Using the prisms of gender and rank to interpret research collaboration power dynamics.
Collaboration is central to modern scientific inquiry, and increasingly important to the professional experiences of academic scientists. While the effects of collaboration have been widely studied, much less is understood about the motivations to collaborate and collaboration dynamics that generate scientific outcomes. A particular interest of this study is to understand how collaboration experiences differ between women and men, and the attributions used to explain these differences. We use a multi-method study of university Science, Technology, Engineering, and Mathematics faculty research collaborators. We employ 177 anonymous open-ended responses to a web-based survey, and 60 semi-structured interviews of academic scientists in US research universities. We find similarities and differences in collaborative activity between men and women. Open-ended qualitative textual analysis suggests that some of these differences are attributed to power dynamics - both general ones related to differences in organizational status, and in power dynamics related specifically to gender. In analysis of semi-structured interviews, we find that both status and gender were used as interpretive frames for collaborative behavior, with more emphasis placed on status than gender differences. Overall, the findings support that gender structures some part of the collaborative experience, but that status hierarchy exerts more clear effects.


Using Extinction-Renewal to Circumvent the Memory Strength Boundary Condition in Fear Memory Reconsolidation.
Reconsolidation is a process by which memories are destabilized, updated, and then restabilized. Strong memories are resistant to undergoing reconsolidation. Here, we addressed whether an overtrained fear memory could be made susceptible to reconsolidation by first extinguishing, and then renewing, the memory. Rats were trained with ten tone-footshock pairings, followed by eight days of tone extinction in the training context. The next day, rats were placed into a second context and memory for the tone was renewed/reactivated with a single tone presentation. Immediately following reactivation, rats received an injection of midazolam or vehicle. Rats were then tested for freezing to the tone in a third context. Midazolam had no effect in rats that did not undergo tone extinction, but significantly attenuated freezing to the tone in extinguished rats. Thus, rats that received tone extinction underwent tone memory reconsolidation following its renewal. In a second experiment, we administered the reactivation session and midazolam injections prior to extinction. Midazolam had no effect and rats extinguished at a rate similar to controls. These data suggest that strong emotional memories are capable of updating following weakening of memory expression through extinction.


Cardiovascular research publications from Latin America between 1999 and 2008. A bibliometric study.
Cardiovascular research publications seem to be increasing in Latin America overall. To analyze trends in cardiovascular publications and their citations from countries in Latin America between 1999 and 2008, and to compare them with those from the rest of the countries. We retrieved references of cardiovascular publications between 1999 and 2008 and their five-year post-publication citations from the Web of Knowledge database. For countries in Latin America, we calculated the total number of publications and their citation indices (total citations divided by number of publications) by year. We analyzed trends on publications and citation indices over time using Poisson regression models. The analysis was repeated for Latin America as a region, and compared with that for the rest of the countries grouped according to economic development. Brazil (n = 6,132) had the highest number of publications in 1999-2008, followed by Argentina (n = 1,686), Mexico (n = 1,368) and Chile (n = 874). Most countries showed an increase in publications over time, leaded by Guatemala (36.5% annually [95%CI: 16.7%-59.7%]), Colombia (22.1% [16.3%-28.2%]), Costa Rica (18.1% [8.1%-28.9%]) and Brazil (17.9% [16.9%-19.1%]). However, trends on citation indices varied widely (from -33.8% to 28.4%). From 1999 to 2008, cardiovascular publications of Latin America increased by 12.9% (12.1%-13.5%) annually. However, the citation indices of Latin America increased 1.5% (1.3%-1.7%) annually, a lower increase than those of all other country groups analyzed. Although the number of cardiovascular publications of Latin America increased from 1999 to 2008, trends on citation indices suggest they may have had a relatively low impact on the research field, stressing the importance of considering quality and dissemination on local research policies.


Fluoroquinolones for treating typhoid and paratyphoid fever (enteric fever).
Fluoroquinolones are recommended as first-line therapy for typhoid and paratyphoid fever, but how they compare with other cheaper antibiotics and different fluoroquinolones is unclear. To evaluate fluoroquinolone antibiotics for treating enteric fever in children and adults compared with other antibiotics, different fluoroquinolones, and different treatment durations of the same fluoroquinolone. We searched the Cochrane Infectious Diseases Group Specialized Register (August 2004), CENTRAL (The Cochrane Library Issue 3, 2004), MEDLINE (1966 to August 2004), EMBASE (1974 to August 2004), LILACS (1982 to August 2004), conference proceedings, reference lists, and contacted researchers. Randomized controlled trials of fluoroquinolones in people with blood or bone marrow culture-confirmed enteric fever. Two reviewers independently assessed the methodological quality of trials and extracted data. We calculated the odds ratio (OR) for dichotomous data with 95% confidence intervals. We analysed norfloxacin separately. Thirty-three trials met the inclusion criteria; 22 had unclear allocation concealment, and 29 were not blinded. Three trials exclusively included children, and two studied outpatients. The main analysis examined clinical failure, microbiological failure, and relapse. Compared with chloramphenicol, fluoroquinolones were not statistically significantly different for clinical (544 participants) or microbiological failure (378 participants) in adults; they reduced clinically diagnosed relapse in adults (OR 0.14, 0.04 to 0.50; 467 participants, 6 trials), but this was not statistically significant in participants with blood culture-confirmed relapse (121 participants, 2 trials). Compared with co-trimoxazole, we detected no statistically significant difference (82 participants, 2 trials). Among adults, fluoroquinolones reduced clinical failure compared with ceftriaxone (OR 0.08, 0.01 to 0.45; 120 participants, 3 trials), but showed no difference for microbiological failure or relapse. We detected no statistically significant difference between fluoroquinolones and cefixime (80 participants, 1 trial) or azithromycin (152 participants, 2 trials). In trials of hospitalized children, fluoroquinolones were not statistically significantly different from ceftriaxone (60 participants, 1 trial, involving norfloxacin) or cefixime (82 participants, 1 trial). Norfloxacin had more clinical failures than other fluoroquinolones (417 participants, 5 trials). Trials comparing different durations of fluoroquinolone treatment showed no statistically significant differences (693 participants, 8 trials). Many trials were small, and methodological quality varied widely. Although enteric fever most commonly affects children, trials in this group were particularly sparse. Insufficient data in all comparisons preclude any firm conclusions to be made regarding superiority of fluoroquinolones over first-line antibiotics in children and adults.


Fullerenol Nanoparticles Eradicate Helicobacter pylori via pH-Responsive Peroxidase Activity.
Helicobacter pylori (H. pylori) eradication by antibiotics and proton pump inhibitor treatment is limited by the low pH microenvironment in the stomach and can lead to antibiotic resistance. We fabricated fullerenol nanoparticles (FNPs) with varied chemical structures responding to a pinacol rearrangement of vicinal hydroxyl to form carbonyls in low pH environments. An obvious increase in C═O/C-O was induced in low pH and was positively correlated with a peroxidase-like activity. The FNPs exerted an excellent effect on H. pylori eradication in vitro and in vivo because of their peroxidase-like activity. FNP treatment of a H. pylori biofilm revealed that FNPs broke down polysaccharides in cell wall components, resulting in collapse of the bacteria. The cycles of FNPs combining and dissociating with the peroxidase substrate were detected by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and confirmed that FNPs enhance peroxidase-like activity. Further, the isothermal titration calorimetry results showed that FNPs with more C═O/C-O had greater affinity to bind the peroxidase substrates. Therefore, we suggest that varied C═O/C-O serves as a switch to respond to low pH in the stomach to kill H. pylori by inducing a peroxidase-like activity. FNPs can also overcome the challenge of antibiotic resistance to achieve H. pylori eradication in the stomach.


[Echocardiographic signs of pulmonary hypertension].
The results of examination of patients with primary and secondary pulmonary hypertension by means of the echocardiographic method are presented in the article. Basing on the analysis of their own data and foreign literature the authors have set out the most informative indices of pulmonary hypertension on the echogram of the vulve of the pulmonary artery and the right ventricle. It has been noted that in the left hypertension the form of the echocardiogram of the left cusp of the pulmonary valve is depressed, the amplitude of the precardiac wave "a" increased, and the amplitude and rate of the cusp opening decreased. The anterior-posterior size of the right ventricle is significantly increased and a parodoxal movement of the interventricular septum appears with a relative insufficiency of the tricupsid valve.


Spontaneous delayed expansion of self-expanding stents in stenotic arteries in Takayasu arteritis.
PURPOSE Despite frequent use of self-expanding stents (SES) in treating obstructive arterial lesions in Takayasu arteritis (TA), spontaneous delayed stent expansion (SDSE) in TA remains unstudied. This study aimed primarily to document and quantify SDSE and secondarily to determine factors that might be associated with this process. METHODS Consecutive TA patients with obstructive arterial lesions undergoing routine percutaneous intervention involving SES use (sized 1:1 with normal vessel diameter but dilated only to 4mm/5mm) were recruited prospectively. Final stent diameters obtained were measured at 1cm intervals along the length of the stent using fluoroscopic images and an indwelling marker catheter. At angiographic follow-up, stent diameters were measured again in identical fashion. Interval change in stent diameter at each point was averaged for each stent. In a small sub-study intravascular ultrasound was used at follow-up to obtain potential mechanistic insights. RESULTS Seventeen TA patients (age 33 ± 13 years, 15 female) had 22 arterial obstructive lesions (16 occlusions, 18 subclavian) treated with one SES each. Follow-up obtained in all patients after 8.7 ± 3.8 months (range 3-18 months) showed interval increase in mean stent diameter of 1.6 ± 0.5 mm, range 0.7-2.8 mm (P < 0.001); 36% of stents achieved 100% of the nominal diameter at follow-up, while 90% of stents achieved ≥90%. The degree of SDSE did not correlate with the segment of artery stented or with TA disease activity at baseline. Intravascular ultrasound in four lesions showed that SDSE was associated with positive medial-adventitial remodelling and that neointimal hyperplasia occurs concurrently, causing in-stent luminal narrowing. CONCLUSION SDSE, to diameters equal or close to nominal, occurs in all stenotic TA lesions treated with SES. The degree of SDSE does not correlate with the segment of artery stented or with TA disease activity at baseline. Preliminary results suggest that the mechanism by which SDSE is accommodated by the arterial wall is by positive medial-adventitial remodelling.


