Clinical evaluation of direct cuspal coverage with posterior composite resin restorations.
Composite resins have esthetic properties; they join the ability to preserve and reinforce sound tooth structure. Conservation is becoming popular for both small to medium defects and more compromised teeth. This study aimed to evaluate the clinical performance of Class II cuspal coverage direct composite restorations. Twenty patients, 18 years or older, were included in this clinical trial restoring 25 vital molar teeth with one or two missing cusps. Criteria for inclusion are two or three surface restorations, replacement of composite and amalgam fillings (secondary decay, fracture of either filling material or tooth structure, aesthetic considerations), or virgin teeth with decay undermining a cusp. Teeth with residual cavity walls less than 1 mm or with complete loss of the clinical crown were excluded. Teeth were restored using a combination of Ultra-Etch 35% phosphoric acid, PQ1 adhesive system, and Vit-l-escence microhybrid composite resin (Ultradent Products, Inc., South Jordan, UT, USA). The enamel peripheral skeleton of the restoration was built up first, followed by dentin and enamel occlusal surface stratification. Wedge-shaped increments of composite resin were placed and cured using the variable intensity polimerizer (VIP) light (Bisco Inc., Schaumburg, IL, USA) through a combination of a pulse and progressive curing technique. All 25 restorations were evaluated at 6-month intervals during the 30-month period using a modified US Public Health Service (USPHS) criteria by two independent evaluators precalibrated at 85% reliability. No failures were reported and alpha scores were recorded for all parameters. Statistical analysis was performed using a Chi-square test (chi(2)) and the Fisher's exact test. Sixteen of the 25 samples (64%) exhibited preoperative sensitivity to air (chi(2)=10.6; p=0.001). A significant difference in tooth sensitivity was reported after completion of the restorations. No teeth exhibited sensitivity both at the 2-week recall and the 30-month follow-up (chi(2)=23.5; p < 0.0001). Microhybrid composite resin demonstrated excellent clinical performance in direct cuspal coverage at completion of a 30-month evaluation. CLINICAL SIGNIFICANCE In selected clinical situations, cuspal coverage direct posterior composite restorations may represent a valid alternative to conventional indirect restorations.


Lipopolysaccharide-induced apoptosis of endothelial cells and its inhibition by vascular endothelial growth factor.
Endothelial injury is a major manifestation of septic shock induced by LPS. Recently, LPS was shown to induce apoptosis in different types of endothelial cells. In this study, we observed that pretreatment with vascular endothelial growth factor (VEGF), a known cell survival factor, blocked LPS-induced apoptosis in endothelial cells. We then further defined this LPS-induced apoptotic pathway and its inhibition by VEGF. We found that LPS treatment increased caspase-3 and caspase-1 activities and induced the cleavage of focal adhesion kinase. LPS also augmented expression of the pro-apoptotic protein Bax and the tumor suppressor gene p53. The pro-apoptotic Bax was found to translocate to the mitochondria from the cytosol following stimulation with LPS. Pretreatment of endothelial cells with VEGF inhibited the induction of both Bax and p53 as well as the activation of caspase-3. These data suggest that VEGF inhibits LPS-induced endothelial apoptosis by blocking pathways that lead to caspase activation.


Positive residues involved in the voltage-gating of the mitochondrial porin-channel are localized in the external moiety of the pore.
The role of positive charges located on the hydrophilic surface of the mitochondrial outer membrane channel was investigated by studying the interaction between LDAO-solubilized porin and a cation-exchanger column. The binding of porin to the column material was inhibited when the elution buffer had a pH of 9 or when 2 mM dextran sulfate was added to the buffer at neutral pH. Interestingly, the addition of a synthetic copolymer of methacrylate, maleate and styrene known as a potent modulator of the voltage-dependence, did not influence the interaction between column material and porin. Incubation of porin with fluorescein isothiocyanate (FITC) resulted in the isolation of a porin fraction in which on average two lysines located on the surface of the pore-forming complex per 35 kDa polypeptide were modified. The voltage-dependence of the fluorescein isothiocyanate modified porin was strongly decreased as compared with the unmodified porin. The experiments presented here give the first biochemical evidence that positively charged lysine residues located on the surface of the channel-forming complex are responsible for the gating of the mitochondrial porin-channel.


Plasma/RBC haloperidol ratios and improvement in acute psychotic symptoms.
In a double-blind controlled study, 20 acutely psychotic inpatients were treated with different haloperidol dosage regimens. Over a 24-hour period, 10 of the patients were treated with rapid intramuscular neuroleptization at 10 mg per dose and 10 at 2 mg per dose. The patients were then treated for 6 more days with an oral dose equivalent to that given over the first 24 hours of treatment, with doctor's choice adjustments as needed. Behavioral change was rated using the Brief Psychiatric Rating Scale (BPRS). Blood samples drawn at baseline and late in the treatment were assayed for plasma and red blood cell haloperidol levels. Although neither of these variables showed a significant correlation with behavioral improvement, the ratio of plasma/RBC haloperidol levels significantly correlated with improvement.


Do We Really Need to Wear Proper Eye Protection When Using Holmium:YAG Laser During Endourologic Procedures? Results from an Ex Vivo Animal Model on Pig Eyes.
We sought to evaluate the effect of holmium:yttrium-aluminum-garnet (Ho:YAG) laser exposure on ex vivo pig eyes and to test the protective action of different glasses in preventing eye lesions in case of accident. We pointed the tip of a Ho:YAG laser fiber from different distances (0, 3, 5, 8, 10, and 20 cm, respectively) toward the center of the pupil of the pig eye. The Ho:YAG laser was activated for 1 or 5 seconds at three different settings (0.5 J-20 Hz, 1 J-10 Hz, and 2 J-10 Hz, respectively). The experiment was repeated using laser safety glasses and eyeglasses. A total of 78 pig eyes were used. The effects of the Ho:YAG laser on pig eyes were assessed by histopathology. Comparable laser emission experiments were performed on thermal paper at different distances using different pulse energies. Ho:YAG laser-induced corneal lesions were observed in unprotected eyes, ranging from superficial burning lesions to full-thickness necrotic areas, and were directly related to pulse energy and time of exposure and inversely related to the distance from the eye. When the laser was placed 5 cm or more, no corneal damage was observed regardless of the laser setting and the time of exposure. Similar distance/energy level relationships were observed on thermal paper. No damage was observed to the lens or the retina in any of the Ho-YAG laser-treated eyes or in any of the eyes protected by laser safety and eyeglasses. Ho:YAG lasers can cause damage when set to high energy, but only to the cornea, from close distances (0-5 cm) and in the absence of eye protection. Eyeglasses are equally effective in preventing laser damage as laser safety glasses.


Commissioning activities and first results from the collective Thomson scattering diagnostic on ASDEX Upgrade (invited).
The collective Thomson scattering (CTS) diagnostic installed on ASDEX Upgrade uses millimeter waves generated by the newly installed 1 MW dual frequency gyrotron as probing radiation at 105 GHz. It measures backscattered radiation with a heterodyne receiver having 50 channels (between 100 and 110 GHz) to resolve the one-dimensional velocity distribution of the confined fast ions. The steerable antennas will allow different scattering geometries to fully explore the anisotropic fast ion distributions at different spatial locations. This paper covers the capabilities and operational limits of the diagnostic. It then describes the commissioning activities carried out to date. These activities include gyrotron studies, transmission line alignment, and beam pattern measurements in the vacuum vessel. Overlap experiments in near perpendicular and near parallel have confirmed the successful alignment of the system. First results in near perpendicular of scattered spectra in a neutral beam injection (NBI) and ion cyclotron resonance heating (ICRH) plasma (minority hydrogen) on ASDEX Upgrade have shown evidence of ICRH heating phase of hydrogen.


Synthetic and real data sets for benchmarking non-cryptographic hash functions.
The overall assessment of non-cryptographic functions is very complex and there is not a widely used benchmark. These data have been collected and created as a benchmark for testing non-cryptographic hash functions. It is made up of eight dataset which comes from two different groups, real and synthetic data sources. The objective when selecting and generating the data has been redundancy and structures present in real-world scenarios. These data have been used for benchmarking non-cryptographic hash functions in [1] and [2].


Tolerance of low temperature and sterilizing irradiation in males of Glossina pallidipes (Diptera: Glossinidae).
Investigations into the possibility of using the chilled adult release system are continuing as an alternative method to the release of sterile tsetse flies, Glossina pallidipes Austen (Diptera: Glossinidae) in cardboard boxes. Exposing tsetse flies to 4°C for 6 h caused negligible mortality. A combination of chilling and irradiation resulted in reduced quantities of seminal contents being transferred to females. Mortality of flies after bulk irradiation was lower when a thermos flask was used than expanded polystyrene. Mortality after removal from cold storage increased with age. Flies that did not have a blood meal for 3 d prior to exposure to cold had a lower overnight survival than flies that were deprived of a blood meal for 1 or 2 d. Exposure of adult male tsetse flies to low temperature should be for as short a duration as is practical, so that the fitness of the released sterile flies is not unduly compromised. It is also necessary to ensure that losses are minimized during bulk irradiation of adult flies. It would be desirable to have minimal losses after the combined effects of irradiation, cold, and transportation, such that a sufficient number of sterile male flies will still be available to successfully compete for mating opportunities with wild females.


The Syrian Refugees' Need for Trauma-Based Services, a Survey of Mental Health Professionals.
Trauma Aid UK (previously HAP UK &Ireland) conducted three EMDR trainings in Turkey: the first was in Istanbul on 28thNovember 2013. The purpose of this study is to assess the needs of the Syrian Refugees for trauma services training and provision as assesses by mental health professionals who work with them. Amongst the 62 participants of two Istanbul EMDR trainings organised by HAP, 53% were Syrian. We felt it is a unique opportunity to assess the needs of Syrian refugees they are working with. We asked all the participants who are all mental health professionals to complete an Arabic translation of 'The Need for Trauma-based Services Questionnaire' in these trainings. The rest of the participants on the course were from Iraq (18%), Jordan (16%), Egypt (7%) and others from Palestine, Sudan & Libya (6%). All participants completed questionnaires. The results of comparing the needs reported by Syrian mental health professionals showed higher prevalence of PTSD seen by the Syrian mental health professionals (72% compared with 56% in the clients seen by the rest of participants). Also, the Syrian mental health professionals could only meet 34% (SD=17.1) of the needs of their client who suffer from PTSD. The unmet need for trauma therapy was reported as 100% by these professionals. This study highlighted the high need for trauma mental health services of the Syrian refugees as reported by mental health professionals working in the neighbouring countries. The needs of the Syrian refugees, arriving to the UK because of the very difficult situations, these refugees are coming from, may be met with EMDR therapy. EMDR can be used to help these refugees to be a productive part of the British society.


