Longstanding presence of HIV-2 infection in Guinea-Bissau (West Africa).
We have retrospectively studied the seroprevalence of the human immunodeficiency virus (HIV) in Guinea-Bissau in a sample of sera collected from the whole country in 1980. We tested a total of 1248 individuals and found 11 individuals who were seropositive for HIV-2 but there were no HIV-1 seropositive samples. The mean age of the HIV-2 seropositive people was significantly higher than the age of the seronegative individuals. In the different areas surveyed, the HIV-2 seroprevalence ranged from 0 to 2.5%. A central region of the country, grossly centred in the capital city of Bissau, presented the highest prevalence of HIV-2 seropositivity (>2%), which contrasts with its virtual absence from the more remote rural areas located near the borders with the neighbouring countries. The overall seroprevalence found for HIV-2 in this study is 0.9% (1.8%, when considering the adult seroprevalence only), which proves that the virus was definitely circulating in Guinea-Bissau at the beginning of the 1980s.


Hospital esophageal cancer resection volume does not predict patient mortality risk.
Insurers often seek to direct esophageal cancer patients to hospitals with high volumes of esophageal resection. However, controversy exists regarding the strength and validity of evidence for the volume-outcome association. The purpose of this study was to evaluate the volume-outcome relationship for esophageal cancer resection in a large population dataset and to compare 3alternative techniques for measuring the effect of volume. Esophageal cancer resection patients were identified in the 2007 Nationwide Inpatient Sample. Hospital volume was measured using a continuous linear function, a nonlinear function using restricted cubic splines, and using quintiles of volume. The statistical significance of the relationship between hospital volume and mortality risk was assessed, and adjusted for patient age, for comorbid disease, and for correlated events within hospitals. A total of 6,248 esophageal cancer resection patients from 217 hospitals were identified. All 3 models demonstrated excellent performance characteristics (C index=0.94, Nagelkerke R2=0.62). However, no significant association was demonstrated between hospital procedure volume and in-hospital mortality in any model. Important predictors of mortality included age, hypertension, weight loss, and peripheral vascular disease (p<0.001). Esophageal cancer resection volume is not a significant predictor of mortality and should not be used as a proxy measure for surgical quality.


Prevalence of excessive daytime sleepiness among patients with atopic dermatitis.
Sleep disorders have received considerable attention from the dermatologic community, especially in patients with atopic dermatitis. We confirmed that excessive daytime sleepiness is a common problem among patients with atopic dermatitis, with it affecting 46.1% of the evaluated subjects. We demonstrated that excessive daytime sleepiness was also significantly associated with disease severity in patients with atopic dermatitis and had a detrimental impact on quality of life, well-being and burden. These findings suggest the importance of careful assessment and the management of sleep disorders in atopic dermatitis patients. Intervention programs for sleep disorders in this population might help to improve their quality of life and their well-being.


Genetically engineered E. coli invade epithelial cells and transfer their genetic cargo into the cells: an approach to a gene delivery system.
Despite advances in gene therapy, the lack of safe and efficient gene delivery systems limited the clinical effectiveness of gene therapy. Due to the inherent potential of bacteria, they can be considered as a good option for the gene transfer system. This study aimed to create a genetically engineered bacterium capable of entering epithelial cells and transferring its genetic cargo to the cell's cytoplasm, eventually expressing the gene of interest in the cell. The invasin (inv) gene from Yersinia pseudotuberculosis and the listeriolysin (hlyA) gene from Listeria monocytogenes were isolated by PCR assay and inserted into a pACYCDuet-1 vector. The recombinant plasmid was then transformed into E. coli strain BL21. Subsequently, pEGFP-C1 plasmids containing a CMV promoter were transformed into the engineered bacteria. Finally, the engineered bacteria containing the reporter genes were incubated with the HeLa and LNCaP cell lines. Fluorescence microscopy, flow cytometry, and TEM were used to monitor bacterial entry into the cells and gene expression. We used native E. coli strain BL21 as a control. A fluorescence microscope showed that, in contrast to the control group, the manipulated E. coli were able to penetrate the cells and transport the plasmid pEGFP-C1 to the target cells. Flow cytometry also showed fluorescence intensity of 54.7% in HeLa cells and 71% in LNCaP cells, respectively. In addition, electron micrographs revealed the presence of bacteria in the cell endosomes and in the cytoplasm of the cells. This study shows that genetically engineered E. coli can enter cells, transport cargo into cells, and induce gene expression in the target cell. In addition, flow cytometry shows that the gene transfer efficiency was sufficient for protein expression.


New analytical approach for neutron beam-hardening correction.
In neutron imaging, the beam-hardening effect has a significant effect on quantitative and qualitative image interpretation. This study aims to propose a linearization method for beam-hardening correction. The proposed method is based on a new analytical approach establishing the attenuation coefficient as a function of neutron energy. Spectrum energy shift due to beam hardening is studied on the basis of Monte Carlo N-Particle (MCNP) simulated data and the analytical data. Good agreement between MCNP and analytical values has been found. Indeed, the beam-hardening effect is well supported in the proposed method. A correction procedure is developed to correct the errors of beam-hardening effect in neutron transmission, and therefore for projection data correction. The effectiveness of this procedure is determined by its application in correcting reconstructed images.


Novel dual-function GC/MS aided ultrasound-assisted hydrodistillation for the valorization of Citrus sinensis by-products: phytochemical analysis and anti-bacterial activities.
A huge-amount of citrus by-products is being wasted every-year. There is a high-need to utilize these by-products with high-efficiency. This study focuses on the essential oil (EO) isolation from the zest of Citrus sinensis (CS) by-products, using a novel dual-function gas-chromatography mass-spectrometry optimized ultrasound-assisted hydrodistillation-prototype (DF-GC/MS-HUS). The CS-EO was GC-analyzed by MS-detector (GC/MS) and optimized by flame-ionization detector (GC/FID). Ultrasound-assisted hydrodistillation (HUS) had a dual-function in CS-EO isolation by utilizing an adequate-energy to break-open the oil-containing glands, and by functioning-as a dispersing-agent to emulsify the organic-phase. The most effective DF-GC/MS-HUS optimized-conditions were isolation under 38 °C and 10 min of 28.9 Hz sonication. The main-components of CS-EO were limonene, β-myrcene, and α-pinene (81.32%, 7.55%, and 4.20%) in prototype, compared to (60.23%, 5.33%, and 2.10%) in the conventional-method, respectively. The prototype CS-EO showed natural antibacterial-potentials, and inhibited the bio-film formation by Staphylococcus aureus, Listeria monocytogenes, and E. coli more-potent than the conventional-method. Compared to conventional-method, the prototype-method decreased the isolation-time by 83.3%, lowered energy-consumption, without carbon-dioxide production, by reducing isolation-temperatures by more-than half, which protected the thermolabile-components, and increased the quantity by 2514-folds, and improved the quality of CE-EO composition and its antibacterial-potentials. Therefore, the DF-GC/MS-HUS prototype method is considered a novel green-technique that minimized the energy-utilization with higher-efficiency.


Drone and Other Hobbyist Aircraft Injuries Seen in U.S. Emergency Departments, 2010-2017.
Recreational radio-controlled hobbyist aircraft-particularly "drones"-have become increasingly popular in the last decade. The purpose of this study is to describe injuries associated with hobbyist drones and compare them with injuries associated with other hobbyist aircraft. In this 2018 cross-sectional analysis of National Electronic Injury Surveillance System data for 2010-2017, case narrative fields were searched to identify emergency department visits related to hobbyist aircraft injuries. The incidence of hobbyist aircraft injuries was estimated, and summary statistics, chi-square tests, and t-tests were used to describe and compare the demographic and clinical characteristics of drone and other hobbyist aircraft-related cases. An estimated 12,842 hobbyist aircraft injuries presented to U.S. emergency departments during 2010-2017. An increased incidence attributable to drone-related injuries emerged in 2015. Overall, most injuries involved male patients aged 50 years on average. Propeller injuries were the leading mechanism. An estimated 270 patients required hospital admission. Patients injured by drones were younger (mean, 34 years vs 58 years; p<0.001) and more likely to be female than patients injured by hobbyist planes. Drone-related injuries were more likely than plane-related injuries to result from blunt trauma (e.g., being struck or falling during aircraft retrieval; 40.5% vs 7.9%, p<0.001). Helicopter-related injuries more closely resembled drone-related injuries than plane-related injuries. Hobbyist aircraft-related injuries are increasing, particularly drone-related injuries. Tailored injury prevention measures and product safety materials are needed to address all hobbyist aircraft-related injuries, with a particular focus on drone-related injury prevention measures.


How far should guidelines be followed?
Clinical guidelines irreparably characterize contemporary medicine. Referring to guidelines has become routine in both medical literature and daily clinical activity, with the risk of becoming the only-or at least the main-inspiring element of the physician's behaviour. This would lead to the mortification of clinical reasoning, a term that is synonymous with an individualized approach, focused on the single patient, and not on a population.


Modulation of the glutamatergic receptors (AMPA and NMDA) and of glutamate vesicular transporter 2 in the rat facial nucleus after axotomy.
Facial nerve axotomy is a good model for studying neuronal plasticity and regeneration in the peripheral nervous system. We investigated in the rat the effect of axotomy on the different subunits of excitatory glutamatergic AMPA (GLuR1-4), NMDA (NR1, NR2A-D) receptors, post-synaptic density 95, vesicular glutamate transporter 2, beta catenin and cadherin. mRNA levels and/or protein production were analyzed 1, 3, 8, 30 and 60 days after facial nerve axotomy by in situ hybridization and immunohistofluorescence. mRNAs coding for the GLuR2-4, NR1, NR2A, B, D subunits of glutamatergic receptors and for post-synaptic density 95, were less abundant after axotomy. The decrease began as early as 1 or 3 days after axotomy; the mRNAs levels were lowest 8 days post-lesion, and returned to normal or near normal 60 days after the lesion. The NR2C subunit mRNAs were not detected in either lesioned or intact facial nuclei. Immunohistochemistry using specific antibodies against GLuR2-3 subunits and against NR1 confirmed this down-regulation. There was also a large decrease in vesicular glutamate transporter 2 immunostaining in the axotomized facial nuclei at early stages following facial nerve section. In contrast, no decrease of NR2A subunit and of post-synaptic density 95 could be detected at any time following the lesion. beta Catenin and cadherin immunoreactivity pattern changed around the cell body of facial motoneuron by day 3 after axotomy, and then, tends to recover at day post-lesion 60 days. Therefore, our results suggest a high correlation between restoration of nerve/muscle synaptic contact, synaptic structure and function in facial nuclei. To investigate the mechanisms involved in the change of expression of these proteins following axotomy, the facial nerve was perfused with tetrodotoxin for 8 days. The blockade of action potential significantly decreased GLuR2-3, NR1and NR2A mRNAs in the ipsilateral facial nuclei. Thus, axotomy-induced changes in mRNA abundance seemed to depend partly on disruption of activity.


