Ablation of Supraventricular Tachycardias From Concealed Left-Sided Nodoventricular and Nodofascicular Accessory Pathways.
Nodoventricular and nodofascicular accessory pathways (AP) are uncommon connections between the atrioventricular node and the fascicles or ventricles. Five patients with nodofascicular or nodoventricular tachycardia were studied. We identified 5 patients with concealed, left-sided nodoventricular (n=4), and nodofascicular (n=1) AP. We proved the participation of AP in tachycardia by delivering His-synchronous premature ventricular contractions that either delayed the subsequent atrial electrogram or terminated the tachycardia (n=3), and by observing an increase in VA interval coincident with left bundle branch block (n=2). The APs were not atrioventricular pathways because the septal VA interval during tachycardia was <70 ms in 3, 1 had spontaneous atrioventricular dissociation, and in 1 the atria were dissociated from the circuit with atrial overdrive pacing. Entrainment from the right ventricle showed ventricular fusion in 4 out of 5 cases. A left-sided origin of the AP was suspected after failed ablation of the right inferior extension of atrioventricular node in 3 cases and by observing a VA increase with left bundle branch block in 2 cases. The nodofascicular and 3 of the nodoventricular AP were successfully ablated from within the proximal coronary sinus (CS) guided by recorded potentials at the roof of the CS, and 1 nodoventricular AP was ablated via a transseptal approach near the CS os. Left-sided nodofascicular and nodoventricular AP appear to connect the ventricles with the CS musculature in the region of the CS os. Mapping and successful ablation sites can be guided by recording potentials within or near the CS os.


Genome sequence comparison and scenarios for gene rearrangements: a test case.
As large portions of related genomes are being sequenced, methods for comparing complete or nearly complete genomes, as opposed to comparing individual genes, are becoming progressively more important. A major, widespread phenomenon in genome evolution is the rearrangement of genes and gene blocks. There is, however, no consistent method for genome sequence comparison combined with the reconstruction of the evolutionary history of highly rearranged genomes. We developed a schema for genome sequence comparison that includes three successive steps: (i) comparison of all proteins encoded in different genomes and generation of genomic similarity plots; (ii) construction of an alphabet of conserved genes and gene blocks; and (iii) generation of most parsimonious genome rearrangement scenarios. The approach is illustrated by a comparison of the herpesvirus genomes that constitute the largest set of relatively long, complete genome sequences available to date. Herpesviruses have from 70 to about 200 genes; comparison of the amino acid sequences encoded in these genes results in an alphabet of about 30 conserved genes comprising 7 conserved blocks that are rearranged in the genomes of different herpesviruses. Algorithms to analyze rearrangements of multiple genomes were developed and applied to the derivation of most parsimonious scenarios of herpesvirus evolution under different evolutionary models. The developed approaches to genome comparison will be applicable to the comparative analysis of bacterial and eukaryotic genomes as soon as their sequences become available.


PKD2 functions as an epidermal growth factor-activated plasma membrane channel.
PKD2, or polycystin 2, the product of the gene mutated in type 2 autosomal dominant polycystic kidney disease, belongs to the transient receptor potential channel superfamily and has been shown to function as a nonselective cation channel in the plasma membrane. However, the mechanism of PKD2 activation remains elusive. We show that PKD2 overexpression increases epidermal growth factor (EGF)-induced inward currents in LLC-PK(1) kidney epithelial cells, while the knockdown of endogenous PKD2 by RNA interference or the expression of a pathogenic missense variant, PKD2-D511V, blunts the EGF-induced response. Pharmacological experiments indicate that the EGF-induced activation of PKD2 occurs independently of store depletion but requires the activity of phospholipase C (PLC) and phosphoinositide 3-kinase (PI3K). Pipette infusion of purified phosphatidylinositol-4,5-bisphosphate (PIP(2)) suppresses the PKD2-mediated effect on EGF-induced conductance, while pipette infusion of phosphatidylinositol-3,4,5-trisphosphate (PIP(3)) does not have any effect on this conductance. Overexpression of type Ialpha phosphatidylinositol-4-phosphate 5-kinase [PIP(5)Kalpha], which catalyzes the formation of PIP(2), suppresses EGF-induced currents. Biochemical experiments show that PKD2 physically interacts with PLC-gamma2 and EGF receptor (EGFR) in transfected HEK293T cells and colocalizes with EGFR and PIP(2) in the primary cilium of LLC-PK(1) cells. We propose that plasma membrane PKD2 is under negative regulation by PIP(2). EGF may reduce the threshold of PKD2 activation by mechanical and other stimuli by releasing it from PIP(2)-mediated inhibition.


Telehealth Remote Monitoring Systematic Review: Structured Self-monitoring of Blood Glucose and Impact on A1C.
The aim was to summarize research on telehealth remote patient monitoring interventions that incorporate key elements of structured self-monitoring of blood glucose (SMBG) identified as essential for improving A1C. A systematic review was conducted using the Medline, Cumulative Index to Nursing and Allied Health Literature, EMBASE, and OVID Medline databases with search terms "Telemedicine" AND "Monitoring, Physiologic" AND "Diabetes Mellitus, Type 2." Study selection criteria included original randomized clinical trials evaluating the impact of telehealth remote patient monitoring on A1C among adults with type 2 diabetes and incorporated 1 or more essential elements of SMBG identified by the International Diabetes Federation (patient education, provider education, structured SMBG profile, SMBG goals, feedback, data used to modify treatment, interactive communication or shared decision making). Fifteen studies were included, with interventions ranging from 3 to 12 months (mean 8 months) with sample sizes from 30 to 1665. Key SMBG elements were grouped into 3 categories: education, SMBG protocols, and feedback. Research incorporating 5 of the 7 elements consistently achieved significant A1C improvements between study groups. Interventions using more SMBG elements are associated with an improvement in A1C. Studies with the largest A1C decrease incorporated 6 of the 7 elements and computer decision support. Two studies with 5 of the 7 elements and active medication management achieved significant A1C decreases. Telehealth remote patient monitoring interventions in type 2 diabetes have not included all structured monitoring elements recommended by the IDF. Incorporating more elements of structured SMBG is associated with improved A1C.


Heartburn is more likely to recur after Toupet fundoplication than Nissen fundoplication.
Toupet (270 degrees) fundoplication is commonly recommended for patients with gastroesophageal reflux (GER) and esophageal dysmotility. However, Toupet fundoplication may be less effective at protecting against reflux than Nissen (360 degrees) fundoplication. We therefore compared the effectiveness and durability of both types of fundoplication as a function of preoperative esophageal motility. From January 1992 through January 1998, 669 patients with GER underwent laparoscopic fundoplication (78 Toupet, 591 Nissen). Patients scored heartburn, regurgitation, and dysphagia preoperatively, and at 6 weeks and 1 year postoperatively, using a 0 ("none") to 3 ("severe") scale. We compared symptom scores (Wilcoxon rank sum test) and redo fundoplication rates (Fisher exact test) in Toupet and Nissen patients. We also performed subgroup analyses on 81 patients with impaired esophageal motility (mean peristaltic amplitude, <30 mm Hg or peristalsis <70% of wet swallows) and 588 patients with normal esophageal motility. Toupet and Nissen patients reported similar preoperative heartburn, regurgitation, and dysphagia. At 6 weeks after operation, heartburn and regurgitation were similarly improved in both groups, but dysphagia was more prevalent among Nissen patients. After 1 year, heartburn and regurgitation were re-emerging in Toupet patients, and dysphagia was again similar between groups. Patients with impaired motility who have Nissen fundoplication are no more likely to suffer persistent dysphagia than their counterparts who have Toupet fundoplication. In addition, patients with normal motility are more likely to develop symptom recurrence after Toupet fundoplication than Nissen fundoplication, with no distinction in dysphagia rates. We conclude that since Toupet patients suffer more heartburn recurrence than Nissen patients, with similar dysphagia, selective use of Toupet fundoplication requires further study.


Pathogenic mechanisms of diseases caused by Rickettsia.
The specter of bioterrorism employing genetically engineered Rickettsia resistant to all antibiotics should reawaken the world's desire to elucidate the pathogenesis of typhus and spotted fever rickettsioses in a search for mechanisms vulnerable to interdiction. The pathogenetic sequence includes rickettsial entry into the dermis, hematogenous dissemination to vascular endothelial cells (most critically in brain and lungs), increased vascular permeability, edema, and immunity mediated by NK cells, IFN-gamma, TNF-alpha, RANTES, antibodies, and cytotoxic T lymphocytes. Silverman has demonstrated the role of reactive oxygen species (ROS) produced by R. rickettsii-infected endothelial cells in peroxidative damage to cell membranes in vitro, and Heinzen has described actin-based rickettsial intracellular mobility and intercellular spread. At this point the availability of sequences of rickettsial genomes and excellent animal models of rickettsioses have yielded insufficient progress towards the identification of rickettsial virulence factors and knowledge of the importance of injury mediated by ROS, phospholipase A(2), protease(s) or other mechanisms in vivo. Attention to the rickettsiosis-associated procoagulant state led to determination that hemostatic mechanisms largely prevent major hemorrhage without disseminated intravascular coagulation or thrombosis-mediated ischemia. Particularly lacking is knowledge of early events in vivo at the portal of entry in skin (or lung), of the effects of the inoculum medium (arthropod saliva or feces), mediators produced by infected endothelium under conditions of flow and of the contributions in vivo of immune effectors to pathology, of the role of apoptosis in rickettsial infection, and of the endothelial cell alterations that account for increased vascular permeability. The host cell receptor for the Rickettsia ligand and the mechanism of rickettsial escape from the phagosome need to be elucidated.


Tissue engineering and regenerative medicine: history, progress, and challenges.
The past three decades have seen the emergence of an endeavor called tissue engineering and regenerative medicine in which scientists, engineers, and physicians apply tools from a variety of fields to construct biological substitutes that can mimic tissues for diagnostic and research purposes and can replace (or help regenerate) diseased and injured tissues. A significant portion of this effort has been translated to actual therapies, especially in the areas of skin replacement and, to a lesser extent, cartilage repair. A good amount of thoughtful work has also yielded prototypes of other tissue substitutes such as nerve conduits, blood vessels, liver, and even heart. Forward movement to clinical product, however, has been slow. Another offshoot of these efforts has been the incorporation of some new exciting technologies (e.g., microfabrication, 3D printing) that may enable future breakthroughs. In this review we highlight the modest beginnings of the field and then describe three application examples that are in various stages of development, ranging from relatively mature (skin) to ongoing proof-of-concept (cartilage) to early stage (liver). We then discuss some of the major issues that limit the development of complex tissues, some of which are fundamentals-based, whereas others stem from the needs of the end users.