Reduced expression of E-cadherin and increased sialylation level in clear cell renal cell carcinoma.
Cancer cells are characterized by an aberrant increase in protein N-glycosylation and by disruption of E-cadherin-mediated adherens junctions. However, the relationship between alterations in N-glycosylation process and loss of E-cadherin adhesion in cancer remains unclear. The mechanisms of altered expression of adhesive glycoproteins in cancer cells have not been fully elucidated. Thus, the aim of this study was to examine the expression of E-cadherin and sialyl Lewisa/x, NeuAcα2-3Gal, NeuAcα2-6Gal/GalNAc structures in the normal renal tissue and intermediate and cancerous tissues from patients with clear cell RCC. Moreover, we attempted to correlate the E-cadherin expression with some specific sugar residues of renal cancer tissue glycoproteins. The expression of E-cadherin was analysed using ELISA test and immunoblotting. Oligosaccharide structures and sialylation level were detected with ELISA test using specific biotinylated lectins or antibodies. A significant decrease of E-cadherin expression as well as a significant increase in sialylated oligosaccharides level in intermediate zone and renal cancer tissue in comparison to normal renal tissue are reported. Significant decrease in expression of cadherins and increase in sialylation of oligosaccharide structures in renal cancer tissue in comparison to normal renal tissue, and in renal cancer tissue in comparison to intermediate zone of renal tissue, are important for the future research concerning detection and quantification of cadherins and sialylated oligosaccharide structures in urine and cells of urinary sediment as possible non-invasive marker of early RCC.


Cardiac molecular signaling after burn trauma.
Research using mammalian burn models has defined significant cardiac deficits after burn injury. The physiologic response to burn and burn complicated by sepsis, including the cardiac dysfunction associated with these insults, remains a very complex physiologic process which, despite active study, remains unclear. The well-characterized inflammatory mediators such as tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 continue to play an active role in mediating cardiac dysfunction. However, perhaps of greater interest are the late mediators, high mobility group box 1 and macrophage migration inhibitory factor, because they offer a very realistic window for therapeutic intervention for controlling the inflammatory response. In addition, several other mediators of cardiac dysfunction have been identified and include the heat shock proteins, apoptosis, and the inflammatory caspases. These new mediators provide opportunities for therapeutic intervention, but further research is needed to clarify the importance of their mechanisms of action and the complex interactions between these various signaling pathways.


Conception and early pregnancy in the mare: lipidomics the unexplored frontier.
Lipids are dynamic biological molecules that play key roles in metabolism, inflammation, cell signalling and structure. They are biologically significant in the physiology of conception and reproduction. Many of the mechanisms surrounding equine conception and the early feto-maternal dialogue are yet to be understood at a biochemical level. Recently, lipidomic technologies have advanced considerably and analytical strategies have been enhanced and diversified. Consequently, in-depth lipidomic exploration now has the potential to reveal new lipid biomarkers and biochemical relationships that improve our understanding of the processes leading to efficient and successful reproduction. This review considers the role of lipids in conception and establishment of pregnancy, providing new insights into the enigmatic pathways governing early reproductive physiology of the mare. This paper discusses the role that lipids play in the very early stages of pregnancy in the mare. Lipids are microscopic non-soluble molecules that are important components of living cells. The manuscript discusses how lipids influence the reproductive cycle of mares, including ovulation and the detailed biological process of becoming pregnant. It explains how lipids are identified in a laboratory setting with a newly developing technology known as 'lipodomics'. The technology may lead to a more detailed understanding of how mares become pregnant. The focus of the paper is on mare reproduction, but it also draws on similarities with reproduction in other mammals. Remarkably there are gaps in much of our knowledge about the finer details of pregnancy in the horse, and the paper summarises what we already know about lipids, highlighting areas for further research.


An autonomous robot inspired by insect neurophysiology pursues moving features in natural environments.
Many computer vision and robotic applications require the implementation of robust and efficient target-tracking algorithms on a moving platform. However, deployment of a real-time system is challenging, even with the computational power of modern hardware. Lightweight and low-powered flying insects, such as dragonflies, track prey or conspecifics within cluttered natural environments, illustrating an efficient biological solution to the target-tracking problem. We used our recent recordings from 'small target motion detector' neurons in the dragonfly brain to inspire the development of a closed-loop target detection and tracking algorithm. This model exploits facilitation, a slow build-up of response to targets which move along long, continuous trajectories, as seen in our electrophysiological data. To test performance in real-world conditions, we implemented this model on a robotic platform that uses active pursuit strategies based on insect behaviour. Our robot performs robustly in closed-loop pursuit of targets, despite a range of challenging conditions used in our experiments; low contrast targets, heavily cluttered environments and the presence of distracters. We show that the facilitation stage boosts responses to targets moving along continuous trajectories, improving contrast sensitivity and detection of small moving targets against textured backgrounds. Moreover, the temporal properties of facilitation play a useful role in handling vibration of the robotic platform. We also show that the adoption of feed-forward models which predict the sensory consequences of self-movement can significantly improve target detection during saccadic movements. Our results provide insight into the neuronal mechanisms that underlie biological target detection and selection (from a moving platform), as well as highlight the effectiveness of our bio-inspired algorithm in an artificial visual system.


Tandem mass spectrometry and ion mobility mass spectrometry for the analysis of molecular sequence and architecture of hyperbranched glycopolymers.
Multidimensional mass spectrometry techniques, combining matrix-assisted laser desorption/ionization (MALDI) or electrospray ionization (ESI) with tandem mass spectrometry (MS(2)), multistage mass spectrometry (MS(n)) or ion mobility mass spectrometry (IM-MS), have been employed to gain precise structural insight on the compositions, sequences and architectures of small oligomers of a hyperbranched glycopolymer, prepared by atom transfer radical copolymerization of an acrylate monomer (A) and an acrylate inimer (B), both carrying mannose ester pendants. The MS data confirmed the incorporation of multiple inimer repeat units, which ultimately lead to the hyperbranched material. The various possible structures of n-mers with the same composition were subsequently elucidated based on MS(2) and MS(n) studies. The characteristic elimination of bromomethane molecule provided definitive information about the comonomer connectivity in the copolymeric AB2 trimer and A2B2 tetramer, identifying as present only one of the three possible trimeric isomers (viz. sequence BBA) and only two of the six possible tetrameric isomers (viz. sequences BBA2 and BABA). Complementary IM-MS studies confirmed that only one of the tetrameric structures is formed. Comparison of the experimentally determined collision cross-section of the detected isomer with those predicted by molecular simulations for the two possible sequences ascertained BBA2 as the predominant tetrameric architecture. The multidimensional MS approaches presented provide connectivity information at the atomic level without requiring high product purity (due to the dispersive nature of MS) and, hence, should be particularly useful for the microstructure characterization of novel glycopolymers and other types of complex copolymers.


Optimal developmental appraisal.
The six components considered to be essential for obtaining an optimal developmental profile of a child are described. It is emphasised that, in order to plan appropriate services for children, the consideration of these components should be made routine in developmental assessment.


Modes of mechanical ventilation and weaning. A national survey of Spanish hospitals. The Spanish Lung Failure Collaborative Group.
Little information exists regarding the proportion of patients treated with mechanical ventilation in intensive care units (ICUs), their underlying disease states, the modes of ventilation used, duration of ventilator support, methods and time required for weaning, and mortality in these patients. We carried out a cross-sectional multicenter study in 47 medical-surgical ICUs in Spain to investigate these issues in 290 patients who required mechanical ventilation for at least 24 hs. Relative frequency of different modes was as follows: assist-control ventilation (AC), 55%; synchronized intermittent mandatory ventilation (SIMV), 26%; pressure support ventilation (PSV), 8%; SIMV plus PSV, 8%; pressure-controlled ventilation (PCV), 1%; and continuous positive airway pressure (CPAP), 2%. Overall duration of mechanical ventilation was 27.1 +/- 1.1 (SE). A variety of techniques were used for weaning: T-tube trials, 24%; SIMV, 18%; PSV, 15%; SIMV plus PSV, 9%; and some combination of two or more methods in succession in 33% of the patients. Time required for weaning using a combination of SIMV and PSV was longer (17.8 days) than with other techniques (about 5 days, p < 0.01). Time between initiation of weaning and removal of mechanical ventilation accounted for 41% of total ventilator time and was particularly high (59%) in patients with chronic obstructive pulmonary disease. Overall mortality rate was 34%, and it was higher in patients who were ventilated for 1 to 10 days than in those ventilated for a longer time. Despite the availability of several new modes of ventilator support, older modes such as AC and SIMV were more commonly used. Weaning constitutes a large portion of total ventilator time, and thus, measures that expedite the weaning process should markedly decrease the duration of mechanical ventilation.


A pilot study to investigate adherence to long-acting opioids among patients with advanced lung cancer.
Uncontrolled pain remains prevalent in patients with advanced cancer and has been associated with worse quality of life and greater health care utilization. Poor adherence to analgesics may represent a modifiable barrier to pain management. This pilot study aimed to establish feasibility/utility of evaluating self-reported adherence to long-acting (LA) opioids in patients with advanced lung cancer, and to explore rates and correlates of adherence. Consecutive patients attending an ambulatory thoracic oncology clinic with a diagnosis of advanced lung cancer and a current LA opioid regimen were approached to complete a brief questionnaire during their clinic visit. Participants reported LA opioid adherence during the past 4 weeks (0%-100%) and knowledge of their LA opioid regimen, and completed the Patient Health Questionnaire-2 (PHQ-2) depression screen. Demographic and clinical information were confirmed via electronic health record review. Fifty-four eligible patients were approached to reach our target sample (n=50; enrollment=92.6%). Self-reported adherence to LA opioids was 85.4% (standard deviation [SD]=21.0). Twenty-eight percent reported a frequency of medication use that did not match the prescribed daily frequency. Lower adherence was associated with inaccurate frequency (p=0.004), positive depression screen (p=0.005), and older age (p=0.04). Our results demonstrate the feasibility of integrating self-report assessments of LA opioid adherence into a thoracic oncology clinic. Patients reported high adherence, but more than one-quarter did not accurately report the prescribed frequency of daily doses. Understanding of LA opioid regimens may be a critical indicator of adherence in patients with advanced cancer.