Expression pattern of neuronal nitric oxide synthase in embryonic zebrafish.
Nitric oxide synthase catalyzes the production of nitric oxide, a multifunctional signaling molecule that affects diverse aspects of animal physiology such as cell proliferation, differentiation, neurotransmission and apoptosis. Here, we report the cloning and expression pattern of the zebrafish nnos. This gene was mapped to zebrafish linkage group 5. The spatial and temporal expression pattern of nnos in embryonic zebrafish was analyzed by whole mount in situ hybridization. nnos is widely expressed in the embryonic nervous system. Expression of zebrafish nnos appeared at 16 hours post-fertilization in the hypothalamus and by 3 days post-fertilization was present in discrete locations in the central nervous system as well as the enteric nervous system. Some nnos-positive cells were mapped to specific locations in the central nervous system using tyrosine hydroxylase as a specific marker indicating that nnos transcripts were present in the olfactory bulb, anterior diencephalon, posterior hypothalamus and anterior hindbrain.


Only extra-high dose of ketamine affects l-glutamate-induced intracellular Ca(2+) elevation and neurotoxicity.
The neurotoxic effects of anesthetics on the developing brain are a concern. Although most of the anesthetics are GABAA agonists or NMDA antagonists, the differences in these effects on prospective glutamate-neurotoxicity in the brain is not fully understood. We examined the degree of L-glutamate-induced intracellular calcium ([Ca(2+)]i) elevation and neurotoxicity in neurons exposed to anesthetics. Primary cortical neurons from E17 rats were preincubated with 1-100 μM of ketamine or thiopental sodium (TPS) for the first 72 h of culturing. Two weeks later, the neurons were exposed to L-glutamate. The extent of glutamate toxicity was evaluated using Ca(2+)-imaging and morphological experiments. Preincubation with 100 μM ketamine but not with other concentrations of ketamine and TPS for the first 72 h in culture significantly enhanced L-glutamate-induced [Ca(2+)]i elevation 2 weeks later. Morphology experiments showed that vulnerability to L-glutamate-mediated neurotoxicity was only altered in neurons preincubated with 100 μM ketamine but not with TPS. Although preincubation with high concentration of ketamine showed enhancement of L-glutamate-induced [Ca(2+)]i elevation 2 weeks later, long-term exposure to TPS or ketamine at clinical doses during developmental periods may not result in a dose-related potentiation of exogenous glutamate-induced neurotoxicity, once the intravenous anesthetics are discontinued.


Creation of a protective space between the rectum and prostate prior to prostate radiotherapy using a hydrogel spacer.
The placement of a polyethylene glycol (PEG) hydrogel spacer is a recently developed technique employed to reduce the radiation dose administered to the rectum during prostate radiotherapy. This procedure has been adopted by urologists and radiation oncologists involved in transperineal prostate biopsy and brachytherapy, and more recently by radiologists with experience in transperineal prostate procedures. Radiologists should be familiar with the product, which may be encountered on computed tomography (CT) or magnetic resonance imaging (MRI). Radiologists may wish to become involved in the delivery of this increasingly utilised procedure. This review familiarises radiologists with the technique and risks and benefits of the use of transperineal delivery of hydrogel spacers with imaging examples.


Bone resorption by isolated chick osteoclasts in culture is stimulated by murine spleen cell supernatant fluids (osteoclast-activating factor) and inhibited by calcitonin and prostaglandin E2.
The question of whether any of the agents known to activate bone resorption in vivo or in organ cultures acts directly on the osteoclast or via intermediate target cells that secondarily secrete locally paracrine factors is important for our understanding of bone remodeling. In an attempt to clarify this issue for some of the agents, we have taken advantage of the recent progress in obtaining and culturing relatively pure populations of osteoclasts. We performed an in vitro bone-resorbing assay in which isolated and partially purified chick osteoclasts were cultured on devitalized, paired and standardized bone disks prepared from rat calvaria prelabeled with both 45Ca and 3H-proline. Some of the isolated osteoclasts attached to the devitalized bone matrix, formed a ruffled border, and acidified the bone-resorbing compartment that they established with the matrix, thereby indicating that they resorbed bone in a physiologic manner. Salmon calcitonin added to these cultures (0.3 U/ml = 60 ng/ml) and prostaglandin E2 (PGE2) (10(-6) M) inhibited both basal and stimulated 45Ca and 3H-proline release. Neither parathyroid hormone (PTH) 1-34 (1 U/ml), 1,25-(OH)2-D3 (10(-8) and 10(-9) M), nor interleukin 1 (IL-1) (purified from P388D1 macrophage culture supernatant fluids or recombinant murine IL-1-alpha) (100 ng/ml) stimulated bone resorption in these cultures. In contrast, supernatant fluids from concanavalin A (Con-A)-activated murine spleen cell cultures (murine osteoclast-activating factor; OAF) consistently and significantly induced a 3- to 5-fold stimulation of bone resorption in this system.


Presumed autoimmune corneal endotheliopathy.
I reviewed 20 previously published cases of presumed autoimmune corneal endotheliopathy. The disease appeared clinically with stromal edema and a slowly migrating line of keratic precipitates. All patients had acute stromal edema and keratic precipitates, and decreased visual acuity. Anterior chamber cells were noted in 11 patients. Inflammatory processes, such as pars planitis and iritis, and intraocular lens implantation were present in 13 patients.


Interpersonal trauma exposure and startle reactivity to uncertain threat in individuals with alcohol use disorder.
Exposure to interpersonal trauma is highly prevalent within individuals with alcohol use disorder (AUD); however, the mechanisms underlying the pathway between trauma exposure and AUD are unclear. Preliminary evidence suggests that heightened reactivity to threats that are uncertain (U-threat) may characterize individuals with AUD and interpersonal trauma exposure and contribute to alcohol abuse within this subgroup of individuals; however, this hypothesis has yet to be tested. The aim of the study was to examine whether heightened reactivity to U-threat characterizes individuals with AUD and a history of interpersonal trauma. Specifically, the study compared defensive reactivity to U-threat (and predictable threat [P-threat]) in those with: 1) AUD and a history of interpersonal trauma (AUD + Trauma); 2) AUD and no history of interpersonal trauma (AUD-Trauma); and 3) matched controls. Participants (N = 77) completed a well-validated threat-of-shock task and startle eyeblink potentiation was collected as an index of aversive responding. Results revealed a group by threat condition interaction (F[4, 142] = 3.17, p = 0.03; ηG2 = 0.08) such that individuals with AUD + Trauma exhibited greater startle reactivity to U-threat, but not P-threat, compared with individuals with AUD-Trauma and controls (who did not differ from each other). The findings were significant even when controlling for current anxiety and depression symptoms. Within individuals with AUD, those with a history of interpersonal trauma exposure may be a neurobiologically unique subtype characterized by exaggerated U-threat reactivity and high levels of anticipatory anxiety. Reactivity to U-threat may be a promising alcohol use prevention and intervention target for trauma-exposed individuals.


A prospective study of growth and rupture risk of small-to-moderate size ascending aortic aneurysms.
The natural history of small-to-moderate size ascending aortic aneurysms is poorly understood. To follow these patients better, we have developed a method to objectively and reproducibly measure ascending aortic volume on the basis of gated contrast computed tomography scans. From 2009 to 2011, 507 patients were referred for management of ascending aortic aneurysms. A total of 232 patients (46%) with small-to-moderate size aneurysms who did not have compelling indications for operation had measurement(s) of ascending aortic and total aortic volume; 166 patients had more than 1 scan, allowing measurement of growth. A total of 66 patients admitted to the emergency department without ascending aortic pathology served as a reference group. None of the patients experienced rupture, dissection, or death; 3 patients ultimately underwent operation. Ascending aortic volume and volume/total aortic volume differed for the surveillance and reference groups: 132.8 ± 39.4 mL versus 78.0 ± 24.5 mL; 38.3% ± 7.4% versus 29.1% ± 3.9%, respectively (both P < .001). Diameters at the sinotubular junction and mid-ascending aortic were 4.1 ± 0.6 cm and 4.4 ± 0.6 cm, respectively, for the surveillance group and 3.0 ± 0.4 cm and 3.2 ± 0.4 cm, respectively, for controls. The increase in ascending aortic volume was 0.95 ± 4.5 mL/year and 0.73% ± 3.7%/year (P = .007 and .012, respectively). Analysis of risk factors for ascending aortic growth revealed only the use of antithrombotic medication as possibly significant. Computed tomography volume measurements provide an objective method for ascertaining aortic size and monitoring expansion. Patients with small-to-moderate ascending aortic aneurysms who are carefully followed and managed appropriately have slow aneurysm growth and a small risk of rupture or dissection. Annual computed tomography screening may not be indicated, and elective resection-absent other surgical indications-is not necessary. The rupture/dissection risk for even larger aneurysms in carefully followed patients may be lower than currently believed.


Serum dual-specificity phosphatase 1 reflects decreased exacerbation risk, correlates with less advanced exacerbation severity and lower inflammatory cytokines in children with asthma.
It is as fact that dual-specificity phosphatase 1 (DUSP1) regulates the T cell activation, pro-allergic response, and inflammation to engage with the pathogenesis of asthma, but its clinical role in children with asthma is unclear. The present study aimed to explore the expression of DUSP1, its association with exacerbation risk, severity, and inflammatory cytokines in children with asthma. Around 52 children with asthma-exacerbation, 50 children in asthma-remission, and 50 healthy children were chosen for the study. The serum levels of DUSP1, as well as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-17 were detected by the enzyme-linked immunosorbent assay. The levels of DUSP1 was the highest in healthy children (median (IQR)=34.305 (25.892- 43.693) ng/mL), the second highest in children in asthma-remission (median (IQR)=21.471 (18.581-27.934) ng/mL), and the lowest in children with asthma-exacerbation (median (IQR)=13.982 (7.901-21.624) ng/mL) (P<0.001). At the same time, DUSP1 was also related to decreased asthma risk with area under curve (AUC) (95%CI) of 0.847 (0.780-0.914), and correlated with its lower exacerbation risk with AUC (95%CI) of 0.755 (0.661-0.849). Besides, DUSP1 was negatively linked with exacerbation severity (rs =-0.338, P=0.014), immunoglobulin E (rs =-0.277, P=0.047), TNF-α (rs =-0.423, P=0.002), IL-1β (rs =-0.389, P=0.004), and IL-17 (rs =-0.293, P=0.035), but not related with other disease features in children with asthma-exacerbation. Meanwhile, DUSP1 was only negatively associated with TNF-α (rs=-0.300, P=0.034) and IL-1β (rs =-0.309, P=0.029) in children in asthma-remission. However, no correlation was found in DUSP1 with inflammatory cytokines or other disease features in healthy children (all P>0.05). DUSP1 reflects the reduced exacerbation risk, and associates with lower exacerbation severity and inflammatory cytokines in children with asthma-exacerbation; it also associates with inflammatory cytokines in children in asthma-remission. These findings suggest that DUSP1 may help to improve the management of asthmatic children.