Characterization of K-ATPase activity in distal nephron: stimulation by potassium depletion.
Intercalated cells of the distal segments of the mammalian nephron are able to reabsorb K through an active mechanism, particularly during K depletion. However, the molecular basis of this transport is unknown. Therefore, we attempted to determine whether a K-ATPase similar to K-H-ATPase described in gastric mucosa and colon might be present in segments of the distal nephron and thereby account for active K reabsorption. K-stimulated ATPase activity was detected in microdissected segments of rabbit nephron: its activity was proportional to the density of intercalated cells, since it was highest in the connecting tubule, intermediate in the cortical collecting tubule, lowest in the outer medullary collecting tubule, and was not detectable in all other nephron segments. K-ATPase had a high affinity for K (Km approximately equal to 0.2-0.4 mM), was inhibited by vanadate and omeprazole, and was insensitive to ouabain, indicating that it is different from Na+-K+-ATPase but similar to K-H-ATPase. In the rat kidney, K-ATPase was also detected in the collecting tubule and its activity was markedly increased (+100-200%) following K depletion. This stimulation occurred before morphological alterations and might therefore be a primary event responsible for K conservation during K depletion. In summary, these results demonstrate the presence of a vanadate-sensitive, ouabain-insensitive K-ATPase activity in distal nephron segments of mammalian tubules. It is suggested that K-ATPase activity originates in intercalated cells where it might account, at least in part, for K reabsorption.


Endothelial Damage and the Microcirculation in Critical Illness.
Endothelial integrity maintains microcirculatory flow and tissue oxygen delivery. The endothelial glycocalyx is involved in cell signalling, coagulation and inflammation. Our ability to treat critically ill and septic patients effectively is determined by understanding the underpinning biological mechanisms. Many mechanisms govern the development of sepsis and many large trials for new treatments have failed to show a benefit. Endothelial dysfunction is possibly one of these biological mechanisms. Glycocalyx damage is measured biochemically. Novel microscopy techniques now mean the glycocalyx can be indirectly visualised, using sidestream dark field imaging. How the clinical visualisation of microcirculation changes relate to biochemical laboratory measurements of glycocalyx damage is not clear. This article reviews the evidence for a relationship between clinically evaluable microcirculation and biological signal of glycocalyx disruption in various diseases in ICU. Microcirculation changes relate to biochemical evidence of glycocalyx damage in some disease states, but results are highly variable. Better understanding and larger studies of this relationship could improve phenotyping and personalised medicine in the future. Damage to the glycocalyx could underpin many critical illness pathologies and having real-time information on the glycocalyx and microcirculation in the future could improve patient stratification, diagnosis and treatment.


HIV transmission dynamics and population-wide drug resistance in rural South Africa.
Despite the scale-up of antiretroviral therapy (ART) in South Africa, HIV-1 incidence remains high. The anticipated use of potent integrase strand transfer inhibitors and long-acting injectables aims to enhance viral suppression at the population level and diminish transmission. Nevertheless, pre-existing drug resistance could impede the efficacy of long-acting injectable ART combinations, such as rilpivirine (an NNRTI) and cabotegravir (an INSTI). Consequently, a thorough understanding of transmission networks and geospatial distributions is vital for tailored interventions, including pre-exposure prophylaxis with long-acting injectables. However, empirical data on background resistance and transmission networks remain limited. In a community-based study in rural KwaZulu-Natal (2018-2019), prior to the widespread use of integrase inhibitor-based first-line ART, we performed HIV testing with reflex HIV-1 RNA viral load quantification on 18,025 participants. From this cohort, 6,096 (33.9%) tested positive for HIV via ELISA, with 1,323 (21.7%) exhibiting detectable viral loads (> 40 copies/mL). Of those with detectable viral loads, 62.1% were ART-naïve, and the majority of the treated were on an efavirenz + cytosine analogue + tenofovir regimen. Deep sequencing analysis, with a variant abundance threshold of 20%, revealed NRTI resistance mutations such as M184V in 2% of ART-naïve and 32% of treated individuals. Tenofovir resistance mutations K65R and K70E were found in 12% and 5% of ART-experienced individuals, respectively, and in less than 1% of ART-naïve individuals. Integrase inhibitor resistance mutations were notably infrequent (< 1%). Prevalence of pre-treatment drug resistance to NNRTIs was 10%, predominantly consisting of the K103N mutation. Among those with viraemic ART, NNRTI resistance was 50%, with rilpivirine-associated mutations observed in 9% of treated and 6% of untreated individuals. Cluster analysis revealed that 20% (205/1,050) of those sequenced were part of a cluster. We identified 171 groups with at least two linked participants; three quarters of clusters had only two individuals, and a quarter had 3-6 individuals. Integrating phylogenetic with geospatial analyses, we revealed a complex transmission network with significant clustering in specific regions, notably peripheral and rural areas. These findings derived from population scale genomic analyses are encouraging in terms of the limited resistance to DTG, but indicate that transitioning to long-acting cabotegravir + rilpivirine for transmission reduction should be accompanied by prior screening for rilpivirine resistance. Whole HIV-1 genome sequencing allowed identification of significant proportions of clusters with multiple individuals, and geospatial analyses suggesting decentralised networks can inform targeting public health interventions to effectively curb HIV-1 transmission.


mTOR eosinophilic renal cell carcinoma: a distinctive tumor characterized by mTOR mutation, loss of chromosome 1, cathepsin-K expression, and response to target therapy.
In the spectrum of oncocytic renal neoplasms, a subset of tumors with high-grade-appearing histologic features harboring pathogenic mutations in mammalian target of rapamycin (mTOR) and hitherto clinical indolent behavior has been described. Three cases (2F,1 M) with histologically documented metastases (lymph node, skull, and liver) were retrieved and extensively investigated by immunohistochemistry, FISH, and next-generation sequencing. Tumors were composed of eosinophilic cells with prominent nucleoli (G3 by ISUP/WHO) arranged in solid to nested architecture. Additionally, there were larger cells with perinuclear cytoplasmic shrinkage and sparse basophilic Nissl-like granules, superficially resembling the so-called spider cells of cardiac rhabdomyomas. The renal tumors, including the skull and liver metastases, showed immunoexpression PAX8, CK8-18, and cathepsin-K, and negativity for vimentin. NGS identified mTOR genetic alterations in the three cases, including the skull and liver metastases. One patient was then treated with Everolimus (mTOR inhibitors) with clinical response (metastatic tumor shrinkage). We present a distinct renal tumor characterized by high-grade eosinophilic cells, cathepsin-K immunohistochemical expression, and harboring mTOR gene mutations demonstrating a malignant potential and showing responsiveness to mTOR inhibitors.


Interfacial study of class II hydrophobin and its mixtures with milk proteins: relationship to bubble stability.
Class II hydrophobin (HFBII) is a very promising ingredient for improving food foam stability. Pure HFBII-stabilized bubbles exhibited exceptional stability to disproportionation (dissolution) but were not stable to bubble coalescence induced by a pressure drop. Bubbles stabilized by mixtures of HFBII + sodium caseinate (SC) or β-lactoglobulin (BL) showed decreased shrinkage rates compared to pure SC or BL and improved the stability to pressure-drop-induced coalescence. Higher bubble stability was more closely correlated with higher surface shear viscosity than the surface dilatational elasticity of the mixed protein systems. Brewster angle microscopy observations and the high shear strength of adsorbed films, including HFBII, even in the presence of hydrophobic and hydrogen-bond-breaking agents, confirm that intermolecular attractive cross-links are unlikely to be the origin of the high strength of HFBII films. Possibly the HFBII molecules form a tightly interlocking monolayer of Janus-like particles at the air-water interface.


The ability of selected pupal parasitoids (Hymenoptera: Pteromalidae) to locate stable fly hosts in a soiled equine bedding substrate.
The ability of Spalangia cameroni Perkins, Spalangia endius Walker, and Muscidifurax raptorellus Kogan and Legner to locate and attack stable fly hosts was evaluated under laboratory conditions. Postfeeding third-instar stable fly larvae were released and allowed to pupate in two arena types: large 4.8 liter chambers containing a field-collected, soiled equine bedding substrate; or 120-ml plastic cups containing wood chips. At the time of fly pupariation, parasitoids were released and permitted 72 h to locate and attack hosts. On average, parasitism rates of freely accessible stable fly pupae in cups were not significantly different between parasitoid species. However, parasitism rates in chambers containing either Spalangia spp. were ≈50-fold more than M. raptorellus. Additional intraspecies analysis revealed that parasitism rates both by S. cameroni and S. endius were not significantly different when pupae were freely accessible or within bedding, whereas M. raptorellus attacked significantly more pupae in cups than in the larger chambers where hosts were distributed within bedding. These results suggest that Spalangia spp. are more suited to successfully locate and attack hosts in habitats created by equine husbandry in Florida. Therefore, commercially available parasitoid mixtures containing Muscidifurax spp. may be ineffective if used as a control measure at Florida equine facilities.


Improved rapid plate method for the isolation of bacteriophages from lysogenic bacteria.
A modification of a recently reported rapid plate method for the isolation of bacteriophages from lysogenic bacteria is described. The velveteen replica plate technique was used for inoculation of mitomycin C-induced colonies onto agar plates, and tetrazolium chloride was used to enhance detection of phage activity on replicated indicator plates.


Morphometric Study of Nasal Bone and Piriform Aperture in Human Dry Skull of Indian Origin.
Nasal bone and piriform aperture shows racial and geographical differences because of variable climate. The aim of this study was to evaluate the dimensions (maximal width and length), the size and the shape of the piriform aperture (PA) and their sexual dimorphism in North Indian adult. In this observational study, dimension of piriform aperture and nasal bone were measured using digital vernier caliper after assessing landmarks around the piriform aperture on the norma frontalis in Frankfurt plane in 40 skull of Indian orgin. The mean width of the piriform aperture was 24.9±1.59 mm in males and 22.77±1.57 mm in females, the mean length was 29.57±3.28mm in females and 31.16±3.58mm in males. The difference between males and females was significant, and our data correlates well with the previously data acquired from humans skulls. Most of North Indian skulls have platyrhine type of piriform aperture (triangular to oval shape with pyriform aperture index of 0.79). Mean length and width of nasal bone were 17.58±2.47mm and 12.1±0.97mm respectively without sexual. Shape and size analysis of the piriform aperture and nasal bone showed the existence of a significant sexual dimorphism. These results encourage us to go further with functional and imaging correlations. This study will also be helpful in forensic research and anthropology.