Community-based settings and sampling strategies: implications for reducing racial health disparities among black men, New York City, 2010-2013.
Rates of screening colonoscopies, an effective method of preventing colorectal cancer, have increased in New York City over the past decade, and racial disparities in screening have declined. However, vulnerable subsets of the population may not be reached by traditional surveillance and intervention efforts to improve colorectal cancer screening rates. We compared rates of screening colonoscopies among black men aged 50 or older from a citywide random-digit-dial sample and a location-based sample focused on hard-to-reach populations to evaluate the representativeness of the random-digit-dial sample. The location-based sample (N = 5,568) was recruited from 2010 through 2013 from community-based organizations in New York City. Descriptive statistics were used to compare these data with data for all black men aged 50 or older from the 2011 cohort of the Community Health Survey (weighted, N = 334) and to compare rates by community-based setting. Significant differences in screening colonoscopy history were observed between the location-based and random-digit-dial samples (49.1% vs 62.8%, P < .001). We observed significant differences between participants with and without a working telephone among the location-based sample and between community-based settings. Vulnerable subsets of the population such as those with inconsistent telephone access are excluded from random-digit-dial samples. Practitioners and researchers should consider the target population of proposed interventions to address disparities, and whether the type of setting reaches those most in need of services.


Error disclosure and family members' reactions: does the type of error really matter?
To describe how Italian clinicians disclose medical errors with clear and shared lines of responsibility. Thirty-eight volunteers were video-recorded in a simulated conversation while communicating a medical error to a simulated family member (SFM). They were assigned to a clear responsibility error scenario or a shared responsibility one. Simulations were coded for: mention of the term "error" and apology; communication content and affect using the Roter Interaction Analysis System. SFMs rated their willingness to have the patient continue care with the clinician. Clinicians referred to an error and/or apologized in 55% of the simulations. The error was disclosed more frequently in the clear responsibility scenario (p<0.02). When the "error" was explicitly mentioned, the SFM was more attentive, sad and anxious (p≤0.05) and less willing to have the patient continue care (p<0.05). Communication was more patient-centered (p<0.05) and affectively dynamic with the SFMs showing greater anxiety, sadness, attentiveness and respectfulness in the clear responsibility scenario (p<0.05). Disclosing errors is not a common practice in Italy. Clinicians disclose less frequently when responsibility is shared and indicative of a system failure. Training programs to improve disclosure practice considering the type of error committed should be implemented.


Nitride micro-LEDs and beyond--a decade progress review.
Since their inception, micro-size light emitting diode (µLED) arrays based on III-nitride semiconductors have emerged as a promising technology for a range of applications. This paper provides an overview on a decade progresses on realizing III-nitride µLED based high voltage single-chip AC/DC-LEDs without power converters to address the key compatibility issue between LEDs and AC power grid infrastructure; and high-resolution solid-state self-emissive microdisplays operating in an active driving scheme to address the need of high brightness, efficiency and robustness of microdisplays. These devices utilize the photonic integration approach by integrating µLED arrays on-chip. Other applications of nitride µLED arrays are also discussed.


Chemical warfare agents: verification of compounds containing the phosphorus-methyl linkage in waste water.
The chemical analysis of the waste water from plants that manufacture chemicals is a nonintrusive method for confirming a suspected violation of the prohibition against the production of chemical warfare agents. The chemical structure of most nerve gases is related to that of methylphosphonic acid, whereas most organo-phosphorus pesticides have the phosphoric acid structure. On the basis of this characteristic difference, a procedure has been developed in which the presence of a nerve gas, its decomposition products, or its starting materials in waste water (Rhine River and Meuse River water) is reflected by the appearance of methylphosphonic acid as a breakdown product after hydrolysis. This acid is concentrated and converted into a volatile compound by methylation. After cleanup, the ester may be separated from related compounds by gas chromatography and is detected by means of a specific detector for phosphorus. The detection limit of nerve gases by this procedure is approximately 1 nanomole per liter of water. The scope and limitations of the method are discussed.


Glycogen synthesis in the perfused liver of the starved rat.
1. In the isolated perfused liver from 48h-starved rats, glycogen synthesis was followed by sequential sampling of the two major lobes. 2. The fastest observed rates of glycogen deposition (0.68-0.82mumol of glucose/min per g fresh liver) were obtained in the left lateral lobe, when glucose in the medium was 25-30mm and when gluconeogenic substrates were present (pyruvate, glycerol and serine: each initially 5mm). In this situation there was no net disappearance of glucose from the perfusion medium, although (14)C from [U-(14)C]glucose was incorporated into glycogen. There was no requirement for added hormones. 3. In the absence of gluconeogenic precursors, glycogen synthesis from glucose (30mm) was 0-0.4mumol/min per g. 4. When livers were perfused with gluconeogenic precursors alone, no glycogen was deposited. The total amount of glucose formed was similar to the amount converted into glycogen when 30mm-glucose was also present. 5. The time-course, maximal rates and glucose dependence of hepatic glycogen deposition in the perfused liver resembled those found in vivo in 48h-starved rats, during infusion of glucose. 6. In the perfused liver, added insulin or sodium oleate did not significantly affect glycogen synthesis in optimum conditions. In suboptimum conditions (i.e. glucose less than 25mm, or with gluconeogenic precursors absent) insulin caused a moderate acceleration of glycogen deposition. 7. These results suggest that on re-feeding after starvation in the rat, hepatic glycogen deposition could be initially the result of continued gluconeogenesis, even after the ingestion of glucose. This conclusion is discussed, particularly in connexion with the role of hepatic glucokinase, and the involvement of the liver in the glucose intolerance of starvation.


A comparison of older longstay psychiatric and learning disability inpatients using the Health of the Nation Outcome Scales.
With increasing longevity, the number of elderly patients with psychiatric or learning disabilities is likely to increase. The degree of overlap of symptoms and needs of these two groups of patients, which may allow for their care within the same service, was examined. Twenty-six longstay, elderly (> 65 years) psychiatric patients resident in psychogeriatric wards of a psychiatric hospital were compared with 23 longstay, elderly patients and 40 longstay patients aged 50-65 years, both resident in the wards of a specialist hospital for learning disabilities. The instrument used was the Health of the Nation Outcome Scales (HoNOS). On the HoNOS, the elderly psychiatric patients scored significantly higher for problems with mood, relationships and occupation/activities. There were no significant differences for any of the scales rated between the 50-65 and > 65 years old patients with learning disabilities. The similarities between the three groups of patients would suggest that for some patients the same services may be utilized. This could reduce the cost of the care in the community and entail more economical use of the facilities and staff. The HoNOS proved to be a concise and simple instrument, which could become a useful tool in monitoring the outcome of healthcare in longstay patients.


Relationship Between PD-L1 Expression and CD8+ T-cell Immune Responses in Hepatocellular Carcinoma.
As PD-1/PD-L1 immune checkpoint inhibitors exhibited promising clinical outcomes in various types of solid tumors, PD-1/PD-L1 blockades have been explored for the treatment of hepatocellular carcinoma (HCC). However, the association of PD-L1 with antitumor immunoregulation is not clearly defined in HCC. Here, we evaluated the characteristics of PD-L1 expression, CD8 T-cell infiltration and their relationship in HCC. A total of 411 resected tumor specimens from HCC patients were immunostained for PD-L1 and CD8. Only 78 (19%) cases showed ≥5% membranous PD-L1 expression on tumor cells, although a significantly positive correlation was found between PD-L1 expression and CD8 T-cell densities. Moreover, patients with higher tumor PD-L1 expression also showed a higher hepatitis B virus load, which was also related to increased CD8 infiltration. Survival analysis suggested that both tumor and stroma PD-L1 status did not significantly affect overall survival or recurrence-free survival in patients. Although high CD8 T-cell density was overall associated with better overall survival and recurrence-free survival, its favorable prognostic value was eliminated by high tumor PD-L1 expression. Further flow cytometric and enzyme-linked immunosorbent assay (ELISA) results from the coculture of HCC cell lines with specific CD8 cytotoxic T lymphocytes (CTLs) demonstrated that CD8 CTLs remarkably upregulated PD-L1 expression on tumor cell lines by HLA class-I specificity, and the overexpression of tumor PD-L1 impaired interferon-γ secretion by CD8 CTLs in a negative feedback regulation mechanism. In conclusion, our findings reveal an interaction between PD-L1 expression and CD8 T-cell immunity in HCC, although PD-L1 is not a prognostic factor for the patients.


Increased risk of psoriasis in subjects with abdominal obesity: A nationwide population-based study.
Psoriasis is a chronic inflammatory skin disease known to be associated with a variety of systemic comorbidities, such as metabolic syndrome and obesity. Obesity represents a major comorbidity and has been suggested to be related to psoriasis. This nationwide population-based prospective cohort study was performed to investigate the impacts of body mass index (BMI) and waist circumference (WC) on psoriasis. We used the health check-up database and the study population consisted of subjects who had undergone health screening between January 2009 and December 2012. This study investigated patients newly diagnosed with psoriasis (International Classification of Disease, Tenth Revision, code L40) by dermatologists during the follow-up period (5.32 years), based on claims data. The total population consisted of 22 633 536 subjects, among whom 399 461 had newly developed psoriasis. Subjects with BMI of more than 30 had a higher risk of psoriasis (hazards ratio [HR], 1.118; 95% confidence interval [CI], 1.100-1.137) compared with the BMI 18.5-23 group. WC showed a dose-dependent association with psoriatic risk. Subjects with WC over 105 cm showed the highest risk of psoriasis (HR, 1.305; 95% CI, 1.261-1.349) compared with subjects with WC lower than 80/75 after adjusting for confounding factors, including BMI. The risk of psoriasis was highest in males with normal BMI and abdominal obesity (HR, 1.175; 95% CI, 1.150-1.200). Our study indicates that WC is a specific factor affecting psoriatic risk and highlights the association between abdominal obesity and psoriasis, thus increasing awareness of the role of abdominal obesity in the pathogenesis and comorbidities of psoriasis.