Ultrasonic measurements of two-component lipid bilayer suspensions.
Two-component lipid bilayers of dipalmitoylphosphatidylcholine and dimyristoylphosphatidylcholine were studied by measuring ultrasonic velocity and absorption at 3 MHz. The phase diagram of the two-component lipid bilayers is discussed based upon the transition anomalies of the ultrasonic velocity as well as absorption, and it is suggested that this binary system has two critical points. The bulk modulus of lipid bilayers was determined from the ultrasonic velocity to be (2.2-3.0) x 10(10) dyne/cm2, whereas the bulk viscosity calculated from the absorption was 10-20 P except for the transition regions.


MyD88S, a splice variant of MyD88, differentially modulates NF-kappaB- and AP-1-dependent gene expression.
MyD88 is an adapter protein that is involved in Toll-like receptor (TLR)- and interleukin-1 receptor (IL-1R)-induced activation of nuclear factor-kappaB (NF-kappaB) and c-Jun N-terminal kinase (JNK). By directly binding IL-1R-associated kinase (IRAK)-1 and IRAK-4, MyD88 serves as a bridging protein, enabling IRAK-4-induced IRAK-1 phosphorylation. We previously identified a lipopolysaccharide-inducible splice variant of MyD88, MyD88(S), which specifically prevents the recruitment of IRAK-4 into the IL-1R complex and thus inhibits IRAK-4-mediated IRAK-1 phosphorylation. MyD88(S) is not able to activate NF-kappaB, and in contrast functions as a dominant negative inhibitor of TLR/IL-1R-induced NF-kappaB activation. Unexpectedly, we here demonstrate that MyD88(S) still allows JNK phosphorylation and activator protein (AP)-1-dependent reporter gene induction upon overexpression in HEK293T cells. These observations indicate that NF-kappaB and JNK activation pathways can already diverge at the level of MyD88. Moreover, the regulated expression of a MyD88 splice variant which specifically interferes with NF-kappaB- but not AP-1-dependent gene expression implies an important role for alternative splicing in the fine-tuning of TLR/IL-1R responses.


Oscillatory axial banding of particles suspended in a rotating fluid.
A nonviscous fluid, completely filling a tube rotating about its horizontal axis, contains a suspension of macroscopic particles. The particles are observed to distribute themselves spontaneously in bands distributed periodically along the axis, with a band separation dependent only on the tube radius and length. In many cases, the bands oscillate periodically between two interleaving patterns. We explain this banding phenomenon as arising from the excitation of inertial standing waves in the rotating fluid.


[Dependence of the radioprotective effect of beta-mercaptoethylamine on the thiol level of the outer cell membrane].
In experiments with Ehrlich ascites tumor cells with the use of a specific thiol blocker, 6,6'-dithiodinicotinic acid, it was shown that thiols of a cell plasmic membrane are necessary for the radioprotective effect of mercaptoethylamine to be realized.


Conformationally restricted analogues of nicotine and anabasine.
A series of conformationally restricted analogues of nicotine has been synthesized and evaluated as agonists of neuronal acetylcholine receptors. Compound 2 (SIB-1663), which selectively activated human recombinant alpha 2 beta 4 and alpha 4 beta 4 nAChRs, was shown to be active in animal models of Parkinson's disease and pain.


Conjoint Feature Representation of GO and Protein Sequence for PPI Prediction Based on an Inception RNN Attention Network.
Protein-protein interactions (PPIs) are pivotal for cellular functions and biological processes. In the past years, computational methods using amino acid sequences and gene ontology (GO) annotations of proteins for prioritizing PPIs have provided important references for biological experiments in the wet lab. Despite the current success, sequence information and ontological annotation in semantic representation have not been integrated into current methods. We propose a deep-learning-based PPI prediction methodology conjointly featuring sequence information and GO annotation. First, we adopt a word-embedding tool, the NCBI-blueBERT model pre-trained on PubMed, to map the GO terms into their semantic vectors. Then, the GO semantic vectors and protein sequence vector serve as the input of the proposed inception recurrent neural network (RNN) attention network (IRAN). The IRAN captures the spatial relationship and the potential sequential feature of the protein sequence and ontological annotation semantics. The extensive experimental results on 12 benchmarks demonstrate that our method achieves superiority over state-of-the-art baselines. In the yeast dataset of a binary PPI prediction, our method improved the performance with the Matthews correlation coefficient increasing from 94.2% to 98.2% and the accuracy from 97.1% to 98.2%. The analogous results were also obtained in other comparison evaluations.


Targeting EZH2 for cancer therapy: From current progress to novel strategies.
EZH2, the catalytic subunit of PRC2, catalyzes histone H3 lysine 27 (H3K27) trimethylation to induce the agglutination of chromosomes and in turn represses the transcription of the target genes. Numerous reports indicate that EZH2 is overexpressed in a variety of malignant tumor tissues. Therefore, targeting EZH2 protein is a promising strategy for cancer treatment. So far, many small molecule EZH2 specific inhibitors have entered clinical trials, but many of them harbored limited clinical efficacy. New technologies and methods are imperative to enhance the anticancer activity of EZH2. In this review, the structure and biological functions of EZH2 protein will be reviewed. The internal relationship between EZH2 and various diseases will be expounded. The development status of specific inhibitors for EZH2, and the latest progress of new strategies such as drug combination, dual-target inhibitors, targeted protein degradation technology and protein-protein interactions (PPI) inhibitors will be emphatically summarized and analyzed.


An integrated course in pain management and palliative care bridging the basic sciences and pharmacy practice.
To describe the development of an integrated pain and palliative care course and to investigate the long-term effectiveness of the course during doctor of pharmacy (PharmD) students' advanced pharmacy practice experiences (APPEs) and in their practice after graduation. Roseman University College of Pharmacy faculty developed a 3-week elective course in pain and palliative care by integrating relevant clinical and pharmaceutical sciences. Instructional strategies included lectures, team and individual activities, case studies, and student presentations. Students who participated in the course in 2010 and 2011 were surveyed anonymously to gain their perception about the class as well as the utility of the course during their APPEs and in their everyday practice. Traditional and nontraditional assessment of students confirmed that the learning outcomes objectives were achieved. Students taking the integrated course on pain management and palliative care achieved mastery of the learning outcome objectives. Surveys of students and practicing pharmacists who completed the course showed that the learning experience as well as retention was improved with the integrated mode of teaching. Integrating basic and clinical sciences in therapeutic courses is an effective learning strategy.


"Everybody in this room can understand": A qualitative exploration of peer support during residency training.
Though peer support groups are often utilized during residency training, the dynamics, content, and impact of social support offered through peer support are poorly understood. We explored trainee perceptions of the benefits, drawbacks, and optimal membership and facilitation of peer support groups. After engaging in a peer support program at an emergency medicine residency program, 15 residents and 4 group facilitators participated in four focus groups in 2018. Interview questions explored the dynamics of group interactions, types of support offered, and psychological impacts of participation. The authors conducted a reflexive thematic analysis of data, performing iterative coding and organization of interview transcripts. Discussions with experienced senior residents and alumni normalized residents' workplace struggles and provided them with insights into the trajectory of their residency experiences. Vulnerable group dialogue was enhanced by the use of "insider" participants; however, residents acknowledged the potential contributions of mental health professionals. Though groups occasionally utilized maladaptive coping strategies and lacked actual solutions, they also enhanced residents' sense of belonging, willingness to share personal struggles, and ability to "reset" in the clinical environment. Participants offered insights into the benefits and drawbacks of peer support as well as optimal peer group composition and facilitation. Support groups may be more effective if they engage a complementary model of alumni and pre-briefed psychologist facilitators, avoid fatalism, and aim to foster intimate connections among residents. These findings can inform the development of future initiatives aiming to create a safe space for trainees to discuss workplace stressors.


Rabbit MHC antigens: occurrence of non-beta-2-microglobulin-associated class I molecules.
Two monoclonal antibodies, L12/36 and L13/112, prepared from spleens of BALB/c mice immunized with extracts of the rabbit lymphoid cell line RL-5, precipitate a 42,000 mol. wt molecule from detergent lysates of this cell line. This molecule is not associated with beta-2-microglobulin (beta 2m) and has been shown by sequential precipitation experiments to be antigenically distinct from the population of class I rabbit MHC (RLA) molecules that is associated with beta 2m. In spite of this antigenic difference, amino acid sequence analyses indicate that the RLA heavy chain precipitated with anti-beta 2m and that precipitated with the monoclonal antibodies, have identical N-terminal sequences. The sequence determined to position 36 is GSHSMRYFYTSVSRPGLGXPRFIIVGYVXXTXFVRF. The isoleucine assigned to position 24 is the first species-specific residue found for RLA class I molecules. Analysis of the beta 2m associated and non-associated molecules by two-dimensional gel electrophoresis revealed no differences between the RLA heavy chains. Differences in the subcellular locations of the determinants were indicated by fluorescence microscopy and confirmed by immunoelectron microscopy. It was shown that the specificity recognized by the monoclonal antibodies is principally located on the cytoplasmic face of the plasma membrane whereas the majority of anti-beta 2m reactive specificities are on the extracellular side of the cell membrane.


The evolution of relapse of adult T cell acute lymphoblastic leukemia.
Adult T cell acute lymphoblastic leukemia (T-ALL) is a rare disease that affects less than 10 individuals in one million. It has been less studied than its cognate pediatric malignancy, which is more prevalent. A higher percentage of the adult patients relapse, compared to children. It is thus essential to study the mechanisms of relapse of adult T-ALL cases. We profile whole-genome somatic mutations of 19 primary T-ALLs from adult patients and the corresponding relapse malignancies and analyze their evolution upon treatment in comparison with 238 pediatric and young adult ALL cases. We compare the mutational processes and driver mutations active in primary and relapse adult T-ALLs with those of pediatric patients. A precise estimation of clock-like mutations in leukemic cells shows that the emergence of the relapse clone occurs several months before the diagnosis of the primary T-ALL. Specifically, through the doubling time of the leukemic population, we find that in at least 14 out of the 19 patients, the population of relapse leukemia present at the moment of diagnosis comprises more than one but fewer than 108 blasts. Using simulations, we show that in all patients the relapse appears to be driven by genetic mutations. The early appearance of a population of leukemic cells with genetic mechanisms of resistance across adult T-ALL cases constitutes a challenge for treatment. Improving early detection of the malignancy is thus key to prevent its relapse.


