A role for DNA methylation in bumblebee morphogenesis hints at female-specific developmental erasure.

Epigenetic mechanisms, such as DNA methylation, are crucial factors in animal development. In some mammals, almost all DNA methylation is erased during embryo development and re-established in a sex- and cell-specific manner. This erasure and re-establishment is thought to primarily be a vertebrate-specific trait. Insects are particularly interesting in terms of development as many species often undergo remarkable morphological changes en route to maturity, that is, morphogenesis. However, little is known about the role of epigenetic mechanisms in this process across species. We have used whole-genome bisulfite sequencing to track genome-wide DNA methylation changes through the development of an economically and environmentally important pollinator species, the bumblebee Bombus terrestris (Hymenoptera:Apidae Linnaeus). We find overall levels of DNA methylation vary throughout development, and we find developmentally relevant differentially methylated genes throughout. Intriguingly, we have identified a depletion of DNA methylation in ovaries/eggs and an enrichment of highly methylated genes in sperm. We suggest this could represent a sex-specific DNA methylation erasure event. To our knowledge, this is the first suggestion of possible developmental DNA methylation erasure in an insect species. This study lays the required groundwork for functional experimental work to determine if there is a causal nature to the DNA methylation differences identified. Additionally, the application of single-cell methylation sequencing to this system will enable more accurate identification of if or when DNA methylation is erased during development.

Infrared thermography can detect previsual bacterial growth in a laboratory setting via metabolic heat detection.

AIMS: Detection of bacterial contamination in healthcare and industry takes many hours if not days. Thermal imaging, the measurement of heat by an infrared camera, was investigated as a potential noninvasive method of detecting bacterial growth. METHODS AND RESULTS: Infrared thermography can detect the presence of Escherichia coli and Staphylococcus aureus on solid growth media by an increase in temperature before they are visually observable. A heat decrease is observed after treatment with ultraviolet light and heat increased after incubation with dinitrophenol. CONCLUSIONS: Infrared thermography can detect early growth of bacteria before they are detectable by other microbiology-based method. The heat observed is due to the cells being viable and metabolically active, as cells killed with ultraviolet light exhibit reduced increase in temperature and treatment with dinitrophenol increases heat detected. SIGNIFICANCE AND IMPACT OF THE STUDY: Infrared thermography detects bacterial growth without the need for specialized temperature control facilities. The method is statistically robust and can be undertaken in situ, thus is highly versatile. These data support the application of infrared thermography in a laboratory, clinical and industrial setting for vegetative bacteria, thus may become into an important methodology for the timely and straightforward detection of early-stage bacterial growth.

Cardiac implanted electronic devices and MRI safety in 2018-the state of play.

Traditionally, the presence of cardiac implanted electronic devices (CIEDs) was a contra-indication to magnetic resonance (MR) imaging. Professional groups from around the world are releasing updated guidelines for the imaging of MR-conditional and legacy CIEDs, reflecting increasing evidence that this can be performed safely when strict protocols are followed. KEY POINTS: • The presence of a pacemaker or automatic implanted cardioverter defibrillator is no longer an absolute contraindication to magnetic resonance imaging. • Strict protocols enable diagnostic quality images to be obtained with minimal risk. • Close collaboration among radiologists, cardiologists and device manufacturer representatives is required.

Radiofrequency Pulmonary Vein Isolation in a Patient with Dextrocardia With Situs Inversus Totalis.

BACKGROUND: We present a case report of a 67-year-old male with dextrocardia situs inversus totalis and persistent atrial fibrillation who presented for radiofrequency pulmonary vein isolation. METHODS: Pulmonary vein isolation was performed using the St Jude Medical Ensite NavX 3D mapping system with AccuNav ICE guidance. RESULTS: All pulmonary veins were successfully isolated. The procedure time was 125 mins with a fluoroscopy time of 44.3 mins. The fluoro dose was 2095cGycm2. There were no procedural complications. CONCLUSIONS: Radiofrequency pulmonary vein isolation can be performed safely and successfully in patients with dextrocardia and situs inversus totalis.

The presence and quantification of splenic ice in the McMurdo Sound notothenioid fish, Pagothenia borchgrevinki (Boulenger, 1902).