Donor's position-specific channel interference in substituted biphenyl molecules.
The channel interference mechanism describes the two-photon absorption process in terms of the relative orientations of different transition dipole moment vectors (TDMVs) in a molecule. Controlling these interferences is a difficult but important task, because it can provide new information about such absorption/emission processes. The present contribution aims to explain the reversal in the nature of these interferences with the relative positions of the donor-acceptor groups in substituted biphenyl molecules. The results obtained from the linear and quadratic response theories indicate that having the donor at the para position leads to a constructive interference whereas having it at any of the other two positions results in a destructive interference. This is explained by a systematic analysis of the relative orientations of all the TDMVs involved in a three-state model.


Molecular cloning and functional analysis of an rpoS homologue gene from Vibrio cholerae N86.
A homologue of the rpoS gene of Escherichia coli was cloned from Vibrio cholerae N86 by complementation of the phenotypes of the E. coli rpoS mutant strain. We determined the DNA sequence of this gene. Sequence alignments have indicated that the rpoS gene of V. cholerae N86 encoding a 39-kDa protein is very similar to that of E. coli. In addition, the nlpD-like gene was found in the upstream region of the rpoS gene in the same order as in E. coli. These results suggest that the organization of these genes is highly conserved between E. coli and V. cholerae.


Comparative study of bacteriology in recurrent tonsillitis among children and adults.
Diagnosis and treatment of acute tonsillitis are one of the most common problems seen at an otorhinolaryngology clinic in both adult and paediatric populations. Much has been written about bacteriology of recurrent tonsillitis but it remains a controversial topic. Despite the fact that tonsillitis is so common, consensus seems to be lacking as to the main causative organism and the differences between children and adults. The tonsillar core bacteriology of 233 patients with recurrent tonsillitis who underwent tonsillectomy from January 2000 to June 2003 is presented. The patient population was divided into two groups, namely: the paediatric group and the adult group. 132 patients, whose age was more than 12 years, were in the adult group. 101 patients aged between two and 12 years, were in the paediatric group. The bacteriology of the children and adults were tabulated according to their species, and were compared. 138 patients grew single pathogenic bacteria in their tonsillar core culture, 52 grew two different pathogenic bacteria, and the rest (43) grew normal bacterial flora. Staphylococcus aureus was the most commonly-isolated bacterium and accounted for 40.9 percent of the total cultures isolated; its prevalence was the same in the adults and children. Beta-haemolytic Streptococcus was isolated in 23 percent of subjects, and was predominantly from group A (Streptococcus pyogens). Group A beta-haemolytic Streptococci was more prevalent in children. Pseudomonas aeruginosa, which rarely cause pathogenicity in tonsils, was cultured from nine (3.8 percent) of our study subjects. This study showed that Staphylococcus aureus is the most common pathogenic bacteria cultured both in adults and children. Klebsiella pneumonia, Streptococcus pneumonia, Escherichia coli and Enterobacter are more prevalent in adults. Haemophilus influenza and Streptococcus pyogens are more prevalent in children. Pseudomonas aeruginosa is not a rare causative organism in recurrent tonsillitis. Since the mechanism of activation of infection in recurrent tonsillitis is unknown, knowing the bacteriology does not help us to treat the disease. However, it may be a stepping stone to eventually understanding whether the bacteria play a role in reactivating recurrent infections. From previous and current studies, there is no relationship between bacteriology and recurrent infections.


A Comparison of Implants Used in Open-Door Laminoplasty: Structural Rib Allografts Versus Metallic Miniplates.
A retrospective case-controlled study. Open-door laminoplasty has been successfully used to address cervical spondylotic myelopathy and ossification of the posterior longitudinal ligament. Two common implants include rib allograft struts and metallic miniplates. The goals of this study were to compare outcomes, complications, and costs associated with these 2 implants. A retrospective review was done on 51 patients with allograft struts and 55 patients with miniplates. Primary outcomes were neck visual analog scale (VAS) pain scores and Nurick scores. Secondary outcomes included length of the procedure, estimated blood loss, rates of complications, and the direct costs associated with the surgery and inpatient hospitalization. There were no differences in demographic characteristics, diagnoses, comorbidities, and preoperative outcome scores between the 2 treatment groups. Mean follow-up was 27 months. The postoperative neck VAS scores and Nurick scores improved significantly from baseline to final follow-up for both groups, but there was no difference between the 2 groups. The average length of operation (161 vs. 136 min) and number of foraminotomies (2.7 vs. 1.3) were higher for the allograft group (P=0.007 and 0.0001, respectively). Among the miniplate group, there was no difference in complications but a trend for less neck pain for patients treated without hard collar at final follow-up (1.8 vs. 2.3, P=0.52). The mean direct costs of hospitalization for the miniplate group were 15% higher. Structural rib allograft struts and metallic miniplates result in similar improvements in pain and functional outcome scores with no difference in the rate of complications in short-term follow-up. Potential benefits of using a plate include shorter procedure length and less need for postoperative immobilization. When costs of bracing and operative time are included, the difference in cost between miniplates and allograft struts is negligible.


Fungal allergy and respiratory disease.
An aerobiological study of three different localities of the Auckland region using Burkard volumetric spore traps was conducted for a 12 month period from September 1979 to August 1980. High counts were recorded of various types of fungal spores of both unknown and recognised potential allergens but the basidiospore group was dominant at all sites forming greater than 50% of the total air spora. Seasonal periodicities as well as regional variations in spore concentrations of five generic group viz Ganoderma, Leptosphaeria, Cladosporium, Alternaria and Aspergillus-Penicilium were recorded. These exhibited summer and/or autumn peaks. The diel periodicities recorded for Ganoderma and Leptosphaeria were of nocturnal type. Cladosporium was diurnal and Aspergillus-Penicillium did not display any clear periodicity. The hospital admissions of acute asthma sufferers were recorded for the period January 1979 to December 1980. The seasonal pattern of airborne basidiospores of the region and the pattern of acute asthma admissions indicate a close relationship between the two.


Obesity and the Risk of Incident Chronic Opioid Use in Rheumatoid Arthritis.
The present study was undertaken to evaluate whether the rate of incident chronic opioid use is higher in obese patients with rheumatoid arthritis (RA). Participants with RA in the FORWARD databank were asked about their use of weak and strong opioid medications on semiannual surveys. Incident chronic opioid use was defined as new reported use extending over 2 contiguous surveys (~7-12 months). Cox proportional hazards models were used to evaluate associations between body mass index (BMI) at enrollment and incident chronic opioid use (overall use and strong opioid use). Models adjusted for demographics, smoking, disease duration, RA treatments, household income, and education level. The predicted 5-year cumulative incidence was calculated from Cox models. Among 19,794 participants, 2,802 experienced an incident episode of chronic opioid use over 93,254 person-years of follow-up. Higher BMI was associated with higher risk of chronic opioid use. Severe obesity (BMI >35 kg/m2 ) was associated with a higher risk of overall use (adjusted hazard ratio [HRadj ] 1.74 [95% confidence interval (95% CI) 1.72-2.04], P < 0.0001) and strong opioid use (HRadj 2.11 [95% CI 1.64-2.71], P < 0.001) compared to normal BMI. This association was partially explained by greater comorbidity, pain, and disability in obese groups. The attributable risk for obesity was 15% of overall opioid use and 24% of strong opioid use. Obesity is associated with a substantially higher risk of incident chronic opioid use. Approximately 1 in 4 cases of incident use of strong opioids may be attributable to obesity, suggesting a major public health impact. Interventions to prevent or reduce obesity could have an important impact on the use of opioids.


Exploiting the mitochondrial unfolded protein response for cancer therapy in mice and human cells.
Fine tuning of the protein folding environment in subcellular organelles, such as mitochondria, is important for adaptive homeostasis and may participate in human diseases, but the regulators of this process are still largely elusive. Here, we have shown that selective targeting of heat shock protein-90 (Hsp90) chaperones in mitochondria of human tumor cells triggered compensatory autophagy and an organelle unfolded protein response (UPR) centered on upregulation of CCAAT enhancer binding protein (C/EBP) transcription factors. In turn, this transcriptional UPR repressed NF-κB-dependent gene expression, enhanced tumor cell apoptosis initiated by death receptor ligation, and inhibited intracranial glioblastoma growth in mice without detectable toxicity. These data reveal what we believe to be a novel role of Hsp90 chaperones in the regulation of the protein-folding environment in mitochondria of tumor cells. Disabling this general adaptive pathway could potentially be used in treatment of genetically heterogeneous human tumors.


West Nile Virus Temperature Sensitivity and Avian Virulence Are Modulated by NS1-2B Polymorphisms.
West Nile virus (WNV) replicates in a wide variety of avian species, which serve as reservoir and amplification hosts. WNV strains isolated in North America, such as the prototype strain NY99, elicit a highly pathogenic response in certain avian species, notably American crows (AMCRs; Corvus brachyrhynchos). In contrast, a closely related strain, KN3829, isolated in Kenya, exhibits a low viremic response with limited mortality in AMCRs. Previous work has associated the difference in pathogenicity primarily with a single amino acid mutation at position 249 in the helicase domain of the NS3 protein. The NY99 strain encodes a proline residue at this position, while KN3829 encodes a threonine. Introduction of an NS3-T249P mutation in the KN3829 genetic background significantly increased virulence and mortality; however, peak viremia and mortality were lower than those of NY99. In order to elucidate the viral genetic basis for phenotype variations exclusive of the NS3-249 polymorphism, chimeric NY99/KN3829 viruses were created. We show herein that differences in the NS1-2B region contribute to avian pathogenicity in a manner that is independent of and additive with the NS3-249 mutation. Additionally, NS1-2B residues were found to alter temperature sensitivity when grown in avian cells.


