Definitive and adjuvant radiotherapy for sinonasal squamous cell carcinomas: a single institutional experience

Background: The aim of this study was to evaluate the disease outcomes of patients treated with definitive and adjuvant radiotherapy for squamous cell carcinomas of the nasal cavity and paranasal sinuses in a single institution. Methods: Between 2007–2012 patients were retrospectively identified from electronic databases who had undergone surgery and adjuvant radiotherapy or definitive radiotherapy for sinonasal squamous cell carcinomas with curative intent. Results: Fourty three patients with sinonasal squamous cell carcinoma were identified (22 nasal cavity, 21 paranasal sinuses). 31/43 (72 %) had T3 or T4 disease; nodal stage was N0 in 38, N1 in 4, Na/b in 0 and N2c in 1 patient. Median age was 67 years (range 41–86). 18 (42 %) received definitive and 25 (58 %) adjuvant radiotherapy. Radiotherapy was delivered using either conventional radiotherapy (n = 39) or intensity modulated radiotherapy (n = 4). Elective neck radiotherapy was delivered to two patients. Chemotherapy was delivered to 6/43 (14 %) of patients. Two-year local control, regional control, distant metastases free survival, progression free survival, cause specific survival and overall survival were 81 %, 90 %, 95 %, 71 %, 84 % and 80 % respectively. There was no significant difference in outcome comparing patients who underwent surgery and adjuvant radiotherapy with patients receiving definitive radiotherapy (2 year locoregional disease free survival 75 % and 70 % respectively, p = 0.98). Pooly differentiated tumours were significantly associated with inferior disease outcomes. Local, regional, combined local and regional, and distant failure occurred in 7 (16 %), 3 (7 %), 1 (2 %) and 2 (5 %) of patients; all 3 regional recurrences were in patients with nasal cavity squamous cell carcinomas who had not undergone elective neck treatment. Conclusions: Definitive or adjuvant radiotherapy provides an effective treatment for sinonasal malignancies. The main pattern of failure remains local, suggesting the need for investigation of intensified local therapy. Whilst remaining uncommon, the cases of regional failure mean that the merits of elective lymph node treatment should be considered on an individual basis

The need of dermatologists, psychiatrists and psychologists joint care in psychodermatology

The mind-skin connection has been studied since the nineteenth century. The last 40 years have set the development of new research areas which allowed the clarifying of how these two dimensions interact. The diseases that involve skin and mind constitute the field of psychodermatology and require that specialists in dermatology, psychiatry and psychology together and integrated take part in it, since skin, nervous system and mind are simultaneously affected. This paper aims to expose how psychodermatoses are currently conceptualized and the need of integration of these three specialties for conveniently treating the patients

The mechanisms of humic substances self-assembly with biological molecules: The case study of the prion protein

Humic substances (HS) are the largest constituent of soil organic matter and are considered as a key component of the terrestrial ecosystem. HS may facilitate the transport of organic and inorganic molecules, as well as the sorption interactions with environmentally relevant proteins such as prions. Prions enter the environment through shedding from live hosts, facilitating a sustained incidence of animal prion diseases such as Chronic Wasting Disease and scrapie in cervid and ovine populations, respectively. Changes in prion structure upon environmental exposure may be significant as they can affect prion infectivity and disease pathology. Despite its relevance, the mechanisms of prion interaction with HS are still not completely understood. The goal of this work is to advance a structural-level picture of the encapsulation of recombinant, non-infectious, prion protein (PrP) into different natural HS. We observed that PrP precipitation upon addition of HS is mainly driven by a mechanism of “salting-out” whereby PrP molecules are rapidly removed from the solution and aggregate in insoluble adducts with humic molecules. Importantly, this process does not alter the protein folding since insoluble PrP retains its α-helical content when in complex with HS. The observed ability of HS to promote PrP insolubilization without altering its secondary structure may have potential relevance in the context of “prion ecology”. These results suggest that soil organic matter interacts with prions possibly without altering the protein structures. This may facilitate prions preservation from biotic and abiotic degradation leading to their accumulation in the environment