SARS-CoV-2 pseudovirus enters the host cells through spike protein-CD147 in an Arf6-dependent manner.
The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants is threatening public health around the world. Endocytosis functions as an important way for viral infection, and SARS-CoV-2 bears no exception. However, the specific endocytic mechanism of SARS-CoV-2 remains unknown. In this study, we used endocytic inhibitors to evaluate the role of different endocytic routes in SARS-CoV-2 pseudovirus infection and found that the viral infection was associated with caveolar/lipid raft- and cytoskeleton-mediated endocytosis, but independent of the clathrin-mediated endocytosis and macropinocytosis. Meanwhile, the knockdown of CD147 and Rab5a in Vero E6 and Huh-7 cells inhibited SARS-CoV-2 pseudovirus infection, and the co-localization of spike protein, CD147, and Rab5a was observed in pseudovirus-infected Vero E6 cells, which was weakened by CD147 silencing, illustrating that SARS-CoV-2 pseudovirus entered the host cells via CD147-mediated endocytosis. Additionally, Arf6 silencing markedly inhibited pseudovirus infection in Vero E6 and Huh-7 cells, while little change was observed in CD147 knockout-Vero E6 cells. This finding indicated Arf6-mediated CD147 trafficking plays a vital role in SARS-CoV-2 entry. Taken together, our findings provide new insights into the CD147-Arf6 axis in mediating SARS-CoV-2 pseudovirus entry into the host cells, and further suggest that blockade of this pathway seems to be a feasible approach to prevent the SARS-CoV-2 infection clinically.


Exposure to Client-Perpetrated Violence in the Child Welfare Service: Prevalence and Outcomes Using Two Different Measurement Methods.
This study compared how two different measurement methods of client-perpetrated violence influence findings on prevalence rates and mental health outcomes in a probability sample of 660 Norwegian public sector child welfare workers. Using a single-item self-labeling approach, 15.4% reported exposure to physical violence, and 19.3% reported exposure to threats. Using a 15-item behavioral experience inventory, the prevalence rates ranged from 4.4% to 65.7%. A comparison of these methods uncovered a high number of false negatives when using the single-item approach as 62.2% of those who indicated that they had not experienced any workplace violence when answering the single-item questions reported being exposed 1 to 2 times when responding to the behavioral inventory. Results based on the behavioral inventory further revealed that the most frequently occurring actions in the child welfare service were direct and indirect forms of threats (24.5%-65.7%), while the least reported behaviors were threats and violence including objects (4.4.%-9.1%). Although client-perpetrated violence was significantly associated with mental health problems (e.g., symptoms of anxiety, depression, and post-traumatic stress [PTS]) for both assessment methods, the magnitude of the effect sizes differed from η2 = .000 to η2 = .121. These findings highlight that the use of different measurement methods for workplace violence has significant consequences for the assessment of prevalence rates, as well as on results of associated outcomes. Consequently, the decision on how to assess workplace violence has practical implications for uncovering how prominent the issue is, as well as the way in which this negative workplace exposure is subsequently addressed and counteracted. Therefore, both scholars and the child welfare service, and similar fields in which workplace violence frequently occurs, should take these findings into consideration for future assessments.


Numerical analysis for the vertical bearing capacity of composite pile foundation system in liquefiable soil under sine wave vibration.
Composite pile foundation has been widely used in ground engineering. This composite pile foundation system has complex pile-soil interactions under seismic loading. The calculation of vertical bearing capacity of composite pile foundation is still an unsolved problem if the soil around piles is partially or completely liquefied under seismic loading. We have completed indoor shaking table model tests to measure the vertical bearing capacity in a liquefiable soil foundation under seismic loading. This paper will use a numerical approach to analyze the change of this vertical bearing capacity under seismic loading. Firstly, the Goodman contact element is improved to include the Rayleigh damping. Such an improvement can well describe the reflection and absorption of seismic waves at the interface of soil and piles. Secondly, the Biot's dynamic consolidation theory incorporated an elastoplastic model is applied to simulate the soil deformation and the generation and accumulation of pore water pressure under seismic loading. Thirdly, after verification with our indoor shaking table test data, this approach is used to investigate the effects of pile spacing on liquefaction resistance of the composite pile foundation in liquefiable soil. The time histories of pore water pressure ratio (PPR') are calculated for the liquefiable soil and the vertical bearing capacity in partially liquefied soil is calculated and compared with our indoor shaking table test data at the 3D, 3.5D, 4D, 5D and 6D cases (D is the pile diameter). It is found that the pile spacing has some influence on the extent of soil liquefaction between piles. The vertical bearing capacity varies with liquefaction extent of inter-pile soil. The optimization of pile spacing varies with liquefaction extent. These results may provide some reference for the design of composite pile foundation under seismic loading.


Hepatic artery aneurysms and biliary surgery: two cases and a literature review.
Two cases of hepatic artery aneurysm are presented. Both occurred as complications of cholecystectomy for gallstone disease. The aneurysm ruptured in both cases leading to very stormy clinical courses and resulting in the death of one patient. The subject of hepatic artery aneurysms is reviewed and proposals for management are made based on the collective experience reported in the literature.


Influence of the thymic extract (TP2) on some humoral and cell mediated immunity reactions in normal or irradiated animals.
The authors have studied the action of a thymic extract (TP2) containing thymic polypeptides with a molecular weight under 10,000 daltons, on humoral and cell-mediated immunity reactions in normal animals or in animals immunologically depressed by X-ray irradiation. The following were investigated: serum antibodies, such as antiflagelar agglutinins of TH Salmonella and anti-influenza antibodies in the rat, the plaque-forming hemolytic cells in the mouse spleen, delayed hypersensitivity reaction in guinea-pigs innoculated with BCG, the lymphocyte rosetting reaction in the mouse spleen, and the inhibition of macrophages migration in the rats innoculated with TH Salmonella typhi vaccine. The results showed that TP2 stimulates both the humoral and the cell-mediated immunity reactions and has a radioprotecting effect.


The Relationship between Tension and Length of the Aortic Adventitia Resected from the Aortic Wall of Acute Aortic Dissection.
To our knowledge, no previous study has described the measurement of the tensile strength of the human aortic adventitia. In the present study, we examined the relationship between the tension and length of the aortic adventitia resected from the aortic wall of patients with acute aortic dissection. We obtained rectangular specimens from the aortic adventitia that was resected in patients with acute aortic dissection during surgery. The specimens were placed on a tension meter (Digital Force Gauge FGS-10, SHIMPO, Kyoto, Japan) within 15 min after resection and stretched until they were pulled apart, and the tension and length were recorded. We obtained 18 specimens during surgery from 11 cases of acute aortic dissection. When the specimen was being pulled apart, the mean tension recorded was 10.2 ± 4.9 N/cm specimen width, whereas the mean elongated length recorded was 4.2 ± 1.1 mm/cm specimen length. We determined that the aortic adventitia is elastic and expandable up to 140% of its original length. This indicates that dilation of the aorta to >4.2 cm in diameter may result in a rupture if the original aortic diameter prior to dissection was 3 cm. (English translation of J Jpn Coll Angiol 2013; 53: 77-81).


[Bullous pemphigoid--a cause of itching of the skin with increasing incidence].
Bullous pemphigoid (BP) is an autoimmune bullous dermatosis of the elderly with increasing incidence. Autoantibodies against dermal collagen XVII cause severe pruritus and large, tense bullae that are clinically evident. Immunofluorescence analysis on perilesional skin is used in the diagnostics and serum BP1 80 levels parallel the disease activity. Topical or systemic steroids are mainly used as treatment, but adjuvant immunosuppressive medication may also be needed. Patients with bullous pemphigoid are more likely to have neurological diseases as comorbidity. In addition, mortality is significantly increased, possibly due to long-term use of systemic corticosteroids.


Perfect prescription for sustainability.
A medical education and clinical teaching centre building currently under construction at the University of Aberdeen has been awarded the highest national rating of "Excellent" in the Bespoke category in the 2008 BREEAM Awards, recognising a range of environmental measures incorporated into the design to reduce its carbon footprint and maximise its use of natural resources. Health Estate Journal reports.


Considerations for skin carcinogenesis experiments using inducible transgenic mouse models.
This study was designed to estimate the percentage of non-malignant skin tumours (papillomas) progressing to malignant squamous cell carcinomas (SCCs) in a carcinogenesis study using established transgenic mouse models. In our skin cancer model, we conditionally induced oncogenic point mutant alleles of p53 and k-ras in undifferentiated, basal cells of the epidermis. Upon activation of the transgenes through administration of tamoxifen, the vast majority of mice (> 80%) developed skin papillomas, yet primarily around the mouth. Since these tumours hindered the mice eating, they rapidly lost weight and needed to be culled before the papillomas progressed to SCCs. The mouth papillomas formed regardless of the route of application, including intraperitoneal injections, local application to the back skin, or subcutaneous insertion of a tamoxifen pellet. Implantation of a slow releasing tamoxifen pellet into 18 mice consistently led to papilloma formation, of which only one progressed to a malignant SCC. Thus, the challenges for skin carcinogenesis studies using this particular cancer mouse model are low conversion rates of papillomas to SCCs and high frequencies of mouth papilloma formation.


Four-Minute Bone SPECT Using Large-Field Cadmium-Zinc-Telluride Camera.
The aim of this study was to determine the minimum acquisition time without decreasing lesion detectability of bone SPECT using a whole-body cadmium-zinc-telluride camera. Patients referred for bone SPECT were retrospectively included. SPECT of 30 patients were reframed from native data (16 s/projection) to produce 10-, 5-, and 3-s/projection data sets. A "critical" acquisition time/projection was defined as that below which the SPECT quality becomes insufficient for interpretation, as determined by 3 reviewers using a 4-point scale (0 = quality insufficient for interpretation, 1 = average, 2 = good, 3 = excellent). Three reviewers (blinded to the acquisition time) evaluated SPECT data sets (n = 79), native and reframed with "critical" acquisition times, in a randomized order. A lesion was defined as any uptake considered pathological by a reviewer. Lesion detectability equivalence between native SPECT and reframed SPECT was assessed by calculating a coefficient (κ) for each reviewer. Image quality of the first sample (n = 30) was significantly and progressively less well graded for the reframed data sets by all reviewers. Only 1 patient was graded 0 by each reviewer for the 5-s/projection data set. For the 3-s/projection data set, 3 patients were graded 0. No patients were graded 0 for 10-s/projection data set. The minimal acquisition time, for each projection, was defined as 5 s/projection. The coefficient κ, between native and reframed, with critical acquisition time/projection SPECT was greater than 0.9 for each reviewer. The more contrasted images of the cadmium-zinc-telluride camera allow performance of 5-s/projection SPECT without loss of lesion detectability. This suggests the possibility of performing whole-body SPECT in a reasonable time or reducing injected doses, especially in pediatric patients.


