Sodium and angiotensin in the pathogenesis of experimental renovascular hypertension.
The effects of simultaneous angiotensin blockade and sodium depletion on the development of one-kidney renovascular hypertension were studied in rats. In sodium-replete rats, systolic blood pressure (SBP) increased from 102 +/- 2 to 153 +/- 11 mmHg by the 12th day after unilateral nephrectomy and subsequent partial occlusion of the renal artery with a 0.22-mm silver clip. When changes in body fluid volume were minimized by sodium restriction in a second group of rats, the increase in SBP from 98 +/- 4 to 149 +/- 7 mmHg after clipping was not different from that in sodium-replete animals. Inhibition of the angiotensin-converting enzyme with SQ 14,225 during sodium restriction prevented the SBP from increasing above 101 +/- 3 mmHg by the 12th day after nephrectomy and clipping. Once SQ 14,225 administration was discontinued, SBP rose significantly to 148 +/- 5 mmHg within 5 days. Because previous studies have shown that neither sodium depletion nor angiotensin blockade alone prevented the development of one-kidney renovascular hypertension, it is concluded that the increase in blood pressure resulting from renal artery constriction and contralateral nephrectomy was prevented only by suppression of both the renin-angiotensin system and body fluid volume.


RME-induced root resorption and repair: a computerised 3-D reconstruction.
This study was designed to evaluate the 3-D relation of epithelial rests of Malassez (ERM) to orthodontically induced resorption lacunae in human tooth roots. First premolars were extracted following rapid maxillary expansion, then they were prepared for transmission electron microscopy and sectioned. Serial 1 micron sections were used for the 3-D reconstructions and ultra thin sections were utilized to verify the identification of epithelial cells and blood vessel types. Each serial section was photographed and profiles of the resorption bays, epithelial cells and blood vessels were digitized and computer reconstructions performed with an IBM-based software programme. The reconstructions supported the view that epithelial cell and blood vessel relation to the resorption lacunae appeared to be related to the level of activity of the bay. Possible functional roles for epithelial cells in the resorptive process are discussed.


PGC-1alpha-mediated adaptations in skeletal muscle.
Lifestyle-related diseases are rapidly increasing at least in part due to less physical activity. The health beneficial effects of regular physical activity include metabolic adaptations in skeletal muscle, which are thought to be elicited by cumulative effects of transient gene responses to each single exercise, but how is this regulated? A potential candidate in this is the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha, which has been identified as a master regulator of mitochondrial biogenesis, but also been shown to regulate proteins involved in angiogenesis and the anti-oxidant defence as well as to affect expression of inflammatory markers. Exercise increases PGC-1alpha transcription and potentially PGC-1alpha activity through post-translational modifications, and concomitant PGC-1alpha-mediated gene regulation is suggested to be an underlying mechanism for adaptations in skeletal muscle, when exercise is repeated. The current review presents some of the key findings in PGC-1alpha-mediated regulation of metabolically related, anti-oxidant and inflammatory proteins in skeletal muscle in the basal state and in response to exercise training, and describes functional significance of PGC-1alpha-mediated effects in skeletal muscle. In addition, regulation of PGC-1alpha expression and activity in skeletal muscle is described. The impact of changes in PGC-1alpha expression in mouse skeletal muscle and the ability of PGC-1alpha to regulate multiple pathways and functions underline the potential importance of PGC-1alpha in skeletal muscle adaptations in humans. The absence of exercise-induced PGC-1alpha-mediated gene regulation during a physical inactive lifestyle is suggested to lead to reduced oxidative capacity of skeletal muscle and concomitant impaired metabolism.


Hands and knees posture in late pregnancy or labour for fetal malposition (lateral or posterior).
Lateral and posterior position of the baby's head (the back of the baby's head facing to the side or the mother's back) may be associated with more painful, prolonged or obstructed labour and difficult delivery. It is possible that certain positions adopted by the mother may influence the baby's position. The objective of this review is to assess the effects of adopting a hands and knees maternal posture in late pregnancy or during labour when the presenting part of the fetus is in a lateral or posterior position, compared with no intervention. We searched the Cochrane Pregnancy and Childbirth Group Trials Register (November 2004) and the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2004). Randomised trials of hands and knees maternal posture compared to other postures or controls. Both review authors assessed trial eligibility and quality. Two trials of hands and knees posture during pregnancy were included. In one trial involving 100 women, four different postures (four groups of 20 women) were combined for the comparison with the control group of 20 women. Lateral or posterior position of the presenting part of the fetus was less likely to persist following 10 minutes in the hands and knees position compared to a sitting position (one trial, 100 women, relative risk (RR) 0.25, 95% confidence interval (CI) 0.17 to 0.37). In a second trial including 2547 women, advice to assume the hands and knees posture for 10 minutes twice daily in the last weeks of pregnancy had no effect on the baby's position at delivery or any of the other pregnancy outcomes measured. No trials of hands and knees posture during labour were included. Use of hands and knees position for 10 minutes twice daily to correct occipitoposterior position of the fetus in late pregnancy cannot be recommended as an intervention. This is not to suggest that women should not adopt this position if they find it comfortable. The use of this position during labour has not been addressed in this review. In view of the promising short-term effects of the technique and its simplicity, further trials are justified to determine whether encouraging the use of hands and knees posture during rather than before labour, has any effect on substantive outcomes.


[Study on medication regularity of traditional Chinese medicine in treatment of COVID-19 based on data mining].
The coronavirus disease 2019(COVID-19) is developing rapidly and posing great threat to public health. There is no specific medicine available for treating the disease. Luckily, traditional Chinese medicine has played a positive role in the fighting against COVID-19. In this paper, We collected and sorted the prescriptions of modern Chinese medicine for COVID-19 released by national government, different provinces, autonomous regions and municipalities, as well as online databases, such as CNKI, WanFang medical network, and VIP database. These prescriptions were combined with the inheritance of traditional Chinese medicine auxiliary V2.5, and the complex system entropy clustering method was used to determine the association rules and frequency of single drug and drug combination in the prescription. In the end, 96 effective prescriptions were included. Among them, the four properties were mainly concentrated in temperature, cold and level, the five tastes were mainly concentrated in bitter, hot and sweet, and the meridians were mainly concentrated in lung, stomach and spleen. The high-frequency drugs were Glycyrrhizae Radix et Rhizoma, Armeniacae Semen Amarum, Gypsum Fibrosum, etc., and the high-frequency combinations are Gypsum Fibrosum-Armeniacae Semen Amarum, Gypsum Fibrosum-Glycyrrhizae Radix et Rhizoma, Armeniacae Semen Amarum-Glycyrrhizae Radix et Rhizoma, the core combinations are Lepidii Semen-Armeniacae Semen Amarum-Gypsum Fibrosum, Pogostemonis Herba-Zingiberis Rhizoma Recens-Magnoliae Officinalis Cortex, Ophiopogonis Radix-Armeniacae Semen Amarum-Scutellariae Radix and so on. Form new prescriptions Lepidii Semen, Armeniacae Semen Amarum, Gypsum Fibrosum, Pogostemonis Herba, Zingiberis Rhizoma Recens, Magnoliae Officinalis Cortex. Ophiopogonis Radix, Armeniacae Semen Amarum, Scutellariae Radix, Schisandrae Sphenantherae Fructus, Panacis Quinquefolii Radix. From the medicinal properties to high-frequency drugs and new prescriptions, it could be seen that the overall treatment of COVID-19 by traditional Chinese medicine was to strengthen body resistance, eliminate pathogenic factors, and give attention to Qi and Yin.


Functional comparative histology. 2. Communication: organismic taxonomy (plant and animal taxonomy).
The historic development of the taxonomy of the animals and plants has been briefly reviewed. The new taxonomy of the six-kingdom approach offers an improved recognition of the taxonomy of organisms with true or with pseudotissues than that of older taxonomy. Table 5 contains a brief description of the Histonia animalia and Histonia plantae and of several prototypes of incomplete tissue development, as well as of the fungi with plectenchymata. Special emphasis is placed upon the macroscopic and histologic characteristics of each taxonomic group. It is also the purpose of the tables to offer the reader of this and especially of future communications a brief, succinct review of the taxa under consideration. The communication on taxa outlined briefly the development of taxonomy of organisms since the times of ancient Greece. To this review, survey of modern taxonomy, with important histologic and other characteristics of the taxa of the Histonia, is added. The new six-kingdom approach reflects more accurately the cellular and histologic conditions in the phyla of the Histonia. In the higher fungi, the plectenchymata are seen; in the highest rhodophyta and phaeophyta, the cauloid, rhizoid and other plant pseudotissues develop. At a somewhat higher phylogenetic stage, there belong the pseudotissues of bryophyta. In comparison to cormophyta, the same holds true for the rather primitive tissue development of bryophyta. They are not directly comparable to the tissues of the highest porifera exhibiting the lowest animal tissues. Metaphyta from the plant kingdom without cell differentiation such as the highest brown algae, partially growing with apical meristems, which reach a length of 120 m, hence belong to the largest plants. By way of contrast, the multicellular animals lower than the Porifera and belonging to the phyla Placozoa and Mesozoa are only a few millimeters in size. Finally, the focus (centre) of the Histonia is represented by those species with true tissues, the Histonia animalia or Eumetazoans and the Histonia plantae, vascular plants, or Tracheophyta. The borderlines are fluid and opinions differ. It would also be possible to consider the pseudotissues of the Rhodophyta, Phaeophyta, and Bryophyta as morphologically lower counterparts of the true tissues of the vascular plants (Tracheophyta) and to consider only the plectenchymata, developing through coalescence and interweaving as non-true or pseudotissues.(ABSTRACT TRUNCATED AT 400 WORDS)


Going ill to work--what personal circumstances, attitudes and work-related factors are associated with sickness presenteeism?
The aim of this study is to assess the impact of a broad range of possible factors relating to work, personal circumstances and attitudes towards sickness absence on a person's decision to go to work despite feeling ill, a phenomenon that has been termed sickness presence (SP), or 'presenteeism', in the literature. Using data from a random sample of 12,935 members from the core Danish work force the hypotheses were tested in a cross-sectional design utilising ordered logistic regression models. The results indicate that more than 70% of the core work force goes ill to work at least once during a 12-month period. This means that SP is just as prevalent a phenomenon as sickness absence. Many of the results from earlier studies of SP were replicated and new factors were discovered: for example time pressure (having a supervisory role and/or working more than 45 h per week) and relationship with colleagues (measured by working in a small company, having non-standard hours and degree of cooperation) both increase the likelihood of SP. However, personal circumstances and attitudes, e.g. treating work as home (cf. Hochschild's thesis) and being over-committed to work, were also found to lead to higher levels of SP. Finally, we found that those with a conservative attitude to absence were most likely to turn up ill at work. Overall, work-related factors seem to be slightly more important than personal circumstances or attitudes in determining people's 'decision' to go ill at work. However, the relatively low explanatory power of these combined factors suggests that there are still many unknowns in this field of research.