Plant-symbiotic fungi as chemical engineers: multi-genome analysis of the Clavicipitaceae reveals dynamics of alkaloid Loci

The fungal family Clavicipitaceae includes plant symbionts and parasites that produce several psychoactive and bioprotective alkaloids. The family includes grass symbionts in the epichloae clade (Epichloë and Neotyphodium species), which are extraordinarily diverse both in their host interactions and in their alkaloid profiles. Epichloae produce alkaloids of four distinct classes, all of which deter insects, and some—including the infamous ergot alkaloids—have potent effects on mammals. The exceptional chemotypic diversity of the epichloae may relate to their broad range of host interactions, whereby some are pathogenic and contagious, others are mutualistic and vertically transmitted (seed-borne), and still others vary in pathogenic or mutualistic behavior. We profiled the alkaloids and sequenced the genomes of 10 epichloae, three ergot fungi (Claviceps species), a morning-glory symbiont (Periglandula ipomoeae), and a bamboo pathogen (Aciculosporium take), and compared the gene clusters for four classes of alkaloids. Results indicated a strong tendency for alkaloid loci to have conserved cores that specify the skeleton structures and peripheral genes that determine chemical variations that are known to affect their pharmacological specificities. Generally, gene locations in cluster peripheries positioned them near to transposon-derived, AT-rich repeat blocks, which were probably involved in gene losses, duplications, and neofunctionalizations. The alkaloid loci in the epichloae had unusual structures riddled with large, complex, and dynamic repeat blocks. This feature was not reflective of overall differences in repeat contents in the genomes, nor was it characteristic of most other specialized metabolism loci. The organization and dynamics of alkaloid loci and abundant repeat blocks in the epichloae suggested that these fungi are under selection for alkaloid diversification. We suggest that such selection is related to the variable life histories of the epichloae, their protective roles as symbionts, and their associations with the highly speciose and ecologically diverse cool-season grasses

Regional differences in lumbar spinal posture and the influence of low back pain

<p>Abstract</p> <p>Background</p> <p>Spinal posture is commonly a focus in the assessment and clinical management of low back pain (LBP) patients. However, the link between spinal posture and LBP is not fully understood. Recent evidence suggests that considering regional, rather than total lumbar spine posture is important. The purpose of this study was to determine; if there are regional differences in habitual lumbar spine posture and movement, and if these findings are influenced by LBP.</p> <p>Methods</p> <p>One hundred and seventy female undergraduate nursing students, with and without LBP, participated in this cross-sectional study. Lower lumbar (LLx), Upper lumbar (ULx) and total lumbar (TLx) spine angles were measured using an electromagnetic tracking system in static postures and across a range of functional tasks.</p> <p>Results</p> <p>Regional differences in lumbar posture and movement were found. Mean LLx posture did not correlate with ULx posture in sitting (r = 0.036, p = 0.638), but showed a moderate inverse correlation with ULx posture in usual standing (r = -0.505, p < 0.001). Regional differences in range of motion from reference postures in sitting and standing were evident. BMI accounted for regional differences found in all sitting and some standing measures. LBP was not associated with differences in regional lumbar spine angles or range of motion, with the exception of maximal backward bending range of motion (F = 5.18, p = 0.007).</p> <p>Conclusion</p> <p>This study supports the concept of regional differences within the lumbar spine during common postures and movements. Global lumbar spine kinematics do not reflect regional lumbar spine kinematics, which has implications for interpretation of measures of spinal posture, motion and loading. BMI influenced regional lumbar posture and movement, possibly representing adaptation due to load.</p

Population‐based cohort study of outcomes following cholecystectomy for benign gallbladder diseases

Background The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all‐cause 30‐day readmissions and complications in a prospective population‐based cohort. Methods Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all‐cause 30‐day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two‐level hierarchical structure with patients (level 1) nested within hospitals (level 2). Results Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16·3 per cent) were performed as an emergency, 4165 (46·8 per cent) as elective operations, and 3293 patients (37·0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7·1 per cent (633 of 8909) and 10·8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. Conclusion Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics

Disease knowledge after an educational program in patients with GERD – a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Patient education has proved beneficial in several but not all chronic disease. Inconsistent findings may rely on varying educational effects of various programs and differential effects on subgroups of patients. Patients' increase in disease knowledge may serve as a feedback to the educator on how well the education program works – but may not be associated to relevant clinical outcomes like quality of life (QoL). This study aimed to investigate the effects of a group based education program for patients with gastroesophageal reflux disease (GERD) on disease knowledge and the association between knowledge and QoL.</p> <p>Methods</p> <p>Patients with GERD were randomly allocated to education (102 patients) or control (109 patients). The education program was designed as a structured dialogue conveying information about pathophysiology, pharmacological and non-pharmacological treatment of GERD, patients' rights and use of healthcare. Outcomes were a 24 item knowledge test on GERD (score 0 – 24) 2 and 12 months after the educational program and disease specific and general QoL (Digestive symptoms and disease impact, DSIQ, and General Health Questionnaire, GHQ).</p> <p>Results</p> <p>Patients allocated to education achieved higher knowledge test scores than controls at 2 months (17.0 vs. 13.1, p < 0.001) and at 12 months (17.1 vs. 14.0, p < 0.001) follow-up. Knowledge test score was positively associated with having completed advanced school and inversely related to psychiatric illness and poor QoL as perceived by the patients at the time of inclusion. Overall, changes in knowledge test score were not associated with change in QoL.</p> <p>Conclusion</p> <p>A group based education program for patients with GERD designed as a structured dialogue increased patients' disease knowledge, which was retained after 1 year. Changes in GERD-knowledge were not associated with change in QoL.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: NCT0061850</p

Identification of a Siglec-F+ granulocyte-macrophage progenitor

In recent years multi-parameter flow cytometry has enabled identification of cells at major stages in myeloid development; from pluripotent hematopoietic stem cells, through populations with increasingly limited developmental potential (common myeloid progenitors and granulocyte-macrophage progenitors), to terminally differentiated mature cells. Myeloid progenitors are heterogeneous, and the surface markers that define transition states from progenitors to mature cells are poorly characterized. Siglec-F is a surface glycoprotein frequently used in combination with IL-5 receptor alpha (IL5Rα) for the identification of murine eosinophils. Here, we describe a CD11b+ Siglec-F+ IL5Rα- myeloid population in the bone marrow of C57BL/6 mice. The CD11b+ Siglec-F+ IL5Rα- cells are retained in eosinophil deficient PHIL mice, and are not expanded upon overexpression of IL-5, indicating that they are upstream or independent of the eosinophil lineage. We show these cells to have GMP-like developmental potential in vitro and in vivo, and to be transcriptionally distinct from the classically described GMP population. The CD11b+ Siglec-F+ IL5Rα- population expands in the bone marrow of Myb mutant mice, which is potentially due to negative transcriptional regulation of Siglec-F by Myb. Lastly, we show that the role of Siglec-F may be, at least in part, to regulate GMP viability

Real-time compression feedback for patients with in-hospital cardiac arrest: a multi-center randomized controlled clinical trial

Objective: To determine if real-time compression feedback using a non-automated hand-held device improves patient outcomes from in-hospital cardiac arrest (IHCA). Methods: We conducted a prospective, randomized, controlled, parallel study (no crossover) of patients with IHCA in the mixed medical–surgical intensive care units (ICUs) of eight academic hospitals. Patients received either standard manual chest compressions or compressions performed with real-time feedback using the Cardio First Angel™ (CFA) device. The primary outcome was sustained return of spontaneous circulation (ROSC), and secondary outcomes were survival to ICU and hospital discharge. Results: One thousand four hundred fifty-four subjects were randomized; 900 were included. Sustained ROSC was significantly improved in the CFA group (66.7% vs. 42.4%, P < 0.001), as was survival to ICU discharge (59.8% vs. 33.6%) and survival to hospital discharge (54% vs. 28.4%, P < 0.001). Outcomes were not affected by intra-group comparisons based on intubation status. ROSC, survival to ICU, and hospital discharge were noted to be improved in inter-group comparisons of non-intubated patients, but not intubated ones. Conclusion: Use of the CFA compression feedback device improved event survival and survival to ICU and hospital discharge