Evaluation of the impact of a brief educational message on clinicians' awareness of risks of ionising-radiation exposure in imaging investigations: a pilot pre-post intervention study.
In the context of increasing availability of computed tomography (CT) scans, judicious use of ionising radiation is a priority to minimise the risk of future health problems. Hence, education of clinicians on the risks and benefits of CT scans in the management of patients is important. An educational message about the associated lifetime cancer risk of a CT scan was added to all CT scan reports at a busy acute teaching hospital in the UK. An online multiple choice survey was completed by doctors before and after the intervention, assessing education and knowledge of the risks involved with exposure to ionising radiation. Of 546 doctors contacted at baseline, 170 (31%) responded. Over a third (35%) of respondents had received no formal education on the risks of exposure to ionising radiation. Over a quarter (27%) underestimated (selected 1 in 30,000 or negligible lifetime cancer risk) the risk associated with a chest, abdomen and pelvis CT scan for a 20 year old female. Following exposure to the intervention for 1 year there was a statistically significant improvement in plausible estimates of risk from 68.3 to 82.2% of respondents (p < 0.001). There was no change in the proportion of doctors correctly identifying imaging modalities that do or do not involve ionising radiation. Training on the longterm risks associated with diagnostic radiation exposure is inadequate among hospital doctors. Exposure to a simple non-directional educational message for 1 year improved doctors' awareness of risks associated with CT scans. This demonstrates the potential of the approach to improve knowledge that could improve clinical practice. This approach is easily deliverable and may have applications in other areas of clinical medicine. The wider and longer term impact on radiation awareness is unknown, however, and there may be a need for regular mandatory training in the risks of radiation exposure.


Correction of whistle deformity secondary to cleft lip repair by V-Y plasty: a simple and effective technique.
Several techniques are available for the surgical repair of the cleft lip, however, avoiding secondary deformities and achieving consistent results remains a challenge. The whistle deformity is a secondary lip deformity characterised by inadequate fullness of the central upper lip with abnormal exposure of the central incisors when the lips are at rest, giving a whistling appearance. The causes include scarring of the vermilion and failure to restore the mucosal or muscular continuity. Various surgical options are available ranging from simple procedures like V-Y plasty and Z-plasty to complex procedures like complete lip redo, locoregional flaps, fillers and grafts. V-Y plasty is a simple, effective procedure for lip lengthening that can be performed under local anaesthesia as an outpatient procedure. It is less technique sensitive and also allows for some degree of muscle repair. We present a case of whistle deformity satisfactorily corrected with V-Y plasty.


[Internal carotid artery stent].
Stent implantation is a well established treatment of vascular stenoses if the result after percutaneous transluminal angioplasty (PTA) is suboptimal, or as a primary treatment to reduce the number of restenoses. Carotid artery stents have only been used in a relatively limited number of cases up till now. The first Scandinavian case of a successful internal carotid artery stent implantation after suboptimal PTA with five months follow-up is presented.


Does image quality matter? Impact of resolution and noise on mammographic task performance.
The purpose of this study was to examine the effects of different resolution and noise levels on task performance in digital mammography. This study created an image set with images at three different resolution levels, corresponding to three digital display devices, and three different noise levels, with noise magnitudes similar to full clinical dose, half clinical dose, and quarter clinical dose. The images were read by five experienced breast imaging radiologists. The data were then analyzed to compute two accuracy statistics (overall classification accuracy and lesion detection accuracy) and performance at four diagnostic tasks (detection of microcalcifications, benign masses, malignant masses, and discrimination of benign and malignant masses). Human observer results showed decreasing display resolution had little effect on overall classification accuracy and individual diagnostic task performance, but increasing noise caused overall classification accuracy to decrease by a statistically significant 21% as the breast dose went to one quarter of its normal clinical value. The noise effects were most prominent for the tasks of microcalcification detection and mass discrimination. When the noise changed from full clinical dose to quarter clinical dose, the microcalcification detection performance fell from 89% to 67% and the mass discrimination performance decreased from 93% to 79%, while malignant mass detection performance remained relatively constant with values of 88% and 84%, respectively. As a secondary aim, the image set was also analyzed by two observer models to examine whether their performance was similar to humans. Observer models differed from human observers and each other in their sensitivity to resolution degradation and noise. The primary conclusions of this study suggest that quantum noise appears to be the dominant image quality factor in digital mammography, affecting radiologist performance much more profoundly than display resolution.


Stabilizing Undercoordinated Zn Active Sites through Confinement in CeO2 Nanotubes for Efficient Electrochemical CO2 Reduction.
Zn-based catalysts hold great potential to replace the noble metal-based ones for CO2 reduction reaction (CO2 RR). Undercoordinated Zn (Znδ+ ) sites may serve as the active sites for enhanced CO production by optimizing the binding energy of *COOH intermediates. However, there is relatively less exploration into the dynamic evolution and stability of Znδ+ sites during CO2 reduction process. Herein, we present ZnO, Znδ+ /ZnO and Zn as catalysts by varying the applied reduction potential. Theoretical studies reveal that Znδ+ sites could suppress HER and HCOOH production to induce CO generation. And Znδ+ /ZnO presents the highest CO selectivity (FECO 70.9 % at -1.48 V vs. RHE) compared to Zn and ZnO. Furthermore, we propose a CeO2 nanotube with confinement effect and Ce3+ /Ce4+ redox to stabilize Znδ+ species. The hollow core-shell structure of the Znδ+ /ZnO/CeO2 catalyst enables to extremely expose electrochemically active area while maintaining the Znδ+ sites with long-time stability. Certainly, the target catalyst affords a FECO of 76.9 % at -1.08 V vs. RHE and no significant decay of CO selectivity in excess of 18 h.


Impact of COVID-19 lockdowns on hospital presentations and admissions in the context of low community transmission: evidence from time series analysis in Melbourne, Australia.
Melbourne, Australia, successfully halted exponential transmission of COVID-19 via two strict lockdowns during 2020. The impact of such restrictions on healthcare-seeking behaviour is not comprehensively understood, but is of global importance. We explore the impact of the COVID-19 pandemic on acute, subacute and emergency department (ED) presentations/admissions within a tertiary, metropolitan health service in Melbourne, Australia, over two waves of community transmission (1 March to 20 September 2020). We used 4 years of historical data and novel forecasting methods to predict counterfactual hospital activity for 2020, assuming absence of COVID-19. Observed activity was compared with forecasts overall, by age, triage category and for myocardial infarction and stroke. Data were analysed for all patients residing in the health service catchment area presenting between 4 January 2016 and 20 September 2020. ED presentations (n=401 805), acute admissions (n=371 723) and subacute admissions (n=15 676) were analysed. Substantial departures from forecasted presentation levels were observed during both waves in the ED and acute settings, and during the second wave in subacute. Reductions were most marked among those aged >80 and <18 years. Presentations persisted at expected levels for urgent conditions, and ED triage categories 1 and 5, with clear reductions in categories 2-4. Our analyses suggest citizens were willing and able to present with life-threatening conditions during Melbourne's lockdowns, and that switching to telemedicine did not cause widespread spill-over from primary care into ED. During a pandemic, lockdowns may not inhibit appropriate hospital attendance where rates of infectious disease are low.


Eleven-year review of data on Pap smears in Saudi Arabia: We need more focus on glandular abnormalities!
We reviewed data from Saudi Arabia on epithelial cell abnormalities (ECA) detected by Pap smear after noticing a slight increase in the incidence of cervical glandular abnormalities in our regional laboratory in recent years. Clarify data on adenocarcinoma (ADCA) on Pap smears in Saudi Arabia. Descriptive, retrospective study. Regional laboratory, Riyadh. We reviewed all Pap smears of adult females between 2006 and 2016 and compared our data with previously published results from Saudi Arabia. Descriptive data on ECAs. Among 19759 cases, atypical squamous cell of undetermined significance (ASC-US) was the most prevalent ECA (1.16%). ADCA occurred more than squamous cell carcinoma (SCC). In a comparison of published data before 2014 and after 2014 (including ours), there was a significant rise in ADCA (28 vs 48 cases; P=.004) with a significant drop in SCC, high-grade squamous intraepithelial lesions (HSIL) and low-grade squamous intraepithelial lesions (LSIL) (P < .0001, .004, and < .0001, respectively). We recommend that pathologists and cytotechnologists be vigilant in screening Pap smears in our population, particularly for glandular abnormalities. We also recommend use of Pap smears in the initial workup of women with suspected gynecological abnormalities, regardless of evolutions in HPV testing. The pooling of data instead of analyzing by study year.


Believing in birth--choosing VBAC: the childbirth expectations of a self-selected cohort of Australian women.
This study explored the childbirth expectations and knowledge of women who had experienced a caesarean and would prefer a vaginal birth in a subsequent pregnancy. Vaginal birth after caesarean is considered best practice. However, in most western world countries, despite the inherent risks of caesarean for both mother and baby, the number of women labouring after a previous caesarean is declining. Newspaper advertisements were used to recruit Western Australian women who had experienced a caesarean. Thematic analysis was used to analyse the interview data collected from women who attempted a vaginal birth (n=24), or stated they would choose this option, in a subsequent pregnancy (n=11). For this cohort of women, their caesarean experience reinforced their previously held expectations about birthing naturally. The women held strong views about the importance of working with their bodies to achieve a vaginal birth, which was considered an integral part of being a woman and mother. Positive support from family and friends and a reluctance to undergo another caesarean was also influential. Women articulated the risks of caesarean and considered vaginal birth enhanced the health and well-being of the mother and baby, promoted maternal infant connection and the eased the transition to motherhood. This study documents how the importance of birth, as a significant life event, remained the focus of these women's childbirth expectations influencing future decisions on birth mode and mediating against the 'pressure' of medical discourse promoting caesarean. Knowledge and appreciation of the multiple dimensions that contribute to women's decisions after a caesarean provides valuable information on which service providers and researchers can draw as they investigate interventions that enhance the uptake and success of women birthing vaginally after a caesarean.


