Perceived effectiveness of four different cigarette health warning label themes among a sample of urban smokers and non-smokers in China.
This study, conducted in China, evaluated the effectiveness of four different themes of health warning labels (HWLs) that used both text and pictures: (1) self-harm from using cigarettes, (2) harming family or children with secondhand smoke, (3) reinforcing compliance with existing smoke-free policies and (4) anticigarette gift giving practices. A cross-sectional randomised experimental survey was conducted among 3247 adult (aged 18+ years) participants in Beijing, Shanghai and Shenzhen in 2017, using quotas for age group, gender and smoking status. Participants were randomly assigned to one of the four HWL themes. Each participant viewed eight HWLs and rated how effective these themed-labels were in terms of credibility, raising awareness of health harms of smoking on family and children, improving compliance with public smoking bans, stopping the practice of gifting cigarettes, thinking about quitting and preventing smoking using a 10-point scale, with 10 being most effective. Analysis of variance and independent t-tests were used to analyse these data. All four HWL themes performed well for each outcome with average ratings >6.5. Harming family or children with secondhand smoke was the theme that received the highest ratings for each outcome, with credibility (8.0, 95% CI 7.86 to 8.09) and prevention of smoking (8.8, 95% CI 8.63 to 8.91) outcomes being significantly higher (p<0.05). Overall, analysis of ratings by gender, income and education did not impact outcomes. All four HWL themes tested could be effective in China; the theme of secondhand smoke harming family or children may be a particularly credible/effective theme.


False-positive radioiodine whole-body scan due to a renal cyst.
Patients affected by differentiated thyroid cancer are treated surgically and by ablative radioiodine therapy. A post-therapy whole-body scan allows detection of thyroid remnants or local and distant metastases, although false-positive findings may be observed. We report a case of a 75-year-old woman with follicular thyroid cancer, who underwent ablative radioiodine treatment. On post-therapy wholebody scan, abnormal uptake in the left upper abdomen was found, although stimulated thyroglobulin level was not suggestive for distant metastases of differentiated thyroid carcinoma. Additional SPECT/CT acquisition revealed focal ¹³¹I uptake located at the posterolateral wall of the left kidney corresponding to a round lesion 47 mm in maximal diameter. In order to verify this finding abdominal ultrasound and abdominal contrast-enhanced CT were performed, confirming multiple renal cysts in the left kidney; the largest one was the site of abnormal radioiodine accumulation. Despite the high incidence of renal cysts, especially in the elderly, radioiodine uptake in renal cysts is extremely rare. Different hypotheses on the mechanism of radioiodine uptake in the cyst were proposed, among them active secretion by sodium-iodide symporter or other transporting proteins. We conclude that abnormal radioiodine uptake in renal cysts can be an exceptional finding mimicking a metastasis.


Fast axonal transport in the presence of high Ca2+: evidence that microtubules are not required.
Microtubules have long been associated with the mechanism of fast axoplasmic transport, although experimental evidence to support an involvement has been equivocal. Electron microscopic studies demonstrated that incubation of the axons of excised rat sciatic nerves in media containing 75 mM Ca2+ caused complete loss of microtubules within 6 hr. To evaluate the role of microtubules in fast anterograde transport, studies of transport in nerves exposed to these conditions were undertaken. Prior to measurement of axoplasmic transport, nerves ligated distal to the dorsal root ganglia were preincubated in vitro in 75 mM Ca2+ for 0-6 hr. Fast axonal transport was subsequently monitored by measuring the amount of trichloroacetic acid-insoluble radioactivity that accumulated at the ligature after incubation for 12-18 hr with L-[3H]proline. Nerves in which microtubules had been depolymerized by preincubation in high Ca2+ maintained control levels of transport. We conclude that intact microtubules are not required for fast anterograde axoplasmic transport.


Tailored preconceptional dietary and lifestyle counselling in a tertiary outpatient clinic in The Netherlands.
Adverse reproductive performance has been linked to unhealthy dietary intake and lifestyles. Our objectives were to investigate the prevalence of unhealthy dietary intake and lifestyles before conception and to evaluate whether tailored preconception counselling modifies these behaviours. Between October 2007 and April 2009, 419 couples received tailored preconception dietary and lifestyle counselling at the outpatient clinic of Obstetrics and Gynaecology of the Erasmus University Medical Center Rotterdam, the Netherlands. A subgroup (n = 110 couples) was counselled twice with a fixed time interval of 3 months. Self-administered questionnaires were used for tailored dietary and lifestyle counselling. A cumulative score based on six Dutch dietary guidelines was displayed in the personal Preconception Dietary Risk score (PDR score). In a similar manner, the Rotterdam Reproduction Risk score (R3 score) was calculated from lifestyle factors (women: 13 items, men: 10 items). Univariate and paired tests were used. Most couples (93.8%) were subfertile. At the second counselling, the percentage consuming the recommended intake of fruit had increased from 65 to 80 in women and from 49 to 68 in men and the percentage of women getting the recommended intake of fish increased from 39 to 52. As a consequence, the median PDR score was decreased [women: 2.6 (95% CI 2.4-2.9) to 2.4 (95% CI 2.1-2.6), men: 2.5 (95% CI 2.3-2.7) to 2.2 (95% CI 1.9-2.4), both P < 0.05]. The median R3 scores were also lower [women: 4.7 (95% CI 4.3-5.0) to 3.1 (95% CI 2.8-3.4), men: 3.0 (95% CI 2.8-3.3) to 2.0 (95% CI 1.7-2.3), both P < 0.01] due to less alcohol use (-14.6%), more physical exercise and folic acid use in women, and less alcohol use in men (-19.4%) (all P < 0.01). The R3 scores in women and men were decreased in all ethnicity, educational level, neighbourhood and BMI categories. However, low educated women appeared to show a larger reduction than better educated women and men with a normal BMI to show a larger decrease than overweight men. The reduction in the PDR score of women was similar in both ethnic groups. More than 85% women and men found the counselling useful and around 70% would recommend it to others. Tailored preconception counselling about unhealthy dietary and lifestyle behaviours of subfertile couples in an outpatient tertiary clinic is feasible and seems to decrease the prevalence of harmful behaviours in the short term. These results with subfertile couples are promising and illustrate their opportunities to contribute to reproductive performance and pregnancy outcome.


Comparison of gefitinib as first- and second-line therapy for advanced lung adenocarcinoma patients with positive exon 21 or 19 del epidermal growth factor receptor mutation.
Gefitinib, a tyrosine kinase inhibitor (TKI) targeting epidermal growth factor receptor (EGFR), shows excellent clinical benefit in treating advanced non-small-cell lung cancer (NSCLC). The aim of this study was to compare the efficacy and toxicity of gefitinib as first-line therapy and second-line therapy for advanced lung adenocarcinoma patients with positive exon 21 (L858R) or exon 19 deletion of EGFR mutation. We retrospectively analyzed the clinical data of 60 EGFR-mutated advanced lung adenocarcinoma patients from July 2011 to November 2015 who have received oral gefitinib 250 mg once daily. Gefitinib was taken until disease progression, intolerable toxicity or death. After a median follow-up of 792 days, one death had occurred. Among the 59 patients who survived, 17 patients progressed. Overall, the median progression-free survival (mPFS) was 10 months (95% confidence interval [CI]: 7.53-12.46 months, p<0.05). The response rate (RR) and disease control rate (DCR) were 33.33% and 71.66%, respectively. However, there was longer mPFS in the first line-therapy than that in the second-line therapy: in the first-line gefitinib therapy, mPFS was 12 months among 41 patients (95% CI: 9.58-14.41 months, p<0.05), and in the second-line therapy, mPFS was 7 months among 19 patients (95% CI: 1.31-12.68 months, p<0.05). Furthermore, in subgroup analyses examining different EGFR mutation types, we noted that mPFS was significantly longer for patients with exon 19 deletion than for those with positive exon 21in both the first-line therapy and second-line therapy. Patients with advance lung adenocarcinoma who were selected by positive exon 21 or 19 deletion mutations had significantly longer mPFS in the first-line therapy than that in the second-line therapy when treated with gefitinib. EGFR mutation types may influence the response to gefitinib therapy.


Role of Intestinal Microbiota in the Bioavailability and Physiological Functions of Dietary Polyphenols.
Polyphenols are categorized as plant secondary metabolites, and they have attracted much attention in relation to human health and the prevention of chronic diseases. In recent years, a considerable number of studies have been published concerning their physiological function in the digestive tract, such as their prebiotic properties and their modification of intestinal microbiota. It has also been suggested that several hydrolyzed and/or fission products, derived from the catabolism of polyphenols by intestinal bacteria, exert their physiological functions in target sites after transportation into the body. Thus, this review article focuses on the role of intestinal microbiota in the bioavailability and physiological function of dietary polyphenols. Monomeric polyphenols, such as flavonoids and oligomeric polyphenols, such as proanthocyanidins, are usually catabolized to chain fission products by intestinal bacteria in the colon. Gallic acid and ellagic acid derived from the hydrolysis of gallotannin, and ellagitannin are also subjected to intestinal catabolism. These catabolites may play a large role in the physiological functions of dietary polyphenols. They may also affect the microbiome, resulting in health promotion by the activation of short chain fatty acids (SCFA) excretion and intestinal immune function. The intestinal microbiota is a key factor in mediating the physiological functions of dietary polyphenols.


A Novel Deep Learning Method to Predict Lung Cancer Long-Term Survival With Biological Knowledge Incorporated Gene Expression Images and Clinical Data.
Lung cancer is the leading cause of the cancer deaths. Therefore, predicting the survival status of lung cancer patients is of great value. However, the existing methods mainly depend on statistical machine learning (ML) algorithms. Moreover, they are not appropriate for high-dimensionality genomics data, and deep learning (DL), with strong high-dimensional data learning capability, can be used to predict lung cancer survival using genomics data. The Cancer Genome Atlas (TCGA) is a great database that contains many kinds of genomics data for 33 cancer types. With this enormous amount of data, researchers can analyze key factors related to cancer therapy. This paper proposes a novel method to predict lung cancer long-term survival using gene expression data from TCGA. Firstly, we select the most relevant genes to the target problem by the supervised feature selection method called mutual information selector. Secondly, we propose a method to convert gene expression data into two kinds of images with KEGG BRITE and KEGG Pathway data incorporated, so that we could make good use of the convolutional neural network (CNN) model to learn high-level features. Afterwards, we design a CNN-based DL model and added two kinds of clinical data to improve the performance, so that we finally got a multimodal DL model. The generalized experiments results indicated that our method performed much better than the ML models and unimodal DL models. Furthermore, we conduct survival analysis and observe that our model could better divide the samples into high-risk and low-risk groups.