H1-antihistamines: inverse agonism, anti-inflammatory actions and cardiac effects.
This review addresses novel concepts of histamine H1-receptor function and attempts to relate them to the anti-inflammatory effects of H1-antihistamines. Furthermore, the molecular mechanisms underlying the cardiotoxic effects of H1-antihistamines are discussed. H1-receptors are G-protein-coupled-receptors (GPCRs), the inactive and active conformations of which coexist in equilibrium. The degree receptor activation in the absence of histamine is its 'constitutive activity'. In this two-state model, histamine acts as an agonist by combining with and stabilizing the activated conformation of the H1-receptor to shift the equilibrium towards the activated state. Drugs classified previously as antagonists act as either inverse agonists or neutral antagonists. Inverse agonists combine with and stabilize the inactive conformation of the receptor to shift the equilibrium towards the inactive state. Thus, they may down-regulate constitutive receptor activity, even in the absence of histamine. Neutral antagonists combine equally with both conformations of the receptor, do not affect basal receptor activity but do interfere with agonist binding. All H1-antihistamines examined to date are inverse agonists. As the term 'H1-receptor antagonists' is obviously erroneous, we suggest that it be replaced by 'H1-antihistamines'. The observations that H1-receptors modulate NF-kappaB activation and that there are complex interactions between GPCRs, has allowed us to postulate receptor dependent-mechanisms for some anti-inflammatory effects of H1-antihistamines, e.g. inhibition of ICAM-1 expression and the effects of bradykinin. Finally, the finding that blockade of HERG1 K+ channels is the mechanism by which some H1-antihistamines may cause cardiac arrhythmias has allowed the development of preclinical tests to predict such activity.


Pseudorabies virus production using a serum-free medium in fixed-bed bioreactors with low cell inoculum density.
Fixed-bed bioreactors packed with macrocarriers show great potential to be used for vaccine process development and large-scale production due to distinguishing features of low shear force, high cell adhering surface area, and easy replacement of culture media in situ. As an initial step of utilizing this type of bioreactors for Pseudorabies virus production (PRV) by African green monkey kidney (Vero) cells, we developed a tube-fixed-bed bioreactor in the previous study, which represents a scale-down model for further process optimization. By using this scale-down model, here we evaluated impacts of two strategies (use of serum-free medium and low cell inoculum density) on PRV production, which have benefits of simplifying downstream process and reducing risk of contamination. We first compared Vero cell cultures with different media, bioreactors and inoculum densities, and conclude that cell growth with serum-free medium is comparable to that with serum-containing medium in tube-fixed-bed bioreactor, and low inoculum density supports cell growth only in this bioreactor. Next, we applied serum-free medium and low inoculum cell density for PRV production. By optimization of time of infection (TOI), multiplicity of infection (MOI) and the harvesting strategy, we obtained total amount of virus particles ~ 9 log10 TCID50 at 5 days post-infection (dpi) in the tube-fixed-bed bioreactor. This process was then scaled up by 25-fold to a Xcell 1-L fixed-bed bioreactor, which yields totally virus particles of 10.5 log10 TCID50, corresponding to ~ 3 × 105 doses of vaccine. The process studied in this work holds promise to be developed as a generic platform for the production of vaccines for animal and human health.


Linoleic-acid-substituted polyethylenimine to silence heat shock protein 90B1 (HSP90B1) to inhibit migration of breast cancer cells.
Breast cancer continues to be one of the leading causes of death in women, and the lack of treatment options for distant metastasis warrants the need to identify and develop more effective approaches. The aim of this study was to identify and validate targets that are associated with the survival and migration of the breast cancer cells in vitro through RNA interference (RNAi) approach. Linoleic-acid-modified polyethylenimine (PEI) polymer was used to screen a short interfering RNA (siRNA) library against numerous cell adhesion and cytoskeleton genes in MDA-MB-231 triple-negative breast cell line, and the functional outcome of silencing was determined by growth and migration inhibition with further target validation studies. Heat shock protein 90B1 (HSP90B1) was identified as a crucial gene that is known to be involved in various breast cancer machineries, including uncontrolled proliferation and brain metastasis. The success of this approach was also due to the use of hyaluronic acid (HA) additive in lipopolymer complexes that showed a profound impact in reducing the cell viability (~50%), migration (~40%), and mRNA transcript levels (~80%) with a physiologically relevant siRNA concentration of 60 nM. The use of Dicer-substrate siRNA proved to be beneficial in target silencing, and a combinational treatment of integrin-β1 (ITGB1) and HSP90B1 was effective in reducing the migration of the MDA-MB-231 and MDA-MB-436 breast cancer cells. This study demonstrates the potential to identify and silence targets using a lipid-modified PEI/siRNA system and highlights the importance of HSP90B1 in the growth and migration of breast cancer cells.


Exploring BODIPY derivatives as photosensitizers for antibacterial photodynamic therapy.
There is an urgent need to develop efficient and safe antimicrobials to augment traditional antibiotics for fighting drug-resistant bacteria. Antimicrobial photodynamic therapy (aPDT), is a promising antimicrobial stize antibiotic resistance and may reduce systemic side effects. Boron-dipyrromethene (BODIPY) is a type of photosensitizer (PSs) for aPDT with tunable structures and rational photophysical features. Herein, six kinds of BODIPY derivatives (BDP1-BDP6) modified with different atoms or groups such as iodine atoms, thiophene, cyano, phenyl, aldehyde and nitro groups were synthesized and their photophysical behaviors were characterized. The results indicated that BDP3, which had 2, 6-diiodo and 8-phenyl substitution, was the best PS candidate with the highest reactive oxygen species (ROS) generation efficacy. BDP3 and BDP5 could rapidly kill Staphylococcus aureus (S. aureus) with the minimum inhibitory concentration (MIC) of 10 nM upon illumination. They also possessed excellent biofilm inhibition ability against S. aureus and could efficaciously restrain the formation of bacterial biofilm. The results of Live/Dead staining assay and scanning electron microscopy (SEM) demonstrated that BDP3 destroyed the cell membrane structure of bacteria by generating ROS, which ultimately led to bacterial lysis and death. Finally, the biosafety evaluation toward the mouse fibroblasts (L929 cells) suggested BDP3 had good cytocompatibility. This work exhibits the great potential of rational designs of PS for aPDT applications.


Assessment of flow profile of left anterior descending coronary artery in hypertrophic cardiomyopathy by transesophageal pulsed Doppler echocardiography.
This study assessed the flow velocity profiles of the left anterior descending coronary artery (LAD) in 7 patients with nonobstructive hypertrophic cardiomyopathy (HC) and in 6 normal subjects by transesophageal pulsed Doppler echocardiography, and evaluated their characteristics and the hemodynamic determinants. Systolic peak flow velocity of the LAD (7 +/- 30 cm/sec) was significantly lower in patients with HC than in normal subjects (34 +/- 11 cm/s, p < 0.05), and there was a significant inverse correlation between systolic peak flow velocity and the thickness of the ventricular septum (r = 0.81, p < 0.01). In 2 cases of HC with ventricular septal thickness of > 20 mm, a remarkable systolic reverse flow was observed in the LAD. However, there was no significant difference in diastolic peak flow velocity between HC and normal subjects. During early diastole, the acceleration time of LAD flow velocity was significantly prolonged (210 +/- 67 vs 95 +/- 15 ms, p < 0.01) and the acceleration rate was significantly decreased (3.6 +/- 2.0 vs 6.6 +/- 1.8 m/s2, p < 0.02) in patients with HC. The time constant of the left ventricular pressure decay was significantly prolonged in patients with HC (55 +/- 6 ms) compared with normal subjects (39 +/- 2 ms, p < 0.001). In HC, increased intramural perivascular pressure of the thickened ventricular septum during systole may be attributed to systolic LAD flow pattern. However, the early and mid-diastolic LAD flow pattern may be affected by impaired left ventricular relaxation.


Role of diabetic microvascular disease in the development of foot wounds.
The influence of microvascular changes in diabetic foot tissue breakdown is not fully known. Research on the role of vascular mediators in diabetes and their effect on the microvasculature may help to create a more unified theory.


Cellular immunogenicity of a multi-epitope peptide vaccine candidate based on hepatitis C virus NS5A, NS4B and core proteins in HHD-2 mice.
To develop a vaccine against hepatitis C virus (HCV), a multi-epitope peptide was synthesized from nonstructural proteins containing HLA-A2 epitopes inducing mainly responses in natural infection. The engineered vaccine candidate, VAL-44, consists of multiple epitopes from the HCV NS5A, NS4B and core proteins. Immunization with the VAL-44 peptide induced higher CTL responses than those by the smaller VL-20 peptide. VAL-44 induced antigen-specific IFN-γ-producing CD4+ T cells and CD8+ T cells. VAL-44 elicited a Th1-biased immune response with secretion of high amounts of IFN-γ and IL-2, compared with VL-20. These results suggest that VAL-44 can elicit strong cellular immune responses. The VAL-44 peptide stimulated IFN-γ production from viral-specific peripheral blood mononuclear cells (PBMCs) of patients infected with HCV. These results suggest that VAL-44 could be developed as a potential HCV multi-epitope peptide vaccine.


Income inequality and suicide in the United States: A spatial analysis of 1684 U.S. counties using geographically weighted regression.
Suicide rates vary considerably across U.S. counties. Spatial non-stationarity may explain mixed findings on the relationship between suicide and income inequality. This ecological study analyzed county-level income inequality and suicide rates for the timespan 2012-2016. Ordinary least squares regression, multilevel regression, and geographically weighted regression models were constructed while adjusting for age, race/ethnicity, gender, education, median income, unemployment, and urbanicity. Ordinary least squares regression and multilevel models found no significant association between income inequality and county suicide rates after adjusting for confounding variables. However, the geographically weighted regression model identified two main areas in which income inequality was negatively associated with suicide rates, as well as several counties across central U.S. in which income inequality was positively associated with suicide rates. Income inequality's effect on county suicide rates may vary across space. Future research should consider spatial non-stationarity when studying suicide and macro-level socioeconomic conditions.