Mortality in Different Mountain Sports Activities Primarily Practiced in the Summer Season-A Narrative Review.
Millions of people engage in mountain sports activities worldwide. Although leisure-time physical activity is associated with significant health benefits, mountain sports activities also bear an inherent risk for injury and death. However, death risk may vary across various types of mountain sports activities. Epidemiological data represent an important basis for the development of preventive measures. Therefore, the aim of this review is to compare mortality rates and potential risk factors across different (summer) mountain sports activities. A comprehensive literature search was performed on the death risk (mortality) in mountain sports, primarily practiced during the summer season, i.e., mountain hiking, mountain biking, paragliding, trekking, rock, ice and high-altitude climbing. It was found that the death risk varies considerably between different summer mountain sports. Mortality during hiking, trekking and biking in the mountains was lower compared to that during paragliding, or during rock, ice or high-altitude climbing. Traumatic deaths were more common in activities primarily performed by young adults, whereas the number of deaths resulting from cardiovascular diseases was higher in activities preferred by the elderly such as hiking and trekking. Preventive efforts must consider the diversity of mountain sports activities including differences in risk factors and practitioners and may more particularly focus on high-risk activities and high-risk individuals.


Barriers to Cervical Cancer Screening in Rural Kenya: Perspectives from a Provider Survey.
Although cervical cancer is highly preventable through screening, it remains the number one cause of cancer-related death in Kenyan women due to lack of funding and infrastructure for prevention programs. In 2012, Family AIDS Care and Education Services in partnership with the Kenya Ministry of Health began offering free screening at eleven rural health facilities. We sought to explore why screening coverage remains low at some sites. We examined the barriers to screening through a survey of 106 healthcare staff. The most frequently cited barriers to service delivery included staffing shortages, lack of trained staff, insufficient space, and supply issues. The patient barriers commonly perceived by the staff included inadequate knowledge, wait time, discomfort with male providers, and fear of pain with the speculum exam. Despite multilateral efforts to implement cervical cancer screening, staff face significant challenges to service provision and increased education is needed for both providers and patients.


Off-Label studies on anakinra in dermatology: a review.
Anakinra (Kineret®) is an interleukin-1 receptor antagonist (IL-1Ra) FDA approved for use in rheumatoid arthritis and in neonatal-onset multisystem inflammatory disease (NOMID). It has been used off-label for a variety of dermatologic conditions. A review of the available studies and cases of these off-label uses would be valuable to the dermatologist considering alternative treatments for these oftentimes poorly studied conditions. The PubMed/MEDLINE, EMBASE, Scopus, and ClinicalTrials.gov databases were searched with the term 'anakinra.' Results were manually screened to identify published data on off-label uses of anakinra in dermatologic conditions and systemic conditions with prominent dermatologic manifestations. Anakinra appears to show efficacy for numerous dermatologic conditions, with the strongest evidence for hidradenitis suppurativa, Bechet's disease, Muckle-Wells syndrome, and SAPHO syndrome. Case reports and case series data are available for numerous other dermatologic conditions. Anakinra is a potential option for patients with certain difficult-to-treat dermatologic diseases, given its relatively benign adverse effect profile and its effectiveness in a wide array of conditions. Overall, anakinra appears to be a promising option in the treatment of numerous dermatologic inflammatory conditions refractory to first line therapies, but further and higher-quality data is needed to clarify its therapeutic role.


The effect of the alpha-particle emitter astatine-211 in the mouse at the minimum toxic dose.
The radioactive halogen astatine-211 was injected into mice in an amount producing minimal toxicity. Histopathological examination of tissues at intervals between 3 d and 16 weeks showed the following changes: 1. Radiation-induced necrosis and progressive fibrosis of the thyroid gland. The gland was reduced to 25% of its original mass with only a few relatively normal follicles persisting. 2. A small, temporary, reduction in peripheral blood lymphocytes, platelets and red cells and a significant persistant increase in polymorphs. 3. Severe reduction in reproductive cells in the testis with some signs of recovery at 16 weeks.


Determination of immunoglobulin G in bovine colostrum and milk powders, and in dietary supplements of bovine origin by protein G affinity liquid chromatography: collaborative study.
An AOAC collaborative study was conducted to evaluate an affinity LC procedure for measuring immunoglobulin G (IgG) in selected dairy powders. The powders were extracted with 0.15 M sodium chloride solution and the pH was adjusted to 4.6 to precipitate caseins, which would otherwise lead to an overestimation of IgG. The analyte was then bound to a commercially available Protein G affinity cartridge and selectively eluted with a glycine buffer at pH 2.5. Detection was at 280 nm and quantification was made against a calibration curve prepared from bovine serum IgG. The samples analyzed included the likely matrixes for which this assay will find commercial use, namely, high- and low-protein-content colostrum powders, tablets containing colostrum powder, and some IgG-containing dairy powders; milk protein isolate, whey protein concentrate, and skim milk powder. Eleven laboratories provided data for the study and assayed blind duplicates of six materials. The repeatability RSD values ranged from 2.1 to 4.2% and the reproducibility RSD values ranged from 6.4 to 18.5%. The Protein G method with casein removal has adequate reproducibility for measuring IgG in colostrum-derived powders that are traded on the basis of IgG content as a colostral marker.


Combination fusion protein therapy of refractory brain tumors: demonstration of efficacy in cell culture.
Primary brain tumors including anaplastic astrocytomas and glioblastoma multiforme are difficult to treat because of their locally invasive nature and relative resistance to chemotherapy and radiation therapy. Novel agents that can kill multi-drug resistant tumor cells and reach tumor cells at distant sites in the brain are needed. One such class of agents is fusion proteins which consist of brain-tumor-selective peptide ligands fused to peptide toxins. The ligand directs the protein to the glioma cell surface; the peptide toxin is then internalized into the cell, translocates to the cytosol and catalytically inactivates protein synthesis leading to cell death. Fusion proteins are toxic to multi-drug resistant brain tumor cells. Because of the large molecular weight of these molecules, a unique delivery system has been developed--convection-enhanced delivery (CED). The method creates a bulk flow which supplements diffusion and achieves drug concentrations in the brain parenchyma orders of magnitude greater than by systemic administration. Patients with recurrent glioma treated with individual fusion protein CED have obtained clinical remissions lasting years. However, toxicities to normal brain have been observed and relapses ultimately occurred. To address the clinical need of these patients and improve upon the therapeutic index observed to date with single fusion protein CED, we generated a novel fusion protein DAB389EGF and tested it in combination with another active fusion protein, IL13PE38QQR. We observed potent glioma cytotoxicity with each fusion protein and synergistic toxicity with the combination. Further, brain tumor cells showed heterogeneous expression of individual receptors suggesting that the combination--DAB389EGF and IL13PE38QQR may show improved efficacy and should undergo further preclinical development for therapy of patients with relapsed high-grade gliomas.


Cost-effectiveness of the 13-valent pneumococcal conjugate vaccine in adults in Portugal versus "no vaccination" and versus vaccination with the 23-valent pneumococcal polysaccharide vaccine.
The burden of pneumococcal disease in adults is substantial from a social and economic point of view. This study assessed the cost-effectiveness of the 13-valent pneumococcal conjugate vaccine (PCV13) for the prevention of invasive pneumococcal disease and pneumococcal pneumonia in adults versus "no vaccination" and versus vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPSV23). A Markov model was used to simulate three strategies: no vaccination, complete vaccination with PPSV23 and complete vaccination with PCV13. The comparison between strategies allowed the estimation of clinical and economic outcomes including incremental cost-effectiveness ratios (ICER) and incremental cost-utility ratios (ICUR). The model took into account the distributions of age, risk profile, vaccination status, type of immunization and time since vaccination in the population. A societal perspective was adopted and a lifetime horizon was considered. Different sources of data and assumptions were used to calibrate PPSV23 and PCV13 effectiveness. Inpatient costs were based on the 2013 diagnosis-related group (DRG) database for National Health Service (NHS) hospitals and expert opinion; NHS official tariffs were the main source for unitary costs. PCV13 shows ICURs of €17,746/QALY and €13,146/QALY versus "no vaccination" and vaccination with PPSV23, respectively. Results proved to be robust in univariate sensitivity analyses, where all ratios were below a €20,000 threshold, with the exception of the scenario with PCV13 effectiveness halved. In a probabilistic sensitivity analysis, 94% of simulations showed cost-effectiveness ratios lower than €20,000/QALY, in both strategies. It was found that PCV13 is a cost-effective strategy to prevent pneumococcal disease in adults in Portugal.


[The thermographic diagnosis of pneumonia in patients with acute craniocerebral trauma].
The article discusses the results of thermovision examination of 75 patients with pneumonia which developed in the acute period of craniocerebral trauma. The method was found to be more informative than the routine radiography of the lungs. The possibilities of the method make it possible to establish an early diagnosis of pulmonary complications and, in some cases, to reveal a precise clinical picture.


Synthesis of very short chain lysophosphatidyloligodeoxynucleotides.
Very short chain 5'-O-lysophosphatidyloligonucleotides [5'-O-(1-O-palmitoyl-sn-glycero-3-phosphoryl)oligodeoxynucleotides, (5'-LyPOdNs)] were synthesized following a two-step chemoenzymatic synthesis. 5'-O-(sn-Glycero-3-phosphoryl)oligodeoxynucleotides (5'-GPOdNs) were first prepared by simply using a phosphoramidite of [(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methanol (1) in a further coupling step after the solid-phase elongation of each desired oligodeoxynucleotide. Next, the regioselective palmitoylation at the C-1 hydroxyl of the glycerol moiety of 5'-GPOdNs was achieved by a lipase-catalyzed transacylation with trifluoroethyl palmitate in organic solvent. Despite of the molecular bulkiness of 5'-GPOdNs, 2-, 3-, and 4-mer 5'-LyPOdNs were prepared by this procedure. Although in very low yield, 5- and 6-mer 5'-LyPOdNs were also obtained by this way.


Postemetic rupture of the esophagus: Boerhaave's syndrome.
Postemetic rupture of the esophagus, also known as spontaneous rupture or Boerhaave's syndrome, was first described by Herman Boerhaave in 1724. This is a severe disease that causes high mortality rates and is difficult to diagnose not only because it is rare but also because it is frequently confused with other severe clinical conditions, such as acute myocardial infarction, perforated peptic ulcer, and acute pancreatitis. Herein, we describe three cases of patients with this syndrome. Two underwent primary repair of the rupture, and one underwent esophagectomy followed by reconstruction. There was one death due to septic shock in the immediate postoperative period. The other two patients presented favorable long-term evolution.