Dipeptides Embedded in a Lipid Bilayer Membrane as Synthetic Water Channels.
Water channels are essential to life sciences and many biological processes. We report a molecular simulation study on dipeptides embedded in a lipid (dipalmitoylphosphatidylcholine) membrane as synthetic water channels. Five dipeptides are examined including FF, FL, LF, and LL (with hydrophilic channels) and AV (with hydrophobic channel). It is found that AV is unstable in the lipid membrane due to incompatible interaction between the hydrophilic external surface of AV and the hydrophobic lipid tails; whereas FF, FL, LF, and LL with hydrophobic external surface exhibit good stability. In the four hydrophilic channels FF, FL, LF, and LL, water chains are formed; the number of chains ranges from multiple, two to one depending on channel diameter; moreover, water undergoes single-file diffusion and the mobility is enhanced with increasing channel diameter. The permeation rate of water in the FF channel is 9.20/ns, about three times that in aquaporin; however, the rate in FL, LF, and LL is much slower. Intriguingly, the rate can be tuned by a lateral stress/strain on the lipid membrane. The simulation study provides fundamental understanding on the stability of dipeptide channels embedded in a lipid membrane, quantitatively characterizing water structure, dynamics, and permeation in the channels. These microscopic insights are useful for the development of new water channels.


Radiofrequency ablation of osteoid osteoma: initial results with a bipolar ablation device.
To report the initial results with percutaneous radiofrequency (RF) ablation of osteoid osteomas with a bipolar ablation device. Twelve patients (seven male patients and five female patients; mean age, 17.3 years; age range, 6-36 y) with clinically and radiologically suspected osteoid osteoma were treated with computed tomography-guided percutaneous bipolar RF ablation. The procedure was performed with the patients under general anesthesia. After localization of the nidus, an 11-gauge hollow drill was introduced into the nidus through a 9-F introducer sheath. A bipolar 18-gauge RF probe with a 9-mm active tip was inserted through the introducer sheath and connected to the RF generator. Energy application was started at 2 W and subsequently increased to a maximum of 5 W. The procedure was terminated if a resistance of 900 Omega was reached. Mean duration of energy deposition was 8.3 +/- 4.0 minutes, with a mean energy application of 1.8 +/- 2.9 kJ (range, 0.3 - 7 kJ). In one patient, the intervention had to be repeated twice to achieve total pain relief. Eleven of 12 patients (92%) remained free of symptoms at a follow-up time of 15.1 +/- 9.5 months (range, 5 - 31 months). One patient had recurrence of pain 16 months after the procedure and was treated surgically. No complications occurred. Patients resumed normal activity within 24 hours. Percutaneous bipolar RF ablation is an efficient and safe treatment of osteoid osteoma. Short-term efficacy of bipolar RF ablation may rival the results of monopolar RF ablation. Further studies are needed to address the long-term efficacy of this technique.


A painful gum.
This middle aged Malaysian man presented complaining of painful gums for a few months. He is known to have had epilepsy since childhood.


Effects of different light wavelengths at equal irradiance on testis weight, protein content, and K-paranitrophenylphosphatase activity in the Syrian hamster.
The effects of different light wavelengths at equal irradiance on testis weight, testis protein content, and testis K-paranitrophenylphosphatase (K-pNPPase) activity were studied in the Syrian hamster. One group (long photoperiod) was maintained on a light:dark cycle of 14:10, and another group (short photoperiod) on a cycle of 10:14. Five other groups were maintained on a cycle of 10:14 but with a one hour pulse of equally intense illumination in the middle of the dark period with UV, blue, green, yellow or red light. Animals exposed to a long photoperiod or UV, blue or green light pulses had significantly greater testis weights--up to eightfold greater than those in the yellow or red or short photoperiod groups. Organ protein content closely paralleled organ weight, but the protein/wet weight ratio was consistently higher in the large organ groups. K-pNPPase and Mg-pNPPase activities were significantly higher in the large organ groups, even when expressed per mg protein. Therefore, at a balanced irradiance of 0.2uW/cm2, light wavelength exerts a profound effect on testicular weight, protein content, and K-pNPPase and Mg-pNPPase activities. Testicular involution is a process that is selective with regard to protein biosynthesis.


The role of cerebral arteriovenous malformations in psychiatric disturbances: case report.
A patient is described who had congenital vascular malformation of the vein of Galen, with several psychiatric, as well as neurologic, manifestations. Prior to this patient's death, there was an increase in some psychiatric manifestations in response to suggestions of surgical therapy for the cerebral venous anomaly. Other symptoms appeared to represent direct organic effects of the lesion. The medical literature on the anomalies of the great vein of Galen reveals a frequent but not specific relationship to concomitant psychiatric manifestations.


Properties of the Shapiro steps in the ac driven Frenkel-Kontorova model with deformable substrate potential.
Properties of the dynamical-mode-locking phenomena are studied in the ac driven overdamped Frenkel-Kontorova model with deformable substrate potential. Appearance of very large subharmonic steps due to deformation of the substrate potential significantly influences the stability and existence of harmonic steps. Strong correlation among harmonic and subharmonic steps has been observed in which the larger the width of half-integer steps, the smaller that of harmonic steps. Amplitude dependence of harmonic steps significantly changes with the deformation of the potential where deviation from the well-known Bessel-like oscillations appears. Strong influence of the frequency of the ac driving force on the appearance and size of subharmonic steps has been observed.


Neuropsychological Profile of a Girl with Wiskott-Aldrich Syndrome.
We report the neuropsychological profile of a 6-year-old girl with Wiskott-Aldrich syndrome, a rare X-linked immunodeficiency disorder associated with thrombocytopenia, eczema, recurrent infections, and malignancy. Wiskott-Aldrich syndrome occurs almost exclusively in males and is extremely rare in females, with no known research focused on cognitive and academic functioning in this population. Our patient was referred due to concerns about her memory and academic functioning. She had a history of progressive thrombocytopenia and hematopoietic stem cell transplantation at age 15 months. Standardized measures of intellectual ability, language, visual-spatial and visual-motor skills, attention, memory, and academic achievement were administered. The results showed average to above-average performance in multiple areas of cognitive and academic functioning, with weaknesses in phonological awareness and rapid naming. The advent of hematopoietic stem cell transplantation has led to considerable improvement in the long-term prognosis of children with Wiskott-Aldrich syndrome. Although the impact of this syndrome and related conditions on neurocognitive development is presently unknown, this case highlights both the importance of considering base rates for commonly occurring conditions and the significant role neuropsychology can play in identifying cognitive strengths and weaknesses in the context of the developing brain.


A novel subgroup of rhadinoviruses in ruminants.
In the course of investigating the malignant catarrhal fever (MCF) subgroup of rhadinoviruses, seven novel rhadinoviruses were identified in a variety of ruminants, including domestic sheep, bighorn sheep, bison, black-tailed deer, mule deer, fallow deer, elk and addax. Based on the DNA polymerase gene sequences, these newly recognized viruses clustered into a second distinct subgroup in ruminants with three members identified previously in cattle, goats and oryx. Phylogenetic analysis revealed that the currently known ruminant rhadinoviruses appear to comprise three distinct genetic lineages: (i) the MCF subgroup, defined by sequence identity and the presence of the 15A antigenic epitope; (ii) a second distinct subgroup, devoid of the 15A epitope, which contains the previously reported bovine lymphotropic herpesvirus and related viruses; and (iii) a third distinct subgroup represented by Bovine herpesvirus 4. Comparison of phylogenetic trees between the rhadinoviruses and their corresponding hosts further supports the gammaherpesvirus and host co-evolution theory.


Brewing Quality of Hop Varieties Cultivated in Central Italy Based on Multivolatile Fingerprinting and Bitter Acid Content.
The brewing value of hops is mainly affected by the content and composition of humulones (α-acids) and essential oil. Interest in hop plantations is increasing more and more in Italy, in parallel with the rising number of microbreweries and brewpubs, which are strongly oriented towards local production chains. In this context, a selection of 15 international hop varieties were grown, under the same conditions, in an experimental field in the Marche region, Central Italy, with the aim of assessing their suitability for beer production. A multivariate analysis approach to experimental data showed a high content of α- and b-acids and myrcene in the Centennial, Brewer's Gold, Sterling, Cascade, Nugget, and Columbus varieties; a consistently lower percentages of humulones and a predominance of sesquiterpene hydrocarbons in the cultivars Mount Hood, Northern Brewer, Northdown, Galena, Willamette, and Fuggle; and a desirable high α-acids content and a sesquiterpene-type aroma in cultivars Chinook, Yeoman, and Hallertau. Further studies are needed to assess the environmental adaptability and the yield performance of hop plants in the pedoclimatic conditions of the Central Italy hills.


[Purinergic P2X family and specific features of the P2X7 subtype].
Purinergic P2X receptors (P2XR), activated by extracellular adenosine 5'-triphosphate (ATP), represent a specific type of ligand-gated ion channels. They form functional trimeric homomers or heteromers which are nonselectively cation-permeable after receptor activation. P2X receptors are widely expressed in excitable and nonexcitable tissues and are involved in many physiological and pathophysiological processes such as platelet aggregation, contraction of smooth muscle, immune responses, cell proliferation and apoptosis or neurotransmission. In mammals, seven P2X subunits (P2X1-P2X7) have been identified. They differ mainly in distribution, pharmacological profile and kinetics of ATP-induced responses. The subtype P2X7 is the most specific in the P2X family and widely differs from other P2X subtypes.


Ultrafast all-optical three-input Boolean XOR operation for differential phase-shift keying signals using periodically poled lithium niobate.
We propose and demonstrate that periodically poled lithium niobate (PPLN) can act as an ultrafast three-input XOR gate for differential phase-shift keying (DPSK) signals based on cascaded sum- and difference-frequency generation. PPLN-based all-optical three-input Boolean XOR operations for 20 Gbits/s return-to-zero DPSK (RZ-DPSK), 40 Gbits/s RZ-DPSK, and 20 Gbits/s non-return-to-zero DPSK signals are all successfully verified in the experiment.


A Catalytically Independent Function of Human DNA Polymerase Kappa Controls the Stability and Abundance of Checkpoint Kinase 1.
DNA polymerase kappa (Pol κ) has been well documented thus far for its specialized DNA synthesis activity during translesion replication, progression of replication forks through regions difficult to replicate, restart of stalled forks, and replication checkpoint efficiency. Pol κ is also required for the stabilization of stalled forks, although the mechanisms are poorly understood. In this study, we unveiled an unexpected role for Pol κ in controlling the stability and abundance of checkpoint kinase 1 (Chk1), an important actor for the replication checkpoint and fork stabilization. We found that loss of Pol κ decreased the Chk1 protein level in the nuclei of four human cell lines. Pol κ and not the other Y family polymerase members is required to maintain the Chk1 protein pool all along the cell cycle. We showed that Pol κ depletion affected the protein stability of Chk1 and protected it from proteasome degradation. Importantly, we also observed that the fork restart defects observed in Pol κ-depleted cells could be overcome by the reexpression of Chk1. Strikingly, this new function of Pol κ does not require its catalytic activity. We propose that Pol κ could contribute to the protection of stalled forks through Chk1 stability.