Comparison of genomic and antigenic properties of Newcastle Disease virus genotypes II, XXI and VII from Egypt do not point to antigenic drift as selection marker.
Newcastle disease (ND), caused by avian orthoavulavirus type-1 (NDV), is endemic in poultry in many regions of the world and causes continuing outbreaks in poultry populations. In the Middle East, genotype XXI, used to be present in poultry in Egypt but has been replaced by genotype VII. We investigated whether virus evolution contributed to superseding and focussed on the antigenic sites within the hemagglutinin-neuraminidase (HN) spike protein. Full-length sequences of an NDV genotype VII isolate currently circulating in Egypt was compared to a genotype XXI isolate that was present as co-infection with vaccine-type viruses (II) in a historical virus isolated in 2011. Amino acid differences in the HN glycoprotein for both XXI and VII viruses amounted to 11.7% and 11.9%, respectively, compared to the La Sota vaccine type. However, mutations within the globular head (aa 126-570), bearing relevant antigenic sites, were underrepresented (a divergence of 8.8% and 8.1% compared to 22.4% and 25.6% within the protein domains encompassing cytoplasmic tail, transmembrane part and stalk regions (aa 1-125) for genotypes XXI and VII, respectively). Nevertheless, reaction patterns of HN-specific monoclonal antibodies inhibiting receptor binding revealed differences between vaccine-type viruses and genotype XXI and VII viruses for epitopes located in the head domain. Accordingly, compared to Egyptian vaccine-type isolates and the La Sota vaccine reference strain, single aa substitutions in 6 of 10 described neutralizing epitopes of HN were found. However, the same alterations in neutralization sensitive epitopes were present in old genotype XXI as well as in newly emerged genotype VII isolates. In addition, isolates were indistinguishable by polyclonal chicken sera raised against different genotypes including vaccine viruses. These findings suggest that factors other than antigenic differences within the HN protein account for facilitating the spread of genotype VII versus genotype XXI viruses in Egypt.


Diagnosing serious infections in older adults presenting to ambulatory care: a systematic review.
to summarise all available evidence on the accuracy of clinical features and blood tests for diagnosing serious infections in older patients presenting to ambulatory care. systematic review, searching seven databases using a comprehensive search strategy. We included cross-sectional prospective diagnostic studies on (1) clinical features, (2) diagnostic prediction rules based on clinical features alone, (3) blood tests and (4) diagnostic prediction rules combining clinical features and blood tests. Study participants had to be community-dwelling adults aged ≥65 years, in whom a physician suspected an infection. We used QUADAS-2 to assess risk of bias. We calculated measures of diagnostic accuracy and present descriptive statistics. out of 13,757 unique articles, only six studies with a moderate to high risk of bias were included. There was substantial clinical heterogeneity across these studies. Clinical features had LR- ≥0.61 and LR+ ≤4.94. Twelve prediction rules using clinical features had LR- ≥0.30 and LR+ ≤2.78. There was evidence on four blood tests of which procalcitonin was the most often investigated: levels <0.37 ng/ml (LR- = 0.20; 95%CI 0.10-0.42) were suitable to rule out sepsis in moderately high prevalence situations. Two diagnostic prediction rules combining clinical features and procalcitonin had LR- of ≤0.12 (95%CI 0.05-0.33) and LR+ of maximum 1.39 (95%CI 1.30-1.49). we found few studies on the diagnostic accuracy of clinical features and blood tests to detect serious infections in older people presenting to ambulatory care. The risk of bias was mostly moderate to high, leading to substantial uncertainty.


Effectiveness of lifestyle interventions on obstructive sleep apnea (OSA): systematic review and meta-analysis.
Obstructive sleep apnea (OSA) is a common sleep disorder associated with several adverse health outcomes. Given the close association between OSA and obesity, lifestyle and dietary interventions are commonly recommended to patients, but the evidence for their impact on OSA has not been systematically examined. To conduct a systematic review and meta-analysis to assess the impact of weight loss through diet and physical activity on measures of OSA: apnea-hypopnea index (AHI) and oxygen desaturation index of 4% (ODI4). A systematic search was performed to identify publications using Medline (1948-2011 week 40), EMBASE (from 1988-2011 week 40), and CINAHL (from 1982-2011 week 40). The inverse variance method was used to weight studies and the random effects model was used to analyze data. Seven randomized controlled trials (519 participants) showed that weight reduction programs were associated with a decrease in AHI (-6.04 events/h [95% confidence interval -11.18, -0.90]) with substantial heterogeneity between studies (I(2) = 86%). Nine uncontrolled before-after studies (250 participants) showed a significant decrease in AHI (-12.26 events/h [95% confidence interval -18.51, -6.02]). Four uncontrolled before-after studies (97 participants) with ODI4 as outcome also showed a significant decrease in ODI4 (-18.91 episodes/h [95% confidence interval -23.40, -14.43]). Published evidence suggests that weight loss through lifestyle and dietary interventions results in improvements in obstructive sleep apnea parameters, but is insufficient to normalize them. The changes in obstructive sleep apnea parameters could, however, be clinically relevant in some patients by reducing obstructive sleep apnea severity. These promising preliminary results need confirmation through larger randomized studies including more intensive weight loss approaches.


Malignant clonal expansion of large granular lymphocytes with a Leu-11+, Leu-7- surface phenotype: in vitro responsiveness of malignant cells to recombinant human interleukin 2.
A 14-year-old Japanese female with neutropenia showed malignant proliferation of the large granular lymphocytes (LGLs). These LGLs were E rosette+ and Fc(IgG) receptor+ and therefore are referred to as T gamma lymphocytes. They were also Leu-11+ and OKT11+; however, they were clearly negative for Leu-7, OKT3, OKT8, OKM1, and HNK-1 antigens as well as for terminal deoxynucleotidyl transferase activity. Karyotype analysis revealed 47, XXX. The LGLs showed no rearrangement of T cell receptor C beta genes. The natural killer (NK) cell activity against K562 target cells was low, but was significantly augmented after stimulation by recombinant human interleukin 2 (IL 2) in contrast to minimal NK boosting by recombinant human gamma-interferon (gamma-IFN). Such a unique responsive ability to lymphokines was quite similar to that noted in fetal and cord blood cells. These LGLs also demonstrated a considerable increase in antibody-dependent cell-mediated cytotoxicity (ADCC) and lymphokine-activated killer (LAK) activity after a short incubation with IL 2. Although in a resting stage they showed no IL 2 receptor expression as examined by anti-Tac antibody, Tac antigen appeared after IL 2 treatment followed by a marked increase in 3H-thymidine incorporation and a remarkable production of gamma-IFN. To investigate the mechanism of neutropenia, in vitro IL 2-stimulated coculture studies of these cells with normal bone marrow cells were performed. Colony formation of myeloid progenitors (CFU-C) was significantly suppressed. In addition, the conditioned medium from IL 2-stimulated LGLs indicated a remarkable suppression of CFU-C. These results suggest that these LGLs with a Leu-11+, Leu-7- surface phenotype might belong to a unique subset of pre-NK cells that are functionally and phenotypically similar to those represented at any early stage of human ontogeny and that they strongly express Tac antigen under the influence of IL 2 administration, followed by remarkable cell proliferation and gamma-IFN production.


Effect of HIV and malaria parasites co-infection on immune-hematological profiles among patients attending anti-retroviral treatment (ART) clinic in Infectious Disease Hospital Kano, Nigeria.
Human immunodeficiency virus (HIV) and malaria co-infection may present worse health outcomes in the tropics. Information on HIV/malaria co-infection effect on immune-hematological profiles is critical for patient care and there is a paucity of such data in Nigeria. To evaluate immune-hematological profiles among HIV infected patients compared to HIV/malaria co-infected for ART management improvement. This was a cross sectional study conducted at Infectious Disease Hospital, Kano. A total of 761 consenting adults attending ART clinic were randomly selected and recruited between June and December 2015. Participants' characteristics and clinical details including two previous CD4 counts were collected. Venous blood sample (4ml) was collected in EDTA tube for malaria parasite diagnosis by rapid test and confirmed with microscopy. Hematological profiles were analyzed by Sysmex XP-300 and CD4 count by Cyflow cytometry. Data was analyzed with SPSS 22.0 using Chi-Square test for association between HIV/malaria parasites co-infection with age groups, gender, ART, cotrimoxazole and usage of treated bed nets. Mean hematological profiles by HIV/malaria co-infection and HIV only were compared using independent t-test and mean CD4 count tested by mixed design repeated measures ANOVA. Statistical significant difference at probability of <0.05 was considered for all variables. Of the 761 HIV infected, 64% were females, with a mean age of ± (SD) 37.30 (10.4) years. Prevalence of HIV/malaria co-infection was 27.7% with Plasmodium falciparum specie accounting for 99.1%. No statistical significant difference was observed between HIV/malaria co-infection in association to age (p = 0.498) and gender (p = 0.789). A significantly (p = 0.026) higher prevalence (35.2%) of co-infection was observed among non-ART patients compared to (26%) ART patients. Prevalence of co-infection was significantly lower (20.0%) among cotrimoxazole users compared to those not on cotrimoxazole (37%). The same significantly lower co-infection prevalence (22.5%) was observed among treated bed net users compared to those not using treated bed nets (42.9%) (p = 0.001). Out of 16 hematology profiles evaluated, six showed significant difference between the two groups (i) packed cell volume (p = <0.001), (ii) mean cell volume (p = 0.005), (iii) mean cell hemoglobin concentration (p = 0.011), (iv) absolute lymphocyte count (p = 0.022), (v) neutrophil percentage count (p = 0.020) and (vi) platelets distribution width (p = <0.001). Current mean CD4 count cell/μl (349±12) was significantly higher in HIV infected only compared to co-infected (306±17), (p = 0.035). A significantly lower mean CD4 count (234.6 ± 6.9) was observed among respondents on ART compared to non-ART (372.5 ± 13.2), p<0.001, mean difference = -137.9). The study revealed a high burden of HIV and malaria co-infection among the studied population. Co-infection was significantly lower among patients who use treated bed nets as well as cotrimoxazole chemotherapy and ART. Six hematological indices differed significantly between the two groups. Malaria and HIV co-infection significantly reduces CD4 count. In general, to achieve better management of all HIV patients in this setting, diagnosing malaria, prompt antiretroviral therapy, monitoring CD4 and some hematology indices on regular basis is critical.


The effects of population bottlenecks on clonal interference, and the adaptation effective population size.
Clonal interference refers to the competition that arises in asexual populations when multiple beneficial mutations segregate simultaneously. A large body of theoretical and experimental work now addresses this issue. Although much of the experimental work is performed in populations that grow exponentially between periodic population bottlenecks, the theoretical work to date has addressed only populations of a constant size. We derive an analytical approximation for the rate of adaptation in the presence of both clonal interference and bottlenecks, and compare this prediction to the results of an individual-based simulation, showing excellent agreement in the parameter regime in which clonal interference prevails. We also derive an appropriate definition for the effective population size for adaptive evolution experiments in the presence of population bottlenecks. This "adaptation effective population size" allows for a good approximation of the expected rate of adaptation, either in the strong-selection weak-mutation regime, or when clonal interference comes into play. In the multiple mutation regime, when the product of the population size and mutation rate is extremely large, these results no longer hold.