[Prognostic analysis of patients with myasthenia gravis after extended thymectomy].
Objective: To identify the long-term outcome of patients with myasthenia gravis (MG) after extended thymectomy, and to analyze the prognostic factors. Methods: The medical data and follow-up results in 72 patients with MG who underwent extended thymectomy in Department of Thoracic Surgery, Anhui Provincial Hospital Affiliated with Anhui Medical University from January 2006 to October 2015 were retrospectively reviewed and analyzed. There were 32 male and 40 female patients, aging from 10 to 70 years with a mean age of 39.5 years. The outcome-related factors including gender, age while being operated on, duration of preoperative period, whether taking steroid before operation, modified Osserman classification, pathology type of thymus were analyzed by χ(2) test and multivariate regression analysis. Results: All patients were followed up from 6 to 75 months (median 37 months). Among them, 21 patients (29.2%) achieved complete stable remission, 18 patients (25.0%) experienced pharmacological remission, 20 patients (27.8%) improved, 9 patients (12.5%) reminded stable and 4 patients (5.6%) deteriorated. Both univariate and multicariate analysis revealed that duration of preoperative period (OR=22.871, 95% CI: 2.813 to 185.917, P=0.003) and Osserman classification (OR=0.103, 95% CI: 0.014 to 0.774, P=0.027) showed significantly associated with the surgical curative effect. Conclusions: Extended thymectomy is an efective measure for MG. The duration of preoperative period and Osserman classification are prognostic factors for thymectomized MG. Those patients with generalized MG or whose duration of preperative period is less than 6 months are likely to have better prognosis.


Skull base erosion and associated complications in sphenoid sinus fungal balls.
Sphenoid sinus fungal balls (SSFB) are rare entities that can result in serious orbital and intracranial complications. There are few published reports of complications that result from SSFB. To review the incidence of skull base erosion and orbital or intracranial complications in patients who present with SSFB. A retrospective review was performed of all the patients with SSFB who were treated at the Massachusetts Eye and Ear Infirmary from 2006 to 2014. Presenting clinical data, radiology, operative reports, pathology, and postoperative course were reviewed. Forty-three patients with SSFB were identified. Demographic data were compared between patients with (39.5%) and those without (61.5%) skull base erosion. Two patients underwent emergent surgery for acute complications of SSFB (one patient with blindness, one patient who had a seizure). Both patients with acute complications had evidence of skull base erosion, whereas no patients with an intact skull base developed an orbital or intracranial complication (p = 0.15). All the patients were surgically managed via an endoscopic approach. SSFBs are rare but may cause significant skull base erosion and potentially severe orbital and intracranial complications if not treated appropriately. Endoscopic sphenoidotomy is effective in treating SSFB and should be performed emergently in patients who presented with associated complications.


A common mechanism for the regulation of vesicular SNAREs on phospholipid membranes.
The SNARE (soluble N -ethylmaleimide-sensitive fusion protein attachment protein receptor) family of proteins is essential for membrane fusion in intracellular traffic in eukaryotic organisms. v-SNAREs (vesicular SNAREs) must engage target SNAREs in the opposing membrane to form the fusogenic SNARE complex. Temporal and spatial control of membrane fusion is important for many aspects of cell physiology and may involve the regulation of the SNAREs resident on intracellular membranes. Here we show that the v-SNARE synaptobrevin 2, also known as VAMP (vesicle-associated membrane protein) 2, is restricted from forming the SNARE complex in chromaffin granules from adrenal medullae to the same degree as in brain-purified synaptic vesicles. Our analysis indicates that the previously reported synaptophysin-synaptobrevin interaction is not likely to be involved in regulation of the v-SNARE. Indeed, the restriction can be reproduced for two distinct v-SNARE homologues, synaptobrevin 2 and cellubrevin/VAMP3, by reconstituting them in pure liposomal membranes. Overall, our data uncover a common mechanism for the control of SNARE engagement where intact phospholipid membranes rather than proteins down-regulate vesicular SNAREs in different cellular organelles.


Expression of endogenous transforming growth factor-beta and its type I and type II receptors in rat burn wounds.
Transforming growth factor-beta is a potent regulator of numerous processes in wound healing. These biological activities require the interaction of the growth factor with two classes of cell surface receptors, namely the type I and type II receptors. To understand the role of transforming growth factor-beta in burn wound healing, we undertook a study to localize this growth factor and its cell surface receptors within dermal burn wounds. Partial-thickness burn injuries were made on the backs of Wistar rats. At 1, 3, 5, 7, 10, 15, and 20 days after burning, samples of wounded and control skin were removed for the isolation of total RNA and immunohistochemistry. Thermal injury induced the expression of mRNA for transforming growth factor-beta and both type I and type II receptors. The expression of transforming growth factor-beta peaked 5 to 7 days after injury, then gradually declined. Of note, the expression of the transforming growth factor-beta receptors returned to normal before the expression of the growth factor. Immunohistochemical analysis showed that transforming growth factor-beta protein levels paralleled mRNA expression, and the protein was primarily localized to the migrating epidermal cells and dermal fibroblasts. The differences between the expression of transforming growth factor-beta and its receptors in the later stages of healing thermal injuries suggests the presence of a well-controlled mechanism to limit the effect of the growth factor on repair cells.


Latent structure of the Centre for Epidemiologic Studies Depression Scale (CES-D) in older adult populations: a systematic review.
Objective: The Center for Epidemiologic Studies Depression Scale (CES-D) is a 20-item, self-report metric intended to measure depression. Despite being one of the most popular depression scales, the psychometric properties, specifically the underlying factor structure of the scale, have come under scrutiny. The latent structure of a scale is a key indicator of its construct validity, i.e. the degree to which the intended variable is captured. To date, a comprehensive review of the latent structure of the CES-D in older adult populations (≥65 years old) has not been conducted. We aimed to examine the latent structure of the CES-D in samples of older adults to assess its ability to capture depressive symptoms.Methods: A systematic review across Scopus, Web of Science, and PsycINFO databases was conducted. Original studies conducting latent variable analysis of the 20-item CES-D in samples aged ≥65 years old were included.Results: Included studies (n = 6) were primarily conducted with community-dwelling older adults in the United States. Studies that conducted exploratory and confirmatory factor analysis (n = 2) revealed two latent factors, whereas those conducting confirmatory factor analysis of previously identified structures (n = 4) revealed four-factor structures in line with the original four-factor structure.Conclusions: A general alignment with the original four-factor structure of the CES-D provides tentative support for continued use amongst older adults; however, further research is required to provide conclusive evidence for these psychometric properties.


Uptake of amplifiable fragments of retrotransposon DNA from the human alimentary tract.
Few attempts have been made to study the transfer of DNA from ingested food across the intestinal barrier. A low uptake of ingested DNA has been observed in mice, cattle and poultry. There have been no reports on humans so far. Maintenance of species barriers, protection against retrotransposons, optimisation of oral DNA vaccines and the fate of genetically modified foodstuffs are issues where this topic is of importance. We therefore used the high-copy-number rabbit retrotransposon RERV-H, and rabbit mitochondrial DNA, to study the transfer of DNA from ingested rabbit meat into the bloodstream of two human volunteers. A quantitative PCR was used to measure RERV-H levels in food and in the blood. Amplification with the primers selected results in the generation of a 250-bp fragment of RERV-H. Transfer across the intestinal epithelium could be demonstrated in both subjects. Levels of the fragment in the bloodstream peaked at 1-3 h after ingestion of the experimental meal. One hour after a meal of rabbit meat containing 10(14) copies of RERV-H DNA, a maximum concentration of 200 copies of RERV-H DNA per ml of peripheral blood was observed, which corresponds to the uptake of approximately 10(6) RERV-H DNA copies in 1 h. RERV-H DNA was detected in both cellular and plasma compartments. Both rabbit retrotransposon and mitochondrial DNA was taken up from the human alimentary tract. The size of the fragments detected is similar to that of SINE retrotransposons (approximately 300 bp). The fate and functionality of alimentary DNA in humans will require further study.


[Rationale supporting basal insulin-incretin combined therapies in type 2 diabetes].
Type 2 diabetes is characterized by an insulin secretory defect that cannot compensate for insulin resistance. Such relative defect is present in the fasting state (insufficient basal insulin levels) and contributes to overnight hyperglycaemia; it is even more pronounced in the postprandial state when it is then the main responsible factor for hyperglycaemia following meals. An original approach to correct these two disturbances is to propose a therapy combining the injection of a basal insulin (most commonly at bedtime to better control fasting glycaemia) and the administration of an incretin-based medication to potentiate insulin response to the three main meals, without inducing hypoglycaemia. This latter effect can be obtained either by blocking the degradation of incretin hormones with an oral inhibitor of dipeptidyl peptidase-4 (gliptin), or by injecting an agonist of glucagon-like peptide-1 (GLP-1) receptors. These basal insulin-incretin combined therapies are well validated in various controlled trials and observational studies. Lixisenatide is the first GLP-1 receptor agonist being reimbursed in this specific indication of combination with basal insulin in Belgium.


Salts and glycine increase reversibility and decrease aggregation during thermal unfolding of ribonuclease-A.
Ribonuclease-A (RNase-A) has been a model for studying protein folding and unfolding. However, we show here that its unfolding at neutral pH is complicated by aggregation. Circular dichroism thermal scans showed that reversibility of RNase-A after heating is only about 63%. In accordance with this observation, native-polyacrylamide gel electrophoresis of the sample heated at 75 degrees C showed formation of soluble oligomers. Ammonium sulfate at 0.4 M caused about a 3 degrees C higher melting temperature and nearly complete reversibility, while glycine and NaCl at 0.4 M significantly increased reversibility and decreased aggregation without affecting melting temperature. These results demonstrate that aggregation makes thermal unfolding of RNase-A at least partially irreversible and salts and glycine increase reversibility and decrease aggregation.