Purine synthesis de novo and its regulation in rat hepatocytes.
Purine synthesis de novo and its regulation were studied in freshly isolated hepatocytes from fed adult male rats. The cells incorporated [14C]formate mainly into purine ribonucleotides. The immediate effect of increasing the concentration of inorganic phosphate in the incubation medium was an increase in 5-phosphoribosyl 1-pyrophosphate (PP-ribose-P) availability and a stimulation of purine synthesis de novo. However, prolonged incubation of cells in 25 mM phosphate resulted in a decreased PP-ribose-P availability and purine synthesis de novo. Methylene blue and phenazine methosulfate decreased PP-ribose-P availability and purine synthesis de novo although they stimulated considerably the pentose phosphate pathway. In contrast, epinephrine and glucagon increased significantly PP-ribose-P availability and purine synthesis de novo, but they did not change the activity of the pentose phosphate pathway. These results show a relationship between PP-ribose-P availability and purine synthesis de novo in rat hepatocytes. They emphasize the complexity of the regulation of PP-ribose-P availability.


Proteomic profiling shows mitochondrial nucleoids are autophagy cargo in neurons: implications for neuron maintenance and neurodegenerative disease.
Neurons depend on macroautophagy/autophagy to maintain cellular homeostasis, and loss of autophagy leads to neurodegeneration. To better understand the role of basal autophagy in neurons, we enriched autophagic vesicles from healthy adult mouse brain and performed mass spectrometry to identify cargos cleared by autophagy. We found that synaptic and mitochondrial proteins comprise nearly half of the unique AV cargos identified in brain. Similarly, synaptic and mitochondrial proteins are major cargos for basal autophagy in neurons. Strikingly, we noted a specific enrichment of mitochondrial nucleoids within neuronal autophagosomes, which occurs through a mechanism distinct from damage-associated mitophagy. Here, we discuss the implications of these findings for our understanding of homeostatic mechanisms in neurons and how the age-dependent decline of autophagy in neurons may contribute to the onset or progression of neurodegenerative disease.


PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection.
Enhancing the response to interferon could offer an immunological advantage to the host. In support of this concept, we used a modified form of the transcription factor STAT1 to achieve hyper-responsiveness to interferon without toxicity and markedly improve antiviral function in transgenic mice and transduced human cells. We found that the improvement depended on expression of a PARP9-DTX3L complex with distinct domains for interaction with STAT1 and for activity as an E3 ubiquitin ligase that acted on host histone H2BJ to promote interferon-stimulated gene expression and on viral 3C proteases to degrade these proteases via the immunoproteasome. Thus, PARP9-DTX3L acted on host and pathogen to achieve a double layer of immunity within a safe reserve in the interferon signaling pathway.


A note on vowel patterns in two normally developing children.
The present paper reports on vowel patterns in two normally developing children, aged 1; 10-2;0 and 2;0-2;2 (years;months;days), during the period of the investigation. The study was undertaken to analyse vowel patterns not previously identified as being widespread among children (Stoel-Gammon and Dunn, 1985). Results indicated the existence of patterns involving [ai], height errors among front vowels, and resyllabification of long vowels.


Kirschner Wire Fixation in Dorsally Displaced Distal Radius Fractures: A Biomechanical Evaluation.
Background There is currently no consensus for the optimum configuration and number of Kirschner wires (K-wires) to use for the stabilization of dorsally displaced distal radius fractures. In this biomechanical study, we compared the load to failure and stiffness of four common K-wire configurations to identify the strongest construct for use in extra-articular dorsally displaced distal radius fractures. Case Description We created a standard distal radius fracture model in turkey tarsometatarsi which was stabilized using two or three K-wires (1.6 mm) in four different configurations. Following a power calculation, 10 fracture models of each configuration underwent testing in cantilever bending and axial compression. Literature Review Recent randomized trials have shown no evidence that volar locking plates are superior to K-wires for the treatment of dorsally displaced distal radius fractures. This has led to an increase in the popularity of much cheaper K-wires. Several different K-wire techniques have been described but there is no strong evidence to determine which is the optimal configuration and number of wires. Clinical Relevance The three-wire interfragmentary configuration was stiffer than the three-wire Kapandji in axial compression and cantilever bending. There was no difference in load to failure in cantilever bending or axial compression. The three-wire interfragmentary technique is the stiffest configuration of K-wires for dorsally displaced distal radius fractures. The two-wire Kapandji technique was significantly weaker than the other configurations, especially in cantilever bending. Conclusion The authors recommend to always use three wires for percutaneous pinning and never to use two intrafocal wires alone.


Nested multiplex RT-PCR for detection and differentiation of West Nile virus and eastern equine encephalomyelitis virus in brain tissues.
A traditional nested reverse transcription-polymerase chain reaction (RT-PCR) assay specific for eastern equine encephalomyelitis (EEE) virus was designed to multiplex with a previously described West Nile (WN) virus nested RT-PCR assay. Differentiation of EEE and WN was based on base pair size of the amplified product. One hundred fifty-seven mammalian and avian brain tissues were tested by EEE/WN nested multiplex RT-PCR, EEE nested RT-PCR, and WN nested RT-PCR, and results were compared with other diagnostic test results from the same animals. Serological and virus isolation testing confirmed the results of the multiplex PCR assay. When compared with cell culture virus isolation, the multiplex assay was shown to be more sensitive in detecting the presence of EEE or WN virus in brain tissues. The multiplex assay was shown to be sensitive and specific for North American EEE and WN and provided a rapid means of identifying both viruses in brain tissues. No apparent sacrifice in sensitivity was observed in the multiplex procedure compared with the individual EEE and WN nested RT-PCR assays. Data collected from an additional 485 multiplex RT-PCR tests conducted during the summer and fall of 2002 further support the validity of the procedure.


Effect of Statins on Serum level of hs-CRP and CRP in Patients with Cardiovascular Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Several studies have reported that statins have anti-inflammatory effects. Nevertheless, results of clinical trials concerning the effect of statins on the levels of C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP) have been inconsistent. Therefore, we performed a systematic review and meta-analysis of randomized clinical trials (RCTs) evaluating the effect of statins on CRP and hs-CRP levels in patients with cardiovascular diseases (CVDs). Literature search of the major databases was performed to find eligible RCTs assessing the effect of statins on serum levels of CRP and hs-CRP from the inception until the last week of April 2021. The effect sizes were determined for weighted mean difference (WMD) and 95% confidence intervals (CI). 26 studies were identified (3010 patients and 2968 controls) for hs-CRP and 20 studies (3026 patients and 2968 controls) for CRP. Statins reduced the serum levels of hs-CRP (WMD = -0.97 mg/L; 95% CI: -1.26 to -0.68 mg/L; P < 0.001) and CRP (WMD = -3.05 mg/L; 95% CI: -4.86 to -1.25 mg/L; P < 0.001) in patients with CVDs. Statins decreased the serum levels of hs-CRP in patients receiving both high-intensity and moderate/low-intensity treatments with these drugs. In addition, the duration of treatment longer than 10 weeks decreased hs-CRP levels. Only high-intensity statin treatment could marginally decrease serum levels of CRP in CVDs patients. This meta-analysis showed the efficacy of statins to reduce the concentrations of CRP and hs-CRP in patients with different types of CVDs.


Intervention study on school meal habits in Norwegian 10-12-year-old children.
The aim of this study was to investigate whether a free school meal every day was associated with children's intake of healthy food during school. A non-randomized study design with an intervention and a control group was used to measure change in children's meal habits at lunchtime. In total, 164 children participated; 55 in the intervention group and 109 in the control group. Children in the intervention group were served a free, healthy school meal every school day. Participating children completed a questionnaire at baseline and at 6 months' follow up. Possible associations were evaluated with a healthy food score, which was calculated based on a food frequency questionnaire on lunch habits at school. Chi-square and Independent Samples t-test were used to analyse the data. At baseline, there was no significant difference in the healthy food score between the intervention and the control group ( p = 0.08). Children in the intervention group increased their healthy food score significantly compared with children in the control group after 6 months ( p ⩽ 0.01). Change in the healthy food score was mainly due to an increase in the intake of fruit ( p ⩽ 0.01), vegetables ( p ⩽ 0.01) and fish spread ( p = 0.02); all in favour of the intervention group. A serving of a free school meal every day for 6 months increased children's intake of healthy food at lunchtime compared with the control group. Further studies are needed to establish possible long-term effects.


Pavement crack detection based on point cloud data and data fusion.
The three-dimensional detection in point cloud data for pavement cracks has drawn the attention of many researchers recently. In the field of pavement surface point cloud detection, the key tasks include the identification of pavement cracks and the extraction of the location and size information of pavement cracks. Based on the point cloud data of pavement surface, we developed two methods to directly extract and detect cracks, respectively. The first method is based on the improved sliding window algorithm by combining the random sample consensus (RANSAC) technique to directly extract the crack information from point clouds. The second method is developed based on YOLOv5 to process the two-dimensional images transformed from point cloud data for automatic pavement crack detection. We also attempted to fuse the point cloud images with greyscale images as input for the YOLOv5. Analysis results show that the improved sliding window algorithm efficiently extracts pavement cracks with less noise, and the YOLOv5-based method obtains a good detection of pavement cracks. This article is part of the theme issue 'Artificial intelligence in failure analysis of transportation infrastructure and materials'.


Measuring research workload to support resource planning.
Clinical research is inherent in clinical practice and recent changes to how medical research is funded and delivered in the U.K. increase the need for managers to understand the effects of research activity in their areas. The U.K. Clinical Research Facilities Network study intensity tool is a research-specific workforce planning tool designed to assess and predict the amount of time and staffing required for individual research studies. This article shows how the tool can be used by non-research managers, organisations, research nurses and allied health professionals to plan, assess and monitor studies, and to maintain a value-for-money service.