Multiplexed Nanomaterial-Based Sensor Array for Detection of COVID-19 in Exhaled Breath.
This article reports on a noninvasive approach in detecting and following-up individuals who are at-risk or have an existing COVID-19 infection, with a potential ability to serve as an epidemic control tool. The proposed method uses a developed breath device composed of a nanomaterial-based hybrid sensor array with multiplexed detection capabilities that can detect disease-specific biomarkers from exhaled breath, thus enabling rapid and accurate diagnosis. An exploratory clinical study with this approach was examined in Wuhan, China, during March 2020. The study cohort included 49 confirmed COVID-19 patients, 58 healthy controls, and 33 non-COVID lung infection controls. When applicable, positive COVID-19 patients were sampled twice: during the active disease and after recovery. Discriminant analysis of the obtained signals from the nanomaterial-based sensors achieved very good test discriminations between the different groups. The training and test set data exhibited respectively 94% and 76% accuracy in differentiating patients from controls as well as 90% and 95% accuracy in differentiating between patients with COVID-19 and patients with other lung infections. While further validation studies are needed, the results may serve as a base for technology that would lead to a reduction in the number of unneeded confirmatory tests and lower the burden on hospitals, while allowing individuals a screening solution that can be performed in PoC facilities. The proposed method can be considered as a platform that could be applied for any other disease infection with proper modifications to the artificial intelligence and would therefore be available to serve as a diagnostic tool in case of a new disease outbreak.


Phenotype Diversity of Macrophages in Osteoarthritis: Implications for Development of Macrophage Modulating Therapies.
Chronic inflammation is implicated in numerous human pathologies. In particular, low-grade inflammation is currently recognized as an important mechanism of osteoarthritis (OA), at least in some patients. Among the signs of the inflammatory process are elevated macrophage numbers detected in the OA synovium compared to healthy controls. High macrophage counts also correlate with clinical symptoms of the disease. Macrophages are central players in the development of chronic inflammation, pain, cartilage destruction, and bone remodeling. However, macrophages are also involved in tissue repair and remodeling, including cartilage. Therefore, reduction of macrophage content in the joints correlates with deleterious effects in OA models. Macrophage population is heterogeneous and dynamic, with phenotype transitions being induced by a variety of stimuli. In order to effectively use the macrophage inflammatory circuit for treatment of OA, it is important to understand macrophage heterogeneity and interactions with surrounding cells and tissues in the joint. In this review, we discuss functional phenotypes of macrophages and specific targeting approaches relevant for OA treatment development.


Aquaporin-4 astrocytopathy in Baló's disease.
Baló's concentric sclerosis (BCS) is considered to be a rare variant of multiple sclerosis and characterized by alternating rings of demyelinated and preserved myelin layers. The mechanism underlying BCS remains to be elucidated. Recently, occurrence of concentric rings of Baló was described in the brainstem of a patient with neuromyelitis optica (NMO). Because selective loss of aquaporin-4 (AQP4) and vasculocentric deposition of complement and immunoglobulins are characteristic in NMO, we aimed to assess AQP4 expression in the concentric demyelinating lesions of BCS patients. We evaluated AQP4 expression relative to expression of another astrocytic marker (glial fibrillary acidic protein), the extent of demyelination, lesion staging and perivascular deposition of complement and immunoglobulin in four cases with BCS, and 30 individuals with other neurological diseases. All cases with BCS demonstrated extensive AQP4 loss in both demyelinated and myelinated layers of all actively demyelinating lesions, with perivascular lymphocytic cuffing of T cells, but no deposition of immunoglobulins or complement around vessels. These findings suggest that AQP4 loss occurs in heterogeneous demyelinating conditions, namely NMO and BCS. Furthermore, acute BCS lesions are characterized by extensive AQP4 loss without vasculocentric deposition of complement or immunoglobulin.


Stable isotope tracer to determine uptake and efflux dynamics of ZnO Nano- and bulk particles and dissolved Zn to an estuarine snail.
Zinc oxide nanoparticles (ZnO NPs) are among the most commercialized engineered nanomaterials. Their biological impact in aquatic organisms has been associated with dissolution, but there is also evidence of nanospecific effects. In this study the waterborne uptake and efflux kinetics of isotopically labeled (68)ZnO NPs (7.8 ± 1.2 nm), in comparison to aqueous (68)Zn and (68)ZnO bulk particles (up to 2 μm), were determined for the estuarine snail Peringia ulvae following a 7 d exposure (nominally 20 μg (68)Zn L(-1)) and 28 d depuration. Detection of the (68)Zn label was achieved by high precision multiple-collector ICP-MS (MC-ICP-MS). Previous characterization in artificial estuarine water revealed that the NPs underwent initial aggregation and solubilized up to 60% within 1-2 days. Bulk and aqueous forms were significantly more bioavailable than (68)ZnO NPs (p < 0.05), but after correcting for dissolution, aqueous (0.074 L(-1) g(-1) d(-1)) and NP (0.070 L(-1) g(-1) d(-1)) uptake rate constants were highly comparable. The rate constant of loss for (68)Zn aqueous (0.012 ± 0.005 d(-1)) and (68)ZnO NPs (0.012 ± 0.007 d(-1)) were identical. These results strongly suggest that in this exposure scenario the bioaccumulation of Zn from ZnO NPs is primarily dependent upon solubility.


Experimental and theoretical study of the absorption properties of thiolated diamondoids.
Nanoscale hybrid systems are a new class of molecular aggregates that offer numerous new possibilities in materials design. Diamondoid thiols are promising nanoscale building blocks for such hybrid systems. They allow the incorporation of functional groups and the investigation of their effects on the unique materials' properties of diamondoids. Here we combine experimental data with ab initio theory to explore the optical properties of diamondoid thiols and their dependence on size and shape. Agreement between theoretically and experimentally obtained absorption spectra allows the identification of the nature of the optical transitions that are responsible for some photophysical and photochemical processes. We show that the optical properties of diamondoid thiols in the deep UV regime depend on the functionalization site but are largely size independent. Our findings provide an explanation for the disappearance of diamondoid UV photoluminescence upon thiolation for smaller diamondoids. However, our theoretical results indicate that for larger diamondoid thiols beyond the critical size of six diamondoid cages the lowest energy transitions are characterized by diamondoidlike states suggesting that UV luminescence may be regained.


Family physician remuneration schemes and specialist referrals: Quasi-experimental evidence from Ontario, Canada.
Understanding how family physicians respond to incentives from remuneration schemes is a central theme in the literature. One understudied aspect is referrals to specialists. Although the theoretical literature has suggested that capitation increases referrals to specialists, the empirical evidence is mixed. We push forward the empirical research on this question by studying family physicians who switched from blended fee-for-service to blended capitation in Ontario, Canada. Using several health administrative databases from 2005 to 2013, we rely on inverse probability weighting with fixed-effects regression models to account for observed and unobserved differences between the switchers and nonswitchers. Switching from blended fee-for-service to blended capitation increases referrals to specialists by about 5% to 7% per annum. The cost of specialist referrals is about 7 to 9% higher in the blended capitation model relative to the blended fee-for-service. These results are generally robust to a variety of alternative model specifications and matching techniques, suggesting that they are driven partly by the incentive effect of remuneration. Policy makers need to consider the benefits of capitation payment scheme against the unintended consequences of higher referrals to specialists.


Diversity and evolution of the transposable element repertoire in arthropods with particular reference to insects.
Transposable elements (TEs) are a major component of metazoan genomes and are associated with a variety of mechanisms that shape genome architecture and evolution. Despite the ever-growing number of insect genomes sequenced to date, our understanding of the diversity and evolution of insect TEs remains poor. Here, we present a standardized characterization and an order-level comparison of arthropod TE repertoires, encompassing 62 insect and 11 outgroup species. The insect TE repertoire contains TEs of almost every class previously described, and in some cases even TEs previously reported only from vertebrates and plants. Additionally, we identified a large fraction of unclassifiable TEs. We found high variation in TE content, ranging from less than 6% in the antarctic midge (Diptera), the honey bee and the turnip sawfly (Hymenoptera) to more than 58% in the malaria mosquito (Diptera) and the migratory locust (Orthoptera), and a possible relationship between the content and diversity of TEs and the genome size. While most insect orders exhibit a characteristic TE composition, we also observed intraordinal differences, e.g., in Diptera, Hymenoptera, and Hemiptera. Our findings shed light on common patterns and reveal lineage-specific differences in content and evolution of TEs in insects. We anticipate our study to provide the basis for future comparative research on the insect TE repertoire.


Design considerations for piezoelectric polymer ultrasound transducers.
Much work has been published on the design of ultrasound transducers using piezoelectric ceramics, but a great deal of this work does not apply when using the piezoelectric polymers because of their unique electrical and mechanical properties. The purpose of this paper is to review and present new insight into seven important considerations for the design of active piezoelectric polymer ultrasound transducers: piezoelectric polymer materials selection, transducer construction and packaging requirements, materials characterization and modeling, film thickness and active area design, electroding selection, backing material design, and front protection/matching layer design. Besides reviewing these design considerations, this paper also presents new insight into the design of active piezoelectric polymer ultrasonic transducers. The design and fabrication of an immersible ultrasonic transducer, which has no adhesive layer between the active element and backing layer, is included. The transducer features direct deposition of poly(vinylidene fluoride-trifluoroethylene) [P(VDF-TrFE)] copolymer onto an insulated aluminum backing substrate. Pulse-echo tests indicated a minimum insertion loss of 37 dB and -6 dB bandwidth of 9.8 to 22 MHz (71%). The use of polymer wear-protection/quarter-wave matching layers is also discussed. Test results on a P(VDF-TrFE) transducer showed that a Mylar/sup TM/ front layer provided a slight increase in pulse-echo amplitude of 15% (or 1.2 dB) and an increase in -6 dB pulse-echo fractional bandwidth from 86 to 95%. Theoretical derivations are reported for optimizing the active area of the piezoelectric polymer element for maximum power transfer at resonance. These derivations are extended to the special case for a low profile (i.e., thin) shielded transducer. A method for modeling the non-linear loading effects of a commercial pulser-receiver is also included.