Subsurface damage of single crystalline silicon carbide in nanoindentation tests.
The response of single crystalline silicon carbide (SiC) to a Berkovich nanoindenter was investigated by examining the indents using a transmission electron microscope and the selected area electron diffraction technique. It was found that the depth of indentation-induced subsurface damage was far larger than the indentation depth, and the damaging mechanism of SiC was distinctly different from that of single crystalline silicon. For silicon, a broad amorphous region is formed underneath the indenter after unloading; for SiC, however, no amorphous phase was detected. Instead, a polycrystalline structure with a grain size of ten nanometer level was identified directly under the indenter tip. Micro cracks, basal plane dislocations and possible cross slips were also found around the indent. These finding provide useful information for ultraprecision manufacturing of SiC wafers.


A Limited Field Cone-beam Computed Tomography-based Evaluation of the Mental Foramen, Accessory Mental Foramina, Anterior Loop, Lateral Lingual Foramen, and Lateral Lingual Canal.
The aim of this retrospective observational study was to evaluate the cone-beam computed tomographic (CBCT)-based characteristics of the mental foramen (MF), accessory mental foramen (AMF), anterior loop (AL), lateral lingual foramen (LLF), lateral lingual canal (LLC) and to explore any relationships between their characteristics. The location and dimension of the MF; the incidence, location, and dimension of the AMF along with its distance to the MF; the presence and dimension of the AL; and the presence, location, angle of entry of the LLF and LLC, and its relation with the mandibular canal (MC) were evaluated in 109 CBCT scans. The data were analyzed descriptively, and associations were tested using the chi-square and analysis of variance tests. The MF was most frequently located between the first and second mandibular premolar teeth (43.5%) or below the second premolar (34.3%). The mean horizontal dimension of the MF was 3.1 mm, the vertical dimension was 2.8 mm, and the mean vertical distance from the alveolar crest was 14.2 mm. An AMF was observed in 12.8% of cases with a mean distance of 4.1 mm from the MF. An AL was present in 47.2% of cases with a mean loop length of 3.38 mm. An LLF was present in 20.4% of cases, predominantly below the first premolar (27.3%) with a mean angle of entry of 148°. The LLC always communicated with the MC and generally not with the tooth apex. A statistically significant association existed between the presence of the LLF and AMF. The anatomic complexity of the MF region was confirmed; hence, CBCT-based evaluation is essential before surgical exploration of this region.


Aberrant methylation of the SPARC gene promoter and its clinical implication in gastric cancer.
Secreted protein acidic and rich in cysteine (SPARC) gene has been shown to be epigenetically silenced in several cancers. We investigated the loss of expression and promoter methylation of this tumor suppressor gene in gastric cancers and correlated the data with clinicopathological features. We observed the loss of SPARC mRNA and SPARC protein expression in 7 of 10 (70%) gastric cancer cell lines. Upon treatment of expression-negative cell lines with a demethylating agent, expression of mRNA and protein was restored in all cells. Methylation rate of SPARC gene was 80% in ten gastric cancer cell lines and 74% (163 of 220) in primary tumors, while it was 5% in normal gastric mucosa (n = 40). In intestinal gastric cancer, SPARC methylation correlated with a negative prognosis (P < 0.001; relative risk 2.754, 95% confidence interval 1.780-4.261). Immunostaining revealed that SPARC protein was overexpressed in stromal fibroblasts adjacent to neoplastic epithelium but rarely expressed in the primary gastric cancer cells. These results implicate SPARC promoter methylation as an important factor in the tumorigenesis of gastric carcinomas and provide new insights into the potential use of SPARC as a novel biomarker and the potential clinical importance in human gastric cancers.


Ankyloblepharon filiforme adnatum.
Two cases of a rare congenital eyelid abnormality, ankyloblepharon filiforme adnatum, are presented, and novel aspects of treatment, associations and classification are discussed.


Does workplace social capital associate with hazardous drinking among Chinese rural-urban migrant workers?
The present study sought to investigate the associations between workplace social capital and hazardous drinking (HD) among Chinese rural-urban migrant workers (RUMW). A cross sectional study with a multi-stage stratified sampling procedure was conducted in Shanghai during July 2012 to January 2013. In total, 5,318 RUMWs from 77 workplaces were involved. Work-place social capital was assessed using a validated and psychometrically tested eight-item measure. The Chinese version of Alcohol Use Disorders Identification Test (AUDIT) was used to assess hazardous drinking. Control variables included gender, age, marital status, education level, salary, and current smoking. Multilevel logistic regression analysis was conducted to test whether individual- and workplace-level social capital was associated with hazardous drinking. Overall, the prevalence of HD was 10.6%. After controlling for individual-level socio-demographic and lifestyle variables, compared to workers in the highest quartile of individual-level social capital, the odds of HD for workers in the three bottom quartiles were 1.13(95%CI: 1.04-1.23), 1.17(95%CI: 1.05-1.56) and 1.26(95%CI: 1.13-1.72), respectively. However, contrary to hypothesis, there was no relationship between workplace-level social capital and hazardous drinking. Higher individual-level social capital may protect against HD among Chinese RUMWs. Interventions to build individual social capital among RUMWs in China may help reduce HD among this population.


Arteriovenous shunt using the sleeve technique in the dog.
Arteriovenous shunts were constructed in 12 dogs for simplified venous access. A modified end-in-end technique was used. In this technique, the donor vessel is telescoped into the recipient vessel and kept in place with two sutures, not exposed to the blood stream. Mean skin-to-skin time was 17 minutes. Ten shunts were patent one week after construction. Nine were open after one month. We have concluded that this anastomotic technique is suitable for the construction of arteriovenous shunts in dogs and that it facilitates venous access.


Tissue reconstitution models of breast cancer.
Oncogenes have been expressed in mammary epithelium by reconstituting epithelium in vivo from mammary cells. Genetically manipulated primary cultures are transplanted into a mammary fat pad from which the natural epithelium has been removed, where they reform an epithelium in which a few cells express the oncogene. Genes can be expressed in other tissues in a similar way. A wide variety of oncogenes have a clearly observable effect on the pattern of growth of mammary epithelium. Expression of individual oncogenes usually produces stable, characteristic patterns of abnormal growth that can be regarded as preneoplastic states. Different oncogenes produce a very diverse variety of such growth patterns, by altering branching pattern, inducing formation of alveoli, causing epithelium to multilayer and/or altering hormone dependence. Myc and wnt1 seem to enable cells to overgrow neighbouring normal cells, suggesting that they promote clonal expansion, whereas others give focal lesions. Oncogene co-operation can be studied by introducing further oncogenes into preneoplastic epithelium, for example the introduction of ras into epithelium that already expresses activated myc gives tumours. The effects of both neu/c-erbB2 and myc on mouse mammary epithelium may mimic events in human breast, encouraging the hope that this will prove a way to model human breast cancer. The tissue reconstitution approach promises to reconstruct tumour development in more detail than the transgenic systems are able to, showing the development of focal lesions, the restraining effects of normal on transformed cells and the expansion of clones of hyperplastic cells at the expense of their normal neighbours.


Breast feeding and acute lower respiratory infection.
The association between breast feeding and acute lower respiratory infection (ALRI) was studied in a case-control study in southern Italy. Two groups of children were studied: the first group comprised 73 infants, aged 0-6 months, whose diagnosis was pneumonia or bronchiolitis; the second group included 88 infants less than 12 months of age with a diagnosis of pertussis-like illness. Control infants were two groups of infants admitted to the same ward. Compared with controls, infants in the first group were less likely to have been breast fed (odds ratio 0.42, 95% CI 0.19-0.90). The protection conferred by breast feeding was stronger among infants who were receiving human milk at the time of admission (odds ratio 0.22, 95% CI 0.09-0.55) and was absent among those infants who had stopped breast feeding for two or more weeks before admission. Among infants who were severely ill, breast feeding was less likely than among those with milder illnesses. There was evidence in the stratified analysis of effect modification by the presence of other children in the family. Among the infants with pertussis-like illness, the incidence and duration of breast feeding were not different compared with controls. The results suggest that breast feeding has a strong protective effect against ALRI in industrialized countries also. No protection seems to be conferred by human milk against pertussis-like illness.


Efficacy and safety of topical diclofenac/menthol gel for ankle sprain: A randomized, double-blind, placebo- and active-controlled trial.
Purpose This study was performed to evaluate topical 1% diclofenac/3% menthol gel in treating ankle sprain. Design In this randomized, double-blind, placebo-controlled trial, adolescents and adults with acute ankle sprain (N = 385) applied 4 g of gel containing 1% diclofenac/3% menthol (n = 117), 1% diclofenac (n = 112), 3% menthol (n = 77), or placebo (n = 75) four times daily. The primary outcome was the area under the curve of pain intensity (PI) on movement [0 (no pain) to 10 (extreme pain)] from 24 to 72 hours post-application (AUC1-3 days). Secondary outcomes included pain relief (PR); PI; time to onset of PR, meaningful PR, cooling, and complete recovery; PI difference; sum of PI difference; total PR; reduction in ankle swelling; and the patient's global assessment of response to treatment. Results There were no statistically significant differences in AUC1-3 between 1% diclofenac/3% menthol and placebo, diclofenac, or menthol gels and no meaningful advantages of 1% diclofenac/3% menthol for any secondary outcome. There was a higher incidence of skin and application-site events with 1% diclofenac/3% menthol than with placebo or 1% diclofenac. Conclusion No significant improvement was observed with topical 1% diclofenac/3% menthol gel compared with placebo, 1% diclofenac, or 3% menthol gel in treating pain from ankle sprain. ClinicalTrials.Gov Identifier: NCT02100670.