Analysis of print news media framing of ketamine treatment in the United States and Canada from 2000 to 2015.
There are multifaceted views on the use of ketamine, a potentially addictive substance, to treat mental health problems. The past 15 years have seen growing media coverage of ketamine for medical and other purposes. This study examined the print news media coverage of medical and other uses of ketamine in North America to determine orientations and trends over time. Print newspaper coverage of ketamine from 2000 to 2015 was reviewed, resulting in 43 print news articles from 28 North American newspapers. A 55-item structured coding instrument was applied to assess news reports of ketamine. Items captured negative and positive aspects, therapeutic use of ketamine, and adverse side effects. Chi-squares tested for changes in trends over time. In the 15-year reviewed period, the three most frequent themes related to ketamine were: abuse (68.2%), legal status (34.1%), and clinical use in anesthesia (31.8%). There was significant change in trends during two periods (2000-2007 and 2008-2015). In 2008-2015, print news media articles were significantly more likely to encourage clinical use of ketamine to treat depression (p = 0.002), to treat treatment resistant depression (p = 0.043), and to claim that ketamine is more effective than conventional antidepressants (p = 0.043). Our review found consistent positive changes in the portrayals of ketamine by the print news media as a therapeutic antidepressant that mirror the recent scientific publications. These changes in news media reporting might influence the popularity of ketamine use to treat clinical depression. Guidance is required for journalists on objective reporting of medical research findings, including limitations of current research evidence and potential risks of ketamine.


Single dose treatment of malaria - current status and perspectives.
Despite increased international efforts for control and ultimate elimination, malaria remains a major health problem. Currently, artemisinin-based combination therapies are the treatment of choice for uncomplicated malaria exhibiting high efficacy in clinical trial settings in sub-Saharan Africa. However, their administration over a three-day period is associated with important problems of treatment adherence resulting in markedly reduced effectiveness of currently recommended antimalarials under real world settings. Antimalarial drug candidates and antimalarial drug combinations currently under advanced clinical development for the indication as single dose antimalarial therapy. Expert commentary: Several new drug candidates and combinations are currently undergoing pivotal proof-of-concept studies or clinical development programmes. The development of a single dose combination therapy would constitute a breakthrough in the control of malaria. Such an innovative treatment approach would simultaneously close the effectiveness gap of current three-day therapies and revolutionize population based interventions in the context of malaria elimination campaigns.


Incidence of next-day anterograde amnesia caused by flurazepam hydrochloride and triazolam.
The incidence of next-day anterograde amnesia was evaluated in hospitalized patients who received flurazepam hydrochloride or triazolam. A blinded observer assessed memory and daytime drowsiness in 154 patients after the bedtime ingestion of flurazepam hydrochloride (n = 54), triazolam (n = 49), or no hypnotic drug (n = 51). The hypnotic agents were administered before midnight. At approximately 0800 the next morning, the patients were shown a picture of an object on colored construction paper and asked to remember it as well as the color of the background. Both the observer and patient assessed drowsiness using the Stanford Sleepiness Scale. The observer also made a note of the items on the patient's breakfast tray. Patients were then revisited at 1100 and asked to recall the object in the picture, the color of the background, and at least three items from their breakfast tray. Ten of the 54 patients in the flurazepam group failed to recall all three items compared with only two in the triazolam group and two in the control group. The 14 patients who experienced memory impairment were significantly more drowsy at 0800 than those who were able to recall the items. Next-day anterograde amnesia occurred more frequently in patients who received flurazepam hydrochloride than in those who received triazolam or no hypnotic drug. This effect may be related to the next-day drowsiness caused by flurazepam and its slowly eliminated active metabolite.


Tryptophan catabolism reflects disease activity in human tuberculosis.
There is limited understanding of the role of host metabolism in the pathophysiology of human tuberculosis (TB). Using high-resolution metabolomics with an unbiased approach to metabolic pathway analysis, we discovered that the tryptophan pathway is highly regulated throughout the spectrum of TB infection and disease. This regulation is characterized by increased catabolism of tryptophan to kynurenine, which was evident not only in active TB disease but also in latent TB infection (LTBI). Further, we found that tryptophan catabolism is reversed with effective treatment of both active TB disease and LTBI in a manner commensurate with bacterial clearance. Persons with active TB and LTBI also exhibited increased expression of indoleamine 2,3-dioxygenase-1 (IDO-1), suggesting IDO-1 mediates observed increases in tryptophan catabolism. Together, these data indicate IDO-1-mediated tryptophan catabolism is highly preserved in the human response to Mycobacterium tuberculosis and could be a target for biomarker development as well as host-directed therapies.


Mapping effects in choice-response and go/no-go variants of the lexical decision task: A case for polarity correspondence.
Previous research has shown that responses to words are faster and more accurate in the go/no-go version of the lexical decision task (LDT) than in the choice-response version. This finding has been attributed to reduced response-selection demands in the go/no-go task. Here, we test an alternative account assuming similar response-selection demands in the two tasks, but an additional impact of polarity correspondence between stimuli and responses in the go/no-go task. Positive and negative polarities have been described as a frequent characteristic of binary stimulus and response dimensions. Only for the go/no-go version of the LDT, an apparent polarity difference between go and no-go responses exists, with go responses having the same polarity as words and no-go responses the same polarity as nonwords. Thus, compared with the choice-response LDT, in the go/no-go LDT, go responses to words should be facilitated by polarity correspondence, and go responses to nonwords should be inhibited by polarity noncorrespondence. In this study, each participant performed a go/no-go LDT and a choice-response LDT. Responses to words were faster and more accurate than responses to nonwords, and-consistent with the alternative account-this difference was larger in the go/no-go LDT than in the choice-response LDT. An analysis of performance by means of sequential-sampling models that take into account a decaying influence of irrelevant stimulus features supported the effect of polarity correspondence in the go/no-go LDT. This analysis suggested an effect in the choice-response LDT as well, though of a smaller size and a faster decay.


Microcirculation and Hemorheology.
Major experimental and theoretical studies on microcirculation and hemorheology are reviewed with the focus on mechanics of blood flow and the vascular wall. Flow of the blood formed elements (red blood cells (RBCs), white blood cells or leukocytes (WBCs) and platelets) in individual arterioles, capillaries and venules, and in microvascular networks is discussed. Mechanical and rheological properties of the formed elements and their interactions with the vascular wall are reviewed. Short-term and long-term regulation of the microvasculature is discussed; the modes of regulation include metabolic, myogenic and shear-stress-dependent mechanisms as well as vascular adaptation such as angiogenesis and vascular remodeling.


Effects of exercise therapy on disability, mobility, and quality of life in the elderly with chronic low back pain: a systematic review and meta-analysis of randomized controlled trials.
Exercise is an effective treatment in chronic low back pain (CLBP), but there are few studies on CLBP in the elderly, and the intervention effect is controversial. We aimed to compare the efficacy of different exercises therapy on CLBP, dysfunction, quality of life, and mobility in the elderly. We searched Web of Science, MEDLINE, Cochrane Library, Chinese National Knowledge Infrastructure, EMBASE, and PubMed from the database inception till December 31, 2022. The publication languages were Chinese and English. Randomized controlled trials (RCTs) of exercise intervention in the elderly (≥ 60 years) with CLBP were included. Two reviewers independently extracted the data and evaluated them using the Revised Cochrane Risk of Bias Tool for Randomized Trials 2 (RoB2). The pooled effect sizes on different aspects of outcome measures were calculated. Sixteen articles (18 RCTs) were included, comprising a total of 989 participants. The quality of included studies was relatively high. Meta-analysis results indicated that exercise therapy could improve visual analog scale (VAS) (WMD = - 1.75, 95% CI - 2.59, - 0.92, p < 0.05), Oswestry disability index (ODI) (WMD = - 9.42, 95% CI - 15.04, - 3.79, p < 0,005), short-form 36-item health survey physical composite summary (SF-36PCS) (WMD = 7.07, 95% CI 1.01, 13.14, p < 0.05), short-form 36-item health survey mental composite summary (SF-36MCS) (WMD = 7.88, 95% CI 0.09, 15.67, p < 0.05), and timed up and go test (TUG) (WMD = - 0.92, 95% CI - 2.22, 0.38, p < 0.005). Exercise therapy effectively improved VAS, ODI, and SF-36 indexes in the elderly. Based on the subgroup, when designing the exercise therapy regimen, aerobics, strength, and mind-body exercise (≥ 12 weeks, ≥ 3 times/week, ≥ 60 min) should be considered carefully, to ensure the safety and effectiveness for the rehabilitation of CLBP patients. More high-quality trials are needed in future to confirm the effect of exercise on SF-36 and TUG indexes.


Theatrical performance in medical education: A fast-track differential approach of emergency cases.
The idea of implementing theatrical acts in medical education has recently been gaining attention, with the inclusion of art-based programs in medical curricula being a growing trend. This study aimed to present an innovative pilot program of presenting medical emergencies through theatrical presentation. Students-members of the theatrical team of Democritus University of Thrace and the Scientific Society of Hellenic Medical Students were appointed into eight groups, supervised by a clinical tutor. The groups were given four weeks to prepare scenarios for eight different medical emergencies and organize a theatrical sketch accordingly. A 25-item questionnaire was formed and distributed to the audience. Each theatrical act lasted 10 min, followed by a 10 min discussion between the tutors and the audience. After the event, the impressions of the attendees were documented in the questionnaire as responses on a Likert scale from one (strongly disagree) to five (strongly agree). Two hundred and thirty-two fully completed questionnaires were returned. The contribution of theatrical presentation to medical education was widely acknowledged (Likert score 4.14 ± 0.68). Theatrical seminars were not deemed insufficient to provide medical information (disagreed or strongly disagreed 53.8 % and 12.1 %, respectively). Most students were optimistic about the long-term maintenance of the theatrical-aided knowledge, with the majority of attendees (52.1 %) adapting a more favorable response after the seminar (p <0.001). The students' efficacy to recognize medical emergencies was improved (from 2.96 to 3.43, p <0.001). Students find the theatrical approach of emergency cases entertaining and educational, facilitating teaching in medicine and enhancing their efficacy to recognize medical emergencies and the commonest pitfalls in their diagnosis and management. Such events may be established as a supplementary educational tools to the classical amphitheatric didactic lectures. Future studies with specific objective tools are needed to validate the abovementioned tasks. HIPPOKRATIA 2020, 24(3): 127-132.