Expression of neurogenin3 reveals an islet cell precursor population in the pancreas.
Differentiation of early gut endoderm cells into the endocrine cells forming the pancreatic islets of Langerhans depends on a cascade of gene activation events controlled by transcription factors including the basic helix-loop-helix (bHLH) proteins. To delineate this cascade, we began by establishing the position of neurogenin3, a bHLH factor found in the pancreas during fetal development. We detect neurogenin3 immunoreactivity transiently in scattered ductal cells in the fetal mouse pancreas, peaking at embryonic day 15.5. Although not detected in cells expressing islet hormones or the islet transcription factors Isl1, Brn4, Pax6 or PDX1, neurogenin3 is detected along with early islet differentiation factors Nkx6.1 and Nkx2.2, establishing that it is expressed in immature cells in the islet lineage. Analysis of transcription factor-deficient mice demonstrates that neurogenin3 expression is not dependent on neuroD1/BETA2, Mash1, Nkx2.2, Nkx6.1, or Pax6. Furthermore, early expression of neurogenin3 under control of the Pdx1 promoter is alone sufficient to drive early and ectopic differentiation of islet cells, a capability shared by the pancreatic bHLH factor, neuroD1/BETA2, but not by the muscle bHLH factor, MyoD. However, the islet cells produced in these transgenic experiments are overwhelmingly (alpha) cells, suggesting that factors other than the bHLH factors are required to deviate from a default * cell fate. These data support a model in which neurogenin3 acts upstream of other islet differentiation factors, initiating the differentiation of endocrine cells, but switching off prior to final differentiation. The ability to uniquely identify islet cell precursors by neurogenin3 expression allows us to determine the position of other islet transcription factors in the differentiation cascade and to propose a map for the islet cell differentiation pathway.


Pathological outcome for Chinese patients with low-risk prostate cancer eligible for active surveillance and undergoing radical prostatectomy: comparison of six different active surveillance protocols.
Active surveillance is one of the therapeutic options for the management of patients with low-risk prostate cancer. This study compared the performance of six different active surveillance protocols for prostate cancer in the Chinese population. Patients who underwent radical prostatectomy for prostate cancer from January 1998 to December 2012 at a university teaching hospital in Hong Kong were reviewed. Six active surveillance protocols were applied to the cohort. Statistical analyses were performed to compare the probabilities of missing unfavourable pathological outcome. The sensitivity and specificity of each protocol in identifying low-risk disease were compared. During the study period, 287 patients were included in the cohort. Depending on different active surveillance protocols used, extracapsular extension, seminal vesicle invasion, pathological T3 disease, and upgrading of Gleason score were present on final pathology in 3.3%-17.1%, 0%-3.3%, 3.3%-19.1%, and 20.6%-34.5% of the patients, respectively. The University of Toronto protocol had a higher rate of extracapsular extension at 17.1% and pathological T3 disease at 19.1% on final pathology than the more stringent protocols from John Hopkins (3.3% extracapsular extension, P=0.05 and 3.3% pathological T3 disease, P=0.03) and Prostate Cancer Research International: Active Surveillance (PRIAS; 8.0% pathological T3 disease, P=0.04). The Royal Marsden protocol had a higher rate of upgrading of Gleason score at 34.5% compared with the more stringent protocol of PRIAS at 20.6% (P=0.04). The specificities in identifying localised disease and low-risk histology among different active surveillance protocols were 59%-98% and 58%-94%, respectively. The John Hopkins active surveillance protocol had the highest specificity in both selecting localised disease (98%) and low-risk histology (94%). Active surveillance protocols based on prostate-specific antigen and Gleason score alone or including Gleason score of 3+4 may miss high-risk disease and should be used cautiously. The John Hopkins and PRIAS protocols are highly specific in identifying localised disease and low-risk histology.


[Proton permeability and electric breakdown of phospholipid membranes after UV-irradiation].
Lipid peroxidation induced in bilayer lipid membranes (BLM) by UV-irradiation leads to two types of effects: selective in proton permeability and electric breakdown of the membranes. Both phenomena are always observed but the contribution of each in the membrane conductivity increase depends on the lipid nature (degree of unsaturation of fatty acids) and the value of transmembrane applied to BLM or generated by the membrane itself.


Agent-based neutral competition in two-community networks.
Competition between alternative states is an essential process in social and biological networks. Neutral competition can be represented by an unbiased random drift process in which the states of vertices (e.g., opinions, genotypes, or species) in a network are updated by repeatedly selecting two connected vertices. One of these vertices copies the state of the selected neighbor. Such updates are repeated until all vertices are in the same "consensus" state. There is no unique rule for selecting the vertex pair to be updated. Real-world processes comprise three limiting factors that can influence the selected edge and the direction of spread: (1) the rate at which a vertex sends a state to its neighbors, (2) the rate at which a state is received by a neighbor, and (3) the rate at which a state can be exchanged through a connecting edge. We investigate how these three limitations influence neutral competition in networks with two communities generated by a stochastic block model. By using Monte Carlo simulations, we show how the community structure and update rule determine the states' success probabilities and the time until a consensus is reached. We present a heterogeneous mean-field theory that agrees well with the Monte Carlo simulations. The effectiveness of the heterogeneous mean-field theory implies that quantitative predictions about the consensus are possible even if empirical data (e.g., from ecological fieldwork or observations of social interactions) do not allow a complete reconstruction of all edges in the network.


Human adipose-derived stem cells reduce receptor-interacting protein 1, receptor-interacting protein 3, and mixed lineage kinase domain-like pseudokinase as necroptotic markers in rat model of Alzheimer's disease.
Alzheimer's disease (AD) is a constant, developing brain impairment that is described as the aggregation of misfolded amyloid-beta-peptide (Ab) and abnormal tau protein in the brain. Stem cell therapy became a favorable candidate for the regeneration of neurodegenerative disorders like AD, but there is still shortage of knowledge about the underlying mechanisms. The goal of this survey was the determination of the necroptotic pathway as the possible mechanism for the effect of human adipose-derived stem cells (hADSCs) in the rat model of AD. Twelve rats were consumed, dividing into four groups: Control, sham, AD model and AD + stem cell groups. We utilized Nissl and Thioflavin S staining for determining histological changes and immunofluorescent techniques for evaluating necroptotic markers in different regions of the hippocampus. The confirmation of AD model was approved with histological examination. The findings indicated more distinct Thio-S stain and an increased number of dead cells in AD rats comparing to other groups. Alternatively, the dead cells number in the CA3 area significantly lessened in AD + stem cell group comparing to AD group. Data showed that hADSCs significantly decreased the expression of necroptotic markers (receptor-interacting protein 1, receptor-interacting protein 3 and mixed lineage kinase domain-like pseudokinase (MLKL)) in AD + stem cell group compared to AD group in different regions of the hippocampus. Our findings revealed that the intravenous injection of hADSCs reduced necroptosis and consequently declined the death of neuronal cells in the hippocampus of AD rats.


Controlled-release mitochondrial protonophore (CRMP) reverses dyslipidemia and hepatic steatosis in dysmetabolic nonhuman primates.
Nonalcoholic fatty liver disease (NAFLD) is estimated to affect up to one-third of the general population, and new therapies are urgently required. Our laboratory previously developed a controlled-release mitochondrial protonophore (CRMP) that is functionally liver-targeted and promotes oxidation of hepatic triglycerides. Although we previously demonstrated that CRMP safely reverses hypertriglyceridemia, fatty liver, hepatic inflammation, and fibrosis in diet-induced rodent models of obesity, there remains a critical need to assess its safety and efficacy in a model highly relevant to humans. Here, we evaluated the impact of longer-term CRMP treatment on hepatic mitochondrial oxidation and on the reversal of hypertriglyceridemia, NAFLD, and insulin resistance in high-fat, fructose-fed cynomolgus macaques (n = 6) and spontaneously obese dysmetabolic rhesus macaques (n = 12). Using positional isotopomer nuclear magnetic resonance tracer analysis (PINTA), we demonstrated that acute CRMP treatment (single dose, 5 mg/kg) increased rates of hepatic mitochondrial fat oxidation by 40%. Six weeks of CRMP treatment reduced hepatic triglycerides in both nonhuman primate models independently of changes in body weight, food intake, body temperature, or adverse reactions. CRMP treatment was also associated with a 20 to 30% reduction in fasting plasma triglycerides and low-density lipoprotein (LDL)-cholesterol in dysmetabolic nonhuman primates. Oral administration of CRMP reduced endogenous glucose production by 18%, attributable to a 20% reduction in hepatic acetyl-coenzyme A (CoA) content [as assessed by whole-body β-hydroxybutyrate (β-OHB) turnover] and pyruvate carboxylase flux. Collectively, these studies provide proof-of-concept data to support the development of liver-targeted mitochondrial uncouplers for the treatment of metabolic syndrome in humans.


Width of keratinized gingiva and the health status of the supporting tissues around dental implants.
This cross-sectional study was performed to determine whether an association exists between the width of keratinized mucosa and the health of implant-supporting tissues. Data on 200 dental implants were collected. Periodontal parameters measured included Plaque Index, Gingival Index, width of keratinized mucosa, thickness of keratinized mucosa, radiographic bone level, and bleeding on probing. Statistical analysis was accomplished with the t test, Wilcoxon rank sum test, and logistic and linear regression models. Significance was established when P was less than .05. The mean Gingival Index score, Plaque Index score, and radiographic bone loss were significantly higher for those implants with a narrow zone (< 2 mm) of keratinized mucosa. Implants with a narrow zone of keratinized mucosa also were more likely to bleed upon probing, even after adjusting for Plaque Index, smoking, thickness of the gingiva, and time since implant placement (adjusted odds ratio, 2.37; 95% confidence interval, 1.04 to 5.83). Significant independent association also was found between the width of keratinized mucosa and radiographic bone loss in favor of wider zone of keratinized mucosa. Increased width of keratinized mucosa around implants is associated with lower mean alveolar bone loss and improved indices of soft tissue health.


ANGPTL8 requires ANGPTL3 to inhibit lipoprotein lipase and plasma triglyceride clearance.
Angiopoietin-like (ANGPTL)3 and ANGPTL8 are secreted proteins and inhibitors of LPL-mediated plasma triglyceride (TG) clearance. It is unclear how these two ANGPTL proteins interact to regulate LPL activity. ANGPTL3 inhibits LPL activity and increases serum TG independent of ANGPTL8. These effects are reversed with an ANGPTL3 blocking antibody. Here, we show that ANGPTL8, although it possesses a functional inhibitory motif, is inactive by itself and requires ANGPTL3 expression to inhibit LPL and increase plasma TG. Using a mutated form of ANGPTL3 that lacks LPL inhibitory activity, we demonstrate that ANGPTL3 activity is not required for its ability to activate ANGPTL8. Moreover, coexpression of ANGPTL3 and ANGPTL8 leads to a far more efficacious increase in TG in mice than ANGPTL3 alone, suggesting the major inhibitory activity of this complex derives from ANGPTL8. An antibody to the C terminus of ANGPTL8 reversed LPL inhibition by ANGPTL8 in the presence of ANGPTL3. The antibody did not disrupt the ANGPTL8:ANGPTL3 complex, but came in close proximity to the LPL inhibitory motif in the N terminus of ANGPTL8. Collectively, these data show that ANGPTL8 has a functional LPL inhibitory motif, but only inhibits LPL and increases plasma TG levels in mice in the presence of ANGPTL3.


