayesha S. Al-Dhaheri, Reem Al-Hemeiri, Jaleel Kizhakkayil, Anas Al-Nabulsi, Aisha Abushelaibi, Nagendra P. Shah, Mutamed Ayyash
Lactic acid bacteria isolated from camel milk exhibit remarkable probiotic and exopolysaccharide (EPS)-producing characteristics. The health-promoting benefits of exopolysaccharide-producing probiotic Lactobacillus plantarum isolated from camel milk used for making low-fat akawi cheese were investigated. Three low-fat akawi cheeses were made using traditional culture (non-EPS-producing, EPS−), commercial EPS-producing (MEPS+), and camel milk EPS-producing (CEPS+) cultures. α-Amylase and α-glucosidase inhibitory activities, antioxidant activities, angiotensin-converting enzyme (ACE) inhibition, and antiproliferative activity were determined. Cheese made with CEPS+ culture exhibited comparable α-amylase inhibition to that of cheeses made with MEPS+. Scavenging rates of cheese made with EPS+ cultures were higher than those of cheese made with EPS− cultures. The percentage of α-glucosidase inhibition ranged from >45% at 0 d to ∼55% at 21 d of storage. After 7 d of storage, the scavenging rate in CEPS+ cheese increased >60% by ABTS assay [2,2'-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid)] and >20% by DPPH assay (1,1-diphenyl-2-picrylhydrazyl). Throughout storage, cheese made with EPS+ cultures showed higher ACE-inhibition activity compared with EPS− cultures. Cheese made with CEPS+ showed ACE inhibition >70% after 7 d of storage. Antiproliferation activity of CEPS+ cheese increased from 38 to 48% during 7 d of storage and was maintained above 45% with prolonged storage. Low-fat akawi cheese produced with these cultures exhibited similar or greater health-promoting benefits compared with cheese made using commercial starter cultures. Therefore, incorporation of these cultures in food is promising for commercial uses.
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Interpretive Summaries, October 2017
Source:Journal of Dairy Science, Volume 100, Issue 10
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Lowering rumen-degradable protein maintained energy-corrected milk yield and improved nitrogen-use efficiency in multiparous lactating dairy cows exposed to heat stress
Source:Journal of Dairy Science, Volume 100, Issue 10
Author(s): J.D. Kaufman, K.R. Kassube, A.G. Ríus
The objective of this study was to examine the effect of reducing rumen-degradable protein (RDP) and rumen-undegradable protein (RUP) proportions on feed intake, milk production, and N-use efficiency in primiparous and multiparous cows exposed to warm climates. Eighteen primiparous and 30 multiparous mid-lactation Holstein cows were used in a completely randomized design with a 2 × 2 factorial arrangement of treatments. Cows were randomly assigned to 1 of 4 dietary treatments formulated to contain 2 proportions of RDP (10 and 8%) and 2 proportions RUP (8 and 6%) of dry matter (DM) indicated as follows: (1) 10% RDP, 8% RUP; (2) 8% RDP, 8% RUP; (3) 10% RDP, 6% RUP; and (4) 8% RDP, 6% RUP. Protein sources were manipulated to obtain desired RDP and RUP proportions. Diets were isoenergetic and contained 50% forage and 50% concentrate (DM basis). Cows were individually fed the 10% RDP, 8% RUP diet 3 wk before treatment allocation. Cows were exposed to the prevailing Tennessee July and August temperature and humidity in a freestall barn with no supplemental cooling. Main effects and their interaction were tested using the Mixed procedure of SAS (least squares means ± standard error of the mean; SAS Institute Inc., Cary, NC). Observed values of nutrient intake and milk production were used to obtain NRC (2001) model predictions. Cows showed signs of heat stress throughout the study. Reducing from 10 to 8% RDP decreased dry matter intake (DMI; 0.9 kg/d) at 8% RUP, but increased DMI (2.6 kg/d) at 6% RUP in primiparous cows. Reducing from 10 to 8% RDP decreased milk yield (10%) at 8% RUP, but increased yield (14%) at 6% RUP. Treatments did not affect yield of energy-corrected milk. For multiparous cows, treatments did not affect DMI. Reducing from 10 to 8% RDP decreased yield of energy-corrected milk (3.4%) at 8% RUP, but increased yield (8.8%) at 6% RUP. Reducing from 10 to 8% RDP and 8 to 6% RUP both increased N-use efficiency for primiparous and multiparous cows. The NRC model underestimated metabolizable protein and RUP supply, and overestimated RUP requirements, resulting in predictive losses of milk yield 1.4 to 5.8 times greater than observed values. In summary, the reduction of RDP and RUP proportions did not affect DMI, whereas the RUP reduction at 10% RDP had a small negative effect on energy-corrected milk yield. However, reduction of RDP and RUP consistently improved N-use efficiency of heat-stressed multiparous cows. The reduction of RDP and RUP proportions reduced DMI and milk yield but did not affect energy-corrected milk yield in primiparous cows, indicating a limited supply of nutrients.