A human purine nucleoside phosphorylase deficiency caused by a single base change.
Purine nucleoside phosphorylase (PNP) deficiency in humans is associated with a severe defect in T-lymphocyte function. The mutant gene was cloned from one PNP-deficient patient who was the offspring of a consanguineous mating. The exons and intron/exon boundaries of the mutant PNP gene were sequenced and compared with the wild-type cDNA sequence. A single base difference was found in the coding region of the mutant gene, a G to A transition in the third exon. This single base mutation alters the codon at position 89 from Glu to Lys, a result which is consistent with previously published peptide mapping data. The patient was demonstrated to be autozygous for the single base mutation on the basis of hybridization of synthetic oligomers to genomic DNA digests. A mammalian expression vector was constructed containing the entire mutant gene under the transcriptional regulation of its own promoter. In another construction, the single base mutation was reverted to the wild-type sequence by in vitro mutagenesis. An isoelectric focusing gel containing extracts of the cells transfected with the mutant and reverted PNP gene was stained histochemically for PNP activity. The proteins from a similar gel were blotted on a nitrocellulose membrane, and immunoreactive human PNP protein was visualized. Cells transfected with the mutant gene contained no human PNP activity, but expressed immunoreactive PNP which focused at an abnormally alkaline pI. Cells transfected with the reverted gene expressed human PNP activity which co-focused with human PNP from a HeLa cell control, proving that the observed single base change was responsible for the loss of catalytic function.


Association of Albuminuria With White Matter Hyperintensities Volume on Brain Magnetic Resonance Imaging in Elderly Japanese - The Hisayama Study.
Both chronic kidney disease and brain white matter hyperintensities (WMH) are known to be risk factors of dementia and mortality.Methods and Results:In 2012, 1,214 community-dwelling Japanese subjects aged ≥65 years underwent brain magnetic resonance imaging (MRI) scans and a comprehensive health examination. This study investigated associations of the urinary albumin : creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) with the WMH volume to intracranial volume (WMHV : ICV) ratio, and the association of the combination of UACR and the WMHV : ICV ratio with cognitive decline and mortality risk. The geometric mean of the WMHV : ICV ratio was 0.223% in the entire study population, and increased significantly with higher UACR levels after adjusting for potential confounding factors (0.213% for normoalbuminuria, 0.248% for microalbuminuria, and 0.332% for macroalbuminuria; Ptrend=0.01). In contrast, there was no clear association between eGFR and the WMHV : ICV ratio. Compared with subjects with normoalbuminuria and a smaller WMHV : ICV ratio (<0.257% [median]), subjects with albuminuria and a larger WMHV : ICV ratio (≥0.257%) had higher probabilities of cognitive decline at baseline and all-cause death during the follow-up. This study suggests that subjects with albuminuria have a greater risk of WMH enlargement and that the combination of albuminuria and WMH enlargement increases the risk of cognitive decline and all-cause mortality in an elderly Japanese population.


Growth factor delivery methods in the management of sports injuries: the state of play.
In recent years there have been rapid developments in the use of growth factors for accelerated healing of injury. Growth factors have been used in maxillo-facial and plastic surgery with success and the technology is now being developed for orthopaedics and sports medicine applications. Growth factors mediate the biological processes necessary for repair of soft tissues such as muscle, tendon and ligament following acute traumatic or overuse injury, and animal studies have demonstrated clear benefits in terms of accelerated healing. There are various ways of delivering higher doses of growth factors to injured tissue, but each has in common a reliance on release of growth factors from blood platelets. Platelets contain growth factors in their alpha-granules (insulin-like growth factor-1, basic fibroblast growth factor, platelet-derived growth factor, epidermal growth factor, vascular endothelial growth factor, transforming growth factor-beta(1)) and these are released upon injection at the site of an injury. Three commonly utilised techniques are known as platelet-rich plasma, autologous blood injections and autologous conditioned serum. Each of these techniques has been studied clinically in humans to a very limited degree so far, but results are promising in terms of earlier return to play following muscle and particularly tendon injury. The use of growth factors in sports medicine is restricted under the terms of the World Anti-Doping Agency (WADA) anti-doping code, particularly because of concerns regarding the insulin-like growth factor-1 content of such preparations, and the potential for abuse as performance-enhancing agents. The basic science and clinical trials related to the technology are reviewed, and the use of such agents in relation to the WADA code is discussed.


[Experience with the application of Kombinil-Duo ear drops for the treatment of diffuse external otitis media].
The objective of the present work was to enhance the effectiveness of the treatment of the patients presenting with diffuse external otitis media with the application of Kombinil-Duo ear drops. The authors carried out a comparative study using Kombinil-Duo ear drops (n=30) and traditional methods (n=25). The study has demonstrated the advantages of the complication of Kombinil-Duo ear drops that allows to more rapidly eliminate such symptoms of diffuse external otitis media as otalgia, ear congestion, hyperemia, and skin infiltration in the external auditory canal.


Dihydroergotamine mesylate-loaded dissolving microneedle patch made of polyvinylpyrrolidone for management of acute migraine therapy.
Migraine is a widespread neurological disease with negative effects on quality of life and productivity. Moderate to severe acute migraine attacks can be treated with dihydroergotamine mesylate (DHE), an ergot derivative that is especially effective in non-responders to triptan derivatives. To overcome limitations of current DHE formulations in subcutaneous injection and nasal spray such as pain, adverse side effects and poor bioavailability, a new approach is needed for DHE delivery enabling painless self-administration, quick onset of action, and high bioavailability. In this study, we developed a dissolving microneedle patch (MNP) made of polyvinylpyrrolidone, due to its high aqueous solubility and solubility enhancement properties, using a MNP design previously shown to be painless and simple to administer. DHE-loaded MNPs were shown to have a content uniformity of 108±9% with sufficient mechanical strength for insertion to pig skin ex vivo and dissolution within 2min. In vivo pharmacokinetic studies were carried out on hairless rats, and DHE plasma levels were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The area under curve (AUC) value after DHE delivery by MNP (1259±917ng/mL min) was not significantly different (p>0.05) as compared to subcutaneous injection, with a relative bioavailability of 97%. Also, appreciable plasma levels of DHE were seen within 5min for both delivery methods and tmax value of MNPs (38±23min) showed no significant difference (p>0.05) compared to subcutaneous injection (24±13min). These results suggest that DHE-loaded MNPs have promise as an alternative DHE delivery method that can be painlessly self-administered with rapid onset and high bioavailability.


Multipole interplay controls optical forces and ultra-directional scattering.
We analyze the superposition of Cartesian multipoles to reveal the mechanisms underlying the origin of optical forces. We show that a multipolar decomposition approach significantly simplifies the analysis of this problem and leads to a very intuitive explanation of optical forces based on the interference between multipoles. We provide an in-depth analysis of the radiation coming from the object, starting from low-order multipole interactions up to quadrupolar terms. Interestingly, by varying the phase difference between multipoles, the optical force as well as the total radiation directivity can be well controlled. The theory developed in this paper may also serve as a reference for ultra-directional light steering applications.


Loneliness and the social monitoring system: Emotion recognition and eye gaze in a real-life conversation.
Based on the belongingness regulation theory (Gardner et al., 2005, Pers. Soc. Psychol. Bull., 31, 1549), this study focuses on the relationship between loneliness and social monitoring. Specifically, we examined whether loneliness relates to performance on three emotion recognition tasks and whether lonely individuals show increased gazing towards their conversation partner's faces in a real-life conversation. Study 1 examined 170 college students (Mage = 19.26; SD = 1.21) who completed an emotion recognition task with dynamic stimuli (morph task) and a micro(-emotion) expression recognition task. Study 2 examined 130 college students (Mage = 19.33; SD = 2.00) who completed the Reading the Mind in the Eyes Test and who had a conversation with an unfamiliar peer while their gaze direction was videotaped. In both studies, loneliness was measured using the UCLA Loneliness Scale version 3 (Russell, 1996, J. Pers. Assess., 66, 20). The results showed that loneliness was unrelated to emotion recognition on all emotion recognition tasks, but that it was related to increased gaze towards their conversation partner's faces. Implications for the belongingness regulation system of lonely individuals are discussed.


Probing the shape and stereochemistry of molecular orbitals in locally flexible aromatic chains: a penning ionization electron spectroscopy and Green's function study of the electronic structure of biphenyl.
We report on the results of an exhaustive study of the interplay between the valence electronic structure, the topology and reactivity of orbitals, and the molecular structure of biphenyl by means of Penning ionization electron spectroscopy in the gas phase upon collision with metastable He*(2(3)S) atoms. The measurements are compared with one-particle Green's function calculations of one-electron and shake-up valence ionization spectra employing the third-order algebraic diagrammatic construction scheme [ADC(3)]. Penning ionization intensities are also analyzed by means of the exterior electron-density model and comparison with photoelectron spectra: in contrast with the lines originating from sigma orbitals, ionization lines belonging to the pi-band system have large Penning ionization cross sections due to their greater extent outside the molecular van der Waals surface. The involved chemi-ionization processes are further experimentally investigated using collision-energy-resolved Penning ionization electron spectroscopy. The cross sections of pi-ionization bands exhibit a markedly negative collision-energy dependence and indicate that the interaction potential that prevails between the molecule and the He*(2(3)S) atom is strongly attractive in the pi-orbital region. On the other hand, the partial ionization cross sections pertaining to sigma-ionization channels are characterized by more limited collision-energy dependencies, as a consequence of rather repulsive interactions within the sigma-orbital region. A comparison of ADC(3) simulations with the Penning ionization electron spectra and UV photoelectron spectra measured by Kubota et al. [Chem. Phys. Lett. 1980, 74, 409] on thin films of biphenyl deposited at 170 and 109 K on copper demonstrates that biphenyl molecules lying at the surface of polycrystalline layers adopt predominantly a planar configuration, whereas within an amorphous sample most molecules have twisted structures similar to those prevailing in the gas phase.