Transcultural adaptation to Spanish of the instrument "Effectiveness of Auditory Rehabilitation" for the assessment of quality of life in patients using hearing aids.
It is becoming increasingly important to have reliable and valid questionnaires. This becomes especially important when evaluating hearing loss. the "Effectiveness of Auditory Rehabilitation" (EAR) questionnaire for the Spanish-speaking population. This instrument assesses quality of life and hearing aspects in patients using hearing aids. Cross-sectional validation study. A cultural adaptation through the use of English to Spanish translations and re-translations was carried out. The validity and reliability of the newly adapted instrument were evaluated. A total of 69 individuals (44 older adults and 25 younger adults) were examined. The pure-tone averages (PTA, 500, 1,000 and 2,000 Hz) were 47.3 dB HL and 47.1 dB HL for the left and right ears, respectively. The mean maximum speech discrimination in silence for monosyllables were 83.3% and 82.9% for the left and right ears, respectively. Internal consistency presented Cronbach alpha values of 0.85 and 0.77 for the internal and external dimensions, respectively. The intraclass correlation coefficients were 0.80 for the internal module and 0.85 for the external module. Construct validity reported a correlation coefficient of 0.71 at baseline and 0.76 at 3 months after the initial assessment for the internal module, and 0.62 at baseline and 0.74 at 3 months after the initial assessment for the external module. The size effects were 1.3 and 1.1 for the internal and external modules, respectively. The Spanish version of the EAR questionnaire seems to be a reliable and valid instrument. The evaluation of audiological aspects, as well as aspects relating to aesthetics and comfort are the main strengths of this instrument. Finally, the EAR scale is more sensitive to change than other scales.


[Comparative evaluation of different meningococcal group-specific erythrocyte diagnostic kits in passive hemagglutination test].
The comparative evaluation of the sensitivity and specificity of serogroup A, C, Y meningococcal antigenic preparations obtained by different methods was carried out by means of the passive hemagglutination test. In case of group 0 (I) human red blood cells sensitized with serogroup A and C vaccinal preparations obtained by Gotschlich's method (designated as A-1 and C-1) were used. In the other case formalin-treated sheep red blood cells sensitized with group-specific polysaccharides obtained by alcohol precipitation from the cultural fluid of group A, C and Y meningococci with subsequent heating (designated as A-2, C-2, Y) were used. Titrations with commercial immune rabbit sera showed that both variants of the antigenic preparations were similar in their specificity and sensitivity. In patients with the symptoms of meningitis the diagnostic titer was 1:40 for preparations A-1, C-1 and 1:80 for preparations A-2, C-2 and Y. The results of the examination of 164 patients (220 serum specimens) demonstrated that these preparations were of equal diagnostic value.


Development of Series of Affinity Tags in Streptomyces.
Streptomyces are of great biological and industrial significance due to their complex morphological development and ability to produce numerous secondary metabolites. However, the intrinsic biochemical mechanisms underlying morphogenesis and secondary metabolism are rarely revealed, partially because of the limited availability of the biochemical tools in Streptomyces. Here we provided series of integrative vectors with various affinity tags, including single tags 3×FLAG, 3×HA, 3×Strep-tag II, 18×His, 13×Myc, and dual tags, all of which were driven from a strong constitutive promoter ermEp*. Using a sigma factor SigT from S. coelicolor as a model, we successfully expressed and immuno-detected SigT fused with all tags. Moreover, after SigT was N-terminally tagged with 3×FLAG and C-terminally tagged with 18×His, we isolated SigT-interactive proteins from the S. coelicolor lysate based on the tandem affinity purification (TAP). Particularly, among the proteins purified, the SigT cognate anti-sigma factor RstA ranked the top with the most total independent spectra. These data suggested the feasibility of these affinity tags in Streptomyces, which will be widely employed to explore the biochemical mechanisms to further understand the dynamic and elaborate regulation in this genus.


Helicobacter pylori infection and dermatologic diseases.
Recent evidence suggests that Helicobacter pylori infections play a role in the pathogenesis of a variety of skin diseases. The best evidence for such a link is found for two diseases: chronic urticaria and immune thrombocytopenic purpura. Other diseases that have a purported, but not yet proven link to H. pylori are: cutaneous pruritus, Behçet's disease, nodular prurigo and lichen planus. Based on the current evidence for a relationship between H. pylori and chronic idiopathic thrombocytopenic purpura the European Helicobacter Study Group consensus 2007 recommended the eradication of Helicobacter pylori infection in affected patients. Lastly, single or few case reports have documented associations between Helicobacter pylori infection and rosacea, aphthous stomatitis, atopic dermatitis, alopecia areata, Schoenlein-Henoch purpura and Sjögren syndrome, but these are only descriptive in nature. Systematic studies examining the relationship between dermatologic entities and infection with H. pylori and documentation of the effect of H. pylori eradication are needed to further our understanding on this topic.


The amygdala is essential for the development of neuronal plasticity in the medial geniculate nucleus during auditory fear conditioning in rats.
The medial geniculate nucleus of the thalamus (MGN) and the basolateral complex of the amygdala (BLA) are critical components of the neural circuit that mediates auditory fear conditioning. Several studies indicate that neurons in both the MGN and BLA exhibit associative plasticity of spike firing during auditory fear conditioning. In the present study, we examined whether the development of plasticity in the MGN requires the BLA. Single units were recorded from chronic multichannel electrodes implanted in the medial division of the MGN of conscious and freely moving rats. Rats received auditory fear conditioning trials, which consisted of a white-noise conditional stimulus (CS) and a co-terminating footshock unconditional stimulus (US). Unpaired (sensitization) controls received the same number of trials as paired animals, but the CS and US were explicitly unpaired. Before fear conditioning, rats received either an intra-amygdala infusion of muscimol, a GABA(A) receptor agonist, to inactivate BLA neurons or an infusion of the saline vehicle. Auditory fear conditioning produced a substantial increase in both CS-elicited spike firing in the MGN and conditional freezing behavior in vehicle-treated rats receiving paired training. Muscimol inactivation of the BLA severely attenuated the development of both conditioning-related increases in CS-elicited spike firing in the MGN and conditional freezing to the auditory CS. Unpaired training did not yield increases in either CS-elicited spike firing or freezing to the tone CS. These results reveal that the BLA is essential to the development of plasticity in the auditory thalamus during fear conditioning.


Evaluation of the treatment guidelines, practices and outcomes of complicated severe acute malnutrition in children aged 0-59 months in sub-Saharan Africa: a study protocol for the SAMAC study.
in hospitals across Africa, the case fatality rates of severe acute malnutrition (SAM) have remained consistently high (over 20%), despite the existence of the WHO treatment guideline. This has been attributed to inconsistencies in the implementation of the WHO treatment guidelines in sub-Saharan African countries. In spite of this awareness, the SAM treatment guidelines adopted by various sub-Saharan African countries and hospitals are unknown. Knowledge of the exact treatment practices employed in the management of SAM in different hospitals in sub-Saharan Africa is not known. This study aims to investigate the admission criteria, in-patient treatment guidelines and practices and outcomes of complicated SAM in sub-Saharan African children aged 0-59 months. this is an observational study which involves the extraction of admission, treatment and discharge data from the medical records of infants and children aged 0-59 months diagnosed and treated for complicated SAM in sub-Saharan Africa. This information is being used to develop a comprehensive database on the treatment of complicated SAM across sub-Saharan Africa. Information on the national and hospital guidelines for the treatment of complicated SAM is also collected. results of this study will serve as a useful resource on the true reflection of the treatment of complicated SAM across sub-Saharan Africa and will provide valuable information for optimising SAM treatment. in order to advocate best practice and reduce SAM-related mortality in sub-Saharan Africa, the identification of the different diagnostic and treatment methods and respective outcomes across different hospitals and countries is imperative.


The Telemedicine for Patients With Inflammatory Bowel Disease (TELE-IBD) Clinical Trial: Qualitative Assessment of Participants' Perceptions.
Inflammatory bowel disease (IBD), comprising Crohn disease and ulcerative colitis, affects 1 to 3 million people in the United States. Telemedicine has shown promise in IBD. The objective of this study, telemedicine for patients with IBD (TELE-IBD), was to compare disease activity and quality of life (QoL) in a 1-year randomized clinical trial of IBD patients receiving telemedicine versus standard care. Treatment groups experienced improvements in disease activity and QoL, but there were no significant differences between groups. Study adherence to the text-based intervention was less than 80%, the targeted goal. To understand adherence to remote monitoring, the goal of this qualitative assessment was to obtain TELE-IBD trial participants' perceptions, including their recommendations for future monitoring. In this study, patients attending 3 tertiary referral centers with worsening IBD symptoms in the previous 2 years were eligible for randomization to remote monitoring via SMS text messages (short message service, SMS) every other week, weekly, or standard care. Participants (n=348) were evenly enrolled in the treatment groups, and 259 (74.4%) completed the study. For this study, a purposive sample of adherent (N=15) and nonadherent (N=14) patients was drawn from the TELE-IBD trial population. Adherence was defined as the completion of 80% (278/348) or more of the weekly or every other week self-assessments. Semistructured interviews conducted by phone surveyed (1) the strengths and benefits of TELE-IBD, (2) challenges associated with using TELE-IBD, and (3) how to improve the TELE-IBD intervention. Interviews were recorded, professionally transcribed, and coded based on a priori concepts and emergent themes with the aid of ATLAS.ti, version.7 qualitative data analysis software. Participants' discussions centered on 3 elements of the intervention: (1) self-assessment questions, (2) action plans, and (3) educational messages. Participants also commented on text-based platform, depression and adherence, TELE-IBD system in place of office visit, and their recommendations for future TELE-IBD systems. Adherent and nonadherent participants prefer a flexible system that is personalized, including targeted education messages, and they perceive the intervention as effective in facilitating IBD self-management. Participants identified clear benefits to the TELE-IBD system, including obtaining a better understanding of the disease process, monitoring their symptoms, and feeling connected to their health care provider. Participants' perceptions obtained in this qualitative study will assist in improving the TELE-IBD system to be more responsive to patients with IBD.