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Development of a new real-time quantitative PCR assay for the detection of Staphylococcus aureus genotype B in cow milk, targeting the new gene adlb
Source:Journal of Dairy Science, Volume 100, Issue 10
Author(s): C. Sartori, R. Boss, I. Ivanovic, H.U. Graber
The specific and reliable diagnosis of mastitis pathogens is essential for successful sanitation programs. The aim of the present study was to develop and evaluate a new real-time quantitative PCR (qPCR) assay for the very sensitive and specific detection of Staphylococcus aureus genotype B in cow milk samples. This mastitis pathogen is contagious and particularly prevalent in Switzerland and other central European countries. The new test is based on a rapid preparation of bacteria, followed by DNA isolation and qPCR for a unique target gene coding for the adhesion-like bovine protein (adlb). The inclusivity of the new target gene was 97% and the exclusivity 98%, meaning that other genotypes and bacterial species could be excluded with high reliability. The limit of detection of the new assay was 235 staphylococcal cell equivalents/mL of culture. The new test shows high intra- and interassay repeatability. Results are available within 2 d after sampling, allowing farmers and veterinarians to apply sanitation measures immediately. Based on the results of a preliminary field study, the diagnostic sensitivity and specificity of the new qPCR assay are 99 and 100%, respectively. The new analytical procedure is straightforward and can be applied for routine diagnostics.
http://ift.tt/2jG6Rln
Fate of Listeria innocua during production and ripening of smeared hard cheese made from raw milk
Source:Journal of Dairy Science, Volume 100, Issue 10
Author(s): P. Hammer, W. Bockelmann, W. Hoffmann
The fate of 2 different Listeria innocua strains was analyzed during the production and ripening of smeared raw milk Greyerzer cheese (Gruyère). These strains were used as surrogates for the pathogenic Listeria monocytogenes, as they are physiologically very similar. Bacterial cells were added to the cheese milk at levels of 105 cfu/mL. During the first 24 h of cheese making, the number of the test strains decreased to a level of below 102 cfu/g. Obviously, the cooking temperature of 56°C and the subsequent slight temperature decrease to 50°C within 70 min contributed to a distinct reduction of Listeria counts. The counts in the cheese cores did not exceed 103 cfu/g within 12 wk of cheese ripening and Listeria was not detectable after 24 wk. In contrast to the cores of the cheeses of the 4 batches in this study, their rinds always contained a high listerial load of approximately 106 to 108 cfu/g throughout the entire ripening period. The smeared surface showed an increase of pH to alkaline values, corresponding to smear microbiota development. Coryneforms and Staphylococcus counts were stable at >107 cfu/cm2 over 175 d, whereas yeast counts decreased to about 105 cfu/cm2 at the end of ripening. The study shows that the smear culture had no noticeable anti-listerial potential. When removing the rind or portioning such smeared cheese loaves with a cutting device, a postprocess contamination of the core might occur, thus presenting a major hygienic risk.