A substituted anilino enaminone acts as a novel positive allosteric modulator of GABA(A) receptors in the mouse brain.
A small library of anilino enaminones was analyzed for potential anticonvulsant agents. We examined the effects of three anilino enaminones on neuronal activity of output neurons, mitral cells (MC), in an olfactory bulb brain slice preparation using whole-cell patch-clamp recording. These compounds are known to be effective in attenuating pentylenetetrazol-induced convulsions. Among the three compounds tested, 5-methyl-3-(4-trifluoromethoxy-phenylamino)-cyclohex-2-enone (KRS-5Me-4-OCF₃) showed potent inhibition of MC activity with an EC₅₀ of 24.5 μM. It hyperpolarized the membrane potential of MCs accompanied by suppression of spontaneous firing. Neither ionotropic glutamate receptor blockers nor a GABA(B) receptor blocker prevented the KRS-5Me-4-OCF(3)-evoked inhibitory effects. In the presence of GABA(A) receptor antagonists, KRS-5Me-4-OCF(3) completely failed to evoke inhibition of MC spiking activity, suggesting that KRS-5Me-4-OCF₃-induced inhibition may be mediated by direct action on GABA(A) receptors or indirect action through the elevation of tissue GABA levels. Neither vigabatrin (a selective GABA-T inhibitor) nor 1,2,5,6-tetrahydro-1-[2-[[(diphenylmethylene)amino]oxy]ethyl]-3-pyridinecarboxylic acid hydrochloride (NNC-711) (a selective inhibitor of GABA uptake by GABA transporter 1) eliminated the effect of KRS-5ME-4-OCF₃ on neuronal excitability, indicating that the inhibitory effect of the enaminone resulted from direct activation of GABA(A) receptors. The concentration-response curves for GABA are left-shifted by KRS-5Me-4-OCF₃, demonstrating that KRS-5Me-4-OCF₃ enhanced GABA affinity and acted as a positive allosteric modulator of GABA(A) receptors. The effect of KRS-5Me-4-OCF₃ was blocked by applying a benzodiazepine site antagonist, suggesting that KRS-5Me-4-OCF₃ binds at the classic benzodiazepine site to exert its pharmacological action. The results suggest clinical use of enaminones as anticonvulsants in seizures and as a potential anxiolytic in mental disorders.


Idiopathic CD4 lymphocytopenia and opportunistic infection--an update.
A severe CD4 T-cell depletion predisposes humans to opportunistic infections. In recent years, reports of cases of opportunistic infections caused by CD4 T-cell depletion without HIV infection have been accumulating. Such cases, termed idiopathic CD4 T lymphocytopenia (ICL), are very rare. The epidemiologic data do not suggest that the condition is caused by a transmissible agent. Unlike HIV infection, the decrease in the CD4 cell counts of patients with ICL is often slow. The clinical spectrum of ICL ranges from an asymptomatic laboratory abnormality to life-threatening opportunistic infections. However, the pathogens, clinical significance and treatment of ICL patients still await systematic research. This review summarizes the current knowledge of the poorly understood syndrome of idiopathic CD4 lymphocytopenia, providing key insights into the pathogenesis and immunologic characteristics, and suggesting approaches to enhance CD4 T-cell counts.


Health-Related Quality of Life of Young Adults Treated with Recombinant Human Growth Hormone during Childhood.
Since recombinant human growth hormone (rhGH) became available in 1985, the spectrum of indications has broadened and the number of treated patients increased. However, long-term health-related quality of life (HRQoL) after childhood rhGH treatment has rarely been documented. We assessed HRQoL and its determinants in young adults treated with rhGH during childhood. For this study, we retrospectively identified former rhGH patients in 11 centers of paediatric endocrinology, including university hospitals and private practices. We sent a questionnaire to all patients treated with rhGH for any diagnosis, who were older than 18 years, and who resided in Switzerland at time of the survey. Three hundred participants (58% of 514 eligible) returned the questionnaire. Mean age was 23 years; 56% were women; 43% had isolated growth hormone deficiency, or idiopathic short stature; 43% had associated diseases or syndromes, and 14% had growth hormone deficiency after childhood cancer. Swiss siblings of childhood cancer survivors and the German norm population served as comparison groups. HRQoL was assessed using the Short Form-36. We found that the Physical Component Summary of healthy patients with isolated growth hormone deficiency or idiopathic short stature resembled that of the control group (53.8 vs. 54.9). Patients with associated diseases or syndromes scored slightly lower (52.5), and former cancer patients scored lowest (42.6). The Mental Component Summary was similar for all groups. Lower Physical Component Summary was associated with lower educational level (coeff. -1.9). Final height was not associated with HRQoL. In conclusion, HRQoL after treatment with rhGH in childhood depended mainly on the underlying indication for rhGH treatment. Patients with isolated growth hormone deficiency/idiopathic short stature or patients with associated diseases or syndromes had HRQoL comparable to peers. Patients with growth hormone deficiency after childhood cancer were at high risk for lower HRQoL. This reflects the general impaired health of this vulnerable group, which needs long-term follow-up.


Calibration of space-resolving VUV and soft X-ray spectrographs for plasma diagnostics.
Vacuum ultraviolet (VUV) and soft X-ray measurements are important means of diagnosing impurities in magnetically confined plasmas used in fusion research. Recently, space- and time-resolving flat-field VUV (150-1050 A) and soft X-ray (20-350 A) spectrographs have been constructed by using aberration-corrected concave gratings with varied-spacing grooves which give a wide simultaneous spectral coverage on a microchannel-plate intensified detector. Calibration experiments have been performed at beamlines 11A and 11C at the Photon Factory of the High Energy Accelerator Research Organization. The relative efficiency of the VUV spectrograph has been measured for P-polarization geometry in the spectrograph. In the soft X-ray spectrograph, efficiencies have been obtained for several different points of irradiation on the grating along the groove direction and for two (S and P) polarization geometries.


Turning mannitol-rich agricultural waste to poly(3-hydroxybutyrate) with Cobetia amphilecti fermentation and recovery with methyl levulinate as a green solvent.
The present study explored the use of mannitol and mannitol-rich agro-industrial wastes as substrates for PHB production by Cobetia amphilecti isolated from the green Ulva sp. seaweed. Cultivation of C. amphilecti on mannitol, celery, and olive leaves (OLs) waste led to 4.20, 6.00, and 5.16 g L-1 of cell dry mass (CDM), 76.3, 25.5, and 12.0% of PHB content in CDM and 3.2, 1.53, and 0.62 g L-1 of PHB concentration, respectively; which suggested that they can be exploited as carbon substrates for the production of PHB. Extraction of PHB from C. amphilecti cultures by solubilization in the green solvent methyl levulinate (ML) (2% w/w, 140 °C, 1 h) indicated that the recovery yield and purity of PHB are above 97 and 90% w/w, respectively. The use of ML could be an attractive method for the recovery of PHB when safe and non-toxic solvents are required.


Trifluridine/tipiracil increases survival rates in peritoneal dissemination mouse models of human colorectal and gastric cancer.
A number of patients exhibit peritoneal dissemination of gastric or colorectal cancer, which is a predominant cause of cancer-associated mortality. Currently, there is no markedly effective treatment available. The present study was designed to determine the efficacy of trifluridine/tipiracil (TFTD), formerly known as TAS-102, which is used for the treatment of patients with unresectable advanced or recurrent colorectal cancer refractory to standard therapies. Four colorectal cancer cell lines and one gastric cancer cell line were intraperitoneally inoculated into nude mice, as models of peritoneal dissemination. TFTD (200 mg/kg/day) was orally administered for 5 consecutive days followed by 2 drug-free days for 6 weeks. The increase in the lifespan (ILS) of the TFTD-treated mice compared with that of the drug-free control mice was 66.7, 43.3, 106.3, 98.3 and 133.3% for DLD-1, DLD-1/5-fluorouracil [5-fluorouracil (5FU)-resistant subline of DLD-1], HT-29 and HCT116 colorectal cancer cell lines, and MKN45 gastric cancer cell line, respectively. This ILS was similar to that of the irinotecan-treated mice (ILS, 70-84%), but was significantly (P<0.05) increased compared with that of the 5FU-, tegafur, gimeracil and potassium oxonate- and cisplatin-treated mice (ILS, 1-53%, 0.8-60% and 85%, respectively). No significant increase in body weight loss was observed during the dosing periods with any of the drugs used. The increase in CEA levels with progressive peritoneal dissemination was inhibited by TFTD treatment. TFTD also exhibited marked anticancer effects against Kirsten rat sarcoma viral oncogene homolog-mutated tumors and 5FU-resistant tumors. The results of the present study indicate that TFTD may be a potential drug against peritoneal dissemination of colorectal and/or gastric cancer in humans and may be utilized for chemo-naïve tumors and recurrent tumors following 5FU treatment.


Relationship between depression and clinical outcome following anterior cervical discectomy and fusion.
Anterior cervical discectomy and fusion (ACDF) is a commonly performed procedure for patients with symptomatic degenerative conditions of the cervical spine. The objective is to assess the impact of preoperative depression and other baseline characteristics on patient reported clinical outcomes following ACDF surgery based on the experience at our institution. This was a retrospective cohort study of some patients undergoing ACDF at a single institution from 2012 to 2014. Ninety-three patients that underwent an ACDF procedure were included. The primary outcome measure was post-operative Nurick score. Sixteen (17.2%) patients had a formal diagnosis of depression compared to 77 (82.8%) patients without depression. On univariate analysis, patients with depression had statistically significantly higher Nurick scores compared to patients without depression after surgery (coefficient =0.55, 95% CI: 0.21-0.90, P=0.002). On multivariate analysis, there was a trend toward higher postoperative Nurick scores in patients that had depression (coefficient =0.31, 95% CI: -0.01-0.63, P=0.057). This small retrospective study reveals an inverse relationship between preoperative depression and functional outcome. Further research should be performed to investigate this relationship and to investigate if treating depression can improve postoperative outcomes.


In vivo reversal of multidrug resistance by two new dihydropyridine derivatives, S16317 and S16324.
Two new dihydropyridine derivatives with low calcium channel affinity, S16317 and S16324, were found to fully overcome multidrug resistance in vitro. These two compounds increased doxorubicin cytotoxicity on the human COLO 320DM cell line and completely reversed the vincristine resistance of murine P388/VCR cells. In vivo, S16324 administered p.o. (200 mg/kg on days 1 to 4) or i.p. (50 mg/kg on days 1, 5, 9) in combination with vincristine (i.p.) restored the antitumor activity of vincristine in P388/VCR-bearing mice. S16317 showed a reversing activity when administered p.o., i.v. (days 1 to 4) or i.p. (days 1, 5, 9) at the same dose (25 mg/kg), suggesting a remarkable bioavailability. Moreover, these two compounds potentiated the antitumor activity of vincristine in the sensitive P388 leukemia, increasing the number of long-term survivors. These results suggest that combination chemotherapy using S16317 or S16324 would be effective not only in circumventing multidrug resistance but also in preventing the emergency of a population of resistant tumor cells in sensitive tumors.


Integrating forward osmosis into microbial fuel cells for wastewater treatment, water extraction and bioelectricity generation.
A novel osmotic microbial fuel cell (OsMFC) was developed by using a forward osmosis (FO) membrane as a separator. The performance of the OsMFC was examined with either NaCl solution or artificial seawater as a catholyte (draw solution). A conventional MFC with a cation exchange membrane was also operated in parallel for comparison. It was found that the OsMFC produced more electricity than the MFC in both batch operation (NaCl solution) and continuous operation (seawater), likely due to better proton transport with water flux through the FO membrane. Water flux from the anode into the cathode was clearly observed with the OsMFC but not in the MFC. The solute concentration of the catholyte affected both electricity generation and water flux. These results provide a proof of concept that an OsMFC can simultaneously accomplish wastewater treatment, water extraction (from the wastewater), and electricity generation. The potential applications of the OsMFC are proposed for either water reuse (linking to reverse osmosis for reconcentration of draw solution) or seawater desalination (connecting with microbial desalination cells for further wastewater treatment and desalination).