Changes in vasomotion--effect of hyperbaric oxygen in patients with diabetes Type 2.
To investigate vasomotion in diabetic patients who underwent sessions of hyperbaric oxygen (HBO2) therapy. Seventy-one patients with diabetes Type 2 and lower-extremity neuropathy were enrolled in a prospective matched case-control study. A total of 39 patients underwent 15 sessions of HBO2 therapy consisting of 90 minutes of breathing 100% oxygen at 2.5 atmospheres; 32 were included in the control group without exposure to hyperbaric oxygen. We used laser Doppler flowmetry for measurement of flowmotion. Spectral analysis of laser Doppler flowmetry signals was performed using the Fast Fourier transform algorithm. The total spectral activity was divided into the subgroup of endothelium, adrenergic, intrinsic smooth muscle, respiratory and cardiac spectral activity. The lateral ankle and the dorsum of the foot were chosen for this study. Heating provocation test was performed on both sites. The measurement was performed 24 hours before the first HBO2 session and 24 hours after the last (15th) session of therapy. We observed a significant increase in respiratory, cardiac and total spectral activity of flowmotion on the ankle as well as a significant increase in cardiac and total spectral activity on the dorsum of the foot in patients without a foot ulcer. In the subgroup of patients with a diabetic ulcer, a decrease of total spectral activity of flowmotion on the dorsum of the foot was observed. Flowmotion (indirectly vasomotion) measured by laser Doppler flowmetry changed significantly after HBO2 therapy. Flowmotion dynamics may partly explain the positive effect of HBO2 on the healing process of a diabetic ulcer.


Experimental allergic encephalomyelitis in Lewis rats: immunoregulation of disease by a single amino acid substitution in the disease-inducing determinant.
A single amino acid substitution in the sequence of the encephalitogenic determinant for Lewis rats destroyed its ability to induce experimental allergic encephalomyelitis (EAE) but generated a potent immunoregulatory sequence capable of suppressing the development of both clinical and histologic signs of EAE. The EAE-inducing determinant (synthetic peptide S6) H-Ala-Gln-Gly-His-Arg-Pro-Gln-Asp-Glu-Asn-OH (residues 75 to 84) of the bovine MBP induced clinical and histologic signs of EAE when it was administered at doses of 0.5 micrograms or higher. Gly substituted for the C-terminal Asn during the synthesis of peptide S6 generated the homologous sequence designated by peptide S79. Peptide S79 failed to induce either clinical or histologic signs of EAE even when it was administered at dosages up to 1000 times higher than those of S6. Similarly, rats pretreated with a single dose of S79 were not only unresponsive to an encephalitogenic challenge but also were capable of transferring unresponsiveness to syngeneic recipients with viable donor lymphocytes. The induction of unresponsiveness that was abrogated by pretreatment with cyclophosphamide suggests the development of an S79-sensitive lymphocyte subset that regulates MBP-induced EAE in Lewis rats.


Nonsteroidal Anti-inflammatory Drug Induced Thrombotic Thrombocytopenic Purpura.
A 21-year-old male presented to the emergency department after a 5-day history of recurrent vomiting and decreased urine output. History revealed ingestion of ibuprofen. During the diagnostic workup, the following was identified: white blood cell count 13.4 (×10(3)/mcL), hemoglobin 11.9 (×10(6)/mcL) with an MCV of 73 fL, hematocrit 34% and platelets were 31,000/mcL, sodium of 130 mmol/L, potassium of 5.1 mmol/L, chloride of 83 mmol/L, bicarbonate of 21 mmol/L, blood urea nitrogen of 184 mg/dL and creatinine of 19.1 mg/dL. He was later diagnosed with thrombotic thrombocytopenic purpura (TTP) based on the fact that he presented with most components of the TTP pentad (except for fever), which included altered mental status, acute kidney injury, thrombocytopenia, and evidence of red cell fragmentation and his ADAMTS13 level was found to be less than 10% prior to therapy. The patient then received plasma exchange, oral corticosteroids, and hemodialysis, which led to a full recovery of platelet count and renal function.


Functional neuroimaging and clinical features of drug naive patients with de novo Parkinson's disease and probable RBD.
The association between Parkinson Disease (PD) and REM sleep behavior disorder (RBD) has been related to a specific, malignant clinical phenotype. Definite RBD diagnosis requires video-polysomnography that is often unfeasible. A malignant clinical PD-RBD phenotype could be expected also in PD patients with probable RBD. Aim of this cross-sectional study was to evaluate whether a more severe neuropsychological and functional neuroimaging phenotype can be identified in PD patients with probable RBD. Thirty-eight de novo, drug naïve PD patients underwent a first-line clinical assessment and a second-line multimodal assessment, including neuropsychological evaluation, (123)I-FP-CIT-SPECT and (18)F-FDG-PET, which were compared between PD patients with (PD + RBD+) and without (PD + RBD-) probable RBD. On first-line assessment, PD + RBD + patients had significantly more constipation (p = 0.02) and showed worse olfaction (p = 0.01) compared with PD + RBD-while the two groups were similar as for age, presence of orthostatic hypotension, UPDRS-III and MMSE scores. On second-line assessment, PD + RBD + patients showed a worse neuropsychological test profile, more severe nigro-striatal dopaminergic impairment, mainly at caudate level in the less affected hemisphere (p = 0.004) and impaired brain glucose metabolism, with relative hypometabolism in posterior cortical regions and relative hypermetabolism mainly in anterior regions of the more affected hemisphere (p = 0.015). PD patients with probable RBD are likely to have a more severe neuropsychological and functional brain-imaging phenotype already at the time of diagnosis.


Low RKIP expression associates with poor prognosis in bladder cancer patients.
Urothelial bladder cancer (UBC) is a heterogeneous type of disease. It is urgent to screen biomarkers of tumour aggressiveness in order to clarify the clinical behaviour and to personalize therapy in UBC patients. Raf kinase inhibitory protein (RKIP) is a metastasis suppressor, and its downregulation is associated with metastatic events in an increasing number of solid tumours. We evaluated the clinical and prognostic significance of RKIP expression in patients with high risk of progression UBC. Using immunohistochemistry, we determined RKIP expression levels in a series of 81 patients with high-grade pT1/pTis or muscle-invasive UBC. Staining of CD31 and D2-40 was used to assess blood and lymphatic vessels, in order to distinguish between blood and lymphatic vessel invasion (LVI). We found that 90 % of pT1/pTis tumours, 94 % of non-muscle invasive papillary tumours and 76 % of the cases without LVI occurrence expressed RKIP in >10 % of cells. In this group, we observed a subgroup of tumours (42 %) in which the tumour centre was significantly more intensely stained than the invasion front. This heterogeneous pattern was observed in 63 % of the cases with LVI. Low RKIP expression was associated with poorer 5-year disease-free and overall survival rates, and remained as an independent prognostic factor for disease-free survival. Loss of RKIP expression may be an important prognostic factor for patients with high risk of progression bladder cancer.


Undertreatment of osteoporosis in residents of nursing homes: population-based study with use of the Systematic Assessment of Geriatric Drug Use via Epidemiology (SAGE) database.
To determine the proportion of nursing home residents >65 years of age with osteoporosis who were receiving antiosteoporosis pharmacotherapy and to identify the predictors of administration of such drugs. We identified 29,357 patients with osteoporosis documented on the Minimum Data Set collected on residents of all nursing home facilities in 5 states during the period from 1992 through 1996. A multiple logistic regression model was used for analysis, with the dependent variable being use of any antiosteoporosis drug. Among the nursing home residents with osteoporosis, 25% received antiosteoporosis drugs. Women were more likely than men to receive antiosteoporosis drugs (adjusted odds ratio [OR], 1.41; 95% confidence interval [CI], 1.26 to 1.57). Both increasing age and level of cognitive impairment were inversely related to receipt of antiosteoporosis drugs. A history of fracture or falls was not predictive of use of such drugs. Treatment was less likely for nursing home residents with > or = 6 medical conditions (OR 0.55, 95% CI 0.51 to 0.59); those admitted to a nursing home from a hospital (OR 0.86, 95% Cl 0.80 to 0.92); and those with a terminal prognosis (OR 0.60,95% CI 0.42 to 0.87). The majority of nursing home residents with osteoporosis in this study did not receive drug therapy for this disabling and treatable disease. Although acceptable reasons may exist in some of these residents,others--especially the oldest old--may not be receiving adequate care.


Analyses of the influencing factors of soil microbial functional gene diversity in tropical rainforest based on GeoChip 5.0.
To examine soil microbial functional gene diversity and causative factors in tropical rainforests, we used a microarray-based metagenomic tool named GeoChip 5.0 to profile it. We found that high microbial functional gene diversity and different soil microbial metabolic potential for biogeochemical processes were considered to exist in tropical rainforest. Soil available nitrogen was the most associated with soil microbial functional gene structure. Here, we mainly describe the experiment design, the data processing, and soil biogeochemical analyses attached to the study in details, which could be published on BMC microbiology Journal in 2015, whose raw data have been deposited in NCBI's Gene Expression Omnibus (accession number GSE69171).


[Gender dysphoria in the structure of psychosis].
This article describes the case of a young man diagnosed with schizoaffective disorder mixed type. The patient expressed dissatisfaction with his gender and showed a desire to change it for two years. He has applied to psychiatrists twice for permission to change his gender, having received preliminary diagnoses of «Gender dysphoria» and «Transsexualism». After treatment, which includes ECT, psychotic symptoms has disappeared, sexual identification has fully restored, and criticism of behavior and experiences has formed.


The cytology of molluscum contagiosum mimicking skin adnexal tumor.
Molluscum contagiosum is a cutaneous viral infection presenting as multiple, umbilicated papules and vesicles. The cytology of molluscum contagiosum in an 11-year-old boy, which presented atypically as a solitary nodule over the right cheek, mimicking a skin adnexal tumor is reported here. Fine needle aspiration cytology plays a vital role in establishing the correct diagnosis of clinically unsuspected cases, and hence, the proper management of such lesions. The cytology of molluscum contagiosum is characterized by the presence of numerous large intracytoplasmic basophilic bodies that push the host nucleus to the periphery, giving a signet ring appearance to the superficial epidermal cells.


Cognitive processing in children using cochlear implants: the relationship between visual memory, attention, and executive functions and developing language skills.
We performed this study to determine whether children using a cochlear implant performed differently from age- and gender-matched hearing aid users on 8 neuropsychological measures of visual memory, attention, and executive functioning. The study also examined whether differences in cognitive skills could account for some of the observed variance in speech perception, vocabulary, and language abilities of hearing-impaired children. In contrast to previous studies, our results revealed no significant cognitive differences between children who use a cochlear implant and children who use hearing aids. Partial correlation analysis indicated that the children's visual memory skills, ie, their recognition memory, delayed recall, and paired associative learning memory skills, correlated significantly with their language skills. When examined at a significance level of .01, attention and executive functioning skills did not relate to the children's developing speech perception, vocabulary, or language skills. The results suggested that differences in visual memory skills may account for some of the variance seen in the language abilities of children using implants and children using hearing aids.