http://ift.tt/2xdHKf6
Multiplex PCR coupled with propidium monoazide for the detection of viable Cronobacter sakazakii, Bacillus cereus, and Salmonella spp. in milk and milk products
Publication date: October 2017
Source:Journal of Dairy Science, Volume 100, Issue 10
Author(s): Shuang Yu, Leina Yan, Xin Wu, Fan Li, Dong Wang, Hengyi Xu
Cronobacter sakazakii, Bacillus cereus, and Salmonella spp. are common food-borne pathogens. The aim of this study was to develop a sensitive, specific, and rapid method for the simultaneous detection of these 3 pathogens in milk and milk products. Three specific primers were designed based on ompA, invA, and cesB of C. sakazakii, Salmonella spp. and B. cereus, respectively, for use in a multiplex PCR (mPCR). To eliminate false-positive results, cells were pretreated with propidium monoazide (PMA) for the selective elimination of the genomic DNA of dead cells. An internal amplification control was applied as an indicator of false-negative results from the interference of inhibitors in the food matrix. Results showed that, in pure culture, the limits of detection of the assay for C. sakazakii, Salmonella Enteritidis, and B. cereus were 9.5 × 104, 7.4 × 102, and 7.5 × 102 cfu/mL, respectively. Moreover, 8 cfu/mL of viable B. cereus cells were detected after 5 h of enrichment, and 9 cfu/mL of viable C. sakazakii and 7 cfu/mL of Salmonella Enteritidis were detected after 7 h of enrichment in spiked pure milk, walnut peanut milk, and whole-wheat milk. To validate the PMA-mPCR assay, the PMA-mPCR assay and the traditional culture method were performed to detect the 3 bacterial strains in 1,165 milk product samples. The PMA-mPCR assay obtained the same results as the culture-based method. Results demonstrated that the PMA-mPCR assay has excellent sensitivity and specificity for the simultaneous detection of viable C. sakazakii, Salmonella Enteritidis, and B. cereus in milk and milk products.
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Relationships between postruminal casein infusion and milk production, and concentrations of plasma amino acids and blood urea in dairy cows: A multilevel mixed-effects meta-analysis
Source:Journal of Dairy Science, Volume 100, Issue 10
Author(s): R. Martineau, D.R. Ouellet, E. Kebreab, R.R. White, H. Lapierre
The relationships between postruminal casein infusion and production variables and concentrations of plasma AA and blood urea were evaluated using multilevel mixed-effects models derived from literature data collected in dairy cows. The data set contained 147 treatment means [i.e., 66 controls (CTL) and 81 casein-infused (CAS) means]. Each CAS mean was paired with its corresponding CTL mean to create 81 mean differences (CAS minus CTL), which were analyzed as absolute and percentage-based units (i.e., percentage increase or decrease in CAS relative to CTL). The primary variable of interest was the difference in estimated metabolizable protein (MP) supply (ΔMP) between CAS and CTL. The other explanatory variables were based on levels in CTL: MP supply, MP balance, the ratio of duodenal microbial protein (MCP) to MP supply (MCPMP), the stage of lactation (early or mid/late) and the type of forage (grass/legume- or corn silage-based). The MP supply and MP balance influenced negatively the relationship between ΔMP and the response of true protein yield. Responses of milk urea, blood urea, and plasma urea cycle AA concentrations were associated positively with ΔMP, indicating that a large amount of infused AA was catabolized to urea. Responses of plasma essential AA concentrations were related positively to ΔMP. The relative effect of ΔMP was highest for responses of plasma His concentration in cows fed grass/legume-based diets and at high MCPMP ratios. This relationship suggests that positive responses of plasma His concentrations are associated with diets relying heavily on microbial protein synthesis (high MCP), low in crude protein (low estimated MP supply), or both. The relationship between ΔMP and responses of plasma group 2 AA (Ile, Leu, Lys, and Val) concentrations was approximately 2 times greater than that for group 1 AA (His, Met, and Phe+Tyr) at mean MCPMP and MP supply. This could reflect the low hepatic removal group 2 AA compared with group 1 AA in dairy cows. Collectively, these results provide novel information on how dietary and cow conditions may alter responses to protein supplementation.