Evidence of quorum sensing in the rumen ecosystem: detection of N-acyl homoserine lactone autoinducers in ruminal contents.
Acyl-homoserine lactone (AHL) based quorum-sensing systems are widespread among gram-negative bacteria, particularly in association with plants and animals. As yet, there have been no reports of AHL signaling in the anaerobic rumen environment, an ecosystem of great complexity in which cell-cell signaling is likely to occur. We detected multiple AHL autoinducers in the rumen contents of 6 out of 8 cattle fed a representative selection of diets. The signals were not associated with feed. Surprisingly, no pure cultures produced AHLs in vitro when grown under the laboratory conditions we tested. Our observations suggest that either (a) a factor specific to the rumen ecosystem is required for the rumen isolates we tested to produce AHLs or (b) a strain (or strains) that we were not able to culture but which grows to a high cell density in the rumen produces the AHLs we detected.


Purification, characterization and crystallization of pyrroline-5-carboxylate reductase from the hyperthermophilic archeon Sulfolobus Solfataricus.
The gene SSO0495 (proC), which encodes pyrroline-5-carboxylate reductase (P5CR) from the thermoacidophilic archeon Sulfolobus solfataricus P2 (Ss-P5CR), was cloned and expressed. The purified recombinant enzyme catalyzes the thioproline dehydrogenase with concomitant oxidation of NAD(P)H to NAD(P)+. This archeal enzyme has an optimal alkaline pH in this reversible reaction and is thermostable with a half-life of approximately 30 min at 80 degrees C. At pH 9.0, the reverse activation rate is nearly 3-fold higher than at pH 7.0. The homopolymer was characterized by cross-linking and size exclusion gel filtration chromatography. Ss-P5CR was crystallized by the hanging-drop vapor-diffusion method at 37 degrees C. Diffraction data were obtained to a resolution of 3.5A and were suitable for X-ray structure determination.


LigQ: A Webserver to Select and Prepare Ligands for Virtual Screening.
Virtual screening is a powerful methodology to search for new small molecule inhibitors against a desired molecular target. Usually, it involves evaluating thousands of compounds (derived from large databases) in order to select a set of potential binders that will be tested in the wet-lab. The number of tested compounds is directly proportional to the cost, and thus, the best possible set of ligands is the one with the highest number of true binders, for the smallest possible compound set size. Therefore, methods that are able to trim down large universal data sets enriching them in potential binders are highly appreciated. Here we present LigQ, a free webserver that is able to (i) determine best structure and ligand binding pocket for a desired protein, (ii) find known binders, as well as potential ligands known to bind to similar protein domains, (iii) most importantly, select a small set of commercial compounds enriched in potential binders, and (iv) prepare them for virtual screening. LigQ was tested with several proteins, showing an impressive capacity to retrieve true ligands from large data sets, achieving enrichment factors of over 10%. LigQ is available at http://ligq.qb.fcen.uba.ar/ .


Streaming potential/current measurement system for investigation of liquids confined in extended-nanospace.
The extended-nanospace, a space on the scale of 10(1)-10(3) nm, is mostly unexplored due to the lack of sufficient experimental technology. Recently, the research of liquid properties in the extended-nanospace has gathered much interest, because the behavior of water molecules in this space is between that of liquid-like bulk phase water molecules and single molecules. Due to the large surface-to-volume ratio in the channel, the surface charge of the wall directly affects the water structure and ion distribution. The streaming potential/current measurement method, which is used to evaluate surface states directly, is an important and useful method to investigate the liquid properties. In this paper, we report a new method for measuring the streaming potential/current in size-controlled 2D extended-nanospace on glass substrate. Nano-in-microfluidic systems were fabricated on fused-silica glass substrates, and the liquid was air-driven using a pressure controller. An equivalent circuit of the detection system was designed to selectively detect the potential and current in the extended-nanospace. The basic measurement principle was verified using several different experiments. The absolute values obtained for the potential and current were also compared with the theoretical values for various channel sizes (360-1650 nm), and good agreement was observed for micrometre-scale channels. This technique will be valuable for the investigation of chemistry and fluidics in the extended-nanospace.


Characterization of the invitro cytotoxic effects of brachydins isolated from Fridericia platyphylla in a prostate cancer cell line.
Brachydins (Br) A, B, and C are flavonoids extracted from Fridericia platyphylla (Cham.) L.G. Lohmann roots (synonym Arrabidaea brachypoda), whose extract previously exhibited cytotoxic and antitumor activity. In vitro cell culture of human prostate tumor cell line (PC-3) was used to determine cell viability as evidenced by MTT, neutral red, and LDH release using nine concentrations (0.24 to 30.72 µM) of each brachydin. A triple-fluorescent staining assay assessed the mechanism resulting in cell death. Genomic instability and protein expression were evaluated using comet assay and western blot analysis, respectively. The pro-oxidant status was analyzed using the5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate (CM-H2DCFDA) probe. The IC50 values for brachydins BrA, BrB, and BrC were 23.41, 4.28, and 4.44 µM, respectively, and all compounds induced apoptosis and necrosis. BrB and BrC increased p21 levels indicating a possible G1 cell cycle arrest. BrA (6 µM) and BrB (3.84 µM) decreased phospho-AKT (AKT serine/threonine kinase) expression, which also influenced cell cycle and proliferation. BrA, BrB, and BrC elevated cleaved PARP (poly (ADP-ribose) polymerase), a protein related to DNA repair and induction of apoptotic processes. Therefore, this study determined the IC50 values of brachydins in the PC-3 cell line as well as the influence on cell proliferation and cell death processes, such as apoptosis and necrosis, indicating the proteins involved in these processes. ANOVA: Analysis of Variance; BrA: Brachydin A; BrB: Brachydin B; BrC: Brachydin C; CGEN: Genetic Heritage Management Council; CID: Compound identification number; CM-H2DCFDA, 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate, acetyl ester; CO2: Carbon dioxide; DMSO: Dimethyl sulfoxide; DNA: Deoxyribonucleic acid; DTT: Dithiothreitol; DXR: Doxorubicin; ECL: Chemiluminescence; EDTA: Ethylenediaminetetraacetic acid; FBS: Fetal bovine serum; H2O2: Hydrogen peroxide; HRMS: High-Resolution Mass Spectrometry; IC50: Half maximal inhibitory concentration; LDH: Lactate dehydrogenase; MTT, 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide; Na3VO4: Sodium Orthovanadate; NaOH: Sodium hydroxide; NCBI: National Center for Biotechnology Information; NMR: Nuclear Magnetic Resonance; PBS: Phosphate buffer saline; PCR: Polymerase chain reaction; PSMF: Phenylmethylsulfonyl fluoride; RPMI: Roswell Park Memorial Institute Medium; SDS-PAGE: Sodium Dodecyl Sulfate-Polyacrylamide gel electrophoresis; STR: Short tandem repeat; TBS-T: Tris-buffered saline and Polysorbate 20; UPHLC: Ultra-Performance Liquid Chromatography.


Botulinum Neurotoxin Therapy for Lingual Dystonia Using an Individualized Injection Method Based on Clinical Features.
Lingual dystonia is a debilitating type of oromandibular dystonia characterized by involuntary, often task-specific, contractions of the tongue muscle activated by speaking or eating. Botulinum neurotoxin (BoNT) has been used to treat lingual dystonia; however, it is known to cause serious complications, such as dysphasia and aspiration. The purpose of this study was to evaluate the efficacy and adverse effects of individualized BoNT therapy for lingual dystonia. One-hundred-and-seventy-two patients (102 females and 70 males, mean age: 46.2 years) with lingual dystonia were classified into four subtypes based on symptoms of involuntary tongue movements: protrusion (68.6%), retraction (16.9%), curling (7.6%), and laterotrusion (7.0%). Patients were treated with BoNT injection into the genioglossus and/or intrinsic muscles via individualized submandibular and/or intraoral routes. Results were compared before and after BoNT therapy. Botulinum neurotoxin was injected in 136 patients (mean: 4.8 injections). Clinical sub-scores (mastication, speech, pain, and discomfort) in a disease-specific rating scale were reduced significantly (p < 0.001) after administration. Comprehensive improvement after BoNT injection, assessed using the rating scale, was 77.6%. The curling type (81.9%) showed the greatest improvement, while the retraction type showed the least improvement (67.9%). Mild and transient dysphasia occurred in 12.5% of patients (3.7% of total injections) but disappeared spontaneously within several days to two weeks. No serious side effects were observed. With careful diagnosis of subtypes and a detailed understanding of lingual muscle anatomy, individualized BoNT injection into dystonic lingual muscles can be effective and safe.


[Importance of x-ray examinations in the diagnosis of ileus].
From 1972-1982 350 operations were performed on 327 patients suffering from ileus. In 315 cases (90%) preoperatively the following X-ray examinations were performed. 315 plain abdominal X-rays (92.7% correct radiological findings), 21 oral gastrografin-passages (95.2%), 52 barium enemas (98.1%). If by all radiological means an exact preoperative diagnosis was possible, the lethality was significantly lower (22%) than in the overall group (33%).


The Efficacy and Safety of Low Molecular Weight Heparin Administration to Improve Survival of Cancer Patients: A Systematic Review and Meta-Analysis.
Low molecular weight heparins (LMWH) are often used as a first-line therapy for the prevention of thrombosis in cancer patients. Preclinical evidence from animal models suggests that LMWH may have antimetastatic properties. Clinical evidence of this effect is inconclusive. The objective of this systematic review is to evaluate the effect of LMWH on overall survival in patients with solid tumor malignancies. MEDLINE, Embase, and The Cochrane Central Register of Controlled trials were searched from inception to November 26, 2018. We included randomized controlled trials that compared LMWH to placebo, a no-treatment arm, or a short-term prophylactic course of LMWH in adult patients with solid tumors. The primary outcome was overall survival. Secondary outcomes included progression-free survival, the occurrence of venous thromboembolism, and major bleeding events. The risk of bias was assessed in duplicate using the Cochrane Risk-of-Bias tool. Forty-five articles were included in the review. Overall, no difference in overall survival was observed between groups (risk ratio: 1.00; 95% confidence interval: 0.98-1.02; I2 = 36.5%). In our a priori defined subgroup analyses, the effect was not shown to vary by the type of LMWH, duration of LMWH use, length of study follow-up, comparator used in the study, or the setting in which the LMWH was administered. The majority of studies had an unclear risk of bias for at least one methodological criterion. Although LMWH is thought to possess antimetastatic properties and thus have the potential to improve survival in cancer patients, existing data do not support this hypothesis.