Polychlorinated biphenyls (PCBs) decrease the placental syncytiotrophoblast volume and increase Placental Growth Factor (PlGF) in the placenta of normal pregnancy.
Polychlorinated biphenyls (PCBs) are a class of biologically active, highly stable compounds. Exposure risks include consumption of fatty fish, meat, dairy products and human breast milk, as well as environmental and occupational settings. Numerous reports have described PCB-dependent adverse effects on human fetal growth, including increased risk for IUGR, changes in endocrine function and hormone metabolism, and immunosuppressive and neurological deficits. Here we test the prediction that in utero PCB exposure adversely effects placental morphology, potentially leading to placental insufficiency en route to fetal growth restriction. PCB homologs (10) were measured in the maternal and fetal blood of a small cohort of normotensive pregnancies (22) by gas chromatography-mass spectrometry. PCB levels were compared with angiogenesis associated proteins Placental Growth Factor (PlGF) and sFlt-1, determined by ELISA, and the total estimated syncytiotrophoblast (ST) volume. Significant associations between PCB exposure and both PlGF and ST volume were identified. PCB effects on placenta morphology and predicted function are discussed. These results demonstrate that the human placenta, including ST, is a target of PCB toxicity, and that current environmental PCB exposure levels are a risk to reproductive health.


Grepafloxacin concentration in ocular tissues after intravenous infusion in rabbits with intraocular inflammation.
To determine the penetration of grepafloxacin into ocular tissues during experimental ocular inflammation. 10 albino and 10 pigmented rabbits underwent a continuous intravenous infusion of the drug 24 h after injecting Salmonella typhimurium toxin intravitreously, creating ocular inflammation. The animals were killed and grepafloxacin levels were determined in plasma and ocular tissues using high performance liquid chromatography. Grepafloxacin levels achieved a steady-state plasma concentration of 1.5 microg/ml. The drug diffused more towards vascularized tissues (chorioretina and iris) in both albino and pigmented rabbits with a tissue/serum ratio higher than 1. Grepafloxacin showed more affinity to pigmented tissue, rising levels of 40,000-50,000 ng/g in the chorioretina and iris in pigmented animals. After inflammation, grepafloxacin intraocular penetration increased in albino animals with levels exceeding the minimum inhibitory concentration for the most common ocular pathogens. Grepafloxacin intraocular penetration is higher in pigmented tissues. Ocular inflammation increases the drug penetration into the vitreous.


History of commercializing sexed semen for cattle.
Although the basic principles controlling the sex of mammalian offspring have been known for a relatively long time, recent application of certain modern cellular methodologies has led to development of a flow cytometric system capable of differentiating and separating living X- and Y-chromosome-bearing sperm in amounts suitable for AI and therefore, commercialization of this sexing technology. After a very long history of unsuccessful attempts to differentiate between mammalian sperm that produce males from those that produce females, a breakthrough came in 1981 when it was demonstrated that precise DNA content could be measured. Although these initial measurements of DNA content killed the sperm in the process, they led to the ultimate development of a sperm sorting system that was capable, not only of differentiating between live X- and Y-sperm, but of sorting them into relatively pure X- and Y-sperm populations without obvious cellular damage. Initial efforts to predetermine the sex of mammalian offspring in 1989 required surgical insemination, but later enhancements provided sex-sorted sperm in quantities suitable for use with IVF. Subsequent advances in flow sorting provided minimal numbers of sperm sufficient for use in AI. It was not until the flow cytometric sorting system was improved greatly and successful cryopreservation of sex-sorted bull sperm was developed that efficacious approaches to commercialization of sexed semen could be implemented worldwide in cattle. A number of companies now offer sex-sorted bovine sperm. Innovative approaches by a diverse group of scientists along with advances in computer science, biophysics, cell biology, instrumentation, and applied reproductive physiology provided the basis for commercializing sexed semen in cattle.


The Opposing Effect of Type I IFN on the T Cell Response by Non-modified mRNA-Lipoplex Vaccines Is Determined by the Route of Administration.
mRNA-lipoplex vaccines are currently being explored in phase II clinical trials for the treatment of patients with advanced solid tumors. Mechanistically, these mRNA-lipoplex vaccines are characterized by the induction of type I interferon (IFN) centered innate responses. Earlier studies have identified type I IFNs as major regulators of the T cell response instigated by mRNA-lipoplex vaccines. However, stimulatory or, in contrast, profound inhibitory effects of type I IFNs were described depending on the study. In this mouse study, we demonstrated that the opposing roles of type I IFN signaling on the magnitude of the vaccine-evoked T cell responses is dependent on the route of mRNA-lipoplex administration and is regulated at the level of the T cells rather than indirectly through modulation of dendritic cell function. This study helps to understand the double-edged sword character of type I IFN induction upon mRNA-based vaccine treatment and may contribute to a more rational design of mRNA vaccination regimens.


Evaluation of pelvic floor function by transabdominal ultrasound in postpartum women.
To investigate the relationship between displacement of the bladder base and genitohiatal distance during voluntary contractions of pelvic floor muscles in postpartum women. Twenty women (age 34.7 ± 4.4 years, BMI 21.1 ± 3.2 kg/m(2)) at about 6 weeks after a vaginal delivery were studied. Displacement of the bladder base and genitohiatal distance were measured by transabdominal and transperineal ultrasound, respectively. Displacement of the bladder base was significantly correlated with shortening of genitohiatal distance (r = 0.772, p < 0.001). The intraclass correlation coefficient of the three measurements in each woman was 0.796 for displacement of the bladder base. There was no significant difference in terms of displacement of the bladder base between continent women and incontinent women. This study suggests a strong positive correlation between displacement of the bladder base and shortening of genitohiatal distance during voluntary contractions of pelvic floor muscles in postpartum women. Measurement of displacement of the bladder base by transabdominal ultrasound can be helpful for evaluating pelvic floor function in postpartum women.


Bioinspired synthesis of highly stabilized silver nanoparticles using Ocimum tenuiflorum leaf extract and their antibacterial activity.
Biosynthesis of nanoparticles is under exploration due to wide biomedical applications and research interest in nanotechnology. We herein reports bioinspired synthesis of silver nanoparticles with the aid of novel, non toxic ecofriendly biological material namely Ocimum tenuiflorum leaf extract. It acts as reducing as well as stabilizing agent. An intense surface plasmon resonance band at ∼450 nm in the UV-visible spectrum clearly reveals the formation of silver nanoparticles. The photoluminescence spectrum was recorded to study excitation and emission. TEM and PSD by dynamic light scattering studies showed that size of silver nanoparticles to be in range 25-40 nm. Face centered cubic structure of silver nanoparticles are confirmed by SAED pattern. The charge on synthesized silver nanoparticles was determined by zeta potential. The colloidal solution of silver nanoparticles were found to exhibit high antibacterial activity against three different strains of bacteria Escherichia coli (Gram negative), Corney bacterium (gram positive), Bacillus substilus (spore forming).


Lessons from a nursing home outbreak of influenza A.
To characterize risk factors for outbreak-associated influenza illness and death in a nursing home. Outbreak investigation with predetermined and concurrently determined risk information. A nursing home service in a multiward chronic care hospital, Honolulu, Oahu, 1989 to 1990. Elderly nursing home patients receiving long-term care. Influenza vaccination, amantadine administration, and infection control measures. Neither routine infection control measures nor vaccination prevented illness, complications, or death in a nursing home outbreak of influenza A. The 55% case-fatality rate resulted from severe pneumonia. Influenza transmission may have been mediated by staff via either contaminated hands or fomites. Data from this and other outbreaks suggest that recommendations for preventing nosocomial influenza in the nation's 1.5 million nursing home residents should be reconsidered.


Triplet pregnancy complicated with one hydatidiform mole and preeclampsia in a 46,XY female with gonadal dysgenesis.
We present a case of triplet pregnancy with a complete hydatidiform mole, a condition carrying a significant risk to both mother and fetuses and, therefore, raising an important issue on prenatal care. A 36-year-old patient with gonadal dysgenesis and a 46,XY karyotype successfully conceived a triplet pregnancy after oocyte donation and in vitro fertilization. At mid-trimester, the pregnancy was seen harboring a hydatidiform mole along with two other fetuses by ultrasound. Fetal karyotyping of both fetuses revealed normal results. Serum human chorionic gonadotropin levels were followed up throughout the remainder of pregnancy. At 33 weeks of gestation, preeclampsia ensued with worsening of maternal renal function and high blood pressure, so cesarean section was arranged to deliver a set of two surviving twins. Prophylactic bilateral gonadectomy was done at the same time to curtail the possibility of future malignancy development. Upon pathologic examination of the placentae, hydropic chorionic villi with central cistern formation and nonpolar trophoblastic hyperplasia with atypia and necrosis were found, compatible with complete hydatidiform mole. The gonads showed streaks of fibrous tissue, which resembled ovarian stroma and hilus cells, and an unremarkable tube. Maternal serum human chorionic gonadotropin levels declined gradually to normal level at two months after delivery. This is the first report of triplet pregnancy complicated with one complete hydatidiform mole and preeclampsia in a 46,XY female with gonadal dysgenesis. Our case demonstrated that prolonged gestation with both surviving fetuses was possible by applying intensive monitoring of the whole pregnancy.


Serum vascular endothelial growth factor-a levels during induction therapy in children with acute lymphoblastic leukemia.
To evaluate serum vascular endothelial growth factor (VEGF) levels in children with acute lymphoblastic leukemia (ALL) during the induction phase of chemotherapy. Prospective sudy. Setting: Hospital-based study over 18 months. 30 children with ALL and 17 healthy age- and sex-matched controls. Serum concentration of VEGF-A-165 isoform (s-VEGF) was measured by enzyme-linked immunoabsorbant assay at diagnosis and at the end of induction chemotherapy. s-VEGF was compared with markers of tumor burden. Kinetics of s-VEGF was assessed in response to induction chemotherapy. Median VEGF was significantly lower in untreated patients than in controls (17.0 vs. 42.6 pg/mL, P=0.004). s-VEGF levels were fairly correlated with WBC count (r=-0.56, P=0.004) and LDH (r=-0.52, P=0.02) at diagnosis. All patients but one were in morphologic remission at the end of induction. Median s-VEGF concentration on day 29/33 was significantly higher than on day 1 (44.2 pg/mL, P=0.009). Untreated children with ALL have significantly lower s-VEGF concentration than controls. At the end of the induction therapy, s-VEGF increased to levels similar to controls. The role of ligand-receptor interaction between VEGF and VEGF receptors on leukemia cells needs to be further delineated.To identify the risk factors for scholastic backwardness in children.