Survival of some polar fishes is associated with high levels of circulating antifreeze glycoproteins (AFGPs). AFGP prevent ice growth giving rise to thermal hysteresis. The inhibiting action of AFGPs implies that polar fish contain ice to which AFGPs adsorb. Cryopelagic Pagothenia borchgrevinki, inhabiting the ice-laden waters of McMurdo Sound, Antarctica, were assayed for ice and ice was found on skin, gills, in the intestine, and in the spleen. Two methods used to assess the number of ice crystals in spleens gave comparable results (12.1+/-1.9 and 22+/-3.8 per spleen). Attempts were made to measure the rate of uptake of ice by P. borchgrevinki held in cages immediately beneath the sub-ice platelet layer in McMurdo Sound; uptake was sporadic. Introduction of ice into fish by spray freezing a small patch of the integument resulted in detection of splenic ice after 1h, illustrating that a mechanism exists for ice transport from the periphery to the spleen. Splenic ice did not seem to be eliminated from fish held in ice-free water at -1.6 degrees C for approximately two months. The relatively small number of splenic ice crystals and the slow rate of ice uptake suggest efficient ice barriers exist in P. borchgrevinki.

Effect of cotrimoxazole prophylaxis taken by human immunodeficiency virus (HIV)-infected persons on the selection of sulfadoxine-pyrimethamine-resistant malaria parasites among HIV-uninfected household members.

The purpose of this prospective cohort study was to assess the effect of cotrimoxazole prophylaxis taken by human immunodeficiency virus (HIV)-infected persons on the selection of sulfadoxine-pyrimethamine (SP)-resistant malaria parasites among HIV-uninfected household members. A total of 2,567 HIV-uninfected persons from 605 households were followed and blood specimens were collected each time an episode of Plasmodium falciparum malaria was diagnosed. Study participants were living in households where HIV-infected persons were either taking (exposed) or not taking (unexposed) cotrimoxazole prophylaxis. From all malaria episodes diagnosed, 50% of the specimens were randomly selected and tested for the presence of five key mutations known to mediate resistance to SP (dihydrofolate reductase [dhfr] Asn-108, Ile-51, and Arg-59, and dihydropteroate synthase [dhps] Gly-437 and Glu-540). Plasmodium falciparum isolates were recovered from 163 specimens in the exposed households and 113 specimens in the unexposed households, with similar proportions containing the dhfr triple mutant (37% versus 45%; P = 0.18), the dhps double mutant (64% versus 62%; P = 0.81), and the dhfr/dhps quintuple mutant (30% versus 32%; P = 0.74). The HIV-uninfected persons living with HIV-infected household members taking cotrimoxazole prophylaxis had a lower incidence of malaria (incidence rate ratio [IRR] = 0.64, 95% confidence interval [CI] = 0.50-0.83, P = 0.001) and fewer malaria episodes due to parasites containing the dhfr/dhps quintuple mutant (IRR = 0.61, 95% CI = 0.41-0.91, P = 0.014). Cotrimoxazole prophylaxis taken by HIV-infected persons did not select for SP-resistant malaria parasites among HIV-uninfected household members, and was associated with a lower overall incidence of SP-resistant malaria among household members.

Bronchogenic carcinoid tumours that are 18F-fluorodeoxyglucose avid on positron emission tomography.

OBJECTIVES: Bronchogenic carcinoid tumours are widely cited as non-fluorodeoxyglucose (FDG) avid. However, three case reports of FDG-avid bronchogenic carcinoid tumours have been published, leading to speculation as to which clinicopathological factors may be associated with increased activity on FDG-positron emission tomography. We reviewed a series of cases from our institution and compared them with the available reports in the literature, to attempt to identify the factors associated with FDG avidity in bronchogenic carcinoids. METHODS: We performed a single-institution retrospective review. RESULTS: One patient was identified at our institution who had a typical carcinoid tumour with a standardized uptake value (SUV) of 26, oncocytic features on histology and positive staining for glucose transporter 1 (GLUT1). Three additional patients were identified in the literature with typical bronchogenic carcinoids with SUVs of 39, 38 and 33. Two of these tumours stained positive for GLUT1, and the remaining patient was not tested. Two of these patients had oncocytic features on histology, and results on the remaining patient are not reported. Additionally, 4 patients at our institution were identified with bronchogenic carcinoids with average SUV of 2.6. All were GLUT1 negative, and none had oncocytic features. In the reported literature, excluding the four most FDG-avid tumours described above, atypical carcinoids had a higher mean SUV than typical carcinoids (5.7 vs 3.4, P = 0.02), but size was not correlated with SUV (r = 0.7, P = 0.3). CONCLUSIONS: FDG uptake is commonly associated with worse prognosis in malignancy; however, bronchogenic carcinoids, particularly oncocytic typical carcinoids, are a possible source of extremely high SUVs on FDG-PET.