Synthesis and antimicrobial evaluation of TAN-1057A/B analogs.
TAN-1057A-D, dipeptides isolated from bacteria Flexibacter sp. PK-74 and PK-176, are new antibiotics with potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). We describe, in detail, the synthesis of several TAN-1057A/B analogs by a convergent route featuring a new method to construct the cyclic amidinourea functional group. The biological activity of these substances against methicillin-resistant Staphylococcus aureus (MRSA) is reported.


HyperapoB: a pleiotropic phenotype characterized by dense low-density lipoproteins and associated with coronary artery disease.
HyperapoB, a lipoprotein phenotype characterized by increased numbers of small, dense, low-density lipoproteins (LDL), is strongly associated with coronary artery disease (CAD). Patients with hyperapoB may be normolipidemic, hypertriglyceridemic, or, when the number of LDL particles increases sufficiently, hypercholesterolemic. Concentrations of high-density lipoprotein (HDL) and its major apolipoprotein, apo A-1, are often low in plasma of patients with hyperapoB. The increased number of dense LDL in hyperapoB is due to increased LDL synthesis, secondary to increased synthesis of very-low-density lipoproteins (VLDL) and apo B. HyperapoB may be a dominant trait, although the existence of a common recessive allele at a very high frequency has not been excluded. The expression of hyperapoB appears delayed, but the phenotype is commonly found in children referred to specialty lipid clinics because of a family history of premature CAD. Published data suggest a biochemical, genetic, and metabolic relationship between hyperapoB, familial combined hyperlipidemia, and the dense LDL subclass patterns described in Mormon families. The biochemical and genetic basis for the overproduction of VLDL apo B is under further study, both molecular investigations of the apo B gene and studies of free fatty acid, triglyceride, and HDL metabolism.


Characteristics of innate lymphoid cells (ILCs) and their role in immunological disorders (an update).
Innate lymphoid cells (ILCs) are a novel family of hematopoietic effectors and regulators of innate immunity. Although these cells are morphologically similar to B cells and T cells, however they do not express antigen receptors. ILCs seems to have emerging roles in innate immune responses against infectious or non-infectious microorganisms, protection of the epithelial barrier, lymphoid organogenesis and inflammation, tissue remodeling and regulating homeostasis of tissue stromal cells. In addition, it has recently been reported that ILCs have a crucial role in several disorders such as allergy and autoimmunity. Based on their phenotype and functions, ILCs are classified into three major groups called ILCs1, ILCs2, and ILCs3. Here we reviewed the most recent data concerning diverse ILC phenotypes, subclasses, functions in immune responses as well as in immune mediated disorders.


Familial dysbetalipoproteinemia in three patients with apoE 2*(Arg136-->Cys) gene variant.
Apolipoprotein E (apoE) is a polymorphic protein which occurs in three common isoforms and more than 25 rare variants. Some of the rare apoE variants have been implicated in a dominant mode of inheritance of familial dysbetalipoproteinemia (FD). We have identified three unrelated apoE 2*(Arg136-->Cys) carriers with FD. This finding supports the notion that although apoE 2*(Arg136-->Cys) mutation is perhaps not sufficient to cause FD itself, the presence of other genetic and/or environmental factors can lead to the phenotypic expression of the disease in the carriers.


[Use of hepatitis B AS04C adjuvanted vaccine in HIV patients].
Co-infection with hepatitis B virus (HBV) in patients with human immunodeficiency virus (HIV) increases associated morbidity and mortality. Vaccination against HBV has been shown to be the most effective method to prevent this situation. Standard vaccination schemes used in this population do not appear to be effective enough. The objective is to identify the response rate following the use of AS04C-adjuvanted hepatitis B vaccine in HIV patients as well as the possible associated adverse reactions. An observational, analytical study with a retrospective cohort of HIV positive patients discharged in 2016 from the Vaccines Unit of a Preventive Medicine and Public Health Service. Patients with antiHBs (-), antiHBcActot (-) and HBsAg (-) at baseline were included, none of them had received prior HBV vaccination. HBV adjuvanted vaccine was used in a 4-dose regimen (0-1-2-6 months). When antiHBs was <10 IU/mL after primovaccination, two additional doses of the same vaccine were applied with an interval of 30 days. A total of 39 patients were included. Of them, 74.4% were men. The mean age was 47.26 years. The response rate after primary vaccination was higher than 92% and up to 100% with the two subsequent doses. No adverse reactions were reported. The administration of AS04C-adjuvanted hepatitis B vaccine in HIV patients showed a 100% response rate, showing an excellent safety profile.


Quinoline anti-malarial drugs inhibit spontaneous formation of beta-haematin (malaria pigment).
Polymerisation of haematin to beta-haematin (haemozoin or malaria pigment) in acidic acetate solutions was studied using infrared spectroscopy. The reaction was found to occur spontaneously between 6 and 65 degrees C, in 0.1-4.5 M acetate and pH 4.2-5.0. The anti-malarial drugs quinine, chloroquine and amodiaquin were found to block spontaneous beta-haematin formation, while the anti-malarially inactive 9-epiquinine and 8-hydroxyquinoline had no effect on the reaction, as did primaquine, a drug which is active only against exo-erythrocytic stages of infection. It is argued that the intra-erythrocytically active anti-malarial agents act by binding to haematin, blocking beta-haematin formation and leaving toxic haematin in the parasite food vacuoles.


Injuries in classical ballet.
The specialised medical knowledge about dancers' injuries is negligible compared with that which surrounds sports medicine. The author discusses his experience in the management of more than 2000 injuries sustained by dancers of classical ballet.


Effect of zinc in enteropathogenic Escherichia coli infection.
Enteropathogenic Escherichia coli (EPEC) infection triggers the release of ATP from host intestinal cells, and the ATP is broken down to ADP, AMP, and adenosine in the lumen of the intestine. Ecto-5'-nucleotidase (CD73) is the main enzyme responsible for the conversion of 5'-AMP to adenosine, which triggers fluid secretion from host intestinal cells and also has growth-promoting effects on EPEC bacteria. In a recent study, we examined the role of the host enzyme CD73 in EPEC infection by testing the effect of ecto-5'-nucleotidase inhibitors. Zinc was a less potent inhibitor of ecto-5'-nucleotidase in vitro than the nucleotide analog alpha,beta-methylene-ADP, but in vivo, zinc was much more efficacious in preventing EPEC-induced fluid secretion in rabbit ileal loops than alpha,beta-methylene-ADP. This discrepancy between the in vitro and in vivo potencies of the two inhibitors prompted us to search for potential targets of zinc other than ecto-5'-nucleotidase. Zinc, at concentrations that produced little or no inhibition of EPEC growth, caused a decrease in the expression of EPEC protein virulence factors, such as bundle-forming pilus (BFP), EPEC secreted protein A, and other EPEC secreted proteins, and reduced EPEC adherence to cells in tissue culture. The effects of zinc were not mimicked by other transition metals, such as manganese, iron, copper, or nickel, and the effects were not reversed by an excess of iron. Quantitative real-time PCR showed that zinc reduced the abundance of the RNAs encoded by the bfp gene, by the plasmid-encoded regulator (per) gene, by the locus for the enterocyte effacement (LEE)-encoded regulator (ler) gene, and by several of the esp genes. In vivo, zinc reduced EPEC-induced fluid secretion into ligated rabbit ileal loops, decreased the adherence of EPEC to rabbit ileum, and reduced histopathological damage such as villus blunting. Some of the beneficial effects of zinc on EPEC infection appear to be due to the action of the metal on EPEC bacteria as well as on the host.


Ultrasonographic evaluation of adrenal involution during antenatal and neonatal periods.
Using real-time ultrasonography, 25 adrenal glands from prenatal to neonatal periods were prospectively examined to assess the process of shrinkage. A similar sonographic structure was seen in both prenatal and neonatal adrenal glands. The area of adrenal gland (AGA) and the rate of decrease were calculated during antenatal and early neonatal periods. The values of AGA were 350 +/- 19 mm2 within a week of delivery, 304 +/- 17 mm2 (87 +/- 2%) just after delivery, 273 +/- 25 mm2 (77 +/- 5%) on the 1st day, 246 +/- 24 mm2 (70 +/- 5%) on the 2nd day, 215 +/- 23 mm2 (61 +/- 5%) on the 3rd day, 196 +/- 22 mm2 (56 +/- 5%) on the 4th day, 173 +/- 18 mm2 (50 +/- 4%) on the 5th day, 154 +/- 14 (44 +/- 4%) on the 6th day, 140 +/- 12 mm2 (40 +/- 2%) on the 7th day, respectively. In conclusion, the postnatal involution of the adrenals was documented by ultrasound.


[Cytogenetic and molecular characterization of partial trisomy 4q and partial monosomy 10q in a patient].
To ascertain the karyotype of a girl with moderate mental retardation and growth retardation, perform correlation analysis between chromosomal variation and phenotype, and investigate the application and superiority of array-based comparative genomic hybridization (array-CGH) in clinical cytogenetic diagnosis. G-banded chromosome analysis, array-CGH, fluorescence in situ hybridization (FISH) and real-time quantitative PCR (RQ-PCR) were used to ascertain the karyotype of the patient and her relatives. G-banding analysis of the patient showed a derivative chromosome 10 with an extra fragment on its long arm terminal, both her father and grandmother had an apparently balanced translocation t(4;10)(q25;q26). Array-CGH revealed that the breakpoint on chromosome 4 was located at 4q26. In addition, a microdeletion of about 0.54 Mb del(10)(q26.3) was identified from the patient. FISH and RQ-PCR confirmed that the del(10)(q26.3) was also present in both her father and grandmother. No recognizable phenotype was associated with del(10)(q26.3). The abnormal phenotypes presented in the patient may be ascribed to the 4q26-q35.2 triplication. Further more, compared with conventional cytogenetic analysis, array-CGH is of high resolution and high accuracy.