Video-assisted thoracoscopic pericardial window for diagnosis and management of pericardial effusions.
Video-assisted thoracoscopy with the creation of a pericardial window is a noninvasive method of pericardial drainage. It also allows an excellent view of both the pleural cavity and pericardium and the precise selection of biopsy sites. We review our 3-year experience with this technique. Between January 2001 and February 2004, 18 patients (10 men, 8 women; mean age 57 years) with echocardiographically diagnosed pericardial effusion underwent video-assisted thoracoscopy at our center. Pericardial windows were created under general anesthesia and single-lung ventilation using 2 to 3 trocars. Mean operating time was 46 minutes. A right thoracic approach was used in 16 patients and a left thoracic approach in 2. Microbiology and virology cultures of the pericardial fluid were negative. Histologic findings were compatible with tuberculosis in 2 cases and granulocytic sarcoma, infiltrating breast carcinoma, and infiltrating nonsmall cell carcinoma in 1 case each. In the remaining patients, the histologic diagnosis was chronic or subacute nonspecific pericarditis. Talc pleurodesis was performed in 3 patients for concomitant malignant pleural effusion. In 4 patients, the pericardial effusion occurred secondary to cardiac surgery; 3 were receiving anticoagulants after valve replacement, and 1 had a heart transplant. There were no complications of the thoracoscopy technique. Video-assisted thoracoscopic fenestration is an effective technique for pericardial drainage and biopsy. Apart from its diagnostic value, it allows the physician to fashion a pleuropericardial window for effective drainage while avoiding the complications of classic surgical procedures. Concomitant pleural and pulmonary disorders may be managed simultaneously.


Paired-eye comparison of corneal endothelial cell counts after unilateral iris-claw phakic intraocular lens implantation.
To compare the corneal endothelial cell density (ECD) after unilateral iris-claw phakic intraocular lens (pIOL) implantation. Instituto de Microcirugia Ocular, Barcelona, Spain. Retrospective interventional nonrandomized paired-eye comparison. Patients who had pIOL implantation in 1 eye and corneal refractive surgery (Group 1) or no surgery in the fellow eye (Group 2) between 1998 and 2010 were included. The main outcome measures were central corneal ECD and the percentage of corneal endothelial cell loss. Secondary outcome measures were uncorrected distance visual acuity, corrected distance visual acuity, manifest refraction, and complications. Outcome measures were analyzed 1, 5, and 10 years postoperatively. Both groups comprised 29 patients. Ten years after surgery, the mean endothelial cell loss was 6.41% ± 8.02% (SD) (Group 1, iris-claw pIOLs), 5.59% ± 5.98% (Group 1, corneal refractive surgery), 7.84% ± 6.83% (Group 2, iris-claw pIOLs), and 6.74% ± 3.97% (Group 2, no surgery). No significant endothelial cell loss was observed after pIOL implantation or corneal refractive surgery at any timepoint (P > .05). No significant differences were observed in the percentage of endothelial cell loss between the groups (P > .05). Iris-claw pIOL implantation did not produce significant corneal endothelial cell loss up to 10 years after surgery compared with corneal refractive surgery and unoperated eyes when strict inclusion criteria were met. Dr. Güell is a consultant to Ophtec BV and Carl Zeiss Meditec AG. No other author has a financial or proprietary interest in any material or method mentioned.


Dynamics of brain tissue changes induced by traumatic brain injury assessed with the Marshall, Morris-Marshall, and the Rotterdam classifications and its impact on outcome in a prostacyclin placebo-controlled study.
The present study evaluates the types and dynamics of intracranial pathological changes in patients with severe traumatic brain injury (sTBI) who participated in a prospective, randomized, double-blinded study of add-on treatment with prostacyclin. Further, the changes of brain CT scan and their correlation to Glasgow Coma Scale score (GCS), maximal intracranial pressure (ICP(max)), minimal cerebral perfusion pressure (CPP(min)), and Glasgow Outcome Score (GOS) at 3, 6, and 12 months were studied. Forty-eight subjects with severe traumatic brain injury were treated according to an ICP-targeted therapy protocol based on the Lund concept with the addition of prostacyclin or placebo. The first available CT scans (CT(i)) and follow-up scans nearest to 24 h (CT(24)) were evaluated using the Marshall, Rotterdam, and Morris-Marshall classifications. There was a significant correlation of the initial Marshall, Rotterdam, Morris-Marshall classifications and GOS at 3 and 12 months. The CT(24) Marshall classification did not significantly correlate to GOS while the Rotterdam and the Morris-Marshall classification did. The CT(i) Rotterdam classification predicted outcome evaluated as GOS at 3 and 12 months. Prostacyclin treatment did not influence the dynamic of tissue changes. The Rotterdam classification seems to be appropriate for describing the evolution of the injuries on the CT scans and contributes in predicting of outcome in patients treated with an ICP-targeted therapy. The Morris-Marshall classification can also be used for prognostication of outcome but it describes only the impact of traumatic subarachnoid hemorrhage (tSAH).


[Comparative research on Seal & Protect for treatment of hypersensitivity of the dentine].
Observation of clinical results in treatment of hypersensitive dentine with two kinds of drugs. Seal & Protect was compared with conventional NaF method for the treatment of 120 teeth with typical hypersensitivity which were divided into two groups. The efficiency of Seal & Protect group was 96.67 % while that of NaF group 76.67%. There was significant difference between two groups. The safe, effective and good method was provided for treating the hypersensitive dentine by use of Seal & Protect.


Changes in the hepatic perfusion index during the development of experimental hepatic tumours.
A model of microscopic liver tumour has been developed in the Fisher rat by intraportal injection of 1.6 x 10(7) Walker 256 carcinosarcoma cells. Rats were studied at 2, 4 and 6 days after the inoculation of live Walker cells. A control group received dead Walker cells. No tumour was visible in control groups at 2, 4 and 6 days after inoculation. Similarly in rats injected with live cells no tumour was visible at 2 days after inoculation but at 4 and 6 days the percentage hepatic replacement was (mean +/- s.d.) 7.0 +/- 2.3 and 27.9 +/- 6.80 respectively. The hepatic perfusion index was significantly raised at 4 and 6 days after inoculation of live cells compared with control animals and those receiving viable cells after 2 days inoculation. Portal flow and portal venous inflow were significantly reduced when the hepatic perfusion index increased but hepatic arterial flow did not alter. Changes in the hepatic haemodynamics were accompanied by increases in the portal and splanchnic vascular resistance and an increase in the amount of arteriovenous shunting through the liver. These findings confirm studies that the hepatic perfusion index is useful in the detection of occult liver metastases but that the change is not a consequence of an increase in the hepatic arterial flow.


Evaluation of the anti-tumor effects of an anti-Human Epidermal growth factor receptor 2 (HER2) monoclonal antibody in combination with CD11b+/Gr-1+ myeloid cells depletion using a recombinant peptibody in 4 T1-HER2 tumor model.
Clinical efficacy of Human Epidermal growth factor Receptor 2 (HER2) targeted strategies is limited due to impaired anti-tumor responses negatively regulated by immunosuppressive cells. We thus, investigated the inhibitory effects of an anti-HER2 monoclonal antibody (1 T0 mAb) in combination with CD11b+/Gr-1+ myeloid cells depletion in 4 T1-HER2 tumor model. BALB/c mice were challenged with human HER2-expressing 4 T1 murine breast cancer cell line. A week post tumor challenge, each mouse received 50 µg of a myeloid cells specific peptibody every other day, or 10 mg/kg of 1 T0 mAb two times a week, and their combination for two weeks. The treatments effect on tumor growth was measured by calculating tumor size. Also, the frequencies of CD11b+/Gr-1+ cells and T lymphocytes were measured by flow cytometry. Peptibody treated mice indicated tumor regression and 40 % of the mice eradicated their primary tumors. The peptibody was capable to deplete notably splenic CD11b+/Gr-1+ cells as well as intratumoral CD11b+/Gr-1+ cells (P < 0.0001) and led to an increased number of tumor infiltrating CD8+ T cells (3.3 folds) and also that of resident tumor draining lymph nodes (TDLNs) (3 folds). Combination of peptibody and 1 T0 mAb resulted in enhanced expansion of tumor infiltrating CD4 + and CD8+ T cells which was associated with tumor eradication in 60 % of the mice. Peptibody is able to deplete CD11b+/Gr-1+ cells and increase anti-tumoral effects of the 1 T0 mAb in tumor eradication. Thus, this myeloid population have critical roles in development of tumors and their depletion is associated with induction of anti-tumoral responses.


A yeast telomere binding activity binds to two related telomere sequence motifs and is indistinguishable from RAP1.
Telomere Binding Activity (TBA), an abundant protein from Saccharomyces cerevisiae, was identified by its ability to bind to telomeric poly(C1-3A) sequence motifs. The substrate specificity of TBA has been analyzed in order to determine whether the activity binds to a unique structure assumed by the irregularly repeating telomeric sequences or whether the activity recognizes and binds to subset of specific sequences found within the telomere repeat tracts. Deletion analysis and DNase I protection assays demonstrate that TBA binds specifically to two poly-(C1-3A) sequences that differ by one nucleotide. The methylation of four guanine residues, located at identical relative positions within these two binding sequences, interferes with TBA binding to the substrates. A synthetic olignucleotide containing a single TBA binding site can function as a TBA binding substrate. The TBA binding site shares homology with the binding sites reported for the Repressor/Activator Protein 1 (RAP1), Translation Upshift Factor (TUF) and General Regulatory Factor (GRFI) transcription factors, and TBA binds directly to RAP1/TUF/GRFI substrate sequences. Yeast TBA preparations and the RAP1 gene product expressed in E. coli cells are both similarly sensitive to in vitro protease digestion. Affinity-purified TBA extracts include a protein indistinguishable from RAP1 in binding specificity, size, and antigenicity. The binding affinity of TBA for the two telomeric poly(C1-3A) binding sites is higher than its affinity for any of the other binding substrates used for its identification. In extracts of yeast spheroplasts prepared by incubation of yeast cells with Zymolyase, an altered, proteolyzed form, of TBA (TBA-S) is present. TBA-S has a faster mobility in gel retardation assays and SDS-PAGE gels, yet it retains the DNA binding properties of standard TBA preparations: it binds to RAP1/TUF/GRFI substrates with the same relative binding affinity and protects poly(C1-3A) tracts from DNase I digestion with a "footprint" identical to that of standard TBA preparations.