Circuit mechanism for suppression of frontal cortical ignition during NREM sleep.
Conscious perception is greatly diminished during sleep, but the underlying circuit mechanism is poorly understood. We show that cortical ignition-a brain process shown to be associated with conscious awareness in humans and non-human primates-is strongly suppressed during non-rapid-eye-movement (NREM) sleep in mice due to reduced cholinergic modulation and rapid inhibition of cortical responses. Brain-wide functional ultrasound imaging and cell-type-specific calcium imaging combined with optogenetics showed that activity propagation from visual to frontal cortex is markedly reduced during NREM sleep due to strong inhibition of frontal pyramidal neurons. Chemogenetic activation and inactivation of basal forebrain cholinergic neurons powerfully increased and decreased visual-to-frontal activity propagation, respectively. Furthermore, although multiple subtypes of dendrite-targeting GABAergic interneurons in the frontal cortex are more active during wakefulness, soma-targeting parvalbumin-expressing interneurons are more active during sleep. Chemogenetic manipulation of parvalbumin interneurons showed that sleep/wake-dependent cortical ignition is strongly modulated by perisomatic inhibition of pyramidal neurons.


Flexible, Miniaturized Sensing Probes Inspired by Biofuel Cells for Monitoring Synaptically Released Glutamate in the Mouse Brain.
Chemical biomarkers in the central nervous system can provide valuable quantitative measures to gain insight into the etiology and pathogenesis of neurological diseases. Glutamate, one of the most important excitatory neurotransmitters in the brain, has been found to be upregulated in various neurological disorders, such as traumatic brain injury, Alzheimer's disease, stroke, epilepsy, chronic pain, and migraines. However, quantitatively monitoring glutamate release in situ has been challenging. This work presents a novel class of flexible, miniaturized probes inspired by biofuel cells for monitoring synaptically released glutamate in the nervous system. The resulting sensors, with dimensions as low as 50 by 50 μm, can detect real-time changes in glutamate within the biologically relevant concentration range. Experiments exploiting the hippocampal circuit in mice models demonstrate the capability of the sensors in monitoring glutamate release via electrical stimulation using acute brain slices. These advances could aid in basic neuroscience studies and translational engineering, as the sensors provide a diagnostic tool for neurological disorders. Additionally, adapting the biofuel cell design to other neurotransmitters can potentially enable the detailed study of the effect of neurotransmitter dysregulation on neuronal cell signaling pathways and revolutionize neuroscience.


[Mathematical assessment of the blood prothrombinase-thrombin activity by the autocoagulation test].
A new method for estimation of the time course of prothrombinase-thrombin activity is suggested. The method is based on approximation of the autocoagulogram appropriate section to the regression straight line and estimation of the angular coefficient B. This coefficient more accurately reflects the rate of the prothrombinase-thrombin activity growth and decline. The method is time-saving and simple, it is recommended for estimation of functional activity of hemostasis major component and of the principal marker of thrombin formation, the blood disseminated intravascular coagulation.


Elastographic measurement of the area and volume of thermal lesions resulting from radiofrequency ablation: pathologic correlation.
Elastography is a promising tool for visualizing the zone of necrosis in liver tissue resulting from radiofrequency tumor ablation. Because heat-ablated tissues are stiffer than normal untreated tissue, elastography may prove useful for following up patients who undergo radiofrequency ablative therapy. We sought to report the initial evaluations of the reliability of elastography for delineating thermal lesion boundaries in liver tissue by comparing lesion dimensions determined by elastography with the findings at whole-mount pathology. Radiofrequency ablation was performed in vitro on liver tissue specimens encased in gelatin phantoms. The imaging plane for elastography was perpendicular to the axis of the radiofrequency electrode so that the ablated region was around the center of the plane. To obtain three-dimensional visualization of thermal lesions, we reconstructed the lesions from multiple elastograms by linearly translating the elastographic scanning plane. Pathology photographs were obtained in the same image plane used for elastography by slicing through the gelatin and tissue phantom using external markers. We used digitized gross pathology photographs obtained at a specified slice thickness to compute the areas and volumes of the lesions. These measurements were then compared to the measurements obtained from the elastograms. In a sample of 40 thermal lesions, we obtained a correlation between in vitro elastographic and pathologic measurements of r = 0.9371 (p < 0.00001) for area estimates and r = 0.979 (p < 0.00001) for volume estimates. We found excellent correlation between the measurements of the dimensions, areas, and volumes of thermal lesions that were based on elastographic images and the measurements that were based on digitized pathologic images. When compared with digitized pathologic measurements, elastographic measurements showed a tendency to slightly underestimate both the areas and volumes of lesions. Nevertheless, elastography is a reliable technique for delineating thermal lesions resulting from radiofrequency ablation.


Enhanced expression of the granulocyte-macrophage colony stimulating factor gene in acute myelocytic leukemia cells following in vitro blast cell enrichment.
Expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene in acute myelocytic leukemia (AML) was assayed by Northern blot analysis. GM-CSF messenger RNA (mRNA) was detected in the freshly obtained mononuclear cells of only one of 48 cases of AML, in contrast with recent reports that GM-CSF mRNA might be detected in half of the cases of AML when RNA is prepared from T-cell- and monocyte-depleted leukemic cells. We did find, however, that expression of the GM-CSF gene was detectable in five of ten cases after in vitro T-cell and monocyte depletion steps. Additional studies suggest that expression of GM-CSF in the bone marrow of the one positive case, rather than being autonomous, was under exogenous control, possibly by a paracrine factor secreted by marrow stromal cells. These studies emphasize the potential for altering in vivo patterns of gene expression by in vitro cell manipulation.


The relationship between mismatch negativity and arousal level. Can mismatch negativity be an index for evaluating the arousal level in infants?
Electrophysiological and behavioral studies have shown that stimulus relevance contributes to auditory processing in sleep and auditory stimuli changes the sleep stages. So we observed changes in auditory processing due to sleep stages by recording infant mismatch negativity (MMN) during different states and investigated the arousal mechanisms. Auditory event-related potentials (ERPs) of 26 neonates were recorded using high-density EGI EEG system. Stimuli consisted of 1000 Hz tones with 90% probability as standard and 1200 Hz with 10% probability as deviant. Study 1 was designed for the confirmation of the recording of MMN from neonates and Study 2 for investigating whether an appropriate stimulus onset asynchrony (SOA) of the stimulus would induce a clear difference in the latency or amplitude. (Study 1) MMN were obtained from all subjects. No differences of the latencies, amplitudes and distribution due to arousal or sleep stage were observed. After the MMN response occurred, a prominent negativity like Nc was seen in response to deviant stimuli in active sleep and waking state. (Study 2) No distinct differences between the difference states were seen in any SOA. Only MMN did not characterize the arousal or sleep stage. But the modality of the auditory evoked potentials (AEPs) may differ according to the state, so further detailed investigation could enable the detection of the infants' state using the AEP.


[Evaluation of syncope in children with tilt table test].
Tilt table testing is a well approached examination for differentiating unexplained syncope and control trial after therapy. It is evaluated at children and is fast and reliable in spite of high personality effort. We present the indication of examination, course of examination, additional procedures like transcranial doppler sonography, reaction models during the tilt table examination and treatment features for neurocardiogenic syncope.


Review article: faecal markers in the assessment of activity in inflammatory bowel disease.
The fundamental pathological process behind ulcerative colitis and Crohn's disease is intestinal inflammation. As the precise cause of this is not yet completely understood, current treatment strategies are aimed at reducing or eliminating the inflammation. Endoscopic examination and histological analysis of biopsy specimens remain the 'gold standard' methods for detecting and quantifying bowel inflammation; however, these techniques are costly, invasive, and repeated examinations are unpopular with patients. Disease activity questionnaires and laboratory 'inflammatory markers', although widely used, show an unreliable correlation with endoscopy and histology. New markers need to be developed to detect and quantify bowel inflammation. These would be of use diagnostically and also an aid to pharmacological treatment.


Induction of Golli-MBP expression in CNS macrophages during acute LPS-induced CNS inflammation and experimental autoimmune encephalomyelitis (EAE).
Microglia are the tissue macrophages of the CNS. Microglial activation coupled with macrophage infiltration is a common feature of many classic neurodegenerative disorders. The absence of cell-type specific markers has confounded and complicated the analysis of cell-type specific contributions toward the onset, progression, and remission of neurodegeneration. Molecular screens comparing gene expression in cultured microglia and macrophages identified Golli-myelin basic protein (MBP) as a candidate molecule enriched in peripheral macrophages. In situ hybridization analysis of LPS/IFNg and experimental autoimmune encephalomyelitis (EAE)-induced CNS inflammation revealed that only a subset of CNS macrophages express Golli-MBP. Interestingly, the location and morphology of Golli-MBP+ CNS macrophages differs between these two models of CNS inflammation. These data demonstrate the difficulties of extending in vitro observations to in vivo biology and concretely illustrate the complex heterogeneity of macrophage activation states present in region- and stage-specific phases of CNS inflammation. Taken altogether, these are consistent with the emerging picture that the phenotype of CNS macrophages is actively defined by their molecular interactions with the CNS microenvironment.


In situ imaging in C. elegans reveals developmental regulation of microtubule dynamics.
Microtubules (MTs) are cytoskeletal polymers that undergo dynamic instability, the stochastic transition between growth and shrinkage phases. MT dynamics are required for diverse cellular processes and, while intrinsic to tubulin, are highly regulated. However, little is known about how MT dynamics facilitate or are regulated by tissue biogenesis and differentiation. We imaged MT dynamics in a smooth muscle-like lineage in intact developing Caenorhabditis elegans. All aspects of MT dynamics change significantly as stem-like precursors exit mitosis and, secondarily, as they differentiate. We found that suppression, but not enhancement, of dynamics perturbs differentiated muscle function in vivo. Distinct ensembles of MT-associated proteins are specifically required for tissue biogenesis versus tissue function. A CLASP family MT stabilizer and the depolymerizing kinesin MCAK are differentially required for MT dynamics in the precursor or differentiated cells, respectively. All of these multidimensional phenotypic comparisons were facilitated by a data display method called the diamond graph.