The R304X mutation of the aryl hydrocarbon receptor interacting protein gene in familial isolated pituitary adenomas: Mutational hot-spot or founder effect?
Mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene have been described in about 15% of kindreds with familial isolated pituitary adenomas and in a minority of early onset sporadic pituitary adenomas (PA). Among the AIP mutations reported so far, the R304X (AIPR304X) represents, together with the "Finnish mutation" Q14X, the most common one. Three AIPR304X Italian families, including a newly reported kindred, have been genotyped for 12 genetic markers surrounding the AIP gene in order to look for a potential founder effect in Italy. Disease penetrance and genotype-phenotype correlations were also addressed. Analysis of chromosome 11' genetic markers revealed a common haplotype in 2 AIPR304X kindreds originating from central Italy. Overall, 17 mutations carriers were identified, including 7 patients and 10 unaffected subjects, respectively, arguing in this case for a disease penetrance of 41%. Mean age at diagnosis was 19.1±6.7 yr old, with females tending to be older than males. Though most PA were somatotropinomas (6/7), a great variability in disease severity was observed, even between subjects sharing the same at-risk haplotype. These data provide strong evidence for a new founder effect of the AIPR304X mutation in central Italy and the observed variations in disease severity point out the role of additional genetic or environmental factors in such kindreds.


Reversal of chemoresistance of lymphoma cells by antisense-mediated reduction of bcl-2 gene expression.
The bcl-2 gene is expressed in many types of human tumours and becomes transcriptionally deregulated in the majority of non-Hodgkin's lymphomas as the result of t(14;18) chromosomal translocations. The 26-kDa Bcl-2 protein has been shown to block programmed cell death (apoptosis) induced by many types of stimuli, including a wide variety of chemotherapeutic drugs and radiation. The presence of bcl-2 in tumor cells has been correlated with poor responses to therapy in patients with some types of cancer. To explore further the relevance of bcl-2 to drug resistance, we used antisense (As) approaches to achieve reductions in the levels of steady state Bcl-2 protein levels in t(14;18)-containing human lymphoma cell lines. Both synthetic bcl-2-As oligonucleotides and inducible expression plasmids that produce bcl-2-As transcripts induced reductions in bcl-2 expression, resulting in a marked enhancement in the sensitivity of neoplastic cells to conventional chemotherapeutic drugs such as cytosine arabinoside (ara-C) and methotrexate (MTX). These results suggest that novel therapeutics targeted against bcl-2 could provide the means for improved treatment of cancer by affecting physiological pathways distal to the targets of cytotoxic drugs.


Changes in BMI-distribution from 1966-69 to 1995-97 in adolescents. The Young-HUNT study, Norway.
The aim of this study was to explore changes in the BMI-distribution over time among Norwegian adolescents. Height and weight were measured in standardised ways and BMI computed in 6774 adolescents 14-18 years who participated in the Young-HUNT study, the youth part of the Health-study of Nord-Trondelag County, Norway in 1995-97. The results were compared to data from 8378 adolescents, in the same age group and living in the same geographical region, collected by the National Health Screening Service in 1966-69. From 1966-69 to 1995-97 there was an increased dispersion and a two-sided change in the BMI-distribution. Mean BMI did not increase in girls aged 14-17, but increased significantly in 18 year old girls and in boys of all ages. In both sexes and all ages there was a significant increase in the upper percentiles, but also a trend towards a decrease in the lowest percentiles. Height and weight increased significantly in both sexes and all ages. The increased dispersion of the BMI-distribution with a substantial increase in upper BMI-percentiles followed the same pattern seen in other European countries and the United States. The lack of increase in mean BMI among girls, and the decrease in the lowest percentiles has not been acknowledged in previous studies, and may call for attention.


Anti-Ro(SSA) antibodies in patients with rheumatoid arthritis--a possible marker for gold induced side effects.
To determine whether anti-Ro antibodies are associated with gold induced side effects. A retrospective chart review of 208 patients with rheumatoid arthritis (RA) and examination of sera for the presence of anti-Ro antibodies by enzyme linked immunosorbent assay. Anti-Ro antibodies were detected in 44 (21%) of our patients with RA and their presence correlated with positive rheumatoid factor, antinuclear antibody, and secondary Sjögren's syndrome. Thirty-three out of 48 patients with gold induced side effects (69%) were anti-Ro positive in contrast to 11 patients (7.5%) with positive antibodies with no side effects (p < 0.001). Mucocutaneous reactions had the only significant correlation (p < 0.01) with the presence of anti-Ro antibodies. Patients with RA with anti-Ro antibodies are prone to develop mucocutaneous side effects to gold salts.


Gender difference in QT interval in patients with primary aldosteronism.
We assessed whether QT interval was still different between male and female patients with primary aldosteronism. We also assessed the gender difference in the relation between serum potassium level and QT interval. The study population consisted of 80 patients with newly diagnosed primary aldosteronism. There were 39 male and 41 female patients. There were no significant (ns) differences in serum potassium (3.6±0.7 mEq/l vs 3.8±0.5mEq/l, p=ns) and QTc interval (423±26 msec vs 427±23 msec, p=ns) between male and female patients. In overall patients, serum potassium level was inversely associated with QTc interval significantly (r=-0.36, p<0.01). In male patients, there was still a significant inverse correlation (r=-0.42, p<0.01). However, this correlation was lost in female patients (r=-0.30, p=ns). Our data suggested that QTc interval was inversely associated with serum potassium level in male patients, but was not in female patients with primary aldosteronism.


Mild ketone formation via Ni-catalyzed reductive coupling of unactivated alkyl halides with acid anhydrides.
Ni-catalyzed ketone formation through mild reductive coupling of a diverse set of unactivated alkyl bromides and iodides with particularly aryl acid anhydrides was successfully developed using zinc as the terminal reductant. These conditions also allow direct coupling of alkyl iodides with aryl acids in the presence of Boc(2)O and MgCl(2).


Gammaphotography.
The Anger scintillation camera greatly broadens the range of studies performed by radioisotope imaging devices. Its ability to view in any direction, to make an image simultaneously of an entire field of view, and to obtain images rapidly, all serve to make scintiphotography analogous to fluoroscopy. Illustrations of its uses in static and dynamic gammaphotography and in numerical data processing are described.


Publication Rates of Heart Failure Clinical Trials Remain Low.
Under-reporting of clinical trial results inhibits dissemination of knowledge, limits understanding of therapeutic interventions, and may ultimately harm patients. This study examined the rates and predictors of heart failure clinical trial publication and how they have changed over time. This study assessed cross-sectional analysis of all heart failure clinical trials registered on ClinicalTrials.gov with at least 2 years follow-up after trial completion. The content area was chosen for the robust clinical trial activity in the field. The primary outcome was manuscript publication with multivariable proportional hazards adjustment to identify associations with publication. Of the 1,429 included studies, 806 (56%) were published as manuscripts, 623 were unpublished, and 97 (7%) reported results without manuscript publication. Of the total, 1,243 were completed after 2007, when the mean 1-year publication rate for interventional trials rose from 12.7% to 19.6% (p = 0.049), which was possibly associated with changes in government regulation. However, there was no further sustained improvement over time, and there was no multivariable association between later completion dates and reporting or publication of results. Funding from the National Institutes of Health and use of clinical (death, hospitalization, myocardial infarction, changes in functional classification) rather than nonclinical primary endpoints were associated with earlier publication. Whether the results were consistent with the primary study hypothesis was not associated with likelihood of publication. The rates of heart failure clinical trial publication or reporting of results remain unacceptably low. Additional efforts by all stakeholders, including investigators, sponsors, regulators, societies, editors, and journals are needed to improve data dissemination.


Cold plasma technology: An insight on its disinfection efficiency of various food systems.
Cold plasma technology is considered as one of the novel potential non-thermal techniques for food disinfection. The acceptability of any food product depends upon its physicochemical properties and shelf life. Recent studies have confirmed that plasma can effectively reduce the pathogenic microbes in various food systems. Further, there are reports that cold plasma showed minimal or no effect on the physicochemical and sensory properties of the foods owing to its low-temperature operation. The present review explores the recent reports on cold plasma technology emphasizing its disinfection efficacy on different food categories. Various researchers have demonstrated that plasma successfully reduced the microorganisms on cereals, milk, meat, fish and spices. Therefore, based on the current research, it can be suggested that cold plasma is an effective disinfectant technology for the inactivation of pathogenic microorganisms, and its non-thermal and environmentally friendly nature is an added advantage over traditional processing technologies.


In Situ Investigation of Electrochemically Mediated Surface-Initiated Atom Transfer Radical Polymerization by Electrochemical Surface Plasmon Resonance.
Electrochemically mediated atom transfer radical polymerization (eATRP) initiates/controls the controlled/living ATRP chain propagation process by electrochemically generating (regenerating) the activator (lower-oxidation-state metal complex) from deactivator (higher-oxidation-state metal complex). Despite successful demonstrations in both of the homogeneous polymerization and heterogeneous systems (namely, surface-initiated ATRP, SI-ATRP), the eATRP process itself has never been in situ investigated, and important information regarding this process remains unrevealed. In this work, we report the first investigation of the electrochemically mediated SI-ATRP (eSI-ATRP) by rationally combining the electrochemical technique with real-time surface plasmon resonance (SPR). In the experiment, the potential of a SPR gold chip modified by the self-assembled monolayer of the ATRP initiator was controlled to electrochemically reduce the deactivator to activator to initiate the SI-ATRP, and the whole process was simultaneously monitored by SPR with a high time resolution of 0.1 s. It is found that it is feasible to electrochemically trigger/control the SI-ATRP and the polymerization rate is correlated to the potential applied to the gold chip. This work reveals important kinetic information for eSI-ATRP and offers a powerful platform for in situ investigation of such complicated processes.


Tests and calibration of NIF neutron time of flight detectors.
The National Ignition Facility (NIF) neutron time of flight (NTOF) diagnostic will measure neutron yield and ion temperature in all NIF campaigns in DD, DT, and THD(*) implosions. The NIF NTOF diagnostic is designed to measure neutron yield from 1x10(9) to 2x10(19). The NTOF consists of several detectors of varying sensitivity located on the NIF at about 5 and 20 m from the target. Production, testing, and calibration of the NIF NTOF detectors have begun at the Laboratory for Laser Energetics (LLE). Operational tests of the NTOF detectors were performed on several facilities including the OMEGA laser at LLE and the Titan laser at Lawrence Livermore National Laboratory. Neutron calibrations were carried out on the OMEGA laser. Results of the NTOF detector tests and calibration will be presented.