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Short communication: Pseudomonas azotoformans causes gray discoloration in HTST fluid milk
Source:Journal of Dairy Science, Volume 100, Issue 10
Author(s): Rachel L. Evanowski, Samuel J. Reichler, David J. Kent, Nicole H. Martin, Kathryn J. Boor, Martin Wiedmann
Pseudomonas species are well recognized as dairy product spoilage organisms, particularly due to their ability to grow at refrigeration temperatures. Although Pseudomonas-related spoilage usually manifests itself in flavor, odor, and texture defects, which are typically due to production of bacterial enzymes, Pseudomonas is also reported to cause color defects. Because of consumer complaints, a commercial dairy company shipped 4 samples of high temperature, short time (HTST)-pasteurized milk with distinctly gray colors to our laboratory. Bacterial isolates from all 4 samples were identified as Pseudomonas azotoformans. All isolates shared the same partial 16S rDNA sequence and showed black pigmentation on Dichloran Rose Bengal Chloramphenicol agar. Inoculation of one pigment-producing P. azotoformans isolate into HTST-pasteurized fluid milk led to development of gray milk after 14 d of storage at 6°C, but only in containers that had half of the total volume filled with milk (∼500 mL of milk in ∼1,000-mL bottles). We conclusively demonstrate that Pseudomonas can cause a color defect in fluid milk that manifests in gray discoloration, adding to the palette of color defects known to be caused by Pseudomonas. This information is of considerable interest to the dairy industry, because dairy processors and others may not typically associate black or gray colors in fluid milk with the presence of microbial contaminants but rather with product tampering (e.g., addition of ink) or other inadvertent chemical contamination.
http://ift.tt/2jIrq0l
Standardization of milk mid-infrared spectrometers for the transfer and use of multiple models
Publication date: October 2017
Source:Journal of Dairy Science, Volume 100, Issue 10
Author(s): C. Grelet, J. A. Fernández Pierna, P. Dardenne, H. Soyeurt, A. Vanlierde, F. Colinet, C. Bastin, N. Gengler, V. Baeten, F. Dehareng
An increasing number of models are being developed to provide information from milk Fourier transform mid-infrared (FT-MIR) spectra on fine milk composition, technological properties of milk, or even cows' physiological status. In this context, and to take advantage of these existing models, the purpose of this work was to evaluate whether a spectral standardization method can enable the use of multiple equations within a network of different FT-MIR spectrometers. The piecewise direct standardization method was used, matching "slave" instruments to a common reference, the "master." The effect of standardization on network reproducibility was assessed on 66 instruments from 3 different brands by comparing the spectral variability of the slaves and the master with and without standardization. With standardization, the global Mahalanobis distance from the slave spectra to the master spectra was reduced on average from 2,655.9 to 14.3, representing a significant reduction of noninformative spectral variability. The transfer of models from instrument to instrument was tested using 3 FT-MIR models predicting (1) the quantity of daily methane emitted by dairy cows, (2) the concentration of polyunsaturated fatty acids in milk, and (3) the fresh cheese yield. The differences, in terms of root mean squared error, between master predictions and slave predictions were reduced after standardization on average from 103 to 17 g/d, from 0.0315 to 0.0045 g/100 mL of milk, and from 2.55 to 0.49 g of curd/100 g of milk, respectively. For all the models, standard deviations of predictions among all the instruments were also reduced by 5.11 times for methane, 5.01 times for polyunsaturated fatty acids, and 7.05 times for fresh cheese yield, showing an improvement of prediction reproducibility within the network. Regarding the results obtained, spectral standardization allows the transfer and use of multiple models on all instruments as well as the improvement of spectral and prediction reproducibility within the network. The method makes the models universal, thereby offering opportunities for data exchange and the creation and use of common robust models at an international level to provide more information to the dairy sector from direct analysis of milk.
http://ift.tt/2jIsqSg
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