FACT and FAIR with Big Data allows objectivity in science: The view of crystallography.
A publication is an important narrative of the work done and interpretations made by researchers securing a scientific discovery. As The Royal Society neatly states though, "Nullius in verba" ("Take nobody's word for it"), whereby the role of the underpinning data is paramount. Therefore, the objectivity that preserving that data within the article provides is due to readers being able to check the calculation decisions of the authors. But how to achieve full data archiving? This is the raw data archiving challenge, in size and need for correct metadata. Processed diffraction data and final derived molecular coordinates archiving in crystallography have achieved an exemplary state of the art relative to most fields. One can credit IUCr with developing exemplary peer review procedures, of narrative, underpinning structure factors and coordinate data and validation report, through its checkcif development and submission system introduced for Acta Cryst. C and subsequently developed for its other chemistry journals. The crystallographic databases likewise have achieved amazing success and sustainability these last 50 years or so. The wider science data scene is celebrating the FAIR data accord, namely, that data be Findable, Accessible, Interoperable, and Reusable [Wilkinson et al., "Comment: The FAIR guiding principles for scientific data management and stewardship," Sci. Data 3, 160018 (2016)]. Some social scientists also emphasize more than FAIR being needed, the data should be "FACT," which is an acronym meaning Fair, Accurate, Confidential, and Transparent [van der Aalst et al., "Responsible data science," Bus Inf. Syst. Eng. 59(5), 311-313 (2017)], this being the issue of ensuring reproducibility not just reusability. (Confidentiality of data not likely being relevant to our data obviously.) Acta Cryst. B, C, E, and IUCrData are the closest I know to being both FACT and FAIR where I repeat for due emphasis: the narrative, the automatic "general" validation checks, and the underpinning data are checked thoroughly by subject specialists (i.e., the specialist referees). IUCr Journals are also the best that I know of for encouraging and then expediting the citation of the DOI for a raw diffraction dataset in a publication; examples can be found in IUCrJ, Acta Cryst D, and Acta Cryst F. The wish for a checkcif for raw diffraction data has been championed by the IUCr Diffraction Data Deposition Working Group and its successor, the IUCr Committee on Data.


Selective Vulnerability of Layer 5a Corticostriatal Neurons in Huntington's Disease.
The properties of the cell types that are selectively vulnerable in Huntington's disease (HD) cortex, the nature of somatic CAG expansions of mHTT in these cells, and their importance in CNS circuitry have not been delineated. Here we employed serial fluorescence activated nuclear sorting (sFANS), deep molecular profiling, and single nucleus RNA sequencing (snRNAseq) to demonstrate that layer 5a pyramidal neurons are vulnerable in primary motor cortex and other cortical areas of HD donors. Extensive mHTT -CAG expansions occur in vulnerable layer 5a pyramidal cells, and in Betz cells, layer 6a, layer 6b neurons that are resilient in HD. Retrograde tracing experiments in macaque brains identify the vulnerable layer 5a neurons as corticostriatal pyramidal cells. We propose that enhanced somatic mHTT -CAG expansion and altered synaptic function act together to cause corticostriatal disconnection and selective neuronal vulnerability in the HD cerebral cortex.


Acute Budd-Chiari syndrome during hepatic vein catheterization.
This case report describes a 4-year-old male with a history of hepatoblastoma, treated with chemotherapy followed by a right extended hepatectomy. Secondary to this, the patient experienced recurrent hepatic vein stenosis. He was treated initially with conventional angioplasty, followed by paclitaxel-coated balloon dilatations in an attempt to prevent episodes of re-stenosis. During the catheterization of the hepatic vein in one of the treatments, hemodynamic instability due to an acute Budd-Chiari syndrome occurred. The hemodynamic compromise became unresponsive to intravascular resuscitation and inotropic support. The patient was then treated with an emergency conventional angioplasty of the hepatic vein, which resulted in a rapid response and eventually in a full recovery. The etiology of this complication remains unclear; however, it may have been secondary to endothelial damage leading to acute thrombosis and/or venous spasm. Conventional angioplasty was successful in managing this complication. Awareness of iatrogenic acute Budd-Chiari syndrome as a potentially fatal complication during hepatic catheterization/dilatation, especially in the posthepatectomy setting, successful management of this complication, and the importance of a multidisciplinary and rapid response, is emphasized.


[Autoimmune haemolytic anaemia].
Autoimmune haemolytic anaemias (AIHA) are acquired haematological disorders caused by increased peripheral erythrocyte destruction mediated by autoantibodies against erythrocyte antigens. They classified according to aetiology into primary and secondary, and according to the type of antibody and reaction temperature into AIHA due to warm antibodies (w-AIHA) and AIHA due to cold antibodies (c-AIHA). The mainstay of management in w-AIHA remains glucocorticoid therapy, and the early addition of rituximab has shown good results in recent studies. Primary c-AIHA is mainly treated with rituximab, alone or in combination with chemotherapy. New drugs such as Syk inhibitors, anti-FcRn Ig and complement inhibitors are in advanced development and will expand the therapeutic arsenal, especially in refractory or relapsed cases.


Comparison of disability and quality of life measures in patients with long-term psychotic disorders and patients with multiple sclerosis: an application of the WHO Disability Assessment Schedule II and WHO Quality of Life-BREF.
The aim of this article is to compare the applications of the WHO Disability Assessment Schedule II (WHODAS II) and WHO Quality of Life-BREF (WHOQOL-BREF) in the assessment of patients with psychotic disorders and multiple sclerosis, and to assess the feasibility and usefulness of such universal measures in the psychiatric as well as physical rehabilitation setting. Twenty patients with psychotic disorders from St Vincent's Mental Health Service and 20 patients from the Medical Rehabilitation Ward of St Vincent's Hospital were assessed. The WHODAS II and WHOQOL-BREF were administered to each patient to obtain their perception of the impact of their disability and their health-related quality of life (HRQoL). The WHODAS II and WHOQOL-BREF interviews were meaningful as they highlighted aspects of patients' disabilities as well as issues that led to impairment in HRQoL. The WHODAS II and WHOQOL-BREF total scores were higher overall for patients with multiple sclerosis, reflecting, in particular, the physical impact of this condition. Patients with psychotic disorders generally did not report difficulty in self-care. Both patients with multiple sclerosis and patients with psychotic disorders reported similar levels of difficulty in the domain of participation in society. Universal measures of disability and HRQoL are feasible for use in patients with long-term physical and psychiatric illnesses. Similarities in the disability profiles of patients in the two groups reflect the consequences of the long-term conditions under investigation. Both groups of patients reported similar levels of social disability, confirming that barriers to participation in society affect all patients with disabling conditions.


A three-dimensional computerized isometric strength measurement system.
The three-dimensional Computerized Isometric Strength Measurement System (CISMS) reliably and accurately measures isometric pull and push strengths in work spaces of paraplegic populations while anticipating comparative studies with other populations. The main elements of the system were: an extendable arm, a vertical supporting track, a rotating platform, a force transducer, stability sensors and a computerized data collection interface. The CISMS with minor modification was successfully used to measure isometric push-up and pull-down strengths of paraplegics and isometric push, pull, push-up and pull-down strength in work spaces for seated and standing able-bodied populations. The instrument has satisfied criteria of versatility, safety and comfort, ease of operation, and durability. Results are accurate within 2N for aligned forces. Costing approximately $1,500 (US) including computer, the system is affordable and accurate for aligned isometric strength measurements.


Erysipeloid.
Erysipelothrix infections have been a well-known clinical entity for over a century. Only a few cases have been studied histologically, and the agent has rarely been cultured from infected patients. We present here a case of erysipeloid of Rosenbach, in which histologic study and electron microscopy document the presence of microorganisms. We also present a complete review of the clinical and pathologic features of Erysipelothrix infections and their treatment. Our observations suggest that Erysipelothrix rhusiopathiae is capable of producing L forms that may revert to a bacterial form and produce sepsis at a later time.


Nanocomposite hydrogel based on chitosan/laponite for sealing and repairing tracheoesophageal fistula.
Tracheoesophageal fistula (TEF) is an abnormal connection between the trachea and esophagus that severely impairs quality of life. Current treatment options have limitations, including conservative treatment, surgical repair, and esophageal stent implantation. Here, we introduced laponite (LP) nano-clay to improve chitosan-based hydrogels' rheological properties and mechanical properties and developed an endoscopically injectable nanocomposite shear-thinning hydrogel to seal and repair fistulas as an innovative material for the treatment of TEF. Excellent injectability, rheological properties, mechanical strength, self-healing, biodegradability, biocompatibility, and tissue repair characterize the new hydrogel. The introduction of LP nano-clay improves the gel kinetics problem of hydrogels to realize the sol-gel transition immediately after injection, avoiding gel flow to non-target sites. The addition of LA nano-clay can significantly improve the rheological properties and mechanical strength of hydrogels, and hydrogel with LP content of 3 % shows better comprehensive performance. The nanocomposite hydrogel also shows good cytocompatibility and can promote wound repair by promoting the migration of HEEC cells and the secretion of VEGF and FGF. These findings suggest that this nanocomposite hydrogel is a promising biomaterial for TEF treatment.


Prolonging the duration of post-infusion scalp cooling in the prevention of anthracycline-induced alopecia: a randomised trial in patients with breast cancer treated with adjuvant chemotherapy.
Scalp cooling as a method to reduce the incidence of chemotherapy-induced alopecia (CIA) is increasingly used in daily practice worldwide. However, in patients treated with 5-fluorouracil, epirubicin and cyclophosphamide (FEC), scalp cooling fails in 48-67% of patients. This study investigated the efficacy of extended duration of post-infusion scalp cooling in breast cancer patients treated with this regimen. In this prospective multi-centre randomised study, 102 patients with early breast cancer treated with adjuvant FEC chemotherapy were randomly assigned in a 1:1 ratio to a post-infusion cooling time of 90 or 150 min. The primary endpoint was the need to wear a wig or other head covering to mask visible hair loss. Sixteen out of 48 patients (33%) treated with 90 min of post-infusion cooling did not need any head covering, compared with 21 out of 46 patients (45%) treated with 150 min of post-infusion cooling (p = 0.2). WHO grades 2-3 (moderate-complete) alopecia were reported more often in patients treated with 90-min post-infusion cooling time (n = 25/51 (49%) versus n = 17/51 (33%); p = 0,02). Scalp cooling was well-tolerated (mean Visual Analogue Score 7.4) and only three patients (3%) stopped due to intolerance during treatment. Extending the duration of 90-min post-infusion scalp cooling to 150 min in patients treated with adjuvant FEC chemotherapy was well-tolerated but did not significantly diminish the need for head covering. However, grades 2-3 alopecia was seen less often with prolonged post-infusion scalp cooling.


Expression pattern and prognostic significance of IGFBP isoforms in anaplastic astrocytoma.
The role of insulin-like growth factors and their regulatory proteins (IGFBP isoforms) in gliomas, particularly glioblastoma, has been a subject of active research in recent years. There is paucity of literature on their expression and impact on clinical outcome in anaplastic astrocytomas. To evaluate the expression patterns of IGFBP isoforms in anaplastic astrocytoma and correlate with clinical outcome, a retrospective study of 53 adult patients operated for supratentorial lobar anaplastic astrocytoma was performed. The protein expression of IGFBP isoforms (IGFBP-2, -3, -5 and -7), was studied by immunohistochemistry on all samples. The patients were followed up and outcome was documented. The median age at presentation in the present study was 35 years. The pattern of staining was intra cytoplasmic, homogenous and diffuse for IGFBP-2, -3 and -5 and granular for IGFBP-7. IGFBP-2 expression was significantly low in anaplastic astrocytoma as compared to other isoforms (P < 0.001). IGFBP-3 expression was higher than the other isoforms. However, its' expression correlated with favorable overall survival and demonstrated a trend towards significance on univariate analysis. The present study is the first of its kind to describe comprehensively the pattern of expression of IGFBP isoforms (IGFBP-2, -3, -5 and -7) in anaplastic astrocytomas. IGFBP-2 and IGFBP-3 expression patterns and correlation to prognosis were distinct in anaplastic astrocytoma patients, contradictory to what has been reported in glioblastoma, thus giving further evidence that anaplastic astrocytomas are molecularly distinct from glioblastoma.