[Retinal and brain infarctions secondary to acute carotid thrombosis in ovarian hyperstimulation syndrome].
Ovarian hyperstimulation syndrome (OHSS) is an uncommon but potentially life-threatening iatrogenic condition that may appear following ovulation induction in the course of some fertility treatments. This may lead to further complications, some of which may be severe, such as thromboembolic events. Though rarely, it can therefore be a potential cause of stroke. We report the case of a 34-year old woman under ovulation induction treatment who developed retinal and brain infarctions secondary to internal carotid occlusion. Oral anticoagulation was administered and recovery was good in spite of the persistence of carotid occlusion in follow-up magnetic ressonance imaging- angiographies. This is the first case of carotid occlusion following an OHSS reported in Spain and the eighth one published in the literature. Current literature on cerebrovascular complications in OHSS is also briefly reviewed.


Variation of muscle tone in the human colon.
It was hypothesized that the human colon is able to relax or constrict to receive materials arriving from above or to hasten distal passage of contents. Dilatation is also a feature of several pathophysiological states and, therefore, the propensity of the colon to dilate might be important in disease. An electromechanical barostat was applied to the human colon, and changes in colonic tone were recorded in response to physiological perturbations. In 16 studies of 14 healthy volunteers, the colon was prepared for colonoscopy and a manometry-barostat assembly was positioned in the ascending (n = 5), transverse (n = 4), or descending (n = 7) colon. The influences of food and overnight sleep were recorded. The barostat continuously monitored, at a constant pressure, the volume of air within a highly compliant 10-cm bag. Changes in tone, as reflected by changes in bag volume, were usually unassociated with waves of intraluminal pressure recorded from adjacent manometric sites. Thus, the barostat revealed a motor phenomenon not readily apparent by conventional manometry. Food caused an immediate though slowly progressive increase in tone; however, bag volumes were greatest during overnight sleep and were decreased on waking. The barostat has the potential to explore another possibly important aspect of colonic function in humans.


Comparison among different classification systems regarding the pathological response of preoperative chemotherapy in relation to the long-term outcome.
Neoadjuvant chemotherapy (NAC) is increasingly used for operable disease. However there are several pathological response classification systems and the correlation between the pathological response to NAC according to each system and the patient outcome is still under debate. From 1998 to 2006, 370 primary breast cancer patients underwent curative surgical treatment after NAC containing both anthracycline and taxane at the National Cancer Center Hospital. We retrospectively evaluated the clinical and pathological response using the cTMN, Fisher's, Chevailler's, and the Japanese Breast Cancer Society classification systems (JBCS) respectively, and analyzed the correlation between each pathological response and disease free survival (DFS). Ninety-five (26%) patients had tumor recurrence. The five-year DFS according to Fisher's system was pCR, 80% and pINV, 63%. The five-year DFS according to Chevallier's system was Grade 1, 83%, Grade 2, 85%, Grade 3, 62%, and Grade 4, 65%. The five-year DFS according to the JBSC system was Grade 3, 77%, Grade 2, 68%, Grade 1a, 68%, Grade 1b, 58%, and Grade 0, 52%. None of the pathological response systems reached a statistically significant difference. In the classification by the post-treatment number of metastatic axillary lymph nodes, the 5-year DFS was n = 0, 86%; n = 1-3, 64%; n = 4-9, 44%; and n > 10 positive: 25% (P < .0001). In pathologically node negative patients, there were no significant differences in the DFS among all the classification systems. All three classifications analyzed were considered inadequate as the prognostic marker of the long-term outcome after NAC and further studies are warranted to optimize the prediction.


Comorbidity Patterns in Older Patients Undergoing Hip Fracture Surgery: A Comorbidity Network Analysis Study.
Comorbidity network analysis (CNA) is a technique in which mathematical graphs encode correlations (edges) among diseases (nodes) inferred from the disease co-occurrence data of a patient group. The present study applied this network-based approach to identifying comorbidity patterns in older patients undergoing hip fracture surgery. This was a retrospective observational cohort study using electronic health records (EHR). EHR data were extracted from the one University Health System in the southeast United States. The cohort included patients aged 65 and above who had a first-time low-energy traumatic hip fracture treated surgically between October 1, 2015 and December 31, 2018 (n = 1,171). Comorbidity includes 17 diagnoses classified by the Charlson Comorbidity Index. The CNA investigated the comorbid associations among 17 diagnoses. The association strength was quantified using the observed-to-expected ratio (OER). Several network centrality measures were used to examine the importance of nodes, namely degree, strength, closeness, and betweenness centrality. A cluster detection algorithm was employed to determine specific clusters of comorbidities. Twelve diseases were significantly interconnected in the network (OER > 1, p-value < .05). The most robust associations were between metastatic carcinoma and mild liver disease, myocardial infarction and congestive heart failure, and hemi/paraplegia and cerebrovascular disease (OER > 2.5). Cerebrovascular disease, congestive heart failure, and myocardial infarction were identified as the central diseases that co-occurred with numerous other diseases. Two distinct clusters were noted, and the largest cluster comprised 10 diseases, primarily encompassing cardiometabolic and cognitive disorders. The results highlight specific patient comorbidities that could be used to guide clinical assessment, management, and targeted interventions that improve hip fracture outcomes in this patient group.


Clinicopathologic Features and Prognostic Factors of Primary Cutaneous Melanoma: a Multicenter Study in Korea.
Malignant melanoma is a cutaneous malignancy with a high mortality rate and high potential for metastases. Detailed information on the clinicopathologic characteristics and prognostic factors of cutaneous melanoma is currently limited in Korea. This study aimed to identify the epidemiological and clinicopathologic characteristics of primary cutaneous melanoma in Korean patients, and to assess which prognostic variables could influence both the development of metastases in primary cutaneous melanoma and overall survival (OS). A total of 261 patients diagnosed with primary cutaneous melanoma in seven medical centers between 1997 and 2017 were retrospectively investigated with regard to clinical presentation, localization of the tumor, histopathologic subtype, and survival time. The nodular histologic subtype, ulceration, and Breslow thickness were significantly associated with the development of metastasis; and overweight and obesity (body mass index > 23) were significantly associated with increased Breslow thickness. The location of the metastases appeared to influence OS: brain metastases were associated with the highest risk of death, followed by gastrointestinal, lung, and extra-regional lymph node metastases. In this study, tumor thickness, nodular histologic subtype, and ulceration predicted metastatic spread of primary cutaneous melanoma. In addition, OS was associated with the location of metastases. Obesity was related to the prognosis of primary cutaneous melanoma. Clinicians should bear these findings in mind when forming a diagnosis because of the risk of a poor prognosis.


Road rage: relationships with borderline personality and driving citations.
The objectives of this study were to determine: (1) the prevalence of self-reported road rage in a primary care sample; (2) the relationship, if any, between road rage and borderline personality disorder (BPD); and (3) whether those with road rage have a greater prevalence of different types of driving citations compared to those without road rage. Using a consecutive, cross-sectional sample of primary care outpatients, we surveyed 419 individuals. The prevalence of self-reported road rage in this sample was 35.3%. BPD was significantly more prevalent among participants with road rage (24.8% vs. 9.8%). Compared to those without road rage, those with road rage reported statistically significantly higher numbers of different types of driving citations, including moving and non-moving violations, as well as having had a driver's license suspended. There were no differences between the groups with regard to vehicular crashes or driving while intoxicated. About one-third of individuals reported road rage. The prevalence of BPD was significantly higher among those with road rage compared to those without road rage, and is likely to be one of the contributory variables to reckless driving. Individuals who reported road rage appear to be less disciplined drivers and are subject to more types of driving citations, although they do not report greater rates of vehicular crashes or driving while intoxicated.


Mortality and chronic obstructive pulmonary disease in patients treated with endovascular revascularization of the infra-inguinal lower limb arteries from retrograde access.
In this trial, our objective was to evaluate the relationship between long-term clinical outcomes in patients with peripheral arterial disease (PAD) treated with retrograde endovascular recanalization (ER) of chronic total occlusions (CTOs) regarding the infra-inguinal lower limb arteries and chronic obstructive pulmonary disease (COPD). A total of 834 consecutive subjects were enrolled in the study. The mean age was 67.8±10.6 years (62.6% males). COPD was diagnosed in 98 patients (11.7%). The infra-inguinal location included the deep, superficial and common femoral artery, popliteal artery or below the knee arteries. During follow-up, we evaluated major adverse cardiac and cerebrovascular events (MACCE) and major adverse limb events (MALE). MACCE was considered as death, stroke/transient ischemic attack, myocardial infarction, percutaneous coronary intervention or coronary artery bypass grafting operation, while MALE regarded amputation, target lesion re-intervention, target vessel re-intervention and surgical action. The mean follow-up was 1,144.9±664.3 days and the interquartile range was 1,110.5 (504.5-1,734.7). Data were collected between 2006 and 2016. We noticed significant differences in death rates among the COPD and non-COPD groups. The cumulative number of events (deaths) was 12.2%, 17.3%, 18.4%, 22.4%, 23.5%, 23.5% and 23.5% in the COPD group and 6.1%, 7.5%, 10.5%, 11.3%, 11.4% 11.5% and 11.5% in the non-COPD group after 1, 2, 3, 4, 5, 6 and 7 years of follow-up, and was notably greater for COPD (P=0.0007). Patients with COPD and PAD treated with the ER and retrograde approach due to CTOs are related to higher mortality than non-COPD patients.


Drug-induced QT-interval prolongation and proarrhythmic risk in the treatment of atrial arrhythmias.
Despite the large number of available antiarrhythmic agents, significant QT-interval prolongation and risk of severe proarrhythmia, including torsade de pointes, limit pharmacological opportunities in the management of atrial arrhythmias. The risk of proarrhythmia has been demonstrated in class I and class III drugs, but significant variability has been observed between agents of the same class. Electrophysiological drug effects found to be important in the etiology of proarrhythmia include QT-interval prolongation through selective blockade of the delayed rectifying potassium current (I(Kr)), early afterdepolarizations, transmural dispersion of repolarization, and a reverse rate dependence. Interestingly, less proarrhythmic potential is seen or anticipated with agents that are able to block multiple ion channels and those with atrial selectivity, despite moderate QT prolongation. This observation has helped steer the development of newer drugs, with some promising preliminary results.