Impact of cattle on the prevalence and severity of trachoma.
Ethiopia is the African country with the largest number of cattle (26 million). Because of the potential impact of cattle on the transmission and severity of trachoma, the major cause of blindness in the country, an attempt is made to document this association to justify the inclusion of the control of cattle pollution in the prevention of blindness. The prevalence of trachoma is lower in pastoralists who herd mainly camels than in pastoralists who herd mainly cattle. In the first group the prevalences of moderate and severe trachoma in children under 10 are 0.9% and trichiasis/entropion in the total population 0.2%, whereas in the second group the prevalences are 45.1% and 4.0% respectively. In Borana pastoralists with and without cattle the prevalence ratio for moderate and severe trachoma is 1.0, whereas the prevalence ratios for severe trachoma and conjunctivitis were higher in the group with cattle, 2.5 and 3.0 (p less than 0.001 for both). The elimination of cattle pollution should reduce the prevalence of severe trachoma by 45.4%. This is the first study presenting evidence of an association between cattle and trachoma. On the basis of this study a strong recommendation is made to the Ministry of Health to control cattle pollution in rural areas as a major strategy to prevent blindness in Ethiopia.


Monocular versus binocular visual acuity as measures of vision impairment and predictors of visual disability.
To examine the relationship between monocular and binocular visual acuities as predictors of visual disability in a population-based sample of individuals 65 years of age and older. Two thousand five hundred twenty community-dwelling residents of Salisbury, Maryland, between the ages of 65 and 84 years of age were recruited for the study. Corrected visual acuity was measured monocularly and binocularly using ETDRS charts. Reading speed, face discrimination, and self-reported difficulty with visual tasks were also determined. Binocular acuity is predicted with reasonable accuracy by acuity in the better eye alone, but not by the widely used American Medical Association (AMA) weighted-average algorithm. The AMA algorithm significantly underestimates binocular acuity when the interocular acuity difference exceeds one line. Monocular acuity and binocular acuity were significantly better predictors of reading speed than the AMA weighted score or a recently proposed Functional Vision Score (FVS). Monocular acuity in the better eye, binocular acuity, and the AMA and FVS algorithms were equally good predictors of self-reported vision disability. None of the acuity measures were good predictors of face recognition ability. The binocular acuities of older individuals can be inferred from measures of monocular acuity. There is little evidence for binocular inhibition when the monocular acuities in the two eyes are unequal, as opposed to the widely used AMA algorithm for computing binocular visual impairment. For tasks that are strongly associated with visual acuity, such as reading, this association can be captured from measures of monocular acuity and does not require separate assessment of binocular acuity.


Quality of life after radical prostatectomy in Japanese men: 2 year longitudinal study.
We performed a 2 year longitudinal survey of health-related quality of life (HRQOL) after radical retropubic prostatectomy (RP) in Japanese men with localized prostate cancer. We measured 112 patients who underwent RP with SF-36 and University of California, Los Angeles Prostate Cancer Index before and 3, 6, 12, 18 and 24 months after surgery. Patients who underwent RP showed problems in some domains of general HRQOL, but these problems diminished over time. Mental health significantly improved throughout the follow-up period. The urinary function substantially declined at 3 months and continued to recover gradually but never returned to the baseline. Urinary bother at 3 months showed a significant decrease, but at 6 months it returned to baseline. The data of sexual function and bother showed a substantially lower score after RP. Patients lost their sexual desire significantly throughout the post-operative period. After 12 months, the nerve sparing group had significantly better improvement in sexual function than the non-nerve sparing group and this improvement continued up to 2 years after operation. Despite reports of problems with sexuality and urinary continence, general HRQOL was mostly unaffected by RP after 6 months. RP had a favorable impact on mental health. Although urinary function did not completely return to the baseline level even at 2 years after RP, recovery from urinary bother was rapid. RP had serious consequences on libido, erectile function and sexual activity. In the second year, the sexual function of those who underwent RP with bilateral nerve sparing procedure continued to improve.


Impaired functional connectivity within and between frontostriatal circuits and its association with compulsive drug use and trait impulsivity in cocaine addiction.
Converging evidence has long identified both impulsivity and compulsivity as key psychological constructs in drug addiction. Although dysregulated striatal-cortical network interactions have been identified in cocaine addiction, the association between these brain networks and addiction is poorly understood. To test the hypothesis that cocaine addiction is associated with disturbances in striatal-cortical communication as captured by resting-state functional connectivity (rsFC), measured from coherent spontaneous fluctuations in the blood oxygenation level-dependent functional magnetic resonance imaging signal, and to explore the relationships between striatal rsFC, trait impulsivity, and uncontrolled drug use in cocaine addiction. A case-control, cross-sectional study was conducted at the National Institute on Drug Abuse Intramural Research Program outpatient magnetic resonance imaging facility. Data used in the present study were collected between December 8, 2005, and September 30, 2011. Participants included 56 non-treatment-seeking cocaine users (CUs) (52 with cocaine dependence and 3 with cocaine abuse) and 56 healthy individuals serving as controls (HCs) matched on age, sex, years of education, race, estimated intelligence, and smoking status. Voxelwise statistical parametric analysis testing the rsFC strength differences between CUs and HCs in brain regions functionally connected to 6 striatal subregions defined a priori. Increased rsFC strength was observed predominantly in striatal-frontal circuits; decreased rsFC was found between the striatum and cingulate, striatal, temporal, hippocampal/amygdalar, and insular regions in the CU group compared with the HCs. Increased striatal-dorsal lateral prefrontal cortex connectivity strength was positively correlated with the amount of recent cocaine use (uncorrected P < .046) and elevated trait impulsivity in the CUs (uncorrected P < .012), and an index reflecting the balance between striatal-dorsal anterior cingulate cortex and striatal-anterior prefrontal/orbitofrontal cortex circuits was significantly associated with loss of control over cocaine use (corrected P < .012). Cocaine addiction is associated with disturbed rsFC in several specific striatal-cortical circuits. Specifically, compulsive cocaine use, a defining characteristic of dependence, was associated with a balance of increased striatal-anterior prefrontal/orbitofrontal and decreased striatal-dorsal anterior cingulate connectivity; trait impulsivity, both a risk factor for and a consequence of cocaine use, was associated with increased dorsal striatal-dorsal lateral prefrontal cortex connectivity uniquely in CUs. These findings provide new insights toward the neurobiological mechanisms of addiction and suggest potential novel therapeutic targets for treatment.


Classification of human ovarian cancer using functional, spectral, and imaging features obtained from in vivo photoacoustic imaging.
We report in this pilot study the diagnostic results of in vivo imaging of patients with ovarian lesions, using a co-registered photoacoustic and ultrasound (PAT/US) system. A total of 39 ovaries from 24 patients were imaged in vivo. PAT functional features, i.e., blood oxygen saturation (sO2) and relative total hemoglobin (rHbT), PAT image features, and PAT spectral features within a region of interest (ROI) in each ovarian tissue were extracted. To select the significant features, a t-test on each feature was performed, and the independent predictors were determined by evaluating correlation between each pair of predictors. To classify the ovarian lesions, we employed a generalized linear model (GLM) and a support vector machine (SVM). We used these classifiers first to distinguish benign/normal lesions from ovaries with invasive epithelial tumors and then to separate normal/benign lesions from all types of ovarian tumors. We developed classifiers once by inclusion of PAT functional features to assess the best diagnostic performance of the classifiers when multiple wavelengths data are available. Second time, we excluded the PAT functional features from the features set to evaluate the best diagnostic performance if only a single wavelength is available. Our results show that using functional features improves the classification performance, especially for distinguishing normal/benign ovarian lesions from all types of tumors. In this case, an area under ROC curve (AUC) of 0.92, 0.93 of testing data was achieved using a GLM and SVM classifier when functional features were included in the feature set while excluding these features resulted in an AUC of 0.89, 0.92, respectively.


Oral health-related quality of life in patients with temporomandibular disorders.
To characterize the level of impairment of oral health-related quality of life (OHRQoL) in a temporomandibular disorder (TMD) patient population. OHRQoL was measured using the German version of the Oral Health Impact Profile (OHIP-G) in a consecutive sample of 416 patients seeking treatment for their complaints in the masticatory muscles and temporomandibular joints and with at least 1 diagnosis according to the German version of the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). The level of impairment of OHRQoL was characterized by the OHIP summary score mean and its 95% confidence interval. OHRQoL was described for each of the 8 RDC/TMD diagnoses (Axis I) and the RDC/TMD Axis II measures (Graded Chronic Pain Scale [GCPS], jaw disability list, depression, and somatization). These findings were compared with the level of impairment of OHRQoL in the adult general population derived from a national sample (n = 2,026). Among the RDC/TMD Axis I measures, all diagnoses were correlated with much higher impacts compared to the normal population (means for all diagnoses were 32.8 to 53.7 versus 15.8 in the general population). All diagnoses had a similar level of impact except for disc displacement with reduction (which had a lower impact). There were larger differences in mean OHIP-G scores among subgroups of RDC/TMD Axis II measures than among subgroups of RDC/TMD Axis I characteristics. The strongest association was with GCPS, with mean OHIP scores of 33.3 for grade I, 48.1 for grade II, 71.7 for grade III, and 88.5 for grade IV. OHRQoL was markedly impaired in TMD patients. The level of OHRQoL varied across diagnostic categories but more across Axis II, ie, the psychosocial axis; the variation was reflected especially in their level of graded chronic pain.


A Changing Force in My Life.
Monika Ahuja was diagnosed with a sarcoma of the left leg that eventually metastasized to the lungs and brain. Eventually as the truth unfolded to her that life is limited, she was unable to discuss with her family her thoughts about her illness due to their reluctance to accept the inevitable, and she started to convey through her songs how broken she feels inside and how deeply she wishes that this suffering will come to an end. She sings songs preparing all those dear to her of how to live and move on in life without her. Such preparedness for death is breathtaking for the author and the rest of the hospice team, and it makes them wonder if they would be able to prepare for their own death in the exemplary manner that Monika is setting. Monika has very strongly reinforced the lessons of life to the author, who wants to pass them on to family, friends, and all those working in health care.