Eukaryotic diversity in an anaerobic aquifer polluted with landfill leachate.
Eukaryotes may influence pollutant degradation processes in groundwater ecosystems by activities such as predation on bacteria and recycling of nutrients. Culture-independent community profiling and phylogenetic analysis of 18S rRNA gene fragments, as well as culturing, were employed to obtain insight into the sediment-associated eukaryotic community composition in an anaerobic sandy aquifer polluted with landfill leachate (Banisveld, The Netherlands). The microeukaryotic community at a depth of 1 to 5 m below the surface along a transect downgradient (21 to 68 m) from the landfill and at a clean reference location was diverse. Fungal sequences dominated most clone libraries. The fungal diversity was high, and most sequences were sequences of yeasts of the Basidiomycota. Sequences of green algae (Chlorophyta) were detected in parts of the aquifer close (<30 m) to the landfill. The bacterium-predating nanoflagellate Heteromita globosa (Cercozoa) was retrieved in enrichments, and its sequences dominated the clone library derived from the polluted aquifer at a depth of 5 m at a location 21 m downgradient from the landfill. The number of culturable eukaryotes ranged from 10(2) to 10(3) cells/g sediment. Culture-independent quantification revealed slightly higher numbers. Groundwater mesofauna was not detected. We concluded that the food chain in this polluted aquifer is short and consists of prokaryotes and fungi as decomposers of organic matter and protists as primary consumers of the prokaryotes.


[Bayesian thinking on its way into medical statistics?].
Bayesian statistical analysis is a paradigm quite different from traditional statistical inference. We wanted to show the usefulness of this approach for some medical problems. We started with Bayes equation as it is used for estimating the probability of illness based on a specific laboratory test. We also looked into a recent Cochrane report on mammography that accepted two studies as valid and five others as biased. In comparison we used examples of clinical trials from other areas that have been misinterpreted by the use of a traditional statistical approach only. We found that by taking into account our prior beliefs about the likely effects on breast cancer mortality of routine radiological screening programmes, the new data fit well into an estimate of a 5% mortality reduction with a 77% chance that there is a positive effect of screening. Bayesian statistics is helpful in making decisions on the basis of experimental evidence by taking into account our prior knowledge, whereas p-values in traditional statistics only give information on how often we will end up with a false positive conclusion in the long run.


Improving identification of candidates for lung cancer screening in a high risk population.
Low dose computerized tomography (LDCT) has been shown to reduce lung cancer specific mortality by 20 %. Despite U.S. Preventive Services Task Force (USPSTF) endorsement, screening of appropriate patients in the U.S. remains low, at 1.9 %. The goal of this study was to assess the number and type of patients that would qualify for lung cancer screening based upon recommendations by various guidelines. We prospectively collected a patient reported questionnaire, including smoking history, family history, exposure history, and demographics, from April-October 2017 from new consults in the Department of Radiation Oncology and Otolaryngology (ORL). Patients smoking status and patient factors were collected and reported. Patients qualifying for screening by USPSTF, the National Comprehensive Cancer Network (NCCN), and Tammemagi scoring criteria were identified. Multivariate analysis assessed the factors associated with positive criteria for screening and the sensitivity of each criterion was calculated. There were 546 new consults during the study period and 528 successfully completed the questionnaire. A total of 104/528 (20 %) patients who completed questionnaires qualified for screening based on any guideline. After exclusion of active lung cancer (n = 19), poor prognosis (n = 24), and CT as part of surveillance (n = 16), 45 (8.5 %) patients would require LDCT. Of the entire population, 10 %, 11 % and 18 % of patients qualified based on USPSTF, NCCN, and Tammemagi, which was reduced to 4.9 %, 5.3 %, and 7.8 %, respectively after exclusions. Patients with head and neck cancer (40 %), skin cancer (27 %), and prostate cancer (11 %) accounted for the majority of patients eligible for screening after exclusions. The sensitivity of the USPSTF, NCCN, and Tammemagi criteria in patients with a diagnosis of lung cancer (n = 26) was 38.5 % (CI95 20.2 %-59.4 %), 46.2 % (CI95 26.6 %-66.6 %), and 61.5 % (CI95 40.6 %-79.8 %), respectively. We successfully identified 9 % of an oncology population at consultation who could benefit from lung cancer screening in survivorship. Distribution of a written or electronic questionnaire at consultation is a simple, low cost, effective method of identifying patients who would benefit from LDCT.


Uterine contraction regularity during labour in White and Black patients.
Irregularity of uterine contractions during labour was compared in 50 White and 50 Black patients. The standard deviation of distances between contractions as seen on cardiotocography and of maximal pressures was used to compare contraction regularity in the two groups of patients. A small standard deviation (SD) indicated regular contractions; a larger SD signified irregular contractions. Mean SDs of peak-to-peak and of base-to-base measurements were both 6,3 mm for White patients and both 7,6 mm for Black patients. The mean SD for maximal uterine pressures was 9,5 mmHg for White patients but 12,7 mmHg for Black patients. All these differences were statistically highly significant, and this implies that uterine contractions are more irregular in Black patients.


Sex distribution and classification of GBA1 variants in an Italian cohort of Parkinson's disease patients analyzed over the last seventeen years.
Heterozygous GBA1 variants are among the most frequent genetic risk factors for Parkinson's disease (PD). Male sex is a risk factor in the development of PD but the sex prevalence of GBA1 carriers in PD patients remains debatable. Molecular analysis of the GBA1 gene is complicated by the presence of a highly homologous pseudogene GBAP1. Starting from 2006, we screened GBA1 gene in a large cohort of 1762 PD patients through different techniques developed over the years. Identified variants were classified employing the GBA1-PD browser and compared on the basis of frequency and sex distribution. Within a group of 684 patients (40.2% Males -M-) analyzed with RFLP technique looking for the two most common GBA1 mutations L444P and N370S, 29 resulted positive (4.23%). Out of 537 patients (67.4% M) analyzed with PCR that amplifies the portion of the gene between exon 8 and exon 11, we found 53 positive carriers (9.87%). Out of 424 patients (60.8% M) analyzed with NGS custom gene panel with allele-specific PCR, 50 resulted positive (11.79%). Since 2022, we also analyzed 117 patients (56.4% M) with long PCR sequenced with NGS, identifying 17 positive samples (14.52%). In our study, we highlight that screening the entire GBA1 gene with specific techniques increases the diagnostic rate. Regarding variants distribution, males have shown a higher frequency of the severe variants and complex alleles, whereas mild variants are equally distributed in both sexes and risk variants are more frequent in females especially the T369 M.


Managing Agroecosystems for Soil Microbial Carbon Use Efficiency: Ecological Unknowns, Potential Outcomes, and a Path Forward.
Agricultural systems are increasingly managed for improving soil carbon (C) accumulation. However, there are limits to C returns in agricultural systems that constrain soil C accumulation capacity. Increasing the efficiency of how soil microbes process C is gaining interest as an important management strategy for increasing soil C and is a key feature of soil C dynamics in many new microbial-explicit models. A higher microbial C use efficiency (CUE) may increase C storage while reducing C system losses and is a fundamental trait affecting community assembly dynamics and nutrient cycling. However, the numerous ecological unknowns influencing CUE limit our ability to effectively manage CUE in agricultural soils for greater soil C storage. In this perspective, we consider three complex drivers of agroecosystem CUE that need to be resolved to develop effective C sequestration management practices in the future: (1) the environment as an individual trait moderator versus a filter, (2) microbial community competitive and faciliatory interactions, and (3) spatiotemporal dynamics through the soil profile and across the microbial lifecycle. We highlight ways that amendments, crop rotations, and tillage practices might affect microbial CUE conditions and the variable outcomes of these practices. We argue that to resolve some of the unknowns of CUE dynamics, we need to include more mechanistic, trait-based approaches that capitalize on advanced methods and innovative field research designs within an agroecosystem-specific context. By identifying the management-level determinants of CUE expression, we will be better positioned to optimize CUE to increase soil C storage in agricultural systems.


Glucose and triiodothyronine both induce malic enzyme in the rat hepatocyte culture: evidence that triiodothyronine multiplies a primary glucose-generated signal.
We have stimulated in a cultured hepatocyte system the synergistic interaction between triiodothyronine (T3) and dietary carbohydrate in the induction of malic enzyme (ME). Kinetic studies revealed that isolated hepatocytes equilibrate with media T3 within 5 min; nuclei equilibrate with media T3 by 45 min; and the half-time of T3 metabolism was 10 h in 10% serum. We demonstrated nuclear T3 receptors in isolated hepatocytes and the induction of ME by T3 in physiological concentrations. However, in the complete absence of T3 glucose could still induce ME. At all concentrations of glucose (100-1,000 mg/dl), T3 (0.3 nM free T3) resulted in a relatively constant (1.4- to 1.7-fold) increase in ME response. The augmentation in ME activity was paralleled by an enhanced rate of enzyme synthesis as determined by [3H]leucine incorporation into immunoprecipitable ME. Cells cultured in serum free media also demonstrated a glucose-dependent increase in ME. Insulin greatly stimulated the glucose induction of ME, whereas dexamethasone had very little influence on ME induction. These studies demonstrate the usefulness of an adult hepatocyte tissue culture model for the study of the effects of T3 on gene expression in cells that are not derived from tumor. They clearly demonstrate that well established effects of T3 can be simulated in such a system at levels of free hormone that approximate those in extracellular body fluids. Our results indicate that an increased concentration of glucose per se can induce the formation of ME in the absence of alterations in extrahepatic hormones or factors. Moreover, our findings confirm inferences from in vivo studies that T3 acts as a multiplier of a glucose-induced signal.


Changes in accessibility of cytoplasmic substances to the pore associated with activation of the cystic fibrosis transmembrane conductance regulator chloride channel.
Opening of the cystic fibrosis transmembrane conductance regulator Cl(-) channel is dependent both on phosphorylation and on ATP binding and hydrolysis. However, the mechanisms by which these cytoplasmic regulatory factors open the Cl(-) channel pore are not known. We have used patch clamp recording to investigate the accessibility of cytoplasmically applied cysteine-reactive reagents to cysteines introduced along the length of the pore-lining sixth transmembrane region (TM6) of a cysteine-less variant of cystic fibrosis transmembrane conductance regulator. We find that methanethiosulfonate (MTS) reagents modify irreversibly cysteines substituted for TM6 residues Phe-337, Thr-338, Ser-341, Ile-344, Val-345, Met-348, Ala-349, Arg-352, and Gln-353 when applied to the cytoplasmic side of open channels. However, the apparent rate of modification by internal [2-sulfonatoethyl] methanethiosulfonate (MTSES), a negatively charged MTS reagent, is dependent on the activation state of the channels. In particular, cysteines introduced far along the axis of TM6 from the inside (T338C, S341C, I344C) showed no evidence of significant modification even after prolonged pretreatment of non-activated channels with internal MTSES. In contrast, cysteines introduced closer to the inside of TM6 (V345C, M348C) were readily modified in both activated and non-activated channels. Access of a permeant anion, Au(CN)(2)(-), to T338C was similarly dependent upon channel activation state. The pattern of MTS modification we observe allows us to designate different pore-lining amino acid side chains to distinct functional regions of the channel pore. One logical interpretation of these findings is that cytoplasmic access to residues at the narrowest region of the pore changes concomitant with activation.


A High Glycemic Burden Relates to Functional and Metabolic Alterations of Human Monocytes in Patients With Type 1 Diabetes.
Diabetes is associated with increased cardiovascular risk and higher occurrence of infections. These complications suggest altered responses of the innate immune system. Recent studies have shown that energy metabolism of monocytes is crucial in determining their functionality. Here we investigate whether monocyte metabolism and function are changed in patients with diabetes and aim to identify diabetes-associated factors driving these alterations. Patients with type 1 diabetes (T1D) (n = 41) and healthy age-, sex-, and BMI-matched control subjects (n = 20) were recruited. Monocytes were isolated from peripheral blood to determine immune functionality, metabolic responses, and transcriptome profiles. Upon ex vivo stimulation with Toll-like receptor (TLR) 4 or TLR-2 agonists, monocytes of patients with T1D secreted lower levels of various cytokines and showed lower glycolytic rates compared with monocytes isolated from matched control subjects. Stratification based on HbA1c levels revealed that lower cytokine secretion was coupled to higher glycolytic rate of monocytes in patients with a higher glycemic burden. Circulating monocytes displayed an enhanced inflammatory gene expression profile associated with high glycemic burden. These results suggest that a high glycemic burden in patients with T1D is related to expression of inflammatory genes of monocytes and is associated with an impaired relationship between metabolism and inflammatory function upon activation.


When gender matters: restless legs syndrome. Report of the "RLS and woman" workshop endorsed by the European RLS Study Group.
Sleep is an essential human behavior that shows prominent gender differences. Disturbed sleep, in particular, is much more prevalent in females than males. Restless legs syndrome (RLS) as one cause of disturbed sleep was observed to be somewhat more common among women than men in Ekbom's 1945 seminal series of clinical cases with the disease. He, however, reported this gender difference mainly for those with more severe symptoms. Since then numerous studies have reported that women are affected by RLS about twice as often as males for mild as well as moderate to severe RLS. The present review focuses on RLS in females from the perspectives of both epidemiology and pathophysiology. RLS will generally become worse or might appear for the first time during pregnancy. Parity increases the risk of RLS later in life suggesting that pregnancy is a specific behavioral risk factor for developing RLS. Some evidence suggests that dysfunction in iron metabolism and high estrogen levels might contribute to RLS during pregnancy. But, menopause does not lower the incidence of RLS nor does hormone replacement therapy lead to an increase, suggesting a quite complex uncertain role of hormones in the pathophysiology of RLS. Therefore, further, preferably longitudinal studies are needed to unravel the factors causing RLS in women. These studies should include genetic, clinical and polysomnographic variables, as well as hormonal measures and variables assessing iron metabolism.


Peritoneoscopy for surgeons.
Peritoneoscopy is an invasive procedure. With attention to detail and a degree of dexterity which is inherent to surgery the procedure has been found safe in over 2,500 cases. Peritoneoscopy must always be a sequel to careful clinical examination. The greatest advantage of peritoneoscopy over all other diagnostic modalities is that peritoneoscopic diagnosis is a final histological diagnosis and has no element of shadow, image or conjecture. Peritoneoscopy has its greatest value in the diagnosis of liver pathology, in ascites, jaundice, malignancy and tuberculosis especially if non-invasive scanning techniques are not available. When used with discretion, it has some value in the management of the acute abdomen. Surgeons will be gratified to find the extent to which the peritoneoscope can help arrive at an early histological diagnosis, plan surgery, reduce morbidity by avoiding unnecessary surgery and shorten hospitalisation.


Applying research in nutrition education planning: a dietary intervention for Bangladeshi chronic kidney disease patients.
Effective nutrition health interventions are theory-based, as well as being drawn from practice and research, aiming to successfully accomplish dietary behavioural changes. However, the integration of theory, research and practice to develop community dietary educational programmes is a challenge that many interventionists feel ill equipped to achieve. In the present study, a community-based education programme was designed for Bangladeshi patients with chronic kidney disease and hypertension. The goal of this programme was to reduce dietary salt intake in this population group, with a view to reducing their blood pressure and slowing kidney disease progression. The present study sets out the first four steps of a six-step model for creating a behaviour change programme. These four steps were concerned with the translation of theory and evidence into intervention objectives, and illustrate how a practical, community-based intervention was developed from behavioural theory, relevant research, knowledge of practice and the target patient group. Steps 5 and 6, which are concerned with implementation and evaluation, will be reported separately.


Endoscopic endonasal repair of encephaloceles of the lateral sphenoid sinus: multiinstitution confirmation of a new classification.
Encephaloceles of the lateral sphenoid sinus are rare. Originally believed to be due to defects in a patent lateral craniopharyngeal canal (Sternberg canal), they are now thought to originate more commonly from idiopathic intracranial hypertension, not unlike encephaloceles elsewhere in the skull base. A new classification of these encephaloceles was recently introduced, which divided them in relation to the foramen rotundum. Whether this classification can be applied to a larger cohort from multiple institutions and whether it might be useful in predicting outcome is unknown. Thus, the authors' goal was to divide a multiinstitutional cohort of patients with lateral sphenoid encephaloceles into four subtypes to determine their incidence and any correlation with surgical outcome. A multicenter retrospective review of prospectively acquired databases was carried out across three institutions. Cases were categorized into one of four subtypes (type I, Sternberg canal; type II, medial to rotundum; type III, lateral to rotundum; and type IV, both medial and lateral with rotundum enlargement). Demographic and outcome metrics were collected. Kaplan-Meyer curves were used to determine the rate of recurrence after surgical repair. A total of 49 patients (71% female) were included. The average BMI was 32.8. All encephaloceles fell within the classification scheme. Type III was the most common (71.4%), followed by type IV (16.3%), type II (10.2%), and type I (2%). Cases were repaired endonasally, via a transpterygoidal approach. Lumbar drains were placed in 78% of cases. A variety of materials was used for closure, with a nasoseptal flap used in 65%. After a mean follow-up of 47 months, there were 4 (8%) CSF leak recurrences, all in patients with type III or type IV leaks and all within 1 year of the first repair. Two leaks were fixed with ventriculoperitoneal shunt and reoperation, 1 with ventriculoperitoneal shunt only, and 1 with a lumbar drain only. Of 45 patients in whom detailed information was available, there were 12 (26.7%) with postoperative dry eye or facial numbness, with facial numbness occurring in type III or type IV defects only. Endoscopic endonasal repair of lateral sphenoid wing encephaloceles is highly successful, but repair may lead to dry eye or facial numbness. True Sternberg (type I) leaks were uncommon. Failures and facial numbness occurred only in patients with type III and type IV leaks.


Cryptococcal yeast cells invade the central nervous system via transcellular penetration of the blood-brain barrier.
Cryptococcal meningoencephalitis develops as a result of hematogenous dissemination of inhaled Cryptococcus neoformans from the lung to the brain. The mechanism(s) by which C. neoformans crosses the blood-brain barrier (BBB) is a key unresolved issue in cryptococcosis. We used both an in vivo mouse model and an in vitro model of the human BBB to investigate the cryptococcal association with and traversal of the BBB. Exposure of human brain microvascular endothelial cells (HBMEC) to C. neoformans triggered the formation of microvillus-like membrane protrusions within 15 to 30 min. Yeast cells of C. neoformans adhered to and were internalized by the HBMEC, and they crossed the HBMEC monolayers via a transcellular pathway without affecting the monolayer integrity. The histopathology of mouse brains obtained after intravenous injection of C. neoformans showed that the yeast cells either were associated with endothelial cells or escaped from the brain capillary vessels into the neuropil by 3 h. C. neoformans was found in the brain parenchyma away from the vessels by 22 h. Association of C. neoformans with the choroid plexus, however, was not detected during up to 10 days of observation. Our findings indicate that C. neoformans cells invade the central nervous system by transcellular crossing of the endothelium of the BBB.


[K(2)CsYb(PO(4))(2)].
The crystal structure of dipotassium caesium ytterbium bis(phosphate) is built up from regular independent PO(4) tetrahedra and YbO(6) octahedra sharing corners and arranged in layers. The structure is, in many respects, similar to that of glaserite.


Long-term retention explained by a model of short-term learning in the adaptive control of reaching.
Extensive theoretical, psychophysical, and neurobiological work has focused on the mechanisms by which short-term learning develops into long-term memory. Better understanding of these mechanisms may lead to the ability to improve the efficiency of training procedures. A key phenomenon in the formation of long-term memory is the effect of over learning on retention-discovered by Ebbinghaus in 1885: when the initial training period in a task is prolonged even beyond what is necessary for good immediate recall, long-term retention improves. Although this over learning effect has received considerable attention as a phenomenon in psychology research, the mechanisms governing this process are not well understood, and the ability to predict the benefit conveyed by varying degrees of over learning does not yet exist. Here we studied the relationship between the duration of an initial training period and the amount of retention 24 h later for the adaptation of human reaching arm movements to a novel force environment. We show that in this motor adaptation task, the amount of long-term retention is predicted not by the overall performance level achieved during the training period but rather by the level of a specific component process in a multi-rate model of short-term memory formation. These findings indicate that while multiple learning processes determine the ability to learn a motor adaptation, only one provides a gateway to long-term memory formation. Understanding the dynamics of this key learning process may allow for the rational design of training and rehabilitation paradigms that maximize the long-term benefit of each session.


Inhibitors of anti-apoptotic Bcl-2 family proteins exhibit potent and broad-spectrum anti-mammarenavirus activity via cell cycle arrest at G0/G1 phase.
Targeting host factors is a promising strategy to develop broad-spectrum antiviral drugs. Drugs targeting anti-apoptotic Bcl-2 family proteins that were originally developed as tumor suppressors have been reported to inhibit multiplication of different types of viruses. However, the mechanisms whereby Bcl-2 inhibitors exert their antiviral activity remain poorly understood. In this study, we have investigated the mechanisms by which obatoclax (OLX) and ABT-737 Bcl-2 inhibitors exhibited a potent antiviral activity against the mammarenavirus lymphocytic choriomeningitis virus (LCMV). OLX and ABT-737 potent anti-LCMV activity was not associated with their pro-apoptotic properties, but rather their ability of inducing cell arrest at G0/G1 phase. OLX and ABT-737 mediated inhibition of Bcl-2 correlated with reduced expression levels of thymidine kinase 1 (TK1), cyclin A2 (CCNA2), and cyclin B1 (CCNB1) cell cycle regulators. In addition, siRNA-mediated knock down of TK1, CCNA2, and CCNB1 resulted in reduced levels of LCMV multiplication. The antiviral activity exerted by Bcl-2 inhibitors correlated with reduced levels of viral RNA synthesis at early times of infection. Importantly, ABT-737 exhibited moderate efficacy in a mouse model of LCMV infection, and Bcl-2 inhibitors displayed broad-spectrum antiviral activities against different mammarenaviruses and SARS-CoV-2. Our results suggest that Bcl-2 inhibitors, actively being explored as anti-cancer therapeutics, might be repositioned as broad-spectrum antivirals. Anti-apoptotic Bcl-2 inhibitors have been shown to exert potent antiviral activities against various types of viruses via mechanisms that are currently poorly understood. This study has revealed that Bcl-2 inhibitors mediated cell cycle arrest at the G0/G1 phase, rather than their pro-apoptotic activity, plays a critical role in blocking mammarenavirus multiplication in cultured cells. In addition, we show that Bcl-2 inhibitor ABT-737 exhibited moderate anti-mammarenavirus activity in vivo , and that Bcl-2 inhibitors displayed broad-spectrum antiviral activities against different mammarenaviruses and SARS-CoV-2. Our results suggest that Bcl-2 inhibitors, actively being explored as anti-cancer therapeutics, might be repositioned as broad-spectrum antivirals.


High HIV incidence and low uptake of HIV prevention services: The context of risk for young male adults prior to DREAMS in rural KwaZulu-Natal, South Africa.
Young men are less likely than young women to engage with HIV prevention and care, and their HIV-related mortality is higher. We describe HIV incidence and uptake of HIV services in men 20-29 years(y) in rural KwaZulu-Natal, South Africa, before the roll-out of DREAMS. We used data from a population-based demographic and HIV surveillance cohort. HIV incidence was estimated from anonymised testing in an annual serosurvey. Service uptake was assessed in 2011 and 2015, through two self-reported outcomes: 1) HIV testing in the past 12 months(m); 2) voluntary medical male circumcision(VMMC). Logistic regression was used to estimate odds ratios(OR) and 95% confidence intervals(CI) for factors associated with each outcome. HIV incidence in 2011-2015 was 2.6/100 person-years (95%CI = 2.0-3.4) and 4.2 (95%CI = 3.1-5.6) among men 20-24y and 25-29y, respectively, with no significant change from 2006-2010. N = 1311 and N = 1221 young men participated in the 2011 and 2015 surveys, respectively. In both years, <50% reported testing for HIV in the past 12m. In 2011, only 5% reported VMMC, but coverage in 2015 increased to 40% and 20% in men 20-24y and 25-29y, respectively. HIV testing was positively associated with higher education and mobility. Testing uptake was higher in men reporting >1 partner in the past 12m, or condom use at last sex, but lower in those reporting a casual partner (adjusted (a)OR = 0.53, 95%CI = 0.37-0.75). VMMC uptake was associated with survey year and higher education. Men aged 25-29y and those who were employed (aOR = 0.66; 95%CI = 0.49-0.89) were less likely to report VMMC. HIV incidence in men 20-29y was very high, and pre-exposure prophylaxis (PrEP) should be considered in this population. Uptake of services was low. VMMC coverage increased dramatically from 2011 to 2015, especially among younger men, suggesting a demand for this service. Interventions designed with and for young men are urgently needed.


Rhizobium leguminosarum as a plant growth-promoting rhizobacterium: direct growth promotion of canola and lettuce.
Early seedling root growth of the nonlegumes canola (Brassica campestris cv. Tobin, Brassica napus cv. Westar) and lettuce (Lactuca sativa cv. Grand Rapids) was significantly promoted by inoculation of seeds with certain strains of Rhizobium leguminosarum, including nitrogen- and nonnitrogen-fixing derivatives under gnotobiotic conditions. The growth-promotive effect appears to be direct, with possible involvement of the plant growth regulators indole-3-acetic acid and cytokinin. Auxotrophic Rhizobium mutants requiring tryptophan or adenosine (precursors for indole-3-acetic acid and demonstrate a new facet of the Rhizobium-plant relationship and that Rhizobium leguminosarum can be considered a plant growth-promoting rhizobacterium (PGPR).


Transapical mitral valved stent implantation: computed tomographic evaluation of different prototype designs.
The evaluation of in vivo shaping of mitral valved stent prototypes using cardiac computed tomography (CT) was the focus of this study. Twelve pigs received a self-expanding mitral valved stent, composed of an atrial element connected to a tubular ventricular body at a modified angle (45°, 90°, 110°) resulting in three designs. Cardiac CT was performed three weeks after implantation, with focus placed on stent design-related parameters: possible left ventricular outflow tract obstruction and stent shaping. CT was successfully conducted in 11/12 animals showing correct stent position within the mitral annulus and no obstruction of the left ventricular outflow tract in 9/11 animals. Minor radial deformations of the stent body were detected. At the atrioventricular junction, deformations of the stent structure were observed in all cases. Stents with a 45° angle exhibited the greatest deflection (≤56.4°±14.5°). The effectiveness of cardiac computed tomography in the development process of valved stents to provide essential information and quantitative data about the in vivo stent geometry was demonstrated. The in vivo mechanical deformations of the stent were quantified, identifying critical design areas: a larger preset angle leads to less deflection and improved alignment and hence reduces the mechanical load.


[The effect of neurotropic agents on the development of toxic brain edema in sexually immature animals].
It was established on two age groups of rats that toxic brain edema in one-month-old animals is prevented by dopegit (100 mg/kg) and aminazine (2.5 mg/kg). The pharmacological correction of the brain edema in two-month-old rats is similar to that in adult animals. The central adrenergic structures play the significant role in the development of the brain edema in sexually immature animals.


Anti-cancer activity of targeted pro-apoptotic peptides.
We have designed short peptides composed of two functional domains, one a tumor blood vessel 'homing' motif and the other a programmed cell death-inducing sequence, and synthesized them by simple peptide chemistry. The 'homing' domain was designed to guide the peptide to targeted cells and allow its internalization. The pro-apoptotic domain was designed to be nontoxic outside cells, but toxic when internalized into targeted cells by the disruption of mitochondrial membranes. Although our prototypes contain only 21 and 26 residues, they were selectively toxic to angiogenic endothelial cells and showed anti-cancer activity in mice. This approach may yield new therapeutic agents.


Dihydrocelastrol induces antitumor activity and enhances the sensitivity of bortezomib in resistant multiple myeloma by inhibiting STAT3-dependent PSMB5 regulation.
Multiple myeloma (MM) is characterized by excessive aggregation of B-cell-derived malignant plasma cells in the hematopoietic system of bone marrow. Previously, we synthesized an innovative molecule named dihydrocelastrol (DHCE) from celastrol, a triterpene purified from medicinal plant Tripterygium wilfordii. Herein, we explore the therapeutic properties and latent signal transduction mechanism of DHCE action in bortezomib (BTZ)-resistant (BTZ-R) MM cells. In this study, we first report that DHCE shows antitumor activities in vitro and in vivo and exerts stronger inhibitory effects than celastrol on BTZ-R cells. We find that DHCE inhibits BTZ-R cell viability by promoting apoptosis via extrinsic and intrinsic pathways and suppresses BTZ-R MM cell proliferation by inducing G0/G1 phase cell cycle arrest. In addition, inactivation of JAK2/STAT3 and PI3K/Akt pathways are involved in the DHCE-mediated antitumor effect. Simultaneously, DHCE acts synergistically with BTZ on BTZ-R cells. PSMB5, a molecular target of BTZ, is overexpressed in BTZ-R MM cells compared with BTZ-S MM cells and is demonstrated to be a target of STAT3. Moreover, DHCE downregulates PSMB5 overexpression in BTZ-R MM cells, which illustrates that DHCE overcomes BTZ resistance through increasing the sensitivity of BTZ in resistant MM via inhibiting STAT3-dependent PSMB5 regulation. Overall, our findings imply that DHCE may become a potential therapeutic option that warrants clinical evaluation for BTZ-R MM.


Sedentary Time, Physical Activity, and Sleep Duration: Associations with Body Composition in Fibromyalgia. The Al-Andalus Project.
To explore the individual-independent relationships of sedentary time (ST) and physical activity (PA) (light and moderate-to-vigorous intensity (MVPA)), with sleep duration and body composition (waist circumference, body mass index (BMI), body fat percentage, and muscle mass index) in women with fibromyalgia, and to determine whether these associations are independent of physical fitness. This cross-sectional study involved 385 women with fibromyalgia. ST and PA were assessed by triaxial accelerometry, sleep duration was self-reported. Waist circumference was measured using an anthropometric tape, and body weight, body fat percentage, and muscle mass were estimated using a bio-impedance analyzer. In individual regression models, ST and sleep were directly associated with waist circumference, BMI, and body fat percentage (β between 0.10 and 0.25; all p < 0.05). Light PA and MVPA were inversely associated with waist circumference, BMI, and body fat percentage (β between -0.23 and -0.12; all p < 0.05). In multiple linear regression models, ST (β between 0.17 and 0.23), light PA (β between -0.16 and -0.21), and sleep duration (β between 0.11 and 0.14) were independently associated with waist circumference, BMI, and body fat percentage (all p < 0.05). MVPA was associated with waist circumference independent of light physical activity (LPA) and sleep duration (β = -0.11; p < 0.05). Except for MVPA, these associations were independent of physical fitness. These results suggest that longer ST and sleep duration, and lower PA levels (especially light intensity PA), are independently associated with greater adiposity, but not muscle mass, in women with fibromyalgia. These associations are, overall, independent of physical fitness.


Auscultation of cervical and ocular bruits in extracranial carotid occlusive disease: a clinical and angiographic study.
The clinical and angiographic features of cervical and ocular bruits were correlated in 50 consecutive patients with severe extracranial internal carotid artery occlusive disease. Cervical bruits, generally localized to the carotid bifurcation, were highly associated (P = 0.004) with "tight" (residual lumen less than or equal to 2 mm) internal carotid artery stenosis, but significantly less often with a widely patent or occluded internal carotid artery. Angiographic features of a "slow-flow" state through a patent, but "tight" stenosis were identified as the apparent explanation for the absence of bruit in some patients. A unilateral ocular bruit contralateral to the side of internal carotid artery occlusion occurred in 9 of 10 patients, more often than an associated cervical bruit, and was interpreted as a sign of augmentation flow.


Epigenetic regulation in African trypanosomes: a new kid on the block.
Epigenetic regulation is important in many facets of eukaryotic biology. Recent work has suggested that the basic mechanisms underlying epigenetic regulation extend to eukaryotic parasites. The identification of post-translational histone modifications and chromatin-modifying enzymes is beginning to reveal both common and novel functions for chromatin in these parasites. In this Review, we compare the role of epigenetics in African trypanosomes and humans in several biological processes. We discuss how the study of trypanosome chromatin might help us to better understand the evolution of epigenetic processes.


Realizing the price of academic freedom.
Since 2010, the number of life science doctoral graduates opting into academic postdoctoral employment has steadily declined. In recent years, this decline has made routine headlines in academic news cycles, and faculty members, universities, and funding bodies alike have begun to take notice. In November 2022, the National Institutes of Health (NIH) convened a special interest group to address the problems in postdoctoral recruitment and retention. In response, the American Physiological Society Science Policy Committee highlighted several key issues in postdoctoral training and working conditions and offered the NIH solutions to consider. There are known issues that affect postdoctoral recruitment and retention efforts: low wages relative to other employment sectors, a heavy workload, and poor job prospects to name a few. Unfortunately, these concerns are frequently dismissed as "the price of doing business in academia," and postdoctoral scholars are promised that if they overcome the trials and tribulations of this training period, the reward at the end, a career with academic freedom to pursue your own interests, justifies the means. However, academic freedom cannot and should not be used as the band-aid in a system where most of us will never actually experience academic freedom. Instead, we should systematically embrace solutions that improve the personal and professional health of early career researchers in all levels of training and independence if the goal is to truly shore up the academic workforce.


Breast cancer risk in rats fed a diet high in n-6 polyunsaturated fatty acids during pregnancy.
Women who took the synthetic estrogen diethylstilbestrol during pregnancy exhibit an elevated risk of breast cancer, whereas those who suffered from preeclampsia, which is associated with low circulating pregnancy estrogens, exhibit a reduced risk. Since a high-fat diet may increase circulating estrogen levels and possibly breast cancer risk, dietary factors during pregnancy could influence the risk of developing this disease. We tested the hypothesis that consumption of a high-fat diet during pregnancy increases carcinogen-induced mammary tumor incidence in rats. Pregnant or virgin female Sprague-Dawley rats that had been previously treated with 10 mg 7, 12-dimethylbenz[a]anthracene (DMBA) by oral gavage when 55 days old were assigned to one of two isocaloric diets containing either 16% calories from fat (low-fat) or 43% calories from fat (high-fat) for the length of pregnancy or for the equivalent time of approximately 21 days. There were 20 pregnant and 10 nonpregnant DMBA-treated rats per group. Ten additional pregnant animals (not previously treated with DMBA) per group were used for hormone analysis. The fat source used was corn oil, which is high in n-6 polyunsaturated fatty acids, primarily linoleic acid. The animals were checked for tumors at least once per week by palpation. The tumor size, number, and latency to appearance after carcinogen exposure were recorded. The statistical significance of observed differences was tested by use of appropriate two-sided tests. Female rats on different diets had virtually identical food intakes and weight gains during pregnancy. On gestation day 19, serum estradiol levels were approximately twofold higher in rats fed a high-fat diet than in rats fed a low-fat diet (P < .02). The serum insulin levels and insulin/glucose ratios (an index of insulin resistance) in rats fed the high-fat diet were approximately twofold lower than in rats fed the low-fat diet, but the differences did not reach statistical significance (P < .09 and P < .09, respectively). On week 18 following DMBA administration, the number of rats developing mammary tumors was significantly higher in the group exposed to a high-fat diet (40% of animals) than in the group exposed to a low-fat diet (10% of animals) during pregnancy (P < .05). Tumor multiplicity, latency to tumor appearance, and size of tumors upon first detection were similar among the dietary groups. No intergroup differences in the mammary tumor incidence were noted in virgin animals that were exposed to the high- or low-fat diets for an equivalent period of time. Our findings indicate that consumption of a diet high in fat (primarily in the form of n-6 polyunsaturated fatty acids) during pregnancy increases the risk of developing carcinogen-induced mammary tumors, possibly by increasing the pregnancy levels of circulating estrogens. If further studies find that the results from animal model studies are applicable to humans, some human breast cancers may be preventable by dietary manipulations during pregnancy.


Ultrastructural localization of calcium ions in ram spermatozoa before and after cold shock as demonstrated by a pyroantimonate technique.
Ram spermatozoa were subjected to cold shock before fixation in pyroantimonate-osmium. Ultrathin sections revealed an electron-dense particulate precipitate in association with the cells. The precipitate was shown to be related to the presence of calcium by exposure of the material to EGTA which reduced or completely eliminated the deposits. In the acrosome region, very little precipitate was evident when the plasma membrane was intact. Cold shock resulted in the disruption of the plasma membrane. When the acrosome remained intact, precipitate was concentrated just anterior to the equatorial segment, but many cells also had acrosomal disruption and then a more even distribution of precipitate was seen on the outer acrosomal membrane. Precipitate was rarely visible within or beneath the acrosome. Post-acrosomally, calcium pyroantimonate deposits were frequently present in the dense lamina beneath the plasma membrane and these became more intense after cold shock. Midpiece sections revealed a few large granules beneath the plasma membrane and a fine particulate precipitate within mitochondria. Similarly, the fine precipitate was also associated with the outer dense fibres in midpieces and tails. Cold shock did not apparently increase the extent or intensity of precipitates in these sites.


[Current pathophysiologic aspects of allergic rhinitis. I].
Allergic rhinitis is a classic example of a type I immunological reaction. After allergic provocation tests a biphasic reaction is seen in the respiratory tract that is more pronounced in the lower than in the upper respiratory tract due to the physiological changes during the nasal cycle. The early phase of the immediate reaction starts some minutes after allergen provocation. After 5-10 h the nasal symptoms (discharge, blockage, sneezing and itching of the nose) reappear, a phenomenon which is called the "late-phase response" (LPR). The LPR is of great clinical importance in the pathophysiology of perennial allergic rhinitis and phenomena such as nasal priming and nasal hyper-reactivity. The most important effector cell of the early phase of the immediate reaction is the mast cell, whereas basophils, eosinophils and neutrophil granulocytes seem to be more important for the LPR. There is also evidence for morphological and functional heterogeneity of mast cells in man. The role of the chemotactically immigrated eosinophils in allergic reactions has not been clear until now: the eosinophil-derived mediators may enhance or inhibit the allergic reaction. Also the eosinophils show different morphological and functional states (so-called hypo- and hyperdense eosinophils). The symptoms of allergic rhinitis (sneezing, discharge, blockage, itching of the nose) are caused by different mediators, of which the most important is histamine. Other mediators or modulators of the allergic reactions are leucotrienes, prostaglandins, PAF, serotonin, and the kallikrein-kinine and complement systems. In recent years many regulatory peptides have been detected in the human nasal mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)


Discovery of Orexant and Anorexant Agents with Indazole Scaffold Endowed with Peripheral Antiedema Activity.
The endocannabinoid system represents an integrated neuronal network involved in the control of several organisms' functions, such as feeding behavior. A series of hybrids of 5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (mimonabant), a well-known inverse agonist of the type-1 cannabinoid receptor (CB1), once used as an antiobesity drug, and the N-(2S)-substitutes of 1-[(4-fluorophenyl)methyl]indazole-3-carboxamide with 1-amino-3-methyl-1-oxobutane (AB-Fubinaca), 1-amino-3,3-dimethyl-1-oxobutane (ADB-Fubinaca), and 3-methylbutanoate (AMB-Fubinaca), endowed with potent agonistic activity towards cannabinoid receptors CB1 and CB2 were in solution as C-terminal amides, acids, methyl esters and N-methyl amides. These compounds have been studied by binding assays to cannabinoid receptors and by functional receptor assays, using rat brain membranes in vitro. The most active among them as an agonist, (S)-1-(2,4-dichlorobenzyl)-N-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl)-1H-indazole-3-carboxamide (LONI11), and an antagonist, (S)-2-(1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxamido)-3-methylbutanoic acid (LONI4), were tested in vivo in mic, to evaluate their ability to stimulate or suppress feeding behavior after intraperitoneal (i.p.) administration. For a LONI11 formalin test and a tail flick test after an administration by the subcutaneous (s.c.) and intracerebroventricular (i.c.v.) routes, respectively, were also carried out in vivo in mice to investigate the antinociceptive property at the central and peripheral levesl. We observed a significant orexant effect for LONI11 and an intense anorexant effect for (S)-methyl 2-(1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate (LONI2) and LONI4. In zymosan-induced edema and hyperalgesia, LONI11 reduced the percent of paw volume increase and paw latency after s.c. administration, also suggesting a possible peripheral anti-inflammatory activity.


Prevalence of congenital heart disease and its related risk indicators among 90,796 Chinese infants aged less than 6 months in Tianjin.
Congenital heart disease (CHD) represents one of the most prevalent congenital malformations. However, few studies use whole-population screening by colour Doppler ultrasonic diagnostic system to identify CHD among live infants. We estimate the prevalence of CHD and its major risk indicators among infants aged less than 6 months in urban Tianjin, China. A colour Doppler ultrasonic diagnostic system was used as the screening tool for the diagnosis of CHD. A total of 90,796 infants aged less than 6 months, living in the nine urban districts of Tianjin, China, participated in the CHD screening programme between July 2009 and June 2011. A total of 1817 children were identified as having CHD. The overall prevalence of congenital heart disease was 16.4 per 1000 live births among 47,697 boys, 24.1 per 1000 live births among 43,099 girls, and 20.0 per 1,000 live births among 90,796 boys and girls combined. Atrial septal defect was the most common heart lesion of CHD, with the prevalence of 10.6 per 1000 live births. Several maternal antenatal factors, such as older age, pregnant infections, pregnancy-induced hypertension, gestational diabetes, family history of CHD, and lower education level, and several child factors, such as early screening age, lower birthweight and short gestational age, were associated with an increased risk of CHD. The prevalence of CHD of live infants in Tianjin was found to be relatively high by using a colour Doppler ultrasonic diagnostic system to screen CHD. Several maternal factors were associated with CHD risk.


Crocodile oil enhances cutaneous burn wound healing and reduces scar formation in rats.
This study was performed to evaluate the burn wound-healing efficacy of crocodile oil from Crocodylus siamensis by employing deep second-degree burns in a Wistar rat model. Twenty-four rats were assigned equally into four groups using a random-number table, and two burns were created on the dorsum of each animal except for the sham group. The three treatment groups received with saline solution (12 burns, served as negative control), silver sulfadiazine (12 burns, served as positive control), or crocodile oil (12 burns). Silver sulfadiazine cream was used as standard care, and the treatments were repeated twice daily for 28 days. After day 28 the animals were euthanized and the wounds were removed for quantitative real-time polymerase chain reaction, histologic, and immunohistochemical study. Crocodile oil accelerated the wound-healing process as indicated by a significant decrease in wound closure time in comparison to the burn control and silver sulfadiazine treatment groups. Histologic results showed well-organized and distributed skin structure and collagen deposition in the animals treated with crocodile oil. Transforming growth factor-β1 (TGF-β1), a key cytokine promoting scarring, was also observed to play a role in the burn wound healing. Immunohistochemical staining results showed the negative expression of TGF-β1 and Smad3 in the 28-days-postburn skin of crocodile oil group versus positive in the epidermis of burn controls. Compared to the burn control group, expressions of TGF-β1 and Smad3 mRNA decreased significantly (p < 0.01) in the 28-days-postburn skin of the crocodile oil group. Our results showed that crocodile oil could enhance cutaneous burn wound healing and reduce scar formation in rats, which might be related to TGF-β1/Smad3 signaling.


Feedback inhibition of the development of macrophage and granulocyte colonies. II. Inhibition by granulocytes.
It has been shown that mature normal rat granulocytes produce a substance that inhibits the activity of the inducer required for the development of macrophages (M) and granulocyte (G) colonies from normal hematopoietic cells seeded in soft agar. The granulocyte inhibitor inhibited the activity of the inducer when tested with normal hematopoietic cells from embryonic or adult organs. The inhibitor was not dialyzable, and was obtained in an active form in granulocyte-conditioned medium. The results indicate that the control mechanism that regulates the growth and development of normal macrophages and granulocytes includes a feedback inhibition of the activity of the inducer by inhibitors produced by mature granulocytes and macrophages, presumably at the end of their differentiation process. The inhibition of both M and G colonies by the feedback inhibitors produced by macrophages and granulocytes suggests that both types of colonies may be derived from a common stem cell. A line of primitive myeloid leukemia did not inhibit the activity of the inducer, and the cells of this line were not inhibited by the feedback inhibitors produced by normal granulocytes and macrophages.


Development of diagnostic reagents to differentiate between Mycobacterium bovis BCG vaccination and M. bovis infection in cattle.
In Great Britain a recent independent scientific review for the government has concluded that the development of a cattle vaccine against Mycobacterium bovis holds the best long-term prospect for tuberculosis control in British herds. A sine qua non for vaccination is the development of a complementary diagnostic test to differentiate between vaccinated animals and those infected with M. bovis so that test-and-slaughter-based control strategies can continue alongside vaccination. In order to assess the feasibility of developing a differential diagnostic test for a live vaccine, we chose M. bovis BCG Pasteur as a model system. Recombinant forms of antigens which are expressed in M. bovis but not, or only at low levels, in BCG Pasteur (ESAT-6, MPB64, MPB70, and MPB83) were produced. These reagents were tested either alone or in combination by using peripheral blood mononuclear cells from M. bovis-infected, BCG-vaccinated, and Mycobacterium avium-sensitized calves. All four antigens induced in vitro proliferation and gamma interferon responses only in M. bovis-infected animals. A cocktail composed of ESAT-6, MPB64, and MPB83 identified infected animals but not those vaccinated with BCG. In addition, promiscuous T-cell epitopes of ESAT-6, MPB64, and MPB83 were formulated into a peptide cocktail. In T-cell assays with this peptide cocktail, infected animals were identified with frequencies similar to those obtained in assays with the protein cocktail, while BCG-vaccinated or M. avium-sensitized animals did not respond. In summary, our results suggest that peptide and protein cocktails can be designed to discriminate between M. bovis infection and BCG vaccination.


Aliphatic alcohol contaminants of illegally produced spirits inhibit phagocytosis by human granulocytes.
Unregulated production of spirits in many countries leads to products containing appreciable levels of aliphatic alcohols (AAs) and is the main source of human exposure to these substances worldwide. Previous studies have confirmed that alcohol abuse can lead to ethanol-induced immunosuppression and thereby increased susceptibility to infectious diseases. Granulocytes, as professional phagocytic cells, play a crucial role in engulfment and killing of pathogenic microorganisms. Thus, a decrease in their phagocytic activity has been invoked as a factor in the impaired antimicrobial defense observed in alcoholics. However, AAs consumed as contaminants of illicit spirits may also influence phagocytosis, thereby contributing to a further decrease in microbicidal activity but, so far, this has not been studied. Therefore, the aim of this study was to measure granulocyte phagocytosis following treatment of granulocytes with those higher alcohols found in illegal spirits. Granulocytes were isolated from human peripheral blood. Then phagocytosis of opsonized zymosan particles by granulocytes treated with AAs individually and in combination was determined. These alcohols inhibited phagocytosis in a concentration-dependent manner and at lower concentrations when combined than when tested individually. Due to their synergistic effects, it is possible that, in combination with ethanol, they may inhibit phagocytosis in a clinically meaningful way in episodic heavy drinkers.


Potential protein activity modifications of amino acid variants in the human transcriptome.
The occurrence of widespread RNA and DNA sequence differences in the human transcriptome was reported in 2011. Similar findings were described in a second independent publication on personal omics profiling investigating the occurrence of dynamic molecular and related medical phenotypes. The suggestion that the RNA sequence variation was likely to affect disease susceptibility prompted us to investigate with a range of algorithms the amino acid variants reported to be present in the identified peptides to determine if they might be disease-causing. The predictive qualities of the different algorithms were first evaluated by using nonsynonymous single-base nucleotide polymorphism (nsSNP) datasets, using independently established data on amino acid variants in several proteins as well as data obtained by mutational mapping and modelling of binding sites in the human serotonin transporter protein (hSERT). Validation of the used predictive algorithms was at a 75% level. Using the same algorithms, we found that widespread RNA and DNA sequence differences were predicted to impair the function of the peptides in over 57% of cases. Our findings suggest that a proportion of edited RNAs which serve as templates for protein synthesis is likely to modify protein function, possibly as an adaptive survival mechanism in response to environmental modifications.


Establishing a Longitudinal Comparable Scale of Chinese Children's Cognitive Development through Calibrated Projection Linking.
In the past decades, the longitudinal approach has been remarkably and increasingly used in the investigations of children's cognitive development. Recently, many researchers have started to realize the importance and necessity of examining measurement invariance for any further longitudinal analysis. However, there are few empirical studies demonstrating how to conduct further analysis when the assumption of measurement invariance of an instrument is violated. The primary purpose of this study is to explore how a newly-developed calibrated projection method can be applied to reduce the impact of lack of parameter invariance in a longitudinal study of preschool children's cognitive development. The sample consisted of 882 children from China who participated in two waves of the cognitive tests when they were 4 and 5 years old. Before this study was conducted, the IRT method was used to examine the measurement invariance of the instrument. The results showed that five items presented difficulty parameter drift and three items presented discrimination/slope parameter drift. In the study, the invariant items were treated as "common items" and calibrated projection linking was used to establish a comparable scale across two time points. Then the linking method was evaluated by three properties: grade-to-grade growth, grade-to-grade variability, and the separation of distributions. The results showed that the grade-to-grade growth across two waves was larger and exhibited a larger effect size; the grade-to-grade variability showed less scale shrinkage, which indicated a smaller measurement error; the separation of distributions showed a larger growth as well.


Cluster-determinant 36 (CD36) impacts on vitamin E postprandial response.
A single nucleotide polymorphism in the cluster determinant 36 (CD36) gene has recently been associated with plasma α-tocopherol concentration, suggesting a possible role of this protein in vitamin E intestinal absorption or tissue uptake. To investigate the involvement of CD36 in vitamin E transport, we first evaluated the effect of CD36 on α- and γ-tocopherol transmembrane uptake and efflux using transfected HEK cells. γ-Tocopherol postprandial response was then assessed in CD36-deficient mice compared with wild-type mice, after the mice had been fully characterized for their α-tocopherol, vitamin A and lipid plasma, and tissue contents. Both α- and γ-tocopherol uptake was significantly increased in cells overexpressing CD36 compared with control cells. Compared with wild-type mice, CD36-deficient mice displayed a significantly decreased cholesterol hepatic concentration, and males exhibited significantly higher triacylglycerol contents in liver, brain, heart, and muscle. Although tissue α-tocopherol concentration after adjustment for lipid content was not modified, γ-tocopherol postprandial response was significantly increased in CD36-deficient mice compared with controls, likely reflecting the postprandial hypertriglyceridemia observed in these mice. Our findings show for the first time that CD36 participates-directly or indirectly-in vitamin E uptake, and that CD36 effect on postprandial lipid metabolism in turn modifies vitamin E postprandial response.


Periprocedural adverse events after endoscopic resection of T1 colorectal carcinomas.
In contrast to the adverse event (AE) risk of endoscopic resection (ER) of adenomas, the intra- and postprocedural AE risks of ER of T1 colorectal cancer (CRC) are scarcely reported in the literature. It is unclear whether ER of early CRCs, which grow into the submucosal layer and sometimes show incomplete lifting, is associated with an increased AE risk. We aimed to identify the AE rate after ER of T1 CRCs and to identify the risk factors associated with these AEs. Medical records of patients with T1 CRCs diagnosed between 2000 and 2014 in 15 hospitals in the Netherlands were reviewed. Patients who underwent primary ER were selected. The primary outcome was the occurrence of endoscopy-related AEs. The secondary outcome was the identification of risk factors. Multivariate logistic regression was performed. Endoscopic AEs occurred in 59 of 1069 (5.5%) patients, among which 37.3% were classified as mild, 59.3% as moderate, and 3.4% as severe. AEs were postprocedural bleeding (n = 40, 3.7%), perforation (n = 13, 1.2%), and postpolypectomy electrocoagulation syndrome (n = 6, 0.6%). No fatal AEs were observed. Independent predictors for AEs were age >70 years (odds ratio, 2.11; 95% confidence interval, 1.12-3.96) and tumor size >20 mm (odds ratio, 2.22; 95% confidence interval, 1.05-4.69). In this large multicenter retrospective cohort study, AE rates of ER of T1 CRC (5.5%) are comparable with reported AE rates for adenomas. Larger tumor size and age >70 years are independent predictors for AEs. This study suggests that endoscopic treatment of T1 CRCs is not associated with an increased periprocedural AE risk.


Dose-dependent selective priming of Th1 and Th2 immune responses is achieved only by an antigen with an affinity over a certain threshold level.
Helper CD4+ T lymphocytes can be divided into two subsets, Th1 and Th2. The types of Th subsets activated during the adaptive immune response inductiondetermine the efficacy of immune responses against thee antigens introduced. Selective differentiation of subsets of CD4+ T lymphocytes has been known to be influenced by several factors, such as the cytokine environment around the T cells, the specificity of antigen recognition bythe T cell receptor, the expression of costimulatory molecules, and/ or the dose of the antigen applied to stimulate the T cells. In this study, we tried to determine the influence of the antigen dose on the selective priming of T lymphocytes when an inefficient antigen was applied since all the conclusions drawn from previous experiments were based on experiments with immune systems which responded well against the antigens introduced. When the recombinant hen egg-white lysozyme (HEL) was used too stimulate immune responses in HEL low-responder C57B3L/6 mice, dose-dependent selective priming of immune responses was not observed. However, when the variant antigen, which had been characterized as an efficientantigen in anti-HEL immune response induction in the low-responder mice, was applied, dose-dependent selective priming of Th immune responses was clearly demonstrated. These results suggested that dose-dependent selective priming of Th immune responses could be achieved only by the antigens with an affinity over a certain level.


Fungal keratitis: A review of clinical presentations, treatment strategies and outcomes.
Infectious keratitis is a significant cause of corneal blindness worldwide. Although less prevalent in the developed world, cases of fungal keratitis account for almost half of all keratitis cases, occurring in the developing countries. These cases are one of the most refractory types of infectious keratitis and present various challenges to the treating physician such as delayed presentation, long waiting time for culture positivity, limited availability effective antifungal drugs, prolonged duration for response to therapy, a highly variable spectrum of anti-fungal drug sensitivity and a high recurrence rate following keratoplasty. The advent of rapid diagnostic tools, molecular methods, in vitro anti-fungal drug sensitivity testing, alternatives to natamycin, targeted drug delivery and most importantly the results of large randomized controlled trials have significantly improved our understanding and approach towards the diagnosis and management of cases with fungal keratitis. Overall, Aspergillus and Fusarium species are the most common causes ones of fungal keratitis. History of antecedent trauma is a significant predisposing factor. Corneal scrapings for microscopic evaluation and culture preparation, is the standard of care for establishing the diagnosis of fungal keratitis. Molecular identification of cultures offers accurate identification of fungal pathogens, especially the rare species. Natamycin is an approved first-line drug. Voriconazole is the best alternative, especially for non-fusarium cases. Management involves administration of drugs usually by a combination of various routes, the treatment regimen being individualized depending upon the response to therapy. Photodynamic therapy is a newer treatment modality, being tried for non-responsive cases, before resorting to a therapeutic graft.


Idiopathic thrombocytopenic purpura complicated by an intracranial hemorrhage secondary to an arteriovenous malformation.
To report a case of idiopathic thrombocytopenic purpura (ITP) complicated by an intracranial hemorrhage (ICH) in a child with a previously undiagnosed arteriovenous malformation. We describe a child with known ITP who developed a severe headache, was evaluated in an emergency department of a community hospital, and was found by computer tomography (CT) scan to have an ICH. Despite treatment with platelets, corticosteroids, and intravenous immunoglobulin, she subsequently developed an acute change in mental status. A second CT scan showed that the hemorrhage had significantly increased in size despite treatment. The patient underwent an emergent splenectomy prior to a craniotomy to remove the hemorrhage. At the time of surgery, it was discovered that she had an arteriovenous malformation at the sight of the hemorrhage. Her recovery was unremarkable and she was discharged to home with no neurologic sequelae. ICH is a rare but life-threatening complication of ITP. Neurologic symptoms in a child with ITP should be quickly evaluated by CT scan. Most experts suggest careful observation for most cases of ITP. However, when neurologic symptoms occur, more aggressive treatment options must be used. Care of this child included an emergency splenectomy prior to her craniotomy. Pediatric emergency medicine practitioners must be aware of these neurologic symptoms and must not hesitate to involve pediatric surgeons and neurosurgeons in the care of the child. Prompt recognition and early intervention are the keys to improving outcomes when ICH complicates ITP.


Education requirements for nurses working with people with complex neurological conditions: relatives' perceptions.
This paper reports on the exploration of relatives' perceptions about the need for education and training of nurses (registered nurses and healthcare assistants) who work with people who have complex neurological long-term conditions. A service evaluation was undertaken to meet the study aim and a cross-sectional, self-administered postal questionnaire was undertaken with relatives related to someone (patient/resident) with a complex neurological condition between October and November 2007 at one specialist hospital in South-West London in the UK. Results indicate that the majority of respondents (87.2%, n = 34) believe that nurses working in this setting require specific complex neurological disability education and training. The perceptions of relatives support the need for the development of specialist education and training for nurses working with this patient population. These findings are similar to other neurological and rehabilitation studies, and warrant further exploration across multiple sites.


Viability evaluation of engineered tissues.
Biohybrid artificial organs encompass all devices capable of substituting for an organ or tissue function and are fabricated from both synthetic materials and living cells. The viability of engineered tissue could be related to the viability of implanted cells. The system of viability assay for mammalian cell culture can be applied to the determination of cell viability for engineered tissue. This review explores various methods of cell viability assay which can be applied to the viability evaluation of engineered tissue. The major criteria employed in viability assays include survival and growth in tissue culture, functional assay, metabolite incorporation, structural altercation, and membrane integrity. Each viability assay method is based on different definitions of cell viability, and has inherent advantages and disadvantages. In order to be able to assess the viability of cells with one assay method, it is desirable to compare the viability measurements from various assays derived from different criteria.


Vascular lesions in tuberculosis.
4 cases of tuberculosis in which the vessels were involved are described: 1 of tuberculous adenitis and arteritis in the region of the carotid artery bifurcation; 1 of tuberculous endometritis associated with aortic pseudoaneurysms and inferior vena cava partial occlusion, and 2 of tuberculous para-aortic adenitis, 1 with complete occlusion of the inferior vena cava, and the other with miliary nodulations of the liver later demonstrated by angiogram. It is suggested that in veiw of the ubiquitous presentations and incidence of tuberculosis in this environment, more vascular studies need be done to demonstrate the frequency and the involvement of the vessels by tuberculosis in cases of tuberculosis. Furthermore, in cases of aortitis and arteritis, tuberculosis must be excluded as an etiological cause.


Avenanthramides, polyphenols from oats, exhibit anti-inflammatory and anti-itch activity.
Oatmeal has been used for centuries as a soothing agent to relieve itch and irritation associated with various xerotic dermatoses; however few studies have sought to identify the active phytochemical(s) in oat that mediate this anti-inflammatory activity. Avenanthramides are phenolic compounds present in oats at approximately 300 parts per million (ppm) and have been reported to exhibit anti-oxidant activity in various cell-types. In the current study we investigated whether these compounds exert anti-inflammatory activity in the skin. We found that avenanthramides at concentrations as low as 1 parts per billion inhibited the degradation of inhibitor of nuclear factor kappa B-alpha (IkappaB-alpha) in keratinocytes which correlated with decreased phosphorylation of p65 subunit of nuclear factor kappa B (NF-kappaB). Furthermore, cells treated with avenanthramides showed a significant inhibition of tumor necrosis factor-alpha (TNF-alpha) induced NF-kappaB luciferase activity and subsequent reduction of interleukin-8 (IL-8) release. Additionally, topical application of 1-3 ppm avenanthramides mitigated inflammation in murine models of contact hypersensitivity and neurogenic inflammation and reduced pruritogen-induced scratching in a murine itch model. Taken together these results demonstrate that avenanthramides are potent anti-inflammatory agents that appear to mediate the anti-irritant effects of oats.