Quality Management System in Clinical Digital Pathology Operations at a Tertiary Cancer Center.
Digital pathology workflows can improve pathology operations by allowing reliable and fast retrieval of digital images, digitally reviewing pathology slides, enabling remote work and telepathology, use of computer-aided tools, and sharing of digital images for research and educational purposes. The need for quality systems is a prerequisite for successful clinical-grade digital pathology adoption and patient safety. In this article, we describe the development of a structured digital pathology laboratory quality management system (QMS) for clinical digital pathology operations at Memorial Sloan Kettering Cancer Center (MSK). This digital pathology-specific QMS development stemmed from the gaps that were identified when MSK integrated digital pathology into its clinical practice. The digital scan team in conjunction with the Department of Pathology and Laboratory Medicine quality team developed a QMS tailored to the scanning operation to support departmental and institutional needs. As a first step, systemic mapping of the digital pathology operations identified the prescan, scan, and postscan processes; instrumentation; and staffing involved in the digital pathology operation. Next, gaps identified in quality control and quality assurance measures led to the development of standard operating procedures and training material for the different roles and workflows in the process. All digital pathology-related documents were subject to regulatory review and approval by departmental leadership. The quality essentials were developed into an extensive Digital Pathology Quality Essentials framework to specifically address the needs of the growing clinical use of digital pathology technologies. Using the unique digital experience gained at MSK, we present our recommendations for QMS for large-scale digital pathology operations in clinical settings.


Ultrastructure of rumen bacterial attachment to forage cell walls.
The degradation of forage cell walls by rumen bacteria was investigated with critical-point drying/scanning electron microscopy and ruthenium red staining/transmission electron microscopy. Differences were observed in the manner of attachment of different morphological types of rumen bacteria to plant cell walls during degradation. Cocci, constituting about 22% of the attached bacteria, appeared to be attached to degraded plant walls via capsule-like substances averaging 58 nm in width (range, 21 to 84 nm). Many bacilli appeared to adhere to forage substrates without distinct capsule-like material, although unattached bacteria with capsules were observed occasionally. Certain bacili appeared to be attached to degraded tissue via small amounts of extracellular material, but others apparently had no extracellular material. Bacilli with a distinct morphology due to an irregularly folded, electron-dense outer layer or layers (about 15 nm thick) and without fibrous extracellular material consituted about 37% of the attached bacteria and were observed to adhere so closely to degraded plant walls that the bacterial shape conformed to the shape of the degraded zone. In the rumen ecosystem, bacteria appeared to adhere to plant substrates during degradation by capsule-like material and by small amounts of extracellular material, as well as by the other means not observable by electron microscopy.


Post-exposure vaccination improves gammaherpesvirus neutralization.
Herpesvirus carriers transmit infection despite making virus-specific antibodies. Thus, their antibody responses are not necessarily optimal. An important question for infection control is whether vaccinating carriers might improve virus neutralization. The antibody response to murine gamma-herpesvirus-68 (MHV-68) blocks cell binding, but fails to block and even enhances an IgG Fc receptor-dependent infection of myeloid cells. Viral membrane fusion therefore remains intact. Although gH/gL-specific monoclonal antibodies can block infection at a post-binding step close to membrane fusion, gH/gL is a relatively minor antibody target in virus carriers. We show here that gH/gL-specific antibodies can block both Fc receptor-independent and Fc receptor-dependent infections, and that vaccinating virus carriers with a gH/gL fusion protein improves their capacity for virus neutralization both in vitro and in vivo. This approach has the potential to reduce herpesvirus transmission.


Level of vascular tie and its effect on functional outcome 2 years after anterior resection for rectal cancer.
Previous research indicates that high tie of the inferior mesenteric artery during anterior resection for rectal cancer might be associated with an increased risk of postoperative functional disturbances. The goal of this population-based retrospective cohort study was to further investigate that association. Patients who underwent anterior resection for rectal cancer from April 2011 to September 2012 were identified through the Swedish Colorectal Cancer Registry. Bowel and urogenital function were assessed by a postal questionnaire 2 years after surgery. Information on the level of mesenteric tie and clinical variables was retrieved from the registry. The outcome was defined as any defaecatory, urinary or sexual dysfunction as reported by the patient. The association between high tie and the outcome was evaluated with multivariable logistic and linear regression with adjustment for confounders, such as sex, body mass index, comorbidity and preoperative radiation. With a response rate of 86%, 805 patients were included in the study. Of these, 46% were operated with high tie. After adjustment for confounders, high tie did not affect the risk of faecal incontinence (OR 0.85; 95% CI 0.59-1.22), urinary incontinence (OR 0.94; 95% CI 0.63-1.41) or various aspects of sexual dysfunction (erectile dysfunction, anejaculation, dyspareunia and coital vaginal dryness). However, an association between high tie and defaecation at night was detected (OR 1.44; 95% CI 1.02-2.03). This study does not support that the level of vascular tie influences the risk of major defaecatory, urinary or sexual disturbances 2 years after anterior resection for rectal cancer.


Secondary phenotype analysis in ascertained family designs: application to the Leiden longevity study.
The case-control design is often used to test associations between the case-control status and genetic variants. In addition to this primary phenotype, a number of additional traits, known as secondary phenotypes, are routinely recorded, and typically, associations between genetic factors and these secondary traits are studied too. Analysing secondary phenotypes in case-control studies may lead to biased genetic effect estimates, especially when the marker tested is associated with the primary phenotype and when the primary and secondary phenotypes tested are correlated. Several methods have been proposed in the literature to overcome the problem, but they are limited to case-control studies and not directly applicable to more complex designs, such as the multiple-cases family studies. A proper secondary phenotype analysis, in this case, is complicated by the within families correlations on top of the biased sampling design. We propose a novel approach to accommodate the ascertainment process while explicitly modelling the familial relationships. Our approach pairs existing methods for mixed-effects models with the retrospective likelihood framework and uses a multivariate probit model to capture the association between the mixed type primary and secondary phenotypes. To examine the efficiency and bias of the estimates, we performed simulations under several scenarios for the association between the primary phenotype, secondary phenotype and genetic markers. We will illustrate the method by analysing the association between triglyceride levels and glucose (secondary phenotypes) and genetic markers from the Leiden Longevity Study, a multiple-cases family study that investigates longevity. © 2017 The Authors. Statistics in Medicine Published by JohnWiley & Sons Ltd.


Field reliability of the SAVRY with juvenile probation officers: Implications for training.
Two complimentary studies were conducted to investigate the inter-rater reliability and performance of juvenile justice personnel when conducting the Structured Assessment of Violence Risk for Youth (SAVRY). Study 1 reports the performance on four standardized vignettes of 408 juvenile probation officers (JPOs) and social workers rating the SAVRY as part of their training. JPOs had high agreement with the expert consensus on the SAVRY rating of overall risk and total scores, but those trained by a peer master trainer outperformed those trained by an expert. Study 2 examined the field reliability of the SAVRY on 80 young offender cases rated by a JPO and a trained research assistant. In the field, intra-class correlation coefficients were 'excellent' for SAVRY total and most domain scores, and were 'good' for overall risk ratings. Results suggest that the SAVRY and structured professional judgment can be used reliably in the field by juvenile justice personnel and is comparable to reliability indices reported in more lab-like research studies; however, replication is essential.


Assessing rabies-free status of Andaman, Nicobar, and Lakshadweep Islands, India.
The Indian Islands of Andaman, Nicobar, and Lakshadweep have been historically rabies-free. However, reliable laboratory evidence to substantiate rabies-free status was lacking. In this background, the study was conducted as a component of the World Health Organization-Association for Prevention and Control of Rabies in India, Indian Multi-Centric Rabies Survey; to assess the rabies-free status of the two Islands and to examine the feasibility of initiating laboratory surveillance for rabies in dogs in Andaman, Nicobar, and Cats in Lakshadweep Islands. A team of medical and veterinary investigators visited these Islands in 2017. A review of 10 years records (2007-2017) in medical and veterinary institutes and interviews with different stakeholders were conducted. Based on the review of records, there was no evidence of human/animal rabies in the Islands. Eight dog brain samples from Andaman, Nicobar Islands, and ten cat brain samples from Lakshadweep Islands were tested negative for rabies by fluorescent antibody test at two rabies diagnostic laboratories at Bengaluru.


Development of Ki-1 lymphoma in a child suffering from multicentric reticulohistiocytosis.
We report a case of Ki-1 lymphoma that developed in a 16-year-old youth who had suffered from multicentric reticulohistiocytosis for 10 years. Over the past 3 years he had had a peculiar sclerosing lesion of the leg for which oral prednisone 5 mg daily was tried for one year, with a moderate effect. He developed a marked swelling of the inguinal lymphadenopathy on the same side as the affected leg lesion, which also developed a prominent swelling of the skin surrounding the sclerosed area. Immunohistochemical analysis of the lymph node biopsy revealed the features of Ki-1 lymphoma. This is the first case of association of multicentric reticulohistiocytosis with Ki-1 lymphoma.


Dexamethasone does not interfere with hormone-sensitive PI hydrolysis.
Serum, but not epidermal growth factor (EGF), stimulated the release of radiolabeled inositol phosphates from human embryo palate mesenchyme (HEPM) cells prelabeled with [3H]-myoinositol. Pretreatment of cells with 10(-6) M dexamethasone (DEX) for 48 h had no effect on the release of inositol phosphates in response to serum. Furthermore, although treatment of the glucocorticoid-sensitive A/J strain of mouse embryo palate mesenchyme (MEPM) cells with 10(-6) M DEX inhibited their proliferation by 40%, it had no effect on the activity of phospholipase(s) C. However, DEX did enhance the incorporation of [3H]-myoinositol into membrane lipids. We interpret these data to mean that 1) serum factors enhance metabolism of inositol lipids in HEPM cells, 2) DEX does not interfere with the primary events by which agonists utilize metabolism of inositol lipids as a mechanism for transmembrane signaling, and 3) DEX may affect synthesis of phosphoinositides, as reported by Grove et al. (Biochem. Biophys. Res. Commun. 110:200-207, 1983; J. Craniofac. Genet. Dev. Biol. Suppl. 2:285-292, 1986).