Outcomes in patients who have failed endoscopic therapy for dysplastic Barrett's metaplasia or early esophageal cancer.

BACKGROUND: Endoscopic therapy (ablation ± mucosal resection) for esophageal high-grade dysplasia (HGD) or intramucosal carcinoma has demonstrated promising results. Little is known about patients who have persistent or progressive disease despite endotherapy. We compared patients who had successful eradication of their disease with those in whom endotherapy failed to try to identify factors predictive of failure and outcomes after salvage therapy. METHODS: We performed a single-institution retrospective review of patients treated with endotherapy from 2007 to 2012. RESULTS: Thirty-eight patients underwent endotherapy: 28 had successful eradication of their disease and endotherapy failed in 10 patients. Patients in whom endotherapy failed were more likely to have high-grade dysplasia (HGD) on initial endoscopy, nodules or ulcers, multifocal dysplasia, and persistent nondysplastic Barrett's metaplasia. Patients in whom endotherapy failed also underwent significantly more endotherapy sessions. Seven patients had persistent dysplasia or progression to cancer, and 3 patients had complete eradication of HGD but presented with intramucosal carcinoma an average of 15 months after eradication. The 10 patients in whom endotherapy failed underwent salvage therapy with esophagectomy (7 patients), definitive chemoradiotherapy (1 patient), and endotherapy (2 patients). Patients treated with esophagectomy were disease free at a mean of 25 months postoperatively. CONCLUSIONS: HGD on initial endoscopy, multifocal dysplasia, mucosal abnormalities, and failure to eradicate nondysplastic Barrett's metaplasia were associated with failure of endotherapy. Patients with these characteristics should be considered at higher risk for treatment failure, and earlier consideration should be given to esophagectomy if there is persistent, progressive, or recurrent neoplasia. Clinical outcomes are good, even after salvage therapy. Continued endoscopic surveillance is mandatory after successful endotherapy because of the risk of recurrent disease.

Thoracoscopic talc versus tunneled pleural catheters for palliation of malignant pleural effusions.

BACKGROUND: A malignant pleural effusion (MPE) is a late complication of malignancy that affects respiratory function and quality of life. A strategy for palliation of the symptoms caused by MPE should permanently control fluid accumulation, preclude any need for reintervention, and limit hospital length of stay (LOS). We compared video-assisted thorascopic (VATS) talc insufflation with placement of a tunneled pleural catheter (TPC) to assess which intervention better met these palliative goals. METHODS: We conducted a retrospective chart review of consecutive MPE at a single institution from 2005 through June 2011. Primary a priori outcomes were reintervention in the ipsilateral hemithorax, postprocedure LOS, and overall LOS. RESULTS: One hundred nine patients with MPE were identified. Fifty-nine patients (54%) had TPC placed, and 50 (46%) were treated with VATS talc. Patients who underwent TPC placement had significantly fewer reinterventions for recurrent ipsilateral effusions than patients treated with VATS talc (TPC 2% [1 of 59], talc 16% [8 of 50], p=0.01). Patients treated with TPC had significantly shorter overall LOS (TPC LOS mean 7 days, mode 1 day; talc mean 8 day, mode 4 days, p=0.006) and postprocedure LOS (TPC post-procedure LOS mean 3 days, mode 0 days; talc mean 6 days, mode 3 days, p<0.001). Type of procedure was not associated with differences in complication rate (TPC 5% [3 of 59], talc 14% [7 of 50], p=0.18), or in-hospital mortality (TPC 3% [2 of 59], talc 8% [4 of 50], p=0.41). CONCLUSIONS: TPC placement was associated with a significantly reduced postprocedure and overall LOS compared with VATS talc. Also, TPC placement was associated with significantly fewer ipsilateral reinterventions. Placement of TPC should be considered for palliation of MPE-associated symptoms.

Prophylaxis and management of wound infections after elective colorectal surgery: a survey of the American Society of Colon and Rectal Surgeons membership.