The incidence and relative risk of stroke in patients with schizophrenia: a five-year follow-up study.
This study aimed to estimate the incidence and relative risk of stroke and post-stroke all-cause mortality in patients with schizophrenia. This study identified a study population from the National Health Insurance Research Database (NHIRD) between 1999 and 2003 that included 80,569 patients with schizophrenia and 241,707 age- and sex-matched control participants without schizophrenia. The participants were randomly selected from the 23,981,020-participant NHIRD, which consists of 96% Taiwanese participants. Participants who had experienced a stroke between 1999 and 2003 were excluded. Using data from the NHIRD between 2004 and 2008, the incidence of stroke (ICD-9-CM code 430-438) and patient survival after stroke were calculated for both groups. After adjusting for confounding risk factors, a Cox proportional-hazards model was used to compare the five-year stroke-free survival rate to the all-cause mortality rate across the two cohorts. Over five years, 1380 (1.71%) patients with schizophrenia and 2954 (1.22%) controls suffered from strokes. After adjusting for demographic characteristics and comorbid medical conditions, patients with schizophrenia were 1.13 times more likely to have a stroke (95% CI=1.05-1.22; P=0.0006). In addition, 1039 (24%) patients who had a stroke died during the follow-up period. After adjusting for patient, physician and hospital variables, the all-cause mortality hazard ratio for patients with schizophrenia was 1.23 (95% CI=1.06-1.41; P=0.0052). During a five-year follow-up, the likelihood of developing a stroke and the all-cause mortality rate were greater among patients with schizophrenia as compared with the control group.


Moods in everyday situations: effects of menstrual cycle, work, and personality.
This study examined women's moods on work and off days during different phases of the menstrual cycle. Self-reports of the moods angry, happy, sad, stressed, tired, and anxious were obtained on two work and two off days during the luteal and follicular phases of the menstrual cycle in 203 nurses. Individual differences in anger expression, anxiety, and hostility were assessed. Ratings of anxious, stressed, and tired were higher and happy and sad were lower on the workday than the off day. Menstrual cycle phase was associated with mood differences depending on the day (work, off work) and individual differences in personality traits. The experience of moods in everyday life is affected by overall levels of stress and phase of the menstrual cycle. The findings suggest the need to refine sociopsychobiological and clinical models of mood regulation and of risk for disease.


Prioritizing the noise control methods by using the Analytical Hierarchy Process (AHP) method in an Iranian tire factory.
Noise is a common harmful physical factor in the work environment. This study sought to prioritize noise control methods using the analytical hierarchy process (AHP) in a tire factory. The study, which adopted a cross-sectional, descriptive, analytical design, was conducted in the baking hall of an Iranian tire manufacturing factory in 2018. 4 criteria (namely implementation and maintenance cost, method applicability, method effectiveness and efficiency, and intervention in the process) and 8 alternatives (including reducing individuals' noise exposure time, designing and installing sound isolation chamber for operators, using of earmuffs and earplug simultaneously, changing processes or operational procedures in machinery with excessive noise generation, forming noise control engineering teams, requiring people in charge to quickly fix the leaks and change baking press washers on time, using acoustic panels in the ceiling and walls, and designing and manufacturing silencer and nuzzle for the steam and compressed air outlet of baking press machinery) were selected. Then, to prioritize noise control methods based on objectives, criteria, and alternatives, an AHP questionnaire was developed and completed by domain experts and noise control specialists. Data analysis was performed using Expert Choice V. 11 and Excel. The results showed that the inconsistency rate in all cases was less than 10%, hence the consistency of responses was approved. Based on experts' opinion about the selected criteria, "implementation and maintenance cost" had the highest weight (0.481), while "method effectiveness and efficiency" recorded the lowest one (0.046). With regard to the alternatives, "change in the process" registered the greatest weight (0.193), whereas "individuals' noise exposure time" had the lowest weight (0.046). Based on the final weights, the most appropriate noise control methods in this industry are changing processes in machinery with excessive noise generation, forming noise control engineering team, and manufacturing silencer and nuzzle for the steam and compressed air outlet of baking press machinery. Furthermore, AHP is a suitable approach for prioritizing decisions related to noise control.


How Should We Assign Large Infiltrative Hepatocellular Carcinomas for Staging?
Infiltrative gross morphology of hepatocellular carcinoma (HCC) is known to be associated with poor prognosis, but this is not considered for staging. A total of 774 HCC patients who underwent curative liver resection were retrospectively reviewed and the prognostic significance of infiltrative type HCC was assessed using the American Joint Committee on Cancer (AJCC) and Barcelona Clinic Liver Cancer (BCLC) staging systems. Seventy-four patients (9.6%) had infiltrative HCCs with a higher proportion of multifocal tumors, larger tumors, vessel invasion, increased tumor marker levels, and advanced T-stages than those with nodular HCC (all, p < 0.01). Infiltrative morphology was independently associated with lower overall survival (OS), but its impact was significant when the tumor size was ≥ 4 cm (p < 0.001). Under current AJCC and BCLC staging criteria, these large infiltrative HCCs were associated with significantly worse OS in early AJCC T-stages (T1b/T2, p < 0.001) and BCLC stage A/B (both, p < 0.01) but not in late AJCC (T3/T4) and BCLC C. The reassignment of this subtype to T3 and T4 increased the discriminatory ability of AJCC T-staging with lower AIC values (3090 and 3088 vs. 3109) and higher c-index (0.69 and 0.69 vs. 0.67), respectively (both, p < 0.001). Similarly, the reassignment of large infiltrative HCC to BCLC stages B and C also improved the prognostic performance. Large infiltrative HCCs should be assigned to more advanced stages in current staging systems for their prognostic impact.


Growth failure and treatment in cystic fibrosis.
Poor growth has long been a characteristic feature of cystic fibrosis (CF) and is significantly linked to lung function and overall health status. Improvements in pulmonary and nutrition care for patients with cystic fibrosis (CF) have resulted in better growth outcomes; however, height gains have not paralleled the improvements in weight in children with CF, and patients with more severe CF mutations remain significantly more affected. Many factors affect the growth hormone-IGF-1 axis and the growth plate of the long bones, including the chronic inflammatory state associated with CF. There are also increasing data on the direct effects of CFTR on bone and implications for CFTR modulators in attaining optimal growth. Treatments aimed at improving growth in CF are also reviewed here.


Trends in lipid profiles and control of LDL-C among adults with diabetes in the United States: An analysis of NHANES 2007-2018.
To determine trends in lipid profiles and lipid control in US adults with diabetes and assess variation in these trends across sex and race/ethnicity from 2007 to 2018. Serial cross-sectional analysis of data from diabetic adults participating in the National Health and Nutrition Examination Survey (NHANES; 2007-2008 to 2017-2018). Among the 6116 participants included (weighted mean age, 61.0 years; 50.7% men), age-adjusted TC (p for trend < 0.001), LDL-C (p for trend < 0.001), TG (p for trend = 0.006), TG/HDL-C (p for trend = 0.014) and VLDL-C (p for trend = 0.015) decreased significantly. Age-adjusted LDL-C levels were consistently higher in women than in men over the study period. Age-adjusted LDL-C improved significantly for diabetic whites and blacks but did not change significantly for the other races/ethnicity. Lipid parameters improved for non-coronary heart disease (CHD) diabetic adults, except for HDL-C, while no lipid parameter significantly changed for diabetic adults with concomitant CHD. Among diabetic adults receiving statin therapy, age-adjusted lipid control remained unchanged from 2007 to 2018, as did adults with concomitant CHD. However, age-adjusted lipid control improved significantly for men (p for trend < 0.01) and diabetic Mexican Americans (p for trend < 0.01). In 2015-2018, female diabetic participants receiving statins had lower odds of achieving lipid control (OR: 0.55; 95% CI: 0.35-0.84; P = 0.006) than men. Differences in lipid control across different races/ethnicities no longer existed. Lipid profiles improved in the US adults with diabetes from 2007 to 2018. Although rates of lipid control did not improve nationally in adults receiving statins, these patterns varied by sex and race/ethnicity.


Bench to bedside strategies for optimizing neuroprotection following perinatal hypoxia-ischaemia in high and low resource settings.
Therapeutic hypothermia gathers impetus in the developed world as a safe and effective therapy for term asphyxial encephalopathy. Although many questions still remain about the optimal application of hypothermic neuroprotection it is difficult to ignore the developing world where the prevalence of asphyxial encephalopathy is much higher. Experimental studies to optimize high tech cooling need to run in parallel with trials to determine the possible benefits of therapeutic hypothermia in low resource settings. We used a validated newborn piglet model of transient HI to determine (i) whether optimal neuroprotection occurs at different temperatures in the cortical and deep grey matter; (ii) the effect of body size on regional brain temperature under normothermia and hypothermia; (iii) the effect of insult severity on the therapeutic window duration; (iv) whether cooling using a water bottle is feasible. In this model hypoxia-ischaemia is induced by reversible occlusion of the common carotid arteries by remotely controlled vascular occluders and simultaneous reduction in the inspired oxygen fraction to 0.12. Intensive care can be administered to the piglet maintaining metabolic and physiological homeostasis throughout the experiment, and cerebral energy metabolism is monitored continuously providing quantitative measures of the HI insult, latent phase and secondary energy failure using phosphorus-31 ((31)P) magnetic resonance spectroscopy (MRS). (i) The optimal temperature for cooling was lower in the cortex than deep grey matter. (ii) Cerebral temperatures were body-weight dependent: a smaller body weight led to a lower brain temperature especially with selective head cooling. (iii) Latent-phase duration is inversely related to insult severity. (iv) Low tech, simple cooling methods using a water bottle can induce and maintain moderate hypothermia. Small shifts in brain temperature critically influence the survival of neuronal cells and body size critically influences brain-temperature gradients - smaller subjects have a larger surface area to brain volume and hence more heat is lost. The clinical implication is that smaller infants may require higher cap or body temperatures to avoid detrimental effects of over-zealous cooling. Latent-phase brevity may explain less effective neuroprotection following severe HI in some clinical studies. "Tailored" treatments which take into account individual and regional characteristics may increase the effectiveness of therapeutic hypothermia in the developed world. Low tech cooling methods using water bottles may be feasible although adequate staffing and monitoring would be required.