Toward clinical microcytogenetics: the aniridia and the retinoblastoma stories.
In conclusion, the aniridia and the retinoblastoma stories tell us the importance of applying high-resolution cytogenetic techniques and of measuring catalase and esterase D activities when screening and investigating patients and their families. They also point to exceptional situations in carcinogenesis, and without doubt the newly devised genetic techniques, such as recombinant DNA, will allow, when applied to these conditions, a far better understanding of carcinogenesis at the molecular level--which is the important one.


Two-dimensional systems with competing interactions: dynamic properties of single particles and of clusters.
Systems with short-range attractive and long-range repulsive interactions are able to form mesophases at sufficiently low temperatures. In two dimensions, such mesophases emerge as clusters, stripes or bubbles. Using extensive Monte Carlo simulations we investigate the static and the dynamic properties of such a cluster-forming system over a broad temperature range and for different densities. Via the static properties we analyse how ordering into close packed configurations sets in both at the level of the particles as well as at the level of the clusters. The dynamic properties provide information on how, at low temperature, the motion of individual particles is influenced by the dynamic slowing down of the clusters. Finally, we discuss the different diffusion mechanisms at play at low and intermediate densities.


Anorexia of aging: An international assessment of healthcare providers' knowledge and practice gaps.
Anorexia of aging is a common geriatric syndrome that includes loss of appetite and/or reduced food intake, with associated undernutrition, unintended weight loss, sarcopenia, functional decline, loss of independence and other adverse health outcomes. Anorexia of aging can have multiple and severe consequences and is often overlooked by healthcare professionals (HCPs). Even more concerningly, clinicians commonly accept anorexia of aging as an inevitable part of 'normal' aging. The aim of this assessment was to identify current gaps in professional knowledge and practice in identifying and managing older persons with anorexia. Results may guide educational programmes to fill the gaps identified and therefore improve patient outcomes. This international assessment was conducted using a mixed-methods approach, including focus group interviews with subject matter experts and an electronic survey of practicing HCPs. The assessment was led by the Society on Sarcopenia, Cachexia and Wasting Disorders (SCWD) and was supported by in-country collaborating organizations. A quantitative survey of 26 multiple-choice questions was completed by physicians, dietitians and other HCPs (n = 1545). Most HCPs (56.8%) recognize a consistent definition of anorexia of aging as a loss of appetite and/or low food intake. Cognitive changes/dementia (91%) and dysphagia (87%) are seen as the biggest risk factors. Most respondents were confident to give nutritional (62%) and physical activity (59.4%) recommendations and engaged caregivers such as family members in supporting older adults with anorexia (80.6%). Most clinicians assessed appetite at each visit (66.7%), although weight is not measured at every visit (41.5%). Apart from the Mini-Nutritional Assessment Short Form (39%), other tools to screen for appetite loss are not frequently used or no tools are used at all (29.4%). A high number of respondents (38.7%) believe that anorexia is a normal part of aging. Results show that treatment is focused on swallowing disorders (78%), dentition issues (76%) and increasing oral intake (fortified foods [75%] and oral nutritional supplements [74%]). Nevertheless, the lack of high-quality evidence is perceived as a barrier to optimal treatment (49.2%). Findings from this international assessment highlight the challenges in the care of older adults with or at risk for anorexia of aging. Identifying professional practice gaps between individual HCPs and team-based gaps can provide a basis for healthcare education that is addressed at root causes, targeted to specific audiences and developed to improve individual and team practices that contribute to improving patient outcomes.


DNA double-strand break repair pathway choice is directed by distinct MRE11 nuclease activities.
MRE11 within the MRE11-RAD50-NBS1 (MRN) complex acts in DNA double-strand break repair (DSBR), detection, and signaling; yet, how its endo- and exonuclease activities regulate DSBR by nonhomologous end-joining (NHEJ) versus homologous recombination (HR) remains enigmatic. Here, we employed structure-based design with a focused chemical library to discover specific MRE11 endo- or exonuclease inhibitors. With these inhibitors, we examined repair pathway choice at DSBs generated in G2 following radiation exposure. While nuclease inhibition impairs radiation-induced replication protein A (RPA) chromatin binding, suggesting diminished resection, the inhibitors surprisingly direct different repair outcomes. Endonuclease inhibition promotes NHEJ in lieu of HR, while exonuclease inhibition confers a repair defect. Collectively, the results describe nuclease-specific MRE11 inhibitors, define distinct nuclease roles in DSB repair, and support a mechanism whereby MRE11 endonuclease initiates resection, thereby licensing HR followed by MRE11 exonuclease and EXO1/BLM bidirectional resection toward and away from the DNA end, which commits to HR.


The Key to Combat Readiness Is a Strong Military-Civilian Partnership.
In peacetime, it is challenging for Army Forward Resuscitative Surgical Teams (FRST) to maintain combat readiness as trauma represents <0.5% of military hospital admissions and not all team members have daily clinical responsibilities. Military surgeon clinical experience has been described, but no data exist for other members of the FRST. We test the hypothesis that the clinical experience of non-physician FRST members varies between active duty (AD) and Army reservists (AR). Over a 3-year period, all FRSTs were surveyed at one civilian center. Six hundred and thirteen FRST soldiers were provided surveys and 609 responded (99.3%), including 499 (81.9%) non-physicians and 110 (18.1%) physicians/physician assistants. The non-physician group included 69% male with an average age of 34 ± 11 years and consisted of 224 AR (45%) and 275 AD (55%). Rank ranged from Private to Colonel with officers accounting for 41%. For AD vs. AR, combat experience was similar: 50% vs. 52% had ≥1 combat deployment, 52% vs. 60% peri-deployment patient load was trauma-related, and 31% vs. 32% had ≥40 patient contacts during most recent deployment (all P > .15). However, medical experience differed for AD and AR: 18% vs. 29% had >15 years of experience in practice and 4% vs. 17% spent >50% of their time treating critically injured patients (all P < .001). These differences persisted across all specialties, including perioperative nurses, certified registered nurse anesthetists, operating room (OR) techs, critical-care nurses, emergency room (ER) nurses, licensed practical nurse (LPN), and combat medics. This is the first study of clinical practice patterns in AD vs. AR, non-physician members of Army FRSTs. In concordance with previous studies of military surgeons, FRST non-physicians seem to be lacking clinical experience as well. To maintain readiness and to provide optimal care for our injured warriors, the entire FRST, not just individuals, should embed within civilian centers.


Analysis of small GTP-binding proteins of the lens by GTP overlay assay reveals the presence of unique GTP-binding proteins associated with fiber cells.
Low molecular weight GTP-binding proteins are molecular switches which are thought to play pivotal roles in cell growth, differentiation, cytoskeletal organization and vesicular trafficking. In this study, members of this family of proteins have been identified and characterized in the eye lens, for the first time. [alpha 33P]GTP blot overlay assays of monkey and human lens water soluble and membranous insoluble fractions revealed the presence of specific GTP-binding proteins in the range of 20-30 kDa (small GTPases) in both fractions, with much higher amounts in the membranous insoluble fraction. In the insoluble fraction, in addition to 20-30 kDa GTPases, there are three distinct GTP-binding proteins, ranging from 33-45 kDa. The small GTPases (20-30 kDa) were present throughout the lens in epithelium, cortex and nucleus, while the 33-45 kDa GTP-binding protein bands were exclusively associated with the cortex and nucleus (fiber cells). Analysis of lens fractions by two-dimensional electrophoresis, immunoprecipitation using monoclonal and sequence specific polyclonal antibodies and C3 exoenzyme mediated ADP-ribosylation demonstrated the presence of Ras, Rap, Rho, Rac, Rab and several other small GTPases. The 33-45 kDa GTP-binding proteins that are associated with lens fiber cells appear to be distinct from the small GTPases and from heterotrimeric GTPases, and were not detected in brain or heart tissue. The presence of different complements of GTP-binding proteins in lens fibers and epithelial, cells suggests their involvement in important regulatory functions, possibly related to cell growth, differentiation and organization of the cytoskeleton.


Transcriptomic network analysis of micronuclei-related genes: a case study.
Mechanistically relevant information on responses of humans to xenobiotic exposure in relation to chemically induced biological effects, such as micronuclei (MN) formation can be obtained through large-scale transcriptomics studies. Network analysis may enhance the analysis and visualisation of such data. Therefore, this study aimed to develop a 'MN formation' network based on a priori knowledge, by using the pathway tool MetaCore. The gene network contained 27 genes and three gene complexes that are related to processes involved in MN formation, e.g. spindle assembly checkpoint, cell cycle checkpoint and aneuploidy. The MN-related gene network was tested against a transcriptomics case study associated with MN measurements. In this case study, transcriptomic data from children and adults differentially exposed to ambient air pollution in the Czech Republic were analysed and visualised on the network. Six genes from the network, i.e. BAX, DMNT1, PCNA, HIC1, p21 and CDC20, were retrieved. Based on these six genes and in combination with p53 and IL-6, a dedicated network was created. This dedicated network is possibly suited for the development of a reporter gene assay that could be used to screen populations complementary to the current MN test assay. In conclusion, we have shown that network analysis of transcriptomics data in relation to the formation of MN is possible and provides a novel mechanistic hypothesis by indicating which genes are regulated and influence others.


Expression of inducible nitric oxide synthase and elevation of tyrosine nitration of a 32-kilodalton cellular protein in brain capillary endothelial cells from rats infected with a neuropathogenic murine leukemia virus.
PVC-211 murine leukemia virus (MuLV) is a neuropathogenic variant of Friend MuLV (F-MuLV) which causes a rapidly progressive spongiform neurodegenerative disease in rodents. The primary target of PVC-211 MuLV infection in the brain is the brain capillary endothelial cell (BCEC), which is resistant to F-MuLV infection. Previous studies have shown that changes in the envelope gene of PVC-211 MuLV confer BCEC tropism to the virus. However, little is known about how infection of BCECs by PVC-211 MuLV induces neurological disease. Previous results suggest that nitric oxide (NO), which has been implicated as a potential neurotoxin, is involved in PVC-211 MuLV-induced neurodegeneration. In this study, we show that expression of inducible nitric oxide synthase (iNOS), which produces NO from L-arginine, is induced in BCECs from PVC-211 MuLV-infected rats. Furthermore, elevated levels of a 32-kDa cellular protein modified by 3-nitrotyrosine, which is a hallmark of NO production, were observed in virus-infected BCECs. BCECs from rats infected with BCEC-tropic but nonneuropathogenic PVF-e5 MuLV, which is a chimeric virus between PVC-211 MuLV and F-MuLV, fail to induce either iNOS expression or elevation of tyrosine nitration of a 32-kDa protein. These results suggest that expression of iNOS and nitration of tyrosine residues of a 32-kDa protein in PVC-211 MuLV-infected BCECs may play an important role in neurological disease induction.