BACKGROUND: Postoperative wound infections are a widespread and costly problem, especially in colorectal surgery. Despite their prevalence, there are few data regarding appropriate management and prevention strategies. MATERIALS AND METHODS: In order to assess current attitudes and practices about this subject, and as a guide to designing a randomized trial to gather evidence in order to support data-driven protocol development, an e-mail survey was sent to the membership of the American Society of Colorectal Surgeons to assess current attitudes and practices pertaining to prevention and management of wound infections. RESULTS: Most respondents estimated that the wound infection rate in their own patients was much lower than commonly reported in the literature. Use of evidence-based perioperative strategies for reducing wound infection, such as the use of a wound protector, hyperoxygenation, and implementation of the Surgical Care Improvement Project guidelines, were far from universal. Management strategies varied widely, without apparent rational basis. CONCLUSION: Based on the practices and beliefs in the surgical community, it is our hope that a multi-institutional study can be carried out to objectify best practices in both the effective and cost-effective management of this common condition and to reduce the wide variation in the treatment of surgical site infections.

Sarcoidosis as a benign cause of lymphadenopathy in cancer patients.

BACKGROUND: Cancer and sarcoidosis have been associated in several small case series. This association makes the cancer patient with lymphadenopathy a diagnostic dilemma: malignant involvement of the lymph nodes is common, but benign diagnoses are possible and must be considered. METHODS: We conducted a retrospective chart review of all patients with a diagnosis of sarcoidosis or mediastinal adenopathy who underwent mediastinoscopy at the Swedish Medical Center and Cancer Institute from 2004 to 2008. RESULTS: Five hundred sixty-five mediastinoscopies were performed. There were 41 cases of biopsy-proven sarcoidosis. Twenty-one cases of sarcoidosis were diagnosed after a diagnosis of cancer. No primary cancer type was predominant. Cancers were of all stages, with and without lymph node involvement. The most common positron emission tomography combined with a computed tomography scan (PET CT) finding was bilateral hilar adenopathy with symmetric standardized uptake values (SUV) in the 4 to 15 range (62%), but many other PET CT patterns were present. CONCLUSIONS: Hypermetabolic lymphadenopathy on staging or surveillance imaging presents a diagnostic dilemma. Sarcoidosis must be considered in the differential diagnosis of patients with a history of malignancy who develop lymphadenopathy. It is imperative to obtain a tissue diagnosis before instituting therapy for presumed cancer recurrence.

Effect of lobe pumping on human albumin: investigating the underlying mechanisms of aggregate formation.

A common problem in the manufacture of liquid protein therapeutics is the tendency for aggregation and particle formation on extended storage. One aspect of processing that might contribute to particle formation is pumping. In the present study, we demonstrate that lobe pumps can promote aggregation in albumin preparations. This is accentuated where the clearance between the pump housing and lobes is increased. Under these conditions, the pump efficiency decreases, resulting in increased exposure of the protein to the pump environment. Depending on the inherent physicochemical stability of the protein, this can lead to aggregate formation, which can influence the long-term stability characteristics of the product.

Effect of lobe pumping on human albumin: development of a lobe pump simulator using smoothed particle hydrodynamics.

Using SPH (smoothed particle hydrodynamics), the motion of a lobe pump under load was simulated in order to predict the level of shear stress experienced by a protein solution. By varying the gap size between the lobes and pump housing, variations in pump efficiency and shear stress were determined. The simulations indicated that pump shear was dependent on gap size, with shear stress levels (0-40 Pa) correlating with those estimated in previous albumin-pumping studies. As gap size increased, the number of fluid particles experiencing low shear (<10 Pa) increased, whereas those experiencing high shear (>20 Pa) showed a decreasing trend. The pump efficiency, however, decreased with gap size, requiring more lobe revolutions to pass a unit volume. Taken together, these observations indicate that lobe pumps operated with increased gaps between the rotors and the housing result in larger number of particles within the fluid experiencing shear stresses. Moreover, the simulations indicate that it is best to use larger lobe pumps operated at high efficiency to transfer protein-containing solutions.

Effect of ice fraction and dilution factor on the antifreeze activity in the hemolymph of the cerambycid beetle Rhagium inquisitor.

The freezing-melting hysteresis in a given volume of hemolymph from the cerambycid beetle Rhagium inquisitor was linearly and negatively related to the logarithm of the mass fraction of ice in the sample. When the ice fraction dropped by a factor of 10, the hysteresis activity increased by about 2 degrees C. When the hemolymph was diluted, the hysteresis activity was linearly and negatively related to the logarithm of the dilution factor. Dilution of the hemolymph by a factor of 2 led to a 1 degree C reduction in hysteresis activity. In the diluted samples, the ice growth took place along the a-axes, implying that the antifreeze peptides of insects block ice growth along the c-axis, in addition to the a-axis.