HHV-8- and EBV-associated nonepidermotrophic large B-cell lymphoma presenting as a foot rash in a man with AIDS.
Human herpesvirus type 8 (HHV-8; Kaposi's sarcoma-associated herpesvirus) is frequently identified in tumor tissue obtained from human immunodeficiency virus (HIV)-infected patients with Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), or multicentric Castleman's disease. The association between HHV-8 and acquired immunodeficiency syndrome (AIDS)-associated solid lymphomas is less clear. Herein, I describe the case of a man with a CD4+ count of 30 cells/microL, and HIV viral load of 90,000 copies/mL, multi-drug resistant HIV infection, and limited stage KS. Biopsy of a progressive dorsal foot rash revealed a dense, deep, lymphoid infiltrate that extended into papillary dermis but without epidermotrophism. Microscopy showed a homogeneous population of anaplastic large B cells that stained positive for CD20 (L26), CD30, and lambda light chain. In situ hybridization of tumor tissue identified Epstein-Barr virus (EBV)-encoded RNA, and polymerase chain reaction amplification yielded HHV-8-specific gene products. Staging studies did not reveal lymphoma elsewhere, and the patient began chemotherapy, but died from septic complications. Autopsy was notable only for the presence of a consolidative pneumonia. Although extranodal presentations are common in the setting of immunodeficiency, reports of AIDS-associated lymphoma presenting as a nonepidermotrophic foot lesion are rare. Such a presentation serves to broaden the differential of skin and foot lesions in the setting of HIV infection. More importantly, this case provides further support that HHV-8 can be associated with solid lymphomas that have an anaplastic large cell morphology.


Stimulating effect of calcium channel activator BAY-K 8644 on calcitonin secretion.
The calcium channel activator BAY-K 8644 injected intravenously produces a significant rise in the calcitonin content of the thyroid. Because adrenalin and noradrenaline play a certain role in the regulation of ionic calcium channels and in the preservation of the secretory tonus of the calcitonin secreting C cells, the effect of BAY-K 8644 was followed-up in adrenalectomized animals and in animals in which propranolol was previously administered. Adrenalectomy of beta receptor blocking does not prevent the effect of BAY-K 8644 on the activation of calcium channels, the calcitonin secretion being stimulated in these conditions too. The data obtained stress the relative independence of the calcium channels or the beta-adrenergic stimulating system in the achievement of calcium ion transfer. However, the calcitonin levels obtained were lower in adrenalectomized animals or following propranolol after stimulation with BAY-K 8644 in those with intact sympatho-adrenergic tonus. This stresses the importance of the integrity of the beta receptors in the activation of the calcium channels.


A preliminary study on the emotional distress of patients with terminal-stage cancer: a questionnaire survey of 1380 bereaved families over a 12-year period.
To clarify the emotional distress of terminal cancer patients, questionnaires were sent to 2826 families of patients who died at the National Kyushu Cancer Center; 1380 replies were obtained. Among the 1380 patients, 37.7% had been aware of the disease name and 19.8% had been unaware. Of the 1380 patients, 43.5% had prepared for and calmly accepted death, but 12.4% had greatly feared and 11.7% rejected death. Patients aware of the disease name had tended to prepare better for death but also had a stronger fear compared with those who were unaware. Patients informed of the exact nature of their disease by their physicians tended to value their remaining life more than those informed by others. Those who had desired notification of the disease name also tended to value their remaining life more than those who had not. They also spent their remaining life more usefully, and were less discouraged after being informed than those who had not expressed a wish to be informed. Thus: 1. The emotional state of the cancer patient should be clearly established before deciding to inform the patient of the true diagnosis. 2. The patient should be notified of the disease by the doctor, even if he/she is already aware of the diagnosis through others. 3. The ability to share bad news with the patient is of crucial importance for physicians when caring for terminal- stage cancer patients.


Detection of adenovirus type 2-induced early polypeptides using cycloheximide pretreatment to enhance viral protein synthesis.
(35S) methionine-labeled polypeptides synthesized by adenovirus type 2-infected cells have been analyzed by polyacrylamide gradient gel electrophoresis and autoradiography. Cycloheximide (CH) was added to infected cultures to accumulate early viral mRNA relative to host cell mRNA. This allowed viral proteins to be synthesized in increased amounts relative to host proteins after removal of CH and pulse-labeling with (35S)methionine. During the labeling period arabinosyl cytosine was added to prevent the synthesis of late viral proteins. This procedure facilitated the detection of six early viral-induced polypeptides, designated EP1 through EP6 (early protein), with apparent molecular weights of 75,000 (75K), 42K, 21K, 18K, 15K, and 11K. Supportive data were obtained by coelectrophoresis of (35S)- and (3H)methionine-labeled polypeptides from infected and uninfected cells, respectively. Three of these early polypeptides have not been previously reported. CH pretreatment enhanced the rates of synthesis of EP4 and EP6 20- to 30-fold and enhanced that of the others approximately twofold. The maximal rates of synthesis of the virus-induced proteins varied, in a different manner, with time postinfection and CH pretreatment. Since CH pretreatment appears to increase the levels of early viral proteins, it may be a useful procedure to assist their isolation and functional characterization.


A comparison of injection pain with articaine with adrenaline, prilocaine with phenylpressin and lidocaine with adrenaline.
The objective of the present study was to investigate the pain on injection of articaine with adrenaline, prilocaine with phenylpressin , and lidocaine with adrenaline. The study sample was comprised of 497 consecutively seen patients received 497 maxillary buccal infiltration injections or inferior alveolar block injections of 4% articaine with 1:200.000 adrenaline, 3% prilocaine with 1.08 mcg phenylpressin, or 2% lidocaine with 1:100.000 adrenaline. Immediately after the injection, patients were asked to rate their injection pain on a six-point scale. There were no significant differences among the anesthetic solutions for injection pain. Patients usually reported mild or no injection pain for all of anesthetic administrations. Under the conditions of this study that lidocaine with adrenaline, articaine with adrenaline and prilocaine with phenylpressin seemed to be similar for pain on injection and they could be quite painless.


Intra-Articular Lactate Dehydrogenase A Inhibitor Oxamate Reduces Experimental Osteoarthritis and Nociception in Rats via Possible Alteration of Glycolysis-Related Protein Expression in Cartilage Tissue.
Osteoarthritis (OA) is the most common form of arthritis and joint disorder worldwide. Metabolic reprogramming of osteoarthritic chondrocytes from oxidative phosphorylation to glycolysis results in the accumulation of lactate from glycolytic metabolite pyruvate by lactate dehydrogenase A (LDHA), leading to cartilage degeneration. In the present study, we investigated the protective effects of the intra-articular administration of oxamate (LDHA inhibitor) against OA development and glycolysis-related protein expression in experimental OA rats. The animals were randomly allocated into four groups: Sham, anterior cruciate ligament transection (ACLT), ACLT + oxamate (0.25 and 2.5 mg/kg). Oxamate-treated groups received an intra-articular injection of oxamate once a week for 5 weeks. Intra-articular oxamate significantly reduced the weight-bearing defects and knee width in ACLT rats. Histopathological analyses showed that oxamate caused significantly less cartilage degeneration in the ACLT rats. Oxamate exerts hypertrophic effects in articular cartilage chondrocytes by inhibiting glucose transporter 1, glucose transporter 3, hexokinase II, pyruvate kinase M2, pyruvate dehydrogenase kinases 1 and 2, pyruvate dehydrogenase kinase 2, and LHDA. Further analysis revealed that oxamate significantly reduced chondrocyte apoptosis in articular cartilage. Oxamate attenuates nociception, inflammation, cartilage degradation, and chondrocyte apoptosis and possibly attenuates glycolysis-related protein expression in ACLT-induced OA rats. The present findings will facilitate future research on LDHA inhibitors in prevention strategies for OA progression.


Multiwall and bamboo-like carbon nanotubes from the Allende chondrite: A probable source of asymmetry.
This study presents multiwall and bamboo-like carbon nanotubes found in samples from the Allende carbonaceous chondrite using high-resolution transmission electron microscopy (HRTEM). A highly disordered lattice observed in this material suggests the presence of chiral domains in it. Our results also show amorphous and poorly-graphitized carbon, nanodiamonds, and onion-like fullerenes. The presence of multiwall and bamboo-like carbon nanotubes have important implications for hypotheses that explain how a probable source of asymmetry in carbonaceous chondrites might have contributed to the enantiomeric excess in soluble organics under extraterrestrial scenarios. This is the first study proving the existence of carbon nanotubes in carbonaceous chondrites.


Theory-based Trial to Promote Uptake and Sustained Use of Face Coverings During the COVID-19 Pandemic.
Transmission of airborne viruses can be mitigated by wearing face coverings but evidence suggests that face covering declines with the removal of relevant legislation, partly due to low automatic motivation. Test whether an intervention based on implementation intentions could support people's automatic motivation and promote face covering during the COVID-19 pandemic. Randomized controlled design. At baseline (May 20 to June 6, 2022), 7,835 UK adults reported how much time they spent wearing face coverings in work, public transport, and indoor leisure settings as well as their capabilities, opportunities, and motivations. 3,871 participants were randomized to form implementation intentions; 3,964 control participants completed questionnaires only. Measures were repeated 6 months postbaseline (November 1 to November 14, 2022). Data were analyzed using mixed measures ANOVAs and Bayes Factors to examine whether the observed data supported the experimental hypothesis. The proportion of time spend wearing face coverings declined substantially across the 6-month study period, from 15.28% to 9.87% in work settings, 38.31% to 24.55% on public transport, and 9.58% to 7.85% in leisure settings. Bayes Factors indicated moderate relative evidence of no effect of implementation intentions on behavior in work and leisure settings, and inconclusive evidence of a positive effect on public transport. In the context of declining COVID-19 rates and removal of legal mandates, implementation intentions were not effective in sustaining face covering. Further research is required to ensure that evidence-based interventions are prepared and deployed in the event of future pandemics.


The impact of cancer development on the risk of mycobacterial diseases among rheumatoid arthritis patients.
Mycobacterial diseases are prevalent in cancer and rheumatoid arthritis (RA) patients, especially those receiving tumor necrosis factor-α inhibitor (TNFi). However, the impact of cancer development on the risk of mycobacterial diseases among RA patients is unknown. Data from the Taiwan National Health Insurance Research Database were used to conduct a retrospective study to assess the occurrence of mycobacterial diseases in RA patients developing cancer (cancer-positive), those using TNFi (TNFi-exposure), those with cancer and using TNFi (cancer-TNFi-comb), and those without cancer and not using TNFi (cancer-TNFi-free). Cancer and TNFi exposure were time-dependent, and independent risk factors of mycobacterial diseases were assessed by Cox regression. Among 1344 RA patients diagnosed during 2000-2013, 68 (5·1%) developed cancer before their end points. The incidence rates of mycobacterial diseases in the cancer-positive (n = 56), TNFi-exposure (n = 290), cancer-TNFi-comb (n = 12), and cancer-TNFi-free (n = 986) subgroups were 6·7, 2·0, 7·6, and 1·3 per 1000 person-years, respectively. As compared with the cancer-TNFi-free group, the risk for mycobacterial diseases increased for the TNFi-exposure group (adjusted HR = 3·6, 95% confidence interval (95% CI) 1·1-11·5, P = 0·032) and remained high for cancer-positive (adjusted HR = 14·6, 95% CI 3·3-63·7, P < 0·001) after adjustment. This study suggested that cancer development increased the risk of mycobacterial diseases in RA patients, and risk assessment for this subgroup should be considered.