Steroid avoidance or withdrawal for kidney transplant recipients.
Steroid-sparing strategies have been attempted in recent decades to avoid morbidity from long-term steroid intake among kidney transplant recipients. Previous systematic reviews of steroid withdrawal after kidney transplantation have shown a significant increase in acute rejection. There are various protocols to withdraw steroids after kidney transplantation and their possible benefits or harms are subject to systematic review. This is an update of a review first published in 2009. To evaluate the benefits and harms of steroid withdrawal or avoidance for kidney transplant recipients. We searched the Cochrane Kidney and Transplant Specialised Register to 15 February 2016 through contact with the Information Specialist using search terms relevant to this review. All randomised and quasi-randomised controlled trials (RCTs) in which steroids were avoided or withdrawn at any time point after kidney transplantation were included. Assessment of risk of bias and data extraction was performed by two authors independently and disagreement resolved by discussion. Statistical analyses were performed using the random-effects model and dichotomous outcomes were reported as relative risk (RR) and continuous outcomes as mean difference (MD) with 95% confidence intervals. We included 48 studies (224 reports) that involved 7803 randomised participants. Of these, three studies were conducted in children (346 participants). The 2009 review included 30 studies (94 reports, 5949 participants). Risk of bias was assessed as low for sequence generation in 19 studies and allocation concealment in 14 studies. Incomplete outcome data were adequately addressed in 22 studies and 37 were free of selective reporting.The 48 included studies evaluated three different comparisons: steroid avoidance or withdrawal compared with steroid maintenance, and steroid avoidance compared with steroid withdrawal. For the adult studies there was no significant difference in patient mortality either in studies comparing steroid withdrawal versus steroid maintenance (10 studies, 1913 participants, death at one year post transplantation: RR 0.68, 95% CI 0.36 to 1.30) or in studies comparing steroid avoidance versus steroid maintenance (10 studies, 1462 participants, death at one year after transplantation: RR 0.96, 95% CI 0.52 to 1.80). Similarly no significant difference in graft loss was found comparing steroid withdrawal versus steroid maintenance (8 studies, 1817 participants, graft loss excluding death with functioning graft at one year after transplantation: RR 1.17, 95% CI 0.72 to 1.92) and comparing steroid avoidance versus steroid maintenance (7 studies, 1211 participants, graft loss excluding death with functioning graft at one year after transplantation: RR 1.09, 95% CI 0.64 to 1.86). The risk of acute rejection significantly increased in patients treated with steroids for less than 14 days after transplantation (7 studies, 835 participants: RR 1.58, 95% CI 1.08 to 2.30) and in patients who were withdrawn from steroids at a later time point after transplantation (10 studies, 1913 participants, RR 1.77, 95% CI 1.20 to 2.61). There was no evidence to suggest a difference in harmful events, such as infection and malignancy, in adult kidney transplant recipients. The effect of steroid withdrawal in children is unclear. This updated review increases the evidence that steroid avoidance and withdrawal after kidney transplantation significantly increase the risk of acute rejection. There was no evidence to suggest a difference in patient mortality or graft loss up to five year after transplantation, but long-term consequences of steroid avoidance and withdrawal remain unclear until today, because prospective long-term studies have not been conducted.


[The interaction of soil micromycetes with "hot" particles in a model system].
A model system which permits observing for a long time and fixing interaction of fungi with a radiation source has been created on the basis of an isolated "hot" particle, deficient mineral medium (saccharose content 60 mg/l) and suspension of fungal conidia. Five species (six strains) of micromycetes isolated from radionuclide-contaminated soils and fifteen "hot" particles have been tested. It has been found out for the first time that Cladosporium cladosporioides and Penicillium roseo-purpureum are able actively overgrow "hot" particles whose radioactivity did not exceed 3.1-1.0(-7) Ci by gamma-spectrum and to destroy them 50-150 days later. Certain changes in morphology of fungi-destructors of "hot" particles are revealed. A problem on ecological significance of the found phenomenon is discussed.


Vaccinating women previously exposed to human papillomavirus: a cost-effectiveness analysis of the bivalent vaccine.
Recent trials have indicated that women with prior exposure to Human papillomavirus (HPV) subtypes 16/18 receive protection against reinfection from the HPV vaccines. However, many of the original models investigating the cost effectiveness of different vaccination strategies for the protection of cervical cancer assumed, based on the trial results at that time, that these women received no protection. We developed a deterministic, dynamic transmission model that incorporates the vaccine-induced protection of women with prior exposure to HPV. The model was used to estimate the cost effectiveness of progressively extending a vaccination programme using the bivalent vaccine to older age groups both with and without protection of women with prior exposure. We did this under a range of assumptions on the level of natural immunity. Our modelling projections indicate that including the protection of women with prior HPV exposure can have a profound effect on the cost effectiveness of vaccinating adults. The impact of this protection is inversely related to the level of natural immunity. Our results indicate that adult vaccination strategies should potentially be reassessed, and that it is important to include the protection of non-naive women previously infected with HPV in future studies. Furthermore, they also highlight the need for a more thorough investigation of this protection.


Emulsifying and foaming properties of commercial yellow pea (Pisum sativum L.) seed flours.
Commercial yellow pea seed flours prepared by a patented wet-milling process and pea protein isolate (PPI) were analyzed for emulsifying and foaming properties at pH 3.0, 5.0, and 7.0 and compared to soybean protein isolate (SPI). PPI and SPI formed emulsions with significantly smaller (p < 0.05) oil droplet sizes, 16-30 and 23-54 microm, respectively, than flours that primarily contained fiber such as Centara III and IV, or those that consisted mainly of starch: Centu-tex, Uptake 80 and Accu-gel. PPI was a better emulsifier than SPI at pH 7.0, and a better foaming agent at pH 3.0 and pH 7.0, although foaming capacity varied with sample concentration. Centu-tex and Uptake 80 have exactly the same chemical composition, but the latter has a much smaller flour particle size range, and had significantly smaller (p < 0.05) emulsion oil droplets. Incorporation of pea starch into SPI emulsions produced a synergistic effect that led to significant increases (p < 0.05) in emulsification capacity (reduced emulsion oil droplet size) when compared to SPI or starch alone. These results showed that PPI had generally significantly higher (p < 0.05) emulsion and foam forming properties than SPI, and that pea starch could be used to improve the quality of SPI-stabilized food emulsions.


Prevention of depression with escitalopram in patients undergoing treatment for head and neck cancer: randomized, double-blind, placebo-controlled clinical trial.
Major depressive disorder develops in up to half the patients undergoing treatment for head and neck cancer, resulting in significant morbidity; therefore, preventing depression during cancer treatment may be of great benefit. To determine whether prophylactic use of the antidepressant escitalopram oxalate would decrease the incidence of depression in patients receiving primary therapy for head and neck cancer. A randomized, double-blind, placebo-controlled trial of escitalopram vs placebo was conducted in a group of nondepressed patients diagnosed as having head and neck cancer who were about to enter cancer treatment. Patients were stratified by sex, site, stage (early vs advanced), and primary modality of treatment (radiation vs surgery). The primary outcome measure was the number of participants who developed moderate or greater depression (scores on the Quick Inventory of Depressive Symptomology-Self Rated of ≥11). From January 6, 2008, to December 28, 2011, 148 patients were randomized. Significantly fewer patients receiving escitalopram developed depression (24.6% in the placebo group vs 10.0% in the escitalopram group; stratified log-rank test, P = .04). A Cox proportional hazards regression model compared the 2 treatment groups after controlling for age, baseline smoking status, and stratification variables. The hazard ratio of 0.37 (95% CI, 0.14-0.96) demonstrated an advantage of escitalopram (P = .04). Patients undergoing radiotherapy as the initial modality were significantly more likely to develop depression than those undergoing surgery (radiotherapy compared with surgery group; hazard ratio, 3.6; 95% CI, 1.38-9.40; P = .009). Patients in the escitalopram group who completed the study and were not depressed rated their overall quality of life as significantly better for 3 consecutive months after cessation of drug use. In nondepressed patients undergoing treatment for head and neck cancer, prophylactic escitalopram reduced the risk of developing depression by more than 50%. In nondepressed patients who completed the trial, quality of life was also significantly better for 3 consecutive months after cessation of drug use in the escitalopram group. These findings have important implications for the treatment of patients with head and neck cancer. clinicaltrials.gov Identifier: NCT00536172.


[Metastatic cancers of the thyroid gland. Diagnostic difficulties].
Metastatic carcinoma of the thyroid is uncommon in surgical pathology and may masquerade as primary thyroid cancer. We studied 6 cases of biopsied and/or surgically resected metastatic carcinoma of the thyroid and their corresponding primary carcinoma, with emphasis on the differential diagnosis. There were 4 men and 2 women patients aged 44 to 77. The primary carcinoma was a breast infiltrating duct carcinoma (3 cases), a colorectal adenocarcinoma (2 cases) and a bronchial oat-cell carcinoma (1 case). The interval between primary carcinoma and secondary thyroid carcinoma was 2 to 9 years in 4 cases; 2 other cases showed simultaneous occurrence. Five patients died with widespread metastases 1 to 14 months following the diagnosis of secondary carcinoma of the thyroid; 1 patient was alive after 24 months. The histological differentiation of secondary from primary thyroid cancer may be difficult in the following situations: clear-cell, Hürthle-cell and signet ring cell changes; positivity of mucins stains; production of melanin; epidermoid differentiation; very rare miscellaneous tumours ("columnar cell carcinoma" and primary thymoma of the thyroid). Immunoperoxidase methods and mucin